‘ . ... .. . . .- .7 .A .- . .‘V . . . -. . .-- .-. .. . wlpvyung ,4.” . . . , ~ . ‘ , ‘ , - , . ' ‘ ~. ‘ I . i“ ' ‘ ‘ ' .' ' ' . > ~ ‘ . ‘- . : A ' . ‘ ‘ . ‘ x _ . j 5‘“ :_' . J .. ‘.- - . . .‘ 4 ‘. .V ‘ * ' ' . f v ~ 1‘ .. I '. ‘ ' " ' ' ' . V . , : '~ ‘ ‘ _, '. -‘ '. ' V‘ ' i ‘ ‘ - i ,1 1' '. V" V .‘ , ‘ ' . V. .f ‘ , , . -. ' , " ' ‘.. : - . ~ .-, -' ~ - - . . U . ‘ . ~ 1" - ‘ 4 ~ A "' is " ;‘U tut-pi. 9007 LIBRARY Michigan State University This is to certify that the dissertation entitled STRUCTURAL EFFECTS IN PHOTOCHEMICAL HYDROGEN ABSTRACTIONS presented by Yana Cen has been accepted towards fulfillment of the requirements for the degree in Chemistry WWW j r Professor’s Signature W /’7 @004 Date MSU is an Affirmative Action/Equal Opportunity Institution PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. MAY BE RECALLED with earlier due date if requested. DATE DUE DATE DUE DATE DUE 2/05 p:/ClRC/DateDue.indd-p.1 STRUCTURAL EFFECTS IN PHOTOCHEMICAL HYDROGEN ABSTRACTIONS By Yana Cen A DISSERTATION Submitted to Michigan State University In partial fulfillment of the requirements For the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 2006 O & P , ‘Q I C . , 0‘ :1 .3 r 5‘ ‘ e t. i- I'r'?‘ ABSTRACT STRUCTURAL EFFECTS IN PHOTOCHEMICAL HYDROGEN ABSTRACTIONS By Yana Cen Conformational effects on photocyclization of various 2-alkoxy-3-alkyl phenyl ketones have been investigated. Actual rate constants for triplet reaction were measured as alkyl substituent was varied, the extent of their increase provides direct measures of conformational equilibria. When these rate constants get large enough, photocyclization can be employed as an internal clock for fast reactions, especially in the solid state. Biradical geometries are also constrained, changes in their lifetimes and product ratios were directly correlated with changes in geometry. Photoinduced carbon-halogen bond cleavage of a series of (1- (haloethoxy)acetophenons and B-(haloethoxy)propiophenones has been studied. This involves competition of cleavage with hydrogen abstraction. Comparisons of product ratios and hydrogen abstraction rate constants of these ketones with those of 6- halovalerophenones reveals that the presence of an oxygen in the skeleton of either 1,4 or 1,5-biradicals facilitates the photocleavage process. Difference in reactivity of both singlet and triplet biradicals derived from o/B-alkoxy aliphatic ketones and the role of environmental and conformational factors in determining the overall efficiency and chemical yield of product formation has been addressed. Steady state kinetics as well as computational study indicate conformational control of reactivity in photocyclization of singlet biradicals. i , _ I 4 I 1 ' ‘_ o Photolysis of a-cyclopropylmethoxyacetophenone confirms that an oxygen conjugated to the radical site would lower the rearrangement rate constant from that for cyclopropylethyl radical. Temperature effect on product ratios shows the triplet biradical lives long enough to allow equilibration. To my parents iv ACKNOWLEDGMENTS ‘The roles of a teacher are preaching the right way; passing on knowledge and solving questions.’ First and foremost, I would like to thank my advisor, Professor Wagner for his guidance, patience, great sense of humor and innumerable entertaining discussions during the course of this work. I am grateful to the National Science Foundation and Michigan State University for financial support in the form of teaching, research assistantships and the Harold Hart fellowship. I would also like to thank the Chemistry Department for the use of its excellent facilities. ‘When I walk along with two others, they may serve as my teachers.’ I would like to thank all my colleagues in Wagner’s group for creating a friendly and stimulating working environment. I owe special thanks to Dr. Ali Zand for continued encouragement and useful discussions. Special thanks are given to all my friends at MSU for their friendship and help. Their support made my graduate career much more enjoyable. Last, but not least, my appreciation is extended to my parents for their continued support, understanding and encouragement during my graduate studies. ‘My life is limited, while knowledge is limitless.’ It will mold me into a better chemist and guide me to choose the right path. TABLE OF CONTENTS LIST OF SCHEMES .............................................................................. viii LIST OF TABLES .................................................................................. xiv LIST OF FIGURES ................................................................................ xix INTRODUCTION .................................................................................... 1 RESULTS ............................................................................................. 16 I. General Procedure ................................................................................ 16 H. Results for 2-Alkoxy-3-alkyl Benzophenones ............................................... 17 A. General Preparation of Ketones ............................................................ 17 B. Identification of Benzofuranols ............................................................. 17 C. Individual Ketones ......................................................................... 18 l. 2-Meth0xy-3-methylbenz0phen0ne (Benzophenone l) .............................. 18 2. 3-Isopr0pyl-2-meth0xybenz0phenone (Benzophenone 2) ........................... 19 3. 3-t-Butyl-2-meth0xybenz0phen0ne (Benzophenone 3) .............................. l9 4. 2-Eth0xy-3-methylbenzophen0ne (Benzophenone 4) ................................. 20 5. 2-Eth0xy-3-is0pr0pylbenzophen0ne (Benzophenone 5) ............................ 21 6. 3-t-Butyl-2-eth0xybenzophen0ne (Benzophenone 6) ................................ 21 7. 2-Benzyloxy-3-methylbenz0furan (Benzophenone 7) ................................ 22 8. 2-Benz'yloxy-3-isopropylbenzophenone (Benzophenone 8) ......................... 23 9. 2-Benzyloxy-3-t-butylbenzophen0ne (Benzophenone 9) ........................... 24 III. Results for 2-Alkoxy-3-alkyl Acetophenones .............................................. 24 A. General Preparation of Ketones ........................................................... 24 B. Identification of Photoproducts ............................................................ 25 1. 2-EIh0xy-3-methylacet0phenone (Acetophenone l0) .............................. 25 2. 2-Eth0xy-3-isopropylacetophenone (Acetophenone ll) ........................... 26 3. 3-t-Buryl-Z-eth0xyacet0phen0ne (Acetophenone 12) ............................... 27 4. 2-Benzyloxy-3-methylacet0phen0ne (Acetophenone 13) ........................... 27 5. 2-Benzyloxy-3-isopropylacetophenone (Acetophenone 14) ....................... 28 6. 2-Benzyloxy-3-t-butylacet0phenone (Acetophenone 15) ........................... 29 IV. Results for a-(Haloethoxy)acetophenones ................................................... 31 A. General Preparation of Ketones ........................................................... 31 B. Identification of Photoproducts ............................................................ 31 C. Individual Ketones .......................................................................... 32 1. a-(Chloroethoxy)acet0phen0ne (16) ................................................... 32 2. a-(Bromoethoxy)acet0phen0ne (17) ................................................... 33 3. a-(Iod0eth0xy)acet0phenone (18) ...................................................... 35 4. a-(2-Br0m0-2-methylpr0p0xy)acet0phenone (l9) ................................... 35 vi V. Results for B-(Haloethoxy)propiophenones .................................................. 36 A. General Preparation of Ketones ............................................................ 37 B. Identification of Photoproducts ............................................................ 37 VI. Results for a-Cyclopropylmethoxyacetophenone (23) ..................................... 38 A. General Preparation ......................................................................... 38 B. Irradiation Conditions ...................................................................... 38 C. Identification of Photoproducts ............................................................ 39 VII. Results for a-Cyclopropylmethoxyacetone (24) .......................................... 41 A. General Preparation ....................................................................... 41 B. Irradiation Conditions .................................................................... 41 C. Identification of Photoproducts ......................................................... 41 VIII. Results for B-Cyclopropylmethoxybutanone (25) ....................................... 42 A. General Preparation ....................................................................... 42 B. Irradiation Conditions .................................................................... 43 C. Identification of Photoproducts ............................................................ 43 DISCUSSION ........................................................................................ 45 I. Conformational Effect on Photobehavior of Substituted Phenyl Ketones ................. 45 A. Substituted Benzophenones .................................................................. 45 B. Substituted Acetophenones .................................................................. 67 II. Photoinduced Carbon-Halogen Bond Cleavage ............................................. 87 A. Substituted Acetophenones .................................................................. 87 B. Substituted Propiophenones ................................................................. 94 III. Triplet Biradical Behavior ..................................................................... 95 IV. Singlet vs. Triplet Behavior .................................................................. 104 A. B-Cyclopropylmethoxybutanone (25) ................................................... 104 B. a-Cyclopropylmethoxyacetone (24) ..................................................... 113 EXPERIMENTAL SECTION ................................................................... 120 I. General Procedures .............................................................................. 120 11. Synthesis: Preparation of Starting Ketones ................................................. 121 A. Substituted 2-Alkoxy-3-alkyl Benzophenones ......................................... 121 B. Substituted 2-Alkoxy-3-alkyl Acetophenones .......................................... 141 C. a-(Haloethoxy)acetophenones ............................................................. 156 D. B-(Haloethoxy)propiophenones ........................................................... 164 E. a/B-Cyclopropylmethoxy Ketones ......................................................... 169 III. Identification of Photoproducts .............................................................. 175 IV. Measurement of Quantum Yields ........................................................... 228 REFERENCES .................................................................................... 298 vii LIST OF SCHEMES Scheme 1. Intramolecular y-Hydrogen Abstraction .............................................. 3 Scheme 2. Intramolecular 5-Hydrogen Abstraction .............................................. 4 Scheme 3. Conformational, Rotational and Ground State Control of Reactivity ............ 4 Scheme 4. Conformational Control of Reactivity ................................................ 4 Scheme 5. Ground State Control of Reactivity ................................................... 5 Scheme 6. Rotational Control of Reactivity ...................................................... 5 Scheme 7. Orientational Requirements for Hydrogen Abstraction ............................ 6 Scheme 8. Effect of Dihedral Angle on Reactivity ............................................... 6 Scheme 9. Chair-Like Transition State for Hydrogen Abstraction ............................. 7 Scheme 10. Rate Enhancement for y-Hydrogen Abstraction ................................... 8 Scheme 11. Rate Enhancement for 6-Hydrogen Abstraction ................................... 8 Scheme 12. Conformational Equilibrium for o-Alkoxyphenyl Ketones .................. 9 Scheme 13. Photochemistry of 5—Halovalerophenones ........................................ 11 Scheme 14. Resonance Structures of 1, 4-Biradical ............................................ 11 Scheme 15. Photochemistry of y-Cyclopropylbutyrophenone ................................ 12 Scheme 16. Photochemistry of a-(2,4,6-Trimethylphenyl)acetone ........................ 15 Scheme 17. Photochemistry of Benzophenone 1 ................................................ 18 Scheme 18. Photochemistry of Benzophenone 2 ................................................ 19 Scheme 19. Photochemistry of Benzophenone 3 ................................................ 19 Scheme 20. Photochemistry of Benzophenone 4 ................................................ 20 Scheme 21. Photochemistry of Benzophenone 5 ................................................ 21 Scheme 22. Photochemistry of Benzophenone 6... ........................................................... 21 viii Scheme 23. Scheme 24. Scheme 25. Scheme 26. Scheme 27. Scheme 28. Scheme 29. Scheme 30. Scheme 31. Scheme 32. Scheme 33. Scheme 34. Scheme 35. Scheme 36. Scheme 37. Scheme 38. Scheme 39. Scheme 40. Scheme 41. Scheme 42. Scheme 43. Scheme 44. Scheme 45. Photochemistry of Benzophenone 7 ................................................ 22 Photochemistry of Benzophenone 8 ................................................ 23 Photochemistry of Benzophenone 9 ............................................................... 24 Photochemistry of Acetophenone 10 .............................................. 25 Photochemistry of Acetophenone 11 .............................................. 26 Photochemistry of Acetophenone 12 .............................................. 27 Photochemistry of Acetophenone 13 ............................................... 28 Photochemistry of Acetophenone 14 .............................................. 29 Photochemistry of Acetophenone 15 ............................................... 30 Photochemistry of 16 in Benzene ................................................... 32 Photochemistry of 16 in Methanol .................................................. 33 Photochemistry of 17 in Benzene Without Additive ............................ 34 Photochemistry of 17 in Benzene With Pyridine ................................. 34 Photochemistry of 18 in Benzene Without Additive ............................ 35 Photochemistry of 18 in Benzene With Pyridine ................................. 35 Photochemistry of 19 in Benzene Without Additive ............................ 36 Photochemistry of 19 in Benzene With Pyridine ................................. 36 Photochemistry of B-(Haloethoxy)propiophenone ............................... 38 Synthesis of 23 ........................................................................ 38 Photochemistry of 23 in Benzene................................ ....39 Photochemistry of 23 in Methanol ................................................. 40 Photochemistry of 24 in Benzene ................................................... 42 Photochemistry of 24 in Methanol ................................................. 42 ix Scheme 46. Scheme 47. Scheme 48. Scheme 49. Scheme 50. Scheme 51. Scheme 52. Scheme 53. Scheme 54. Scheme 55. Scheme 56. Scheme 57. Scheme 58. Scheme 59. Scheme 60. Scheme 61. Scheme 62. Scheme 63. Scheme 64. Scheme 65. Scheme 66. Scheme 67. Scheme 68. Photochemistry of 25 in Benzene ................................................... 43 Photochemistry of 25 in Methanol ................................................. 44 Conformational Equilibrium of o-Alkoxypheny] Ketones ...................... 48 Excited State Equilibrium of 2-Alkoxy-3-alkyl Benzophenones ............... 49 Proposed Mechanism for 2-Alkoxy-3-alkyl Benzophenones .................. 54 Biradical Geometries of 9 ........................................................... 66 Proposed Mechanism for 2-Ethoxy-3-alkyl Acetophenones ................... 69 Biradical Geometry of 2-Ethoxy—3-alkyl Acetophenones ........................ 70 Proposed Mechanism for o-Benzyloxyacetophenone ........................... 71 Photochemistry of 2-Benzyloxy-3-a1kyl Acetophenones ....................... 71 Proposed Mechanism for 2—Benzyloxy-3-a1kyl Acetophenones ............... 74 Photochemistry of 15 ................................................................ 83 Proposed Mechanism for a-(Haloethoxy)acetophenones ....................... 91 Photochemistry of 19 in Benzene Without Additive ............................ 91 Proposed Mechanism for 19 ......................................................... 92 Anchimeric Assistance ............................................................... 93 Proposed Mechanism for B-(Haloethoxy)propiophenones ..................... 95 Photochemistry of 69 ................................................................ 96 Dihedral Angles of 23 .............................................................. 102 Photochemistry of B-Allyloxybutanone .......................................... 108 Norrish Type H Reaction of 24 .........114 Synthesis of l ........................................................................ 121 Synthesis of 2 124 Scheme 69. Scheme 70. Scheme 71. Scheme 72. Scheme 73. Scheme 74. Scheme 75. Scheme 76. Scheme 77. Scheme 78. Scheme 79. Scheme 80. Scheme 81. Scheme 82. Scheme 83. Scheme 84. Scheme 85. Scheme 86. Scheme 87. Scheme 88. Scheme 89. Scheme 90. Scheme 91. Synthesis of 3 ........................................................................ 126 Synthesis of 4 ........................................................................ 128 Synthesis of 5 ........................................................................ 131 Synthesis of 6 ........................................................................ 133 Synthesis of 7 ........................................................................ 136 Synthesis of 8 ........................................................................ 138 Synthesis of 9 ........................................................................ 139 Synthesis of 10 ...................................................................... 142 Synthesis of 11 ...................................................................... 144 Synthesis of 12 ...................................................................... 145 Synthesis of 13 ...................................................................... 147 Synthesis of 14 ...................................................................... 150 Synthesis of 15 ....................................................................... 153 Synthesis of 16 ...................................................................... 157 Synthesis of 17 ...................................................................... 159 Synthesis of 18 ...................................................................... 161 Synthesis of 19 ............................................................................................. 162 Synthesis of 20 ...................................................................... 164 Synthesis of 21 ...................................................................... 167 Synthesis of 22 ....................................................................... 168 Synthesis of 23 ...................................................................... 170 Synthesis of 24 ...................................................................... 171 Synthesis of 25 ...................................................................... 173 xi Scheme 92. Photoproduct from 1 ................................................................ 175 Scheme 93. Photoproduct from 2 ................................................................ 177 Scheme 94. Photoproduct from 3 ................................................................ 178 Scheme 95. Photoproducts from 4 ............................................................... 180 Scheme 96. Photoproducts from 5 ............................................................... 181 Scheme 97. Photoproducts from 6 ............................................................... 183 Scheme 98. Photoproducts from 7 ............................................................... 185 Scheme 99. Photoproducts from 8 ............................................................... 187 Scheme 100. Photoproducts from 9 ............................................................. 190 Scheme 101. Photoproducts from 10 ............................................................ 192 Scheme 102. Photoproducts from 11 ............................................................ 194 Scheme 103. Photoproduct from 12 .............................................................. 196 Scheme 104. Photoproducts from 13 ............................................................ 197 Scheme 105. Photoproducts from 14 ............................................................ 200 Scheme 106. Photoproducts from 15 ............................................................ 203 Scheme 107. Photoproducts from 16 in Benzene .............................................. 205 Scheme 108. Photoproducts from 16 in Methanol ............................................. 206 Scheme 109. Photoproducts from 17 in Benzene ............................................ 208 Scheme 110. Photoproducts from 17 in Benzene With Pyridine...............................208 Scheme 111. Photoproduct from 18 in Benzene ............................................... 211 Scheme 112. Photoproduct from 18 in Benzene With Pyridine ............................. 211 Scheme 113. Photoproducts from 19 in Benzene .............................................. 212 Scheme 114. Photoproducts from 19 in Benzene With Pyridine ............................ 212 xii Scheme 115. Photoproduct from 20 ............................................................. 213 Scheme 116. Photoproduct from 21 ............................................................. 214 Scheme 117. Photoproduct from 22 ............................................................. 215 Scheme 118. Photoproducts from 23 in Benzene ............................................. 216 Scheme 119. Photoproducts from 23 in Methanol.................................................217 Scheme 120. Photoproducts from 24 in Benzene .............................................. 220 Scheme 121. Photoproducts from 24 in Methanol ............................................. 221 Scheme 122. Photoproducts from 25 in Benzene .............................................. 224 Scheme 123. Photoproducts from 25 in Methanol ............................................. 225 xiii LIST OF TABLES Table 1. 2-Alkoxy-3-alkyl Benzophenones ....................................................................... 17 Table 2. 2-Alkoxy—3-alkyl Acetophenones ....................................................... 25 Table 3. a-(Haloethoxy)acetophenones .......................................................... 31 Table 4. B-(Haloethoxy)propiophenones ......................................................... 37 Table 5. Kinetic Results on 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25°C ...... 46 Table 6. kg Values for 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25°.. . . . . . . ........47 Table 7. Chemical Shift of the Alkoxy Carbons of 2-A1koxy—3-alkyl Benzophenones ............................................................................ 50 Table 8. Excited State Equilibrium Constants for 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25°C ....................................................................... 51 Table 9. Solvent Effects on Quantum Yields of 2-Alkoxy-3-alkyl Benzophenones. ......53 Table 10. Arrhenius Data for 2-A1koxy-3-alkyl Benzophenones ............................. 55 Table 11. Temperature Effect on 2-Alkoxy-3-a1kyl Benzophenones .......................... 58 Table 12. Kinetic Results on 2-Ethoxy-3-alkyl Acetophenones in Benzene at 25°C ...... 67 Table 13. k” Values for 2-Alkoxy-3-alkyl Acetophenones in Benzene at 25°C ............ 68 Table 14. 13C Chemical Shifts for 2-Benzyloxy—3-alkyl Acetophenones .................... 72 Table 15. Quantum Yields of 2-Benzyloxy-3-alkyl Acetophenones in Benzene at 25°C ...................................................................... 73 Table 16. Quantum Yields of u-(Haloethoxy)acetophenones at 25°C ....................... 89 Table 17. Kinetic Results on a-(Haloethoxy)acetophenones in Benzene with Pyridine at 25°C ................................................................... 93 Table 18. Kinetic Results on B-(Haloethoxy)propiophenones in Benzene with Pyridine at 25°C ................................................................... 94 Table 19. Quantum Yields of Product Formation for 69 and 23 at 25°C .................... 97 xiv Table 20. Table 21. Table 22. Table 23. Table 24. Table 25. Table 26. Table 27. Table 28. Table 29. Table 30. Table 31. Table 32. Table 33. Table 34. Table 35. Product Ratio for Photolysis of 23 ..................................................... 99 Temperature Effect on Cyclization Stereoselectivity of 23 in Toluene .............................................................................. 100 Quantum Yields for Product Formation of 25 at 25°C ............................ 106 Product Ratio for Photolysis of 25 ..................................................... 107 Quantum Yields for Ketone Disappearance and Product Formation of 24 in Benzene at 25°C .................................................................... 116 Product Quantum Yield of 2-Methoxy-3-methylbenzophenone in Benzene ............................................................................... 235 Product Quantum Yield of 2-Methoxy-3-methylbenzophenone in Methanol ............................................................................. 236 Product Quantum Yield of 3-Isopropyl-2-methoxybenzophenone in Benzene .............................................................................. 237 Product Quantum Yield of 3-Isopropyl-2-methoxybenzophenone in Methanol ............................................................................. 238 Product Quantum Yield of 3-t-Butyl—2-methoxybenzophenone in Benzene ............................................................................... 239 Product Quantum Yield of 3-t-Butyl-Z-methoxybenzophenone in Methanol ............................................................................. 240 Products Quantum Yield of 2-Ethoxy-3-methylbenzophenone in Benzene ............................................................................... 241 Products Quantum Yield of 2-Ethoxy-3-methylbenzophenone in Methanol ............................................................................. 242 Products Quantum Yield of 2-Ethoxy-3-isopropy1benzophenone in Benzene .............................................................................. 243 Products Quantum Yield of 2-Ethoxy—3-isopropylbenzophenone in Methanol ............................................................................. 244 Products Quantum Yield of 3-t-Butyl-2-ethoxybenzophenone in Benzene .............................................................................. 245 XV Table 36. Table 37. Table 38. Table 39. Table 40. Table 41. Table 42. Table 43. Table 44. Table 45. Table 46. Table 47. Table 48. Table 49. Table 50. Table 51. Products Quantum Yield of 3-t-Butyl-2-ethoxybenzophenone in Methanol ............................................................................. 246 Products Quantum Yield of 2-Benzyloxy-3-methylbenzophenone in Benzene .............................................................................. 247 Products Quantum Yield of 2-Benzyloxy—3-methylbenzophenone in Methanol ............................................................................. 248 Products Quantum Yield of 2-Benzyloxy-3-isopropylbenzophenone in Benzene .............................................................................. 249 Products Quantum Yield of 2-Benzyloxy-3-isopropylbenzophenone in Methanol ............................................................................. 250 Products Quantum Yield of 2-Benzyloxy-3-t—butylbenzophenone in Benzene .............................................................................. 251 Products Quantum Yield of 2-Benzyloxy-3-t-buty1benzophenone in Methanol ............................................................................. 252 Product Quantum Yield of 2-Ethoxy-3-methylacetophenone in Benzene .............................................................................. 253 Product Quantum Yield of 2-Ethoxy-3-isopropylacetophenone in Benzene .............................................................................. 254 Product Quantum Yield of 3-t-Butyl-2-ethoxyacetophenone in Benzene .............................................................................. 255 Products Quantum Yield of 2-Benzyloxy-3-methylacetophenone in Benzene .............................................................................. 256 Products Quantum Yield of 2-Benzyloxy-3-isoprpopylacetophenone in Benzene .............................................................................. 258 Products Quantum Yield of 2-Benzyloxy-3-t-butylacetophenone in Benzene ............................................................................... 260 Products Quantum Yield of a-(Chloroethoxy)acetophenone in Benzene with Pyridine ............................................................. 262 Products Quantum Yield of a-(Chloroethoxy)acetophenone in Benzene ............................................................................... 263 Product Quantum Yield of a-(Chloroethoxy)acetophenone xvi Table 52. Table 53. Table 54. Table 55. Table 56. Table 57. Table 58. Table 59. Table 60. Table 61. Table 62. Table 63. Table 64. Table 65. Table 66. Table 67. Table 68. in Acetonitrile ........................................................................... 264 Products QUantum Yield of u-(Bromoethoxy)acetophenone in Benzene with Pyridine .............................................................. 265 Products Quantum Yield of a-(Bromoethoxy)acetophenone in Benzene .............................................................................. 266 Product Quantum Yield of a-(Iodoethoxy)acetophenone in Benzene with Pyridine ............................................................. 267 Product Quantum Yield of a-(Iodoethoxy)acetophenone in Benzene ......... 268 Product Quantum Yield of B-(Chloroethoxy)propiophenone in Benzene. .....269 Product Quantum Yield of B-(Bromoethoxy)pr0piophenone in Benzene. .....270 Product Quantum Yield of B-(Iodoethoxy)propiophenone in Benzene... . .....271 Products Quantum Yield of a-Cyclopropylmethoxyacetophenone in Benzene ............................................................................... 272 Products Quantum Yield of a-Cyclopropylmethoxyacetophenone in Methanol ............................................................................. 273 Products Quantum Yield of u-Cyclopropylmethoxyacetone in Benzene ...... 275 Products Quantum Yield of B-Cyclopropylmethoxybutanone in Benzene....276 Products Quantum Yield of B-Cyclopropylmethoxybutanone in Methanol. . .277 Quenching of the Product Formation in 2-Methoxy-3-methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 278 Quenching of the Product Formation in 3-Isopropyl-2-methoxybenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 279 Quenching of the Product Formation in 3-t-Butyl-2-methoxybenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ........................ 280 Quenching of the Products Formation in 2-Ethoxy-3-methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 281 Quenching of the Products Formation in 2-Ethoxy-3-isopropylbenzophenone with 2,5-Dimethy1-2,4-hexadiene at 313 nm in Benzene ......................... 282 xvii Table 69. Table 70. Table 71. Table 72. Table 73. Table 74. Table 75. Table 76. Table 77. Table 78. Table 79. Table 80. Table 81. Table 82. Table 83. Quenching of the Products Formation in 3-t-Butyl-2-ethoxybenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 283 Quenching of the Products Formation in 2-Benzyloxy-3—methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 284 Quenching of the Products Formation in 2-Benzyloxy-3-isopropylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ............................... 285 Quenching of the Products Formation in 2-Benzyloxy—3-t-butylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 286 Quenching of the Products Formation in 2-Ethoxy-3-methylacetophenone with 2,5~Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 287 Quenching of the Products Formation in 2-Ethoxy-3-isopropylacetophenone with 2,5—Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 288 Quenching of the Products Formation in 3-t-Butyl-2-ethoxyacetophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 289 Quenching of the Products Formation in u-(Chloroethoxy)acetophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ........................ 290 Quenching of the Products Formation in a-(Bromoethoxy)acetophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene .......................... 291 Quenching of the Product Formation in a-(Iodoethoxy)acetophenone with 2,5-Dimethy1-2,4-hexadiene at 313 nm in Benzene ......................... 292 Quenching of the Product Formation in B-(Chloroethoxy)propiophenone with 2,5-Dimethy1-2,4-hexadiene at 313 nm in Benzene ......................... 293 Quenching of the Product Formation in B-(Bromoethoxy)propiophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 294 Quenching of the Product Formation in B-(Iodoethoxy)propiophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene ......................... 295 Quenching of the Products Formation in B-Cyclopropylmethoxybutanone with 2,5-Dimethyl—2,4-hexadiene at 313 nm in Benzene ......................... 296 Quenching of Starting Material Disappearence in a-Cyclopropylmethoxyacetone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene .................................................................. 297 xviii LIST OF FIGURES Figure 1. Jablonski Diagram ......................................................................... 1 Figure 2. Correlation Diagram ..................................................................... 14 Figure 3. Arrhenius plot of 23 .................................................................... 100 Figure 4. Stern-Volmer Quenching Plot of 25 .................................................. 105 Figure 5. Stem-Volmer Quenching Plot of 24 .................................................. 113 xix Introduction Photochemistry is chemical change brought by light. For light to be absorbed, the molecule must have an energy level corresponding in energy to that of the radiation. Organic photochemical reactions involve excited electronic states. Depending on functionality, organic compounds can have electronic absorption bands from the far ultraviolet to the visible region of the spectrum. When a molecule absorbs a quantum of light, the electronic configuration changes to correspond to an excited state. After excitation of a molecule, various intramolecular photophysical processes can occur.1 J ablonski diagram (Figure 1) shows how these processes can be represented and related. There are absorption of a photon by the ground state to produce an excited singlet state, radiative decay processes, namely fluorescence and phosphorescence, and non-radiative decay processes, namely internal conversion and intersystem crossing. excited vibrational states ;/ (excited rotational states not shown) It A- photon absorption F= fluorescence (emisswn) P = phosphorescence S a singlet state T = triplet state IC = internal conversion ISC = intersystem crossing \Q/k. T2 1 electronic ground state Figure 1. Jablonski Diagram Ketones feature prominently in accounts of the earliest systematic studies of both synthetic and mechanistic organic photochemistry. Aliphatic ketones absorb weakly at around 280 nm as a result of an n—>7t* transition that is forbidden on both symmetry and overlap grounds. Intersystem crossing from the n, 7t* singlet to the corresponding triplet is generally efficient, and because the energy and electronic distribution of the 11, 7t* triplet state are not very different from those of the corresponding singlet, the two states often react in the same overall manner.” Intersystem crossing is very efficient for aromatic ketones, so that most of their photochemical reactions are the result of triplet- state processes.4 For many aromatic ketones, the n, 7t* and 7t, 7t* triplet states are similar in energy. This is important because photochemical reaction normally occurs through the lowest state, and the radical-like properties of n, it"‘ states are not shared by 1t, 7t* states. This means that the type of product or the efficiency of reaction can be affected quite drastically by substituents that influence the relative energy levels, and even by the nature of the solvent for borderline cases. n, 7t* excited states of ketones resemble alkoxy radicals in their ability to abstract a hydrogen atom from a suitable donor. This process can also occur from a position within the ketone molecule, and this generates a biradical that may cyclize by combination of the radical centers.5 The efficiency of photochemical abstraction from ketones with it, rt* lowest triplet is quite low as compared to those with 11, 7t* lowest triplet because reaction takes place from low equilibrium populations of the reactive upper triplet.6 This underlines the difference in the electronic nature of the two types of excited states. In an unstrained system a ketone n, rt* excited state shows a preference for abstraction from the y-position, which can be understood on the basis of an energetic preference for reaction by way of a six-atom transition state. y-Hydrogen abstraction generates a 1,4- biradical that can cyclize to give a cyclobutanol, and this type of biradical can also undergo cleavage to give an alkene and the enol of a shorter-chain ketone. The overall photoelimination reaction has been known as Norrish type II reaction7 (Scheme 1). Scheme 1. Intramolecular y-Hydrogen Abstraction Conformational factors undoubtedly play a large part in determining the cyclization/cleavage ratio for the biradical,8 mainly because the two singly occupied orbitals in the biradical and the bonding orbital corresponding to the C(a)-C(B) bond that is broken on cleavage need to be aligned in a parallel way for efficient cleavage. Conformational preferences that inhibit this alignment will promote cyclization. Mechanistic interpretation is complicated by the possibility of reverse hydrogen transfer in the biradical to give ground state of the starting ketone, and it is essential to compare reactivities in terms of rate constant rather than overall quantum yields. The nature of the solvent has a considerable effect in the quantum yield.9 In hydrogen- bonding solvents the hydroxyl group is more strongly solvated, and reverse hydrogen transfer from oxygen to carbon is hindered. Product formation therefore increases in efficiency. The predominant formation of 1,4-biradical in photoinduced internal hydrogen abstraction of ketones can be explained in terms of preferred 1,5-hydrogen transfer in radical chemistry. However, S-hydrogen abstraction does compete with y-hydrogen abstraction: either in a cyclic system with conformational restraint,10 or in ketones that have no y-hydrogen and very reactive B-C-H bonds (Scheme 2).11 Ho Phw Ph““éo + Ph“" 0 Scheme 2. Intramolecular 6-Hydrogen Abstraction The rate constant for hydrogen abstraction and the behavior of l, x-biradicals have revealed the strong influence of conformational effects on such intramolecular processes. The competition between conformational change, reaction and decay provides three boundary conditions:12 (1) conformational equilibrium (2) ground state control (3) rotational control (Scheme 3). o H-C o' H-C OH '0 ULUeO ll ml \ 0— C-HL O— C-H —kd—> other decay Scheme 3. Conformational, Rotational and Ground State Control of Reactivity Alexander has reported that an excited state equilibrium between the two triplet ketone conformers is an important factor in the photochemistry of benzoylcyclobutanesl3 (Scheme 4). 0 Ph H 0 Ph HO Ph V H H V H V H l l J O 3 O 7 HO Ph h lSC Afiph—i’fi A(“\Ph H H Scheme 4. Conformational Control of Reactivity Lewis reported that for 1-methylcyclohexyl phenyl ketones, there exist two different ketone triplets each leading to different photoproducts14 (Scheme 5): the ketone conformer with the benzoyl group in an axial position undergoes y-hydrogen abstraction followed by cyclization; while the other conformer having the benzoyl group in an equatorial position undergoes acyl cleavage giving rise to benzaldehyde. It has been found that the ratio of products from the two pathways is entirely dependent upon the ground state population of each ketone conformer. CH3 —’ é‘CHg, HIGH! i: ficowhv ficoph ——> (5 + Phco —> PhCHO Scheme 5. Ground State Control of Reactivity Another type of conformational effect, rotational control, is found in the photoenolization of o-alkylphenyl ketones.”15 Wagner has proposed a mechanism involving two kinetically distinct ketone rotamers, designated syn and anti (Scheme 6). The anti triplet must first rotate into the syn conformer before enolization can occur. CH3 0 CH3 0‘ OH Ej/KR A. GAR _. [HQ/KR CH3 R CH3 R Scheme 6. Rotational Control of Reactivity LII Four ground state parameters: (1, the distance between O and H; n, the O-H-C angle; v, the C=O—H angle; and a), the dihedral angle that the O-H vector makes with respect to the nodal plane of the carbonyl have been considered to be the most important in determining the rate and efficiency of hydrogen abstraction. Scheffer suggests the theoretically ‘ideal’ values for these parameters shown in Scheme 7.'6 The fact that a few ketones react with larger values of d probably reflects a varying degree of molecular flexibility in different structures. The value of 0 obviously can vary significantly from the linear arrangement thought to be preferable. Likewise, the value of a) can depart from the ‘ideal’ 0°. Both of these have long been known from the reactivity of many steroidal ketones. The meaning of A is the least clear since n, rt* only lengthens carbonyl bonds. d\J"C o“. ideal: A: 90-120° 9: 180° (1): 0° d52.7 A Scheme 7. Orientations] Requirements for Hydrogen Abstraction Sauers has compared the strain energies calculated for the transition states for intramolecular hydrogen abstraction in a variety of cyclic and polycyclic ketones with the observed quantum efficiencies.l7 Several unreactive ketones (Scheme 8) have hydrogens close enough to the carbonyl for reaction but at an angle a) of 90°.18 The short triplet lifetimes of these ketones were attributed to a reversible Norrish type I cleavage that generates very short lives biradicals. OHH 0HPh 0 Scheme 8. Effect of Dihedral Angle on Reactivity H3O H H3O Br 0 Simple straight chain ketones normally have their largest a-substituent eclipsing the carbonyl. The most populated conformer is in a geometry very close to that required for reaction, requiring only rotation around the B-C—y-C bond. The ketone can attain a chair or twist-chair transition state geometry quite easily (Scheme 9).19 This angle is much less than the linear arrangement calculated by theoretical models. It was proposed that the torsional strain present in the cycloheptane-like transition state for 1,6-hydrogen transfer is responsible for the slow rate of 5-hydrogen abstraction in straight chain system. Wagner also suggested that coplanar hydrogen abstraction is not a strict requirement for the t e II rocess and ro osed a coszco de endence for abstraction.20 YP P P P P 0' H H o-CH2': Ph . .~‘ ,8 Ph/5250H2R ‘_—_‘_ PhVH ——> O"H‘ R H H H ’H H Scheme 9. Chair-Like Transition State for Hydrogen Abstraction Intramolecular photochemical y-hydrogen abstraction has been found to be much faster in cyclic ketones than in acyclic ones.21 This is due to an immobilization of the possible rotations involved in the formation of the six-membered transition state required for y- hydrogen abstraction.22 2-Benzoy1norborane requires about the same activation energy for hydrogen abstraction as valerophenone (3.6 i 0.2 kcal/mol). However, the activation entropy for hydrogen abstraction in 2—benzoylnorborane is approximately 8 cu more than for valerophenone (Scheme 10). Therefore, the rate enhancement observed for y- hydrogen abstraction in 2-benzoylnorborane is purely the result of easing the entropic requirements necessary for transition state formation. In light of the results above, a comparison of B-ethoxypropiophenone and a- alkoxyacetophenone with o-benzyloxyphenyl ketones (Scheme 11) provides an estimated MW .3 kn 1.st108 .0x1085 .s70x109 Scheme 10. Rate Enhancement for y-Hydrogen Abstraction rate constant of at least 108 s", ten times faster than what is reported. k 39"28" o o o \(E'HR1R2 R PHW PHJSOIO RH 107 s'1 109 s'1 108 s'1 (predicted) 107 5'1 (observed) Scheme 11. Rate Enhancement for fi-Hydrogen Abstraction Similar result has been reported by Wagner for o-alkoxyphenyl ketones.23 The most important general findings are that acetophenones are much less reactive than benzophenones and give more byproducts; even the benzophenone triplets have small rate constants for 5-hydrogen abstraction. The low rate constants for 8-hydrogen abstraction in these ketones clearly are due to conformational factors, in particular a low equilibrium population of the rotamers in which the alkyl group of the o-alkoxy is syn to the carbonyl (Scheme 12). The fact that o-benzyloxy ketones are much more reactive than o-methoxy ketones, as expected by their relative C-H bond strengths, indicates that reactions are not limited by bond rotation rates but rather involve rotational equilibrium prior to rate-determining hydrogen abstraction. 2,6-Diacy1 methoxy and benzyloxy compounds all display triplet reaction rates at least ten times faster than those for monoketones. This fact substantiates the unfavorable rotational equilibrium about the benzene-oxygen bond. The comparable reactivities of 2-alkoxy and 2,6-dialkoxy ketones indicate that the triplets achieve rotational equilibrium about the benzene-acyl bond before reaction, and this equilibrium favors the reactive rotamer. R RH RCH2\O RCH2\O OCH2 (5*6‘ (5* (5*?" Scheme 12. Conformational Equilibrium for o-Alkoxyphenyl Ketones All of the benzophenones studied have n, 7t* lowest triplets. The significant lower kH values observed for the acetophenones reflect their 7t, 1t* lowest triplet configurations. Any further 3n, 7t*-stabilizing substitution would lower rate constants so much that hydrogen abstraction would occur only in very low quantum efficiency. Blankspoor reported that a methyl group ortho to the alkoxy group enhances the quantum yield for reaction of comparable quinines by changing the conformational equilibrium.24 This effect will be examined in 2-alkoxy-3-alkylbenzophenones and acetophenones for the following reasons: 1) actual rate constants for triplet reaction can be measured as alkyl group is varied, the extent of their increase will provide direct measures of conformational equilibria; 2) biradical geometries also will be constrained, changes in product ratio can then be directly correlated with changes in geometry. Many free radical processes involve carbon—halogen bond breaking as the rate determining step or as a competing reaction. Compounds which undergo photochemically-induced carbon-halogen bond cleavage are useful as synthetic intermediates and as initiators for free radical polymerizations.”26 Although the photochemical cleavage of carbon-halogen bonds has been known for some time, few attempts have been made to measure or even estimate the rate of bond cleavage. The general trend of higher yields and greater ease of reaction for the series: C- I>C-Br>C-Cl>>>C-F is in agreement with bond strengths.27 A practical method for measurement of the rates of carbon-halogen cleavage could involve competition of cleavage with some other well-defined photochemical process. By measuring the relative amounts of cleavage versus the competing reaction, the relative rates can be measured. If the competing reaction has rate constants which are known or easily measured, absolute rates for carbon-halogen bond cleavage can be calculated. A further requirement for the competing process is its ability to be incorporated into the same molecule as the carbon-halogen moiety and to react from excited states that also cleave carbon-halogen bonds. The Norrish type H reaction is ideal for monitoring rate constants of competing excited state reactions. Rate constants for y-hydrogen abstraction can be determined from maximized quantum yields and triplet lifetimes and can vary depending on structures, thus providing a highly variable clock.28 The regioselectivity of the reaction makes it easy to monitor both biradical and radical reactions. Due to the intense interest in B-haloalkyl radicals,29‘3’0‘31 Wagner’s group has studied the photochemistry of several 8-halovalerophenones.32 They undergo loss of HX competitive with type II elimination (Scheme 13). The halogens are eliminated from 1,4- biradical intermediate involved in type H photoelimination. The results provided the first extensive set of relative B-cleavage rates of radicals. Another intriguing phenomenon is the large acceleration of 1,4-biradical decay caused by an oxygen atom between the two radical sites.33 A probable contributor to the lifetime-shortening effect of B-oxygen is the decreased average distance between the 10 (Ni // C) ,/ .+ x--—————» -+ HX ' Ph Scheme 13. Photochemistry of 6-Halovalerophenones —> ——-> + Ph Ph ' Ph’fl\\ I Ph unpaired electrons due to the resonance form (Scheme 14). Other explanations might derive from conformations which provide an angle of approximately 90° between the oxygen 2p orbital and the half-filled p orbital at the adjacent terminus. Such conformations will provide maximal spin orbital coupling. Some behavior of 1,5- biradicals is very similar to that of 1,4-biradicals, such as they do have shorter lifetime with an oxygen atom as part of the skeleton, which is ascribed to different conformational freedoms of the biradicals. i + .. t l C-C-O-C C-C-O- 0 Scheme 14. Resonance Structures of 1, 4-Biradical We have studied the photobehavior of several a-haloethoxyacetophenones and B- haloethoxypropiophenones at various environments to gain better understanding of the factors that control the B-haloelimination reactivity. These results in conjunction with the results of 6-halovalerophenones have been used to compare and contrast biradical/radical reactivity with an oxygen in skeleton versus their carbon analogues. The behavior of biradical is of great interest especially whether monoradical reactions of biradicals occur with the same rate constants as those of simple radicals. In the case of intramolecular rearrangement occurred in y—cyclopropylbutyrophenone (Scheme 15),34 the rate constant for ring opening is the same in the biradical as in the model 11 cyclopropylethyl radical. It is believed that the two unpaired electrons are too weakly coupled to affect rate constants for reactions of biradicals with singlet species. + Ph Ph ' Ph/lK ‘_ UV OH / _' O Q Ph ' + Ph ' Pit/[WV Scheme 15. Photochemistry of y-Cyclopropylbutyrophenone One of the most intriguing questions in organic photochemistry is whether the differences in spin multiplicity between singlet and triplet states will be reflected in their reactivity in primary photochemical processes. Yang has shown that in aliphatic ketones that rate of cleavage from the triplet is about one hundred times faster than the singlet.35 Dialkylketones are known to undergo hydrogen abstraction in both the T1 and S] states.36'37’38 Photolysis of the optically active ketone (S)-(+)-5-methy1—2-heptanone showed that photoracemization occurs from the triplet state, suggesting the existence of a triplet biradical sufficiently long lived to allow racemization at the y-carbon.39 The results obtained with the optically active ketone showed that the total quantum yield of observed events from T1 is only 0.14. Since (DISC was determined to be 0.11 and the quantum yield for reaction from S] is 0.07, the remaining quantum yield of 0.79 must represent non radiative decay from S]. This decay appears to lead to no racemization and is not affected by changes on the solvent, which implies that if it does involve formation of a singlet biradical and subsequent back hydrogen transfer, then the biradical must be extremely short-lived. 12 It has also been suggested that Norrish type II reaction from 81 may occur via a concerted pathway.38 Heller has proposed that the electronic energy might be transferred into vibrational stretching energy of a C-H bond, with further partitioning into a pair of radicals (or biradical) or to a relaxed ground state.40 Hammond has also postulated that chemical reactions of the excited states are special forms of radiationless decay."’1 Salem has calculated the activation energies and surface crossing for singlet and triplet state hydrogen abstractions.42 It has been shown that simple symmetry considerations indicate that the n, 7t* singlet of the carbonyl correlates with the singlet biradical product, whereas the ground state correlates with a zwitterionic species. Since the plane of symmetry is not maintained in most hydrogen abstractions, an avoided crossing between the excited and ground state surfaces occur (Figure 2). Hydrogen abstraction therefore requires a radiationless decay which can occur easiest at the point of the smallest energy difference between the two surfaces. Conversion of the electronic energy into vibrational energy populates the ground state at a maximum, from which relaxation to biradical product or to ground state reactant can occur. Scaiano has studied fluorescence quenching of acetone by several hydrogen donors.43 They reported the excited singlet of acetone to be 2-10 times more reactive than the triplet toward hydrogen donors. They have ascribed this to a more exothermic reaction from the singlet which results in a lower activation energy for hydrogen abstraction. The lower quantum yield for product formation from the singlet is lower than in the triplet. They attributed this inefficiency to deactivation of the excited state to yield the reactant from an avoided crossing before a radical pair is reached. It was concluded that the interaction of the singlets with hydrogen donors is not a 13 chemical reaction but a physical quenching mechanism, where the hydrogen donor causes deactivation by accepting part of the electronic excitation energy as vibrational energy and promoting internal conversion from S1 to 80.37’42 ti ii Correlation Diagram AHf (kcal moi“ ) 4L 45 o A + H-SnBu3 X + 'SnB'Is Figure 2. Correlation Diagram Wagner’s group has studied the photobehavior of several a-(o-alkylphenyl) and a- (2,4,6-trialkylphenyl)acetones (Scheme 16) at various temperature.44 Quenching studied indicate that 6-hydrogen abstraction occurs from the singlet while a-cleavage occurs from the triplet; temperature effects on quantum yields demonstrated that there is an enthalpic barrier to hydrogen abstraction at low temperature whereas intersystem crossing has 14 none; diastereoselectivity indicated conformational control of reactivity in photocyclization of singlet biradicals. Chandra’s group found the presence of ether oxygen in a position B to the carbonyl group in a-alkoxyacetones leads to an overall decrease in the energy of activation and an hv . OH + O I 0 ”’CH3 Scheme 16. Photochemistry of I1-(2,4,6-Trimethylphenyl)acetone increase in the exothermic nature of the intramolecular y—hydrogen abstraction process relative to the corresponding alkyl ketones.45 Their theoretical analysis showed that the singlet 1,4-biradical derived from u-alkoxyacetones can cyclize readily to form 3- oxetanol although experimental results have not been reported. From a mechanistic point of view, the difference in the reactivity of both singlet and triplet biradicals derived from a/B—alkoxy aliphatic ketones and the role of environmental and conformational factors in determining the overall efficiency and chemical yield of product formation must be addressed. To examine the influence of these factors, we decided to study the photolysis of fi-cyclopropylmethoxybutanone and a- cyclopropylmethoxyacetone. By comparing the results for these ketones with their aromatic counterparts, we hope to gain a better understanding of the factors that control singlet state and/or singlet biradical reactivity. 15 Results 1. General Procedures The common protocol for the photochemical studies was to first conduct NMR screening experiments. The experiments provided several advantages over conventional analysis (gas chromatography and HPLC) especially if the resulting photoproducts were thermally labile or readily air oxidized. A 1H NMR spectrum was acquired prior to irradiation. The sample was then irradiated at the appropriate wavelength and a second 1H NMR spectrum is acquired at low conversion, usually after 20 or 30 minutes. The reaction was monitored periodically depending on the efficiency of the reaction. If the photochemical reaction was successful then a large scale reaction was conducted in the equivalent non—deuterated NMR solvent and monitored by NMR, GC, or HPLC. Comparing the NMR screening results with the large scale results provided information about the stability of the resulting photoproducts. This information was necessary in order to distinguish the excited state chemistry from the thermal chemistry. When possible the products of the photoreaction were isolated by silica gel column chromatography. However it was not always possible to isolate the photoproducts due to their thermal lability and acid sensitivity. In such cases, the products were identified by their crude IH NMR spectrum. Quantum yields were measured by irradiation of degassed solutions of ketones in tubes containing a fixed amount of internal standard parallel to valerophenone actinometer. The product concentrations were determined by GC, HPLC or 1H NMR. The quenching studies were conducted in the same manner as the quantum yields but with various concentrations of 2,5-dimethyl-2,4-hexadiene as a quencher. l6 II. Results for 2-Alkoxy-3-alkyl Benzophenones A. General Preparation of Ketones The substituted 2-alkoxy-3-alkyl benzophenones were synthesized by ortho-lithiation. The corresponding aromatic ether was allowed to react with n-butyl lithium. The aryl lithium species was then reacted with benzaldehyde in diethyl ether. The resulting alcohol was oxidized with FCC to yield the desired benzophenone. Table 1 provides the structures of the ketones studied. ORO ”W Table 1. 2-Alkoxy-3-alkyl Benzophenones Ketone R R’ Abbreviation 2-meth0xy-3-methylbenz0phen0ne CH3 CH3 1 3-isopr0pyl-2-meth0xybenz0phen0ne CH3 CH(CH3)2 2 3-t-butyl-2-methoxybenzophenone CH3 C(CH3)3 3 2-eth0xy-3-methylbenzophenone CH3CH2 CH3 4 2-eth0xy-3-isopropylbenzophenone CH3CH2 CH(CH3)2 5 3-t-buryl-Z-ethoxybenzophenone CH3CH2 C(CH3)3 6 2-benzyloxy-3-methylbenzophen0ne PhCHz CH3 7 Z-benzyloxy-3-isopr0pylbenzophen0ne PhCHz CH(CH3)2 8 2-benzyloxy-3-t-butylbenzophen0ne PhCHz C(CH3)3 9 B. Identification of Benzofuranols l7 Irradiation of degassed benzene solution of various 2-alkoxy-3-alky1 benzophenones produced the corresponding substituted 3-hydroxy-2,3-dihydrobenzofuranols as the major products. Cis and trans refer to the position of the 2-substituent and the hydroxyl group. Most of the chemical shifts for the hydrogens at C-2 appear between 4.2 and 5.6ppm. The appearance of this resonance was used to gauge the progress of the photochemical reaction. Structural assignments were based on spectral data obtained for these compounds (1H and '3 C NMR, IR and mass spectrum). The stereochemical assignments of the dihydrobenzofuranols were based on nOe experiments: irradiation of 3-hydroxy proton caused an enhancement of the C—2 proton signal. This suggests that the benzofuranol has a trans-stereochemistry. C. Individual Ketones 1. Z-Methoxy-B-methylbenzophenone (Benzophenone 1) CH30 o O OH hv, rex O O 756’»? O O 1 26 Scheme 17. Photochemistry of Benzophenone 1 Irradiation of a 0.048 M benzene-d6 solution gave only one product, benzofuranol 26 (Scheme 17), in quantitative yield. The reaction was complete (100% conversion) after 20 minutes of irradiation. The formation of 26 was independent of light source and was formed by irradiation with either a medium pressure mercury arc lamp (Pyrex filtered) or in a Rayonet reactor (300nm lamps). The quantum yield for 26 formation was measured at 313 nm by GC and found to be 0.51 (7.3% conversion). The singlet at 3.36ppm for 2- 18 methoxy group disappeared at the same rate as the growth of two doublets at 4.27ppm (J: 10.2 Hz) and 4.42ppm (J: 9.9 Hz) in benzene—d6. 2. 3-Isopropyl-2-methoxybenzophenone (Benzophenone 2) CH30 o O OH hv, Eyrex 0606 2 27 Scheme 18. Photochemistry of Benzophenone 2 Irradiation of a 0.039 M benzene-d6 solution of 2 gave quantitatively benzofuranol 27 (Scheme 18). The reaction was complete (100% conversion) after 20 minutes of irradiation with Pyrex filtered light. During the course of the reaction the methyl signal at 3.60ppm disappeared with the simultaneous formation of two new signals at 4.29 and 4.38ppm. The quantum yield for 27 formation was measured at 313 nm by GC and found to be 0.64 (8.4% conversion). 3. 3-t-Butyl-2-methoxybenzophenone (Benzophenone 3) CH30 o O OH hv, rex O O 73‘s" O O 3 28 Scheme 19. Photochemistry of Benzophenone 3 Irradiation of 0.039 M 3 in benzene-d6 at room temperature gave benzofuranol 28 quantitatively within 15 minutes (Scheme 19). The quantum yield for 28 formation was measured at 313 nm by GC and found to be 0.79 (6.6% conversion). The methyl singlet l9 at 3.55ppm disappeared at the same rate as the growth of two doublets at 4.28 and 4.44ppm in benzene-d6. 4. 2-Ethoxy-3-methylbenzophenone (Benzophenone 4) 4.44ppm 1.31 ppm 0.82%: :./60ppm '1! CH3 1.28ppm H3C' H 72ppm EtO O 0 0H/ 0 '- OH/L hv, rex O O + O O 4 ole-29 trans-29 Scheme 20. Photochemistry of Benzophenone 4 Irradiation of a 0.040 M solution of 4 at room temperature in benzene-d6 resulted in formation of two products (Scheme 20). Preparative scale irradiation in benzene followed by column chromatography using 2% ethyl acetate in hexanes, resulted in isolation of photoproducts which were identified by their NMR spectra (in C(,D(,) as two isomeric benzofuranols (cis-29 and trans-29). Methyl doublets were most informative because it is generally accepted that a methyl cis to the phenyl is significantly shielded relative to the one trans. The chemical shift of methyl group of trans isomer was shifted much more upfield than that of cis isomer. It was also noteworthy that the methine hydrogen cis to the phenyl was more shielded than the one trans to phenyl. NOe experiments were also performed. Irradiation of the methine quartet of one isomer at 4.60ppm caused an enhancement of the OH signal at 1.72ppm. However, irradiation of the methine quartet of the other isomer at 4.44ppm did not result in signal enhancement of the OH hydrogen at 1.28ppm. Thus, the former was assigned as the trans while the latter was assigned as the cis isomer. The ratio of the two isomeric benzofuranols were 3.3: 1, 4.521 and 4.9:1 at - 78°C, 0°C and 25°C, respectively. 20 5. 2-Ethoxy-3-isopropylbenzophenone (Benzophenone 5) 4.48ppm 1.33ppm 0.82ppm 4.62ppm lj CH3 1.29ppm H3Q H 17299") BO 0 0 '° OH/ 0 ' OH hv,P rex O O —L» O O + O O 5 ale-30 trans-30 Scheme 21. Photochemistry of Benzophenone 5 Irradiation of 5 in benzene (Scheme 21) resulted in formation of two isomeric benzofuranols (cis-30 and trans-30). Preparative scale irradiation in benzene followed by column chromatography (hexanes: ethyl acetate 40:1) resulted in isolation of the photoproducts which were identified by their corresponding NMR spectra. Stereochemical assignment of the two isomers was made using nOe experiments. Irradiation of the methine quartet signal in the trans isomer at 4.62ppm resulted in enhancement of the OH signal at 1.72ppm, while similar irradiation in the cis isomer resulted in no such enhancement. The product ratios were determined by NMR analysis. The ratio of the two isomeric benzofuranols were 2.9:1, 4.2:] and 45:1 at -78°C, 0°C and 25°C, respectively. Irradiation of crystalline 5 resulted in a 1.821 cis/trans benzofuranol ratio. 6. 3-t-Butyl-2-ethoxybenzophenone (Benzophenone 6) 4.47ppm typpm 0.81ppm 4.60ppm "1 CH3 H39 171 BO 0 O ._ OH’/1.29ppm O ,- OH’/. ppm hv, Eyrex O 0 + O O 6 ate-31 trans-31 Scheme 22. Photochemistry of Benzophenone 6 21 Irradiation of a 0.037 M solution of 6 in benzene-d6 at room temperature resulted in formation of two products (Scheme 22). Preparative scale irradiation in benzene followed by column chromatography, using 2% ethyl acetate in hexanes, resulted in isolation of photoproducts which were identified by their NMR spectra (in C6D6) as two isomeric benzofuranols (cis-3l and trans-31). The chemical shift of methyl group of trans isomer was shifted much more upfield than that of cis isomer. It was also noteworthy that the methine hydrogen cis to the phenyl was more shielded than the one trans to phenyl. NOe experiments were also performed. Irradiation of the methine quartet of one isomer at 4.60ppm caused an enhancement of the OH signal at 1.71ppm. However, irradiation of the methine quartet of the other isomer at 4.47ppm did not result in signal enhancement of the OH hydrogen at 1.29ppm. Thus, the former was assigned as the trans while the latter was assigned as the cis isomer. The ratio of the two isomeric benzofuranols were 1:2.7, 13:1, 19:1 and 2.421 at —78°C, -20°C, 0°C and 25°C, respectively. 7. 2-Benzyloxy-3-methylbenzophenone (Benzophenone 7) 5. 57 ppm 5/ 61 ppm 1 /53ppm OP“ HO Hg. .OOppm BnO 0 DO 7 ole-32 trans-32 Scheme 23. Photochemistry of Benzophenone 7 Irradiation of 7 in benzene-d6 resulted in formation of two products (Scheme 23) which were identified as two isomeric benzofuranols (cis-32 and trans-32) by their NMR spectra. Preparative scale irradiation in benzene followed by column chromatography (hexanes: ethyl acetate 30:1~20:1) resulted in separation of photoroducts. The product 22 ratios were determined by comparing the NMR integration of the methine singlets at 5.57ppm and 5.61ppm of two isomers. Stereocherrrical assignment of the two isomers was made using nOe experiments. Irradiation of the methine singlet signal in the trans isomer at 5.61ppm resulted in enhancement of the OH signal at 2.00ppm, while similar irradiation in the cis isomer resulted in no such enhancement. It was also noteworthy that the OH hydrogen cis to the phenyl was more shielded than the one trans to phenyl. Irradiation of 7 at -78°C, -20°C, 0°C and 25°C resulted in a 24:1, 3.8:], 4.0:1 and 4.7:1 ratio, respectively. 8. 2-Benzyloxy-3-isopropylbenzophenone (Benzophenone 8) BnO O hv, Pyrex 0 O toluene-d8 5.61 ppm 5.62ppm Scheme 24. Photochemistry of Benzophenone 8 Benzophenone 8 (0.031 M) in deuterated toluene was irradiated with Pyrex filtered light from a medium pressure mercury arc lamp. The reaction was complete within 20 rrrinutes and two isomeric benzofuranols (cis-33 and trans-33) formed (Scheme 24). The product ratios were determined by comparing the NMR integration of the OH singlets at 1.53ppm and 1.96ppm of two isomers. Stereochemical assignment of the two isomers was made using nOe experiments. Irradiation of the methine singlet signal in the trans isomer at 5.62ppm resulted in enhancement of the OH signal at 1.96ppm, while similar irradiation in the cis isomer resulted in no such enhancement. It was also noteworthy that the OH hydrogen cis to the phenyl was more shielded than the one trans to phenyl. 23 Irradiation of 8 at -78°C, -20°C, 0°C and 25°C resulted in a 1.821, 2.621, 2.9:] and 3.421 ratio, respectively. 9. 2-Benzyloxy-3-t-butylbenzophenone (Benzophenone 9) 5.63ppm 5.60ppm P11 H 1.86ppm 800 o o ‘ 0H hv, rex e o—% o o 9 trans-34 Scheme 25. Photochemistry of Benzophenone 9 Irradiation of 9 in toluene-d8 (Scheme 25) resulted in formation of a mixture of two isomeric benzofuranols (cis-34 and trans-34). Preparative scale irradiation in benzene followed by column chromatography (hexanes: ethyl acetate 30:1~20:1) resulted in separation of the benzofuranols. The product ratios were measured by NMR analysis to be 1:27, 1:12, 1:1 and 14:1 at -78°C, -20°C, 0°C and 25°C, respectively. They were determined by NMR integration of the OH singlet signal of the cis-isomer at 1.56ppm to that of the trans-isomer at 1.86ppm. Stereochemical assignment of the two isomers was made using nOe experiments. Irradiation of the methine singlet signal in the trans isomer at 56me resulted in enhancement of the OH signal at 1.86ppm, while similar irradiation in the cis isomer resulted in no such enhancement. It was also noteworthy that the OH hydrogen cis to the phenyl was more shielded than the one trans to phenyl. III. Results for 2-Alkoxy-3-alkyl Acetoghenones A. General Preparation of Ketones 24 The substituted 2-alkoxy-3-alkyl acetophenones were synthesized by ortho-lithiation. The corresponding aromatic ether was allowed to react with n-butyl lithium. The aryl lithium species was then reacted with acetaldehyde in diethyl ether. The resulting alcohol was oxidized with FCC to yield the desired acetophenone. Table 2 provides the structures of the ketones studied. ORO Table 2. 2-Alkoxy-3-alkyl Acetophenones Ketone R R’ Abbreviation 2-ethoxy~3-methylacet0phenone CH3CH2 CH3 10 2-eth0xy-3-is0pr0pylacet0phen0ne CH3CH2 CH(CH3)2 11 3 -t-butyl -2-eth0xyacet0phen0ne CH3CH2 C(CH3)3 12 2-benzyloxy-3-methylacetophen0ne PhCH2 CH3 13 2-benzyl0xy-3-isopropylacetophenone PhCHz CH(CH3)2 14 2-benzyloxy-3-t-butylacetophenone PhCHz C(CH3)3 15 B. Identification of Photoproducts 1. 2-Ethoxy-3-methylacetophenone (Acetophenone 10) 4.03pm: 1f8ppm 1.30 (1.37) ppm «5.06 5.18 m E10 0 QCHs 15019:“ H3C H ( ) pp OH O OH\ _hV»_P)"e_X- .., + 2.26 (2.35) ppm 0606 CH3\ 1 26ppm 10 619-35 36 Scheme 26. Photochemistry of Acetophenone 10 25 The photobehavior of 10 at room temperature was conversion dependent. At low conversion cis-35 and two isomeric hemiketals (36) were the major products (Scheme 26). The two hemiketals were identified by the following NMR signals in benzene: methyl doublets at 1.30 and 1.37ppm, methine quartets at 5.06 and 5.18ppm, OH singlets at 2.26 and 2.35ppm. At high conversion the benzofuranol was the only observable photoproduct. The cis-stereochemistry was assigned based on nOe experiment: irradiation of the methine quartet at 4.03ppm caused an enhancement of the methyl singlet at 1.26ppm. Preparative scale irradiation was carried out upon low conversion of the starting ketone, stability of the two hemiketals allowed them to be isolated by column chromatography on deactivated silica gel. They were obtained as a 1:1 mixture. 2. 2-Ethoxy-3-isopropylacetophenone (Acetophenone 11) 4.05ppm 1231 ppm 1 .36 (1 .43) ppm \ H30 H‘- 5.22 (5.34) ppm EtO O H CH3 096ppm CBDG ”’CH3\ CH3 \ 1.26ppm 1.70 (1.77) ppm 11 eta-37 38 Scheme 27. Photochemistry 0f Acetophenone 11 The photobehavior of 11 at room temperature was conversion dependent. At low conversion cis-37 and two isomeric hemiketals (38) were the major products (Scheme 27). The two hemiketals were identified by the following NMR signals in benzene: methyl doublets at 1.36 and 1.43ppm, methine quartets at 5.22 and 5.34ppm, allylic methyl singlets at 1.70 and 1.77ppm. At high conversion the benzofuranol was the only observable photoproduct. The cis-stereochemistry was assigned based on nOe experiment: irradiation of the methine quartet at 4.05ppm caused an enhancement of the 26 methyl singlet at 1.26ppm. Preparative scale irradiation was carried out upon low conversion of the starting ketone. The two hemiketals could not be isolated due to a rapid decomposition on silica gel. 3. 3-t-Butyl-2-ethoxyacetophenone (Acetophenone 12) BO 0 hv, rex C606 1 2 ole-39 3.98ppm 1 .22ppm \ 1:1 CH3 /0.89I39m O'OH CH3 \1.19ppm Scheme 28. Photochemistry of Acetophenone 12 Benzophenone 12 (0.025 M) in deuterated benzene was irradiated with Pyrex filtered light from a medium pressure mercury arc lamp. The reaction was complete within 30 minutes and only one product (cis-39) formed (Scheme 28). The stereochemical assignment was made based on nOe experiment: irradiation of the methine quartet at 3.98ppm caused an enhancement of the methyl singlet at 1.19ppm. 4. 2-Benzyloxy-3-methylacetophenone (Acetophenone l3) Irradiation of a 0.019 M solution of 13 at room temperature in benzene-d6 resulted in formation of a mixture of products (Scheme 29). Preparative scale irradiation in benzene followed by column chromatography, using 3% ethyl acetate in hexanes, resulted in isolation of photoproducts which were identified by their NMR spectra (C6D6 or CDC13) as one benzofuranol (cis-40), one benzyl transfer product (41), one debenzylation product (42), dimerized hydroxyacetophenone (44). The two hemiketals (43) formed during the irradiation could not be isolated due to rapid decomposition on silica gel, their presence 27 was confirmed by the two singlets at 5.84 and 5.96ppm in the NMR spectrum of the reaction mixture. The chemical shift of the OH signal from the benzofuranol indicated a cis configuration relative to the 2-phenyl, nOe experiment was also performed: irradiation of benzylic methine signal at 5.00ppm caused an enhancement of the methyl singlet at 1.39ppm. 5.00ppm 2.16ppm \H Ph 0.96ppm \ OH O ’1./88p pm ’. / H C O 3 CH 1.39ppm 3 ”CH3 + Bn 1:19-40 41 1 1 .9ppm (C0013) 2.24ppm (CDCI3) / 2.61 ppm (CDCI3) BnO O \ HO O hv, Pyrex + H30 CH3 (3st 13 42 2.69ppm (CDCI3) 5.96 5.84 \ 2.32 CDCl ( )ppm CH3 * ppm( 3) O OH + + HO OH O 43 44 Scheme 29. Photochemistry of Acetophenone 13 5. 2-Benzyloxy-3-isopropylacetophenone (Acetophenone 14) Irradiation of a 0.020M solution of 14 at room temperature in benzene-d6 resulted in formation of a mixture of products (Scheme 30). Preparative scale irradiation in benzene followed by column chromatography, using 3% ethyl acetate in hexanes, resulted in isolation of photoproducts which were identified by their NMR spectra (C6D6 or CDC13) 28 as one benzofuranol (cis-45), one benzyl transfer product (46), one debenzylation product (47), dimerized hydroxyacetophenone (49). The two hemiketals (48) formed during the irradiation could not be isolated due to rapid decomposition on silica gel, their presence was confirmed by the two singlets at 5.92 and 6.05ppm in the NMR spectrum of the reaction mixture. The chemical shift of the OH signal from the benzofuranol indicated a cis configuration relative to the 2-phenyl, nOe experiment was also performed: irradiation of benzylic methine signal at 5.04ppm caused an enhancement of the methyl singlet at 1.38ppm. 5-04ppm 1 .28Epm \H Ph ’/1.02ppm CH3 OH O 1.97ppm O . OH popm CH3 "’CH3 + Bn cis-45 46 11.8ppm (CDCI3) 1.22ppm (CDCla) 2,52ppm (CDCI3) BnO o \H3C HO 0 / hv, rex 14 47 2.03ppm (CDC'S) 1,33ppm (CDC'3) 5.92 (6.05) ppm CH3 PhH 0 CH3 + O OH + HO O O OH 0 48 49 Scheme 30. Photochemistry of Acetophenone 14 6. 2-Benzyloxy-3-t-butylacetophenone (Acetophenone 15) 29 5.06ppm 1 .43ppm \l-l Ph ’/0.94ppm J30 HO O 1.83ppm O . OH 1.38ppm CH3 "’CH3 + Bn ole-50 51 12.1 ppm (CDCls) 1.40ppm (CDCla) 2,62ppm (CDCI3) BnO o \HSC HO 0 / hv, Pyrex W 0606 + WCHS 15 52 2.70ppm (CDC'3) 1_46ppm (CDCI3) 5.85 (5.98) ppm CH3 Ph H 0 CH3 0 OH + + HO O O OH O 53 54 Scheme 31. Photochemistry of Acetophenone 15 Irradiation of a 0.018M solution of 15 at room temperature in benzene-d6 resulted in formation of a mixture of products (Scheme 31). Preparative scale irradiation in benzene followed by column chromatography, using 1% ethyl acetate in hexanes, resulted in isolation of photoproducts which were identified by their NMR spectra (C6D6 or CDCl3) as one benzofuranol (cis-50), one benzyl transfer product (51), one debenzylation product (52), dimerized hydroxyacetophenone (54). The two hemiketals (53) formed during the irradiation could not be isolated due to rapid decomposition on silica gel, their presence was confirmed by the two singlets at 5.85 and 5.98ppm in the NMR spectrum of the reaction mixture. The chemical shift of the OH signal from the benzofuranol indicated a cis configuration relative to the 2-phenyl, nOe experiment was also performed: irradiation 30 of benzylic methine signal at 5.06ppm caused an enhancement of the methyl singlet at 1.38ppm. IV. Results for a-(Haloethoxy[acetophenones A. General Preparation of Ketones a-(Haloethoxy)acetophenones were prepared by basic condition ring opening of styrene oxide, tosylation with tosyl chloride, Dess—Martin oxidation and substitution with halides. a-(2-bromo—2-methylpropoxy)acetophenone was prepared by basic condition ring opening of styrene oxide, PCC oxidation followed by Markovnikov addition of HBr to alkene. Table 3 provides the structures of the ketones studied. 0 RR' ©JK/OQ4X Table 3. a-(Haloethoxy)acetophenones Ketone X R R’ Abbreviation a-(chloroethoxy)acet0phenone C] H H 16 a—(bromoethoxykzcetophenone Br H H 17 a-(iodoethoxy)acetophenone I H H 18 a-(2-br0m0-2-methylpropoxy)acet0phen0ne Br CH3 CH3 l9 B. Identification of Photoproducts NMR scale irradiations were carried out using 0.03~0.04M solutions of ketones in 31 deuterated benzene or methanol. The solutions were irradiated through a Pyrex filter (>290nm). In C6D6 with the presence of pyridine, most ketones underwent loss of HX competitive with type H elimination. In the case of 16, oxetanol and acetophenone were detected after irradiation. Irradiations in benzene-d6 without pyridine or in methanol-d4 always resulted in formation of a complex mixture of several products due to competitive reactions and secondary reactions. Preparative irradiations were carried out in benzene with or without pyridine. C. Individual Ketones 1. a-(Chloroethoxy)acetophenone (16) 4.87ppm (CDCI3) 2.51ppm (CDCI3) H“/4.77ppm (CDCI3) O O ‘ o __'1v__.. 0 ©/“\/ \/\CI benzene-d5 ©/u\ + "1H /5.05ppm (CDCI3) ‘ Cl 16 55 cIs-SG Scheme 32. Photochemistry of 16 in Benzene Irradiation of 16 in benzene-d6 (Scheme 32) resulted in formation of two products which were identified as acetophenone (55) and an oxetanol (cis-56) by their NMR spectra. Preparative scale irradiation in benzene followed by column chromatography (hexanes: ethyl acetate 40:1~20:1) resulted in separation of photoproducts. The product ratio was determined by comparing the NMR integration of the methyl singlet of acetophenone at 2.06ppm to that of the methine signal of the oxetanol at 4.82ppm. Irradiation with the presence of pyridine gave the same outcome as the one without pyridine. During the reaction process, the solutions kept water-white. The cis- 32 stererochemistry of the oxetanol was determined by performing nOe experiment: irradiation of the methine signal at 5.05ppm caused an enhancement of one of the aryl proton signals (7.53ppm). O O\/\C| hV methanol-d4 4 31 ppm 15 3. 46ppm ('3' R :YKH/ 4. 10ppm 6. 54ppm Scheme 33. Photochemistry of 16 in Methanol The behavior of 16 in deuterated methanol is conversion dependent. At low conversion, irradiation resulted in formation of a mixture of compounds (Scheme 33). 58 was identified by the following NMR signals in methanol: two vinyl protons at 4.31 and 4.10ppm, a vinylidene proton at 6.54ppm. 57 showed a triplet at 3.46ppm corresponding to the OH proton. The two isomeric oxetanols (56) were identified by the triplets at 4.63 and 4.71ppm corresponding to the methylenes on the four-membered rings. At high conversion, the signals corresponding to 58 disappeared. The cis:trans oxetanol ratio decreased as irradiation time increased, ranging from 1.5:1 to 1.3:1. No attempt was made to isolate the products. 2. a-(Bromoethoxy)acetophenone (17) The behavior of 17 was environment dependent. Irradiation of 17 in benzene or toluene 33 O 2.07ppm O 4.32ppm O 55 4.43, 4.52ppm O\/\Br hV / \ benzene-d6 H H HO O 17 + /1.88ppm H CH3 / 5 81ppm Scheme 34. Photochemistry of 17 in Benzene Without Additive without pyridine resulted in formation of a mixture of compounds (Scheme 34). Preparative scale irradiation followed by column chromatography (hexanes: ethyl acetate 8:1) resulted in the separation of photoproducts. The structural assignments of 55 and 57 were based on their NMR spectra as well as comparison with authentic samples of 55 and 57. The oxetanol (59) formed was identified by the following signals in the NMR spectrum of the photolysis mixture: a methine quartet at 5.8lppm (J: 5.4 Hz), a methyl doublet at 1.88ppm (J: 5.4 Hz), two doublets at 4.43 and 4.52ppm corresponding to two methylene protons. 4.13ppm O O O O\/\ Br _hv_. 0% H\ benzene-d6 + H 3.93ppm pyridine \6'31po 17 55 58 Scheme 35. Photochemistry of 17 in Benzene With Pyridine When the irradiation was carried out in benzene-d6 with the presence of pyridine resulted in the formation of two products (Scheme 35): 55 and 58. They were isolated by preparative irradiation followed by column chromatography (hexanes: ethyl acetate 20:1) 34 and identified by their NMR spectra. The product ratio was determined by comparing the NMR integration of the methyl singlet of 55 to that of the vinylidene quartet of 58. Irradiation of 17 in deuterated methanol resulted in formation of a complex mixture. Their structures were uninterpretable due to signal overlap. 3. a-(Iadoethoxy)acetophenone (18) O O benzene-d6 18 57 Scheme 36. Photochemistry of 18 in Benzene Without Additive The behavior of 18 was also environment dependent. Irradiation of 18 in deuterated benzene gave only one product (Scheme 36): 57, and the solution turned dark red after irradiation. In the same solvent with pyridine, photolysis resulted in formation of 58, and the solution remained colorless with some white precipitates (Scheme 37). O O O\/\ | hv 0% benzene-d6 pyridine 18 58 Scheme 37. Photochemistry of 18 in Benzene With Pyridine 4. a-(2-Bromo-2-methylpropoxy)acetophenone (19) The NMR scale photoreaction of 19 in benzene-d6 yielded three photoproducts: 55, 57 and 60 (Scheme 38). Structural assignment of 60 was based on the following signals in the NMR spectrum of the photolysis mixture: two methyl doublets at 1.07 and 1.13ppm (J: 6.6 Hz), a methine multiplet at 2.20ppm, another methine doublet at 5.83ppm (J: 3.6 35 Hz), two doublets at 4.53 and 4.54ppm corresponding to the methylene protons. No attempt was made to isolate the products. 1.07.1. 13ppm OH3/\C CH3 0 0% H.\5 83ppm Br hv benzene-d6 O O 19 OH + + 55 57 Scheme 38. Photochemistry of 19 in Benzene Without Additive The NMR scale reaction was also canied out in deuterated toluene with the presence of pyridine. Irradiation gave two major products (Scheme 39): 55 and 61. The structure of 61 was determined by the following signals in the NMR spectrum of the photolysis mixture: two methyl singlets at 1.45 and 1.71ppm, a vinylidene signal at 5.66ppm and a singlet at 4.35ppm corresponding to the methlyene protons. During the irradiation the solution remained colorless with the formation of some white precipitates. No attempt was made to isolate the products. 145171ppm O 0 Br CH dk/ toluene-d8 ©/U\:1OH/: 3 + ©/u\ pyridine \5. 66ppm 19 Scheme 39. Photochemistry of 19in Benzene With Pyridine V. Results for - Haloethox ro io henones 36 A. General Preparation of Ketones B-(Haloethoxy)propiophenones were prepared by Michael addition of ethylene glycol to phenyl vinyl ketone, tosylation with tosyl chloride followed by substitution with halides. Table 4 provides the structures of the ketones studied. (3va Table 4. B-(Haloethoxy)propiophenones Ketone X Abbreviation fl-(chloroethoxy)prpi0phen0ne C l 20 ,6-(bromoethoxy)propiophenone Br 21 ,B-(iodoethoxy)propi0phenone I 22 B. Identification of Photoproducts NMR scale irradiations were carried out using 0.03 M solutions of ketones in deuterated benzene with the presence of pyridine. The solutions were irradiated through a Pyrex filter (>290 nm). The ketones underwent loss of HX to yield 62 (Scheme 40). Its structure was determined by the following NMR signals: two triplets at 3.33 and 4.13ppm corresponding to two methylenes, two vinyl protons at 4.02 and 4.24ppm, and a vinylidene signal at 6.45ppm. All the reaction solutions remained colorless during the irradiation with the formation of white precipitates. As for 20, NMR scale reaction was also carried out in methanol-d4 with pyridine. Results were conversion dependent: at low conversion, the only observable product was 62; at high conversion, the irradiation gave a 37 complex mixture. Preparative irradiation was carried out in benzene with pyridine. 4.13ppm 6. /45ppm 0 4. 02ppm WON X @840 03;,H/ benzene- -d6 H pyridine 5.4.24po 3. 33ppm 20, 21 or 22 62 Scheme 40. Photochemistry of B-(Haloethoxy)propiophenone VI. Results for a-C clo ro lmethox aceto henone 23 A. General Preparation Cyclopropylmethanol was treated with sodium hydride in THF solution with the presence of HMPA, then styrene oxide was added dropwise to this solution to afford a benzylic alcohol. The following Swem oxidation gave desired product 23 (Scheme 41). O OH a. NaH, HMPA OVA a-(COC')2-DM50 of HO/V THF, reflux _ CH2C|2,-78°C 2 b. styrene oxide? b.E13N,-78°C~rt , 23 Scheme 41. Synthesis of 23 B. Irradiation Conditions NMR scale irradiations were carried out using 0.04~0.05 M solutions of 23 in deuterated benzene, toluene, acetonitrile and methanol. The solutions were irradiated through a Pyrex filter. The ketone was irradiated at -70°, -15°, 25° and 80°C to determine the effect of temperature on product ratios. The desired temperatures were attained by dry 38 ice-acetone, NaCl-ice, water (at RT) and heated silicon oil baths, respectively. Preparative irradiations were carried out in t-butanol and methanol. C. Identification of Photoproducts 4.84ppm 4.64ppm \ / H ‘H 0 HO ' ©/u\ + ©\“. 0 O\/A hv, Pyrex 55 ”9'83 benzene-d6 4.99ppm ;68me 23 \H \H ",H/4.30ppm Hag: o + O = = H\ 4.09ppm A trans-63 Scheme 42. Photochemistry of 23 in Benzene Acetophenone 23 (0.035 M) in deuterated benzene was irradiated with Pyrex-filtered light from a medium pressure mercury arc lamp. The reaction resulted in formation of three products (Scheme 42): two isomeric oxetanols (63) and acetophenone (55). The reaction was repeated at different temperaures and product ratios were determined by NMR. The stereochemical assignments of the two oxetanols were based on nOe experiment: irridiation of the methine doublet at 4.09ppm in the minor isomer caused an enhancement of the OH signal, irridiation of the methine doublet at 4.30ppm in the major isomer caused an enhancement of one of the aryl proton signals. It was also noteworthy that the methine hydrogen cis to the phenyl was less shielded than the one trans to phenyl. These data strongly suggest that the minor isomer has a trans-stereochemistry, 39 and the major isomer has a cis-stereochemistry. Irradiation in deuterated toluene and acetonitrile resulted in the same three products. Temperature effect has also been investigated at various temperature in toluene. The diastereomeric ratio of oxetanols was determined by NMR integration of the methine doublet signals corresponding to each isomer. Preparative irradiation was conducted in t-butanol followed by column chromatography on deactivated silica gel. NMR scale irradiation was also carried out in methanol-d4 and four products formed (Scheme 43). Besides two isomeric oxetanols (63) and 55, a rearrangement product 64 was also observed. Its structure was determined by the following NMR signals: a methyl triplet at 0.95ppm, a doublet of quartet at 1.93ppm corresponding to the methylene protons, two vinylidene signals at 4.89 and 6.31ppm. The E—stereochemistry of the double bond was determined by coupling constant of the two vinylidene protons (J: 12.5 Hz). Preparative irradiation in methanol followed by column chromatography on deactivated silica gel resulted in the isolation of photoproducts. 4N89p m 63?? .. \ O 6. 31/ ppm H‘\1.9 93ppm O\/A hv, Pyrex 52 methanol-d4 so 0 HO HO + + + z A 46 ale-61 trans-61 O. 95ppm Scheme 43. Photochemistry of 23 in Methanol 40 VII. Results for a-Cyclopropylmethoxyacetone (24) A. General Preparation Cyclopropylmethanol was treated with sodium hydride in THF solution with the presence of HMPA, then propylene oxide was added dropwise to this solution to afford a secondary alcohol. The following Swem oxidation gave desired product 24. B. Irradiation Conditions NMR scale irradiations were canied out using 0.04 M solutions of 24 in deuterated benzene, acetonitrile and methanol. The solutions were irradiated through a Pyrex filter. Preparative irradiations were carried out in benzene and methanol. C. Identification of Photoproducts Irradiation of 24 in benzene-d6 resulted in the formation of acetone and an oxetanol (cis-65) (Scheme 44). The product ratio was determined by NMR integration of the methine doublet signal of the oxetanol and the methyl singlet signal of acetone. The structural assignment of the oxetanol (cis-65) was accomplished by performing nOe experiments. Irridiation of the methine doublet at 3.89ppm caused an enhancement of the methyl signal, this suggests that this oxetanol has a cis-stereochemistry. Photolysis of 24 in deuterated acetonitrile gave the same two products. Preparatory scale reaction was conducted in benzene, the following column chromatography resulted in the isolation of products. The behavior of 24 in methanol-d4 was quite different from that in benzene or 41 4.35, 4.39ppm O h , El! 0 . /u\/0\A betrzenree-Zs /U\ + 24 ale-65 Scheme 44. Photochemistry of 24 in Benzene acetonitrile. Irradiation also gave two products (Scheme 45): acetone and an acetal (66). The acetal has the following NMR signals in CDCl3Z methyl singlet at 1.33ppm, methoxy signal at 3.20ppm, two methylene signals at 3.31 and 3.4lppm. Considering the acidity of deuterated methanol, the preparative reaction was conducted in purified methanol. However, the same result as that of the NMR scale reaction was obtained. The following column chromatography resulted in the isolation of 66. 0 __3L.h. 0 H 988% )J\/0\/A mgthamrjfd, /U\ + f3 H HH ii 24 66 Scheme 45. Photochemistry of 24 in Methanol VIII. Results for fi-Cyclopropylmethoxybutanone (25) A. General Preparation 25 was prepared by Michael addition of cyclopropylmethanol to methyl vinyl ketone under basic condition. 42 B. Irradiation Conditions NMR scale irradiations were carried out using 0.04~0.06 M solutions of 25 in deuterated benzene, toluene and methanol. The solutions were irradiated through a Pyrex filter. The ketone was irradiated at -78°, 25° and 0°C to determine the effect of temperature on product ratios. The desired temperatures were attained by dry ice-acetone, ice water and water (at RT), respectively. Preparative irradiation was carried out in benzene. C. Identification of Photoproducts 5.85ppm 6.171313"1 \ 4.34ppm o H/ o ,/ MOM + /U\/\O)\£H H‘ZJQppm M M. 0% benzene-d5 135me 1.43ppm 25 \ HO H3C + H3O! .\ + HO’ O \ r 275me 1.70ppm cls-68 Scheme 46. Photochemistry of 25 in Benzene 25 (0.038 M) in deuterated benzene was irradiated with Pyrex-filtered light from a medium pressure mercury arc lamp. The reaction resulted in formation of four products (Scheme 46): two isomeric tetrahydrofuranols (68) and two isomeric 4- butenyloxybutanones (67). The stereochemical assignments of the two THFs were based on nOe experiment: irradiation of the methine doublet at 2.75ppm in the major isomer caused an enhancement of the methyl signal, irradiation of the methine signal at 2.94ppm 43 in the minor isomer caused an enhancement of the OH signal. These data suggest that the major isomer has a cis-stereochemistry and the minor isomer has a trans-stereochemistry. The stereochemical assignments of the two 4-butenyloxybutanones were determined by coupling constant of the two vinylidene protons: the coupling constant for E—isomer was 12.6 Hz, for Z—isomer was 6.9 Hz. Irradiation in deuterated toluene resulted in the same four products. Product ratio was determined by NMR integration of the vinyl proton signals of 67 and the methine signals (doublets) of the THFs. Preparative irradiation conducted in benzene followed by column chromatography resulted in isolation of photoproducts. NMR scale irradiation was also carried out in methanol-d4 and two isomeric THFs (68) formed (Scheme 47). A» Scheme 47. Photochemistry of 25 in Methanol Discussion I. Conformational Effect on Photobehavior of Substituted Phenyl Ketones A. Substituted Benzophenones It is widely accepted that the rate constant for the quenching of triplets by energy transfer in benzene at 25°C is 506.0 x 109 M'ls".46’47 Wagner has shown that energy transfer is sensitive to the degree of steric congestion ortho to the carbonyl.23 kq values were measured by nanosecond laser flash spectroscopy for a number of o—alkoxyphenyl ketones, having o-alkoxy substituents of various sizes. Most ketones have kq values on the order of 2.9 x 109 M’ls'l. The steric bulk of the o-alkoxy substituents prevent complete overlap of the n—orbitals of ketone and quencher. The result is a lower than normal kq value for those ketones. Reciprocal triplet lifetimes were calculated from the slopes of Stern-Volmer quenching plots (k4) assuming that kq= 2.9 x 109 M'ls'l for all ketones. These reciprocal triplet lifetimes are presented in Table 5. The reciprocal triplet lifetime, 1:4, is a sum of the rate constants for hydrogen abstraction, k”, and the triplet decay, kd. That is, I": k” + kd. Wagner has found kd values for o-alkoxybenzophenones on the order of 1.7 x 105 3".48 There is no known reason why kd values should be sensitive to an extra alkyl substituent, i.e., kd’s for 2-alkoxy-3-alkyl benzophenones and o-alkoxybenzophenones should be equal. 5-Hydrogen abstraction rate constants calculated from reciprocal triplet lifetimes and assumed kd value are presented in Table 6. 45 Table 5. Kinetic Results on 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25°C Ketone R R’ qua, M'1 1'", ns 1 CH3 CH3 629.7 217 2 CH3 CH(CH3)2 673 232 3 CH3 C(CH3)3 333.3 114.9 4 CH3CH2 CH3 91.6 31.6 5 CH3CH2 CH(CH3)2 105.5 36.4 6 CH3CH2 C(CH3)3 65.7 22.7 7 PhCHz CH3 19.1 6.6 8 PhCHz CH(CH3)2 60 20.7 9 PhCHz C(CH3)3 l 1 3.8 aValue obtained by Stern-Volmer quenching of product formation. bkq= 2.9 x 109 M's“. The quantum yield for photoproduct formation from these ketones can be represented by. (I) = (Disckuta where (Disc = intersystem crossing quantum yield k” = rate constant for S-hydrogcn abstraction T = ketone triplet lifetime or = efficiency with which biradical converts to product Intersystem crossing quantum yield for aromatic ketone is 1.0. If a is 1.0, then (1)1" equals k“. If a is less than unity, this product represents a lower limit for k“. Values calculated from both assumptions are presented in Table 6. 46 Table 6. kn Values for 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25°C Ket‘m R R, (1,. 16:51 1531:“ 1105;" 1 CH3 CH3 0.51 4.61 4.44 2.35 2 CH3 CH(CH3)2 0.64 4.31 4.14 2.76 3 CH3 C(CH3)3 0.79 8.70 8.53 6.87 4 CH3CH2 CH3 0.47 31.6 31.4 14.9 5 CH3CH2 CH(CH3)2 0.53 27.5 27.3 14.6 6 CH3CH2 C(CH3)3 0.75 44.1 43.9 33.1 7 PhCHz CH3 0.68 151.5 151.3 103.0 8 PhCHz CH(CH3)2 0.74 48.3 48.1 35.7 9 PhCHz C(CH3)3 0.90 263.2 263.0 236.9 aTotal quantum yield. bCalculated from 1/1.', assuming kd = 1.7 x lO5 8‘. cProduct of (D and 1/1. Discrepancies between the two calculated kH values may come when 01 is less than one. Biradical inefficiencies are well known in ketone photochemistry, that is probably the case for these ketones. S-Hydrogen abstraction rate constants are sensitive to the reactivity of the alkoxy hydrogens. Benzophenone 7 is 34 times more reactive than 1 and 4.8 times more reactive than 4, reflecting the greater reactivity of a benzylic hydrogen in comparison with a primary or secondary hydrogen. The same trend has also been observed for 3-isopropyl- and 3-t-butylbenzophenones. Previous study in our group showed that o—alkoxyphenyl ketones undergo slow 5- 47 hydrogen abstraction from their triplets because the alkoxy group prefers a conformation unfavorable to reaction, as shown in Scheme 48.23 Blankespoor reported that a methyl group ortho to the alkoxy group enhances the quantum efficiency for reaction of comparable anthraquinones by changing the conformational equilibrium.24 This effect has been examined in 2-alkoxy-3-alkyl benzophenones. F1 R OJ 0 |\O O (DAR. ._ (DAR, syn. syn anti, syn Scheme 48. Conformational Equilibrium of o-Alkoxyphenyl Ketones For o-alkoxybenzophenones, coplanarity of the alkoxy substituted benzene ring with the carbonyl and rotation about the acyl-phenyl bond do not have significant effect on the rate of hydrogen abstraction. 2,6-Diacylalkoxybenzenes have been used as models for the (syn, syn) conformer, the large kn values for these compounds indicate that the alkoxy group rotation is important to the overall hydrogen abstraction mechanism, and the interconversion of the two conformers resulting from such a rotation is due to excited state equilibrium. The preferred excited state conformation of o-alkoxybenzophenones is one in which the alkoxy group is rotated away from the carbonyl group, then the alkoxy hydrogens are not as available to the carbonyl oxygen in this arrangement as they would be if the alkoxy group was pointing towards the carbonyl. Hence, 5-hydrogen abstraction may be more efficient for 2-alkoxy-3-alkyl benzophenones than for o-alkoxybenzophenones. In all cases, this rate enhancement is observed for 2-alkoxy 3-alkyl benzophenones (Table 6). A mechanism based upon excited state equilibrium is summarized in Scheme 49. 48 OO 00 Kex 00 W77. JRI O), OH O OH 00 Scheme 49. Excited State Equilibrium of 2-Alkoxy-3-alkyl Benzophenones The 13C NMR chemical shifts of the alkoxy carbons in 3-substituted 2- alkoxybenzophenones are 6 to 7ppm downfield relative to those of their 0- alkoxybenzophenone counterparts (Table 7). In this system, increasing bulky alkyl substituents force the alkoxy group out of the plane of the benzene ring, thereby disrupting conjugation of the alkoxy oxygen with the aromatic system. This loss of conjugation is manifested by the higher chemical shift values of the alkoxy carbons of theses compounds. The exact geometry of the (syn, syn) conformer is most likely one in which the alkoxy group is not totally coplanar with the aromatic system, but approaches co-planarity as far as steric repulsions from the carbonyl will allow it. This conformation is still reactive since the alkoxy hydrogens are still quite accessible to the carbonyl oxygen. Excited state equilibrium constants can be calculated from the ratio of kH for an 2- 49 Table 7. Chemical Shift of the Alkoxy Carbons of 2-Alkoxy-3-alkyl Benzophenones OCHZR‘ R COPh R R’ 60-0mm, ppm H H 55.5 CH3 H 61 . 8 CH(CH3)2 H 62.9 C(CH3)3 H 62.1 H CH3 63 .9 CH3 CH3 70.4 CH(CH3)2 CH3 71.4 C(CH3)3 CH3 70.8 H Ph 70.0 CH3 Ph 76.5 CH(CH3)2 Ph 77.5 C(CH3)3 Ph 76.7 alkoxy-3-alkyl benzophenone to that of its 2,6-diacylalkoxybenzene analogue. This calculation assumes that the 2,6-diacylalkoxybenzenes provide an accurate measure of k" for the (syn,syn) conformer of the corresponding 2-alkoxy-3-alkyl benzophenones. That is, R“ for 2,6-diacylalkoxybenzenes represent the intrinsic kH values for their corresponding 2-alkoxy-3—alkyl benzophenone analogues. The calculation was based on Winstein ——Holness principle.49 This principle, which holds only for systems in which 50 conformational changes are faster than reaction, states that, kHobs = K“ kHint where kHObS = observed rate constant for hydrogen abstraction (kg for 2-alkoxy-3-a1kyl benzophenone) Kex = excited state fractional equilibrium population of the reactive conformer knit" = intrinsic hydrogen abstraction rate constant (kH for the appropriate 2,6-diacylalkoxybenzene) These excited state equilibrium constants are summarized in Table 8. Table 8. Excited State Equilibrium Constants for 2-Alkoxy-3-alkyl Benzophenones in Benzene at 25 °C R R’ kg, 10‘ s’1 K... H CH3 2.35 0.107 H CH(CH3)2 2.76 0.126 H C(CH3)3 6.87 0.314 H COPh 21.9 Ph CH3 103.0 0.417 Ph CH(CH3)2 35.7 0.145 Ph C(CH3)3 236.9 0.959 Ph COPh 247.0 51 The Kex values for 2-methoxy and 2-benzyloxybenzophenones are quite different. This would seem to indicate that the magnitude of Kex is influenced by the size of the alkoxy substituents. Excited state equilibrium favors the unreactive conformer in 2-methoxy—3- methylbenzophenone (1) by nearly 9:1, that number drops to 3:1 in 3-t-butyl-2- methoxybenzophenone (3). The same trend has also been found for their 2-benzyloxy counterparts, especially for 2-benzyloxy-3-t-butylbenzophenone (9) the excited state equilibrium highly favors the reactive conformer with a Kex almost equals to 1. Hence, the steric repulsion due to the 3-alkyl groups gets stronger than that due to the carbonyl group with the size of the 3-alkyl substituents. The hydrogen abstraction rate constants for 3-isopropyl benzophenones do not differ much from their 3-methyl analogues. It is well known that methyl and isopropyl have similar conformational energies,27 with the value for the isopropyl group (2.1 kcal/mol) being only slightly larger than that of the methyl group (1.8 kcal/mol). The similar values of the two substituents reflect the fact that rotation about the bond between the substituent and the ring allows the isopropyl to adopt a conformation that minimizes the effect of its additional methyl substituents. A t-butyl (>4.5 kcal/mol) substituent experience a strong van der Waals repulsion with the o-alkoxy group which cannot be relieved by rotation about the bond to the ring. The quantum efficiency for cyclization is lower in methanol than in benzene (Table 9), in sharp contrast to the solvent effects observed on quantum efficiencies of product formation for o-alkoxybenzophenones. It is well known that pyridine and other weak Lewis bases, such as t-butyl alcohol, solvate the 1,5-biradical derived from 0- 52 Table 9. Solvent Effects on Quantum Yields of 2-Alkoxy-3-alkyl Benzophenones ”8*. RI J O O 0 O hv R l RI H 5' 0’0H ”fl Solvent R R’ (has (Dam (bum Benzene CH3 H 0.5 1 Methanol CH3 H 0.35 Benzene CH(CH3)2 H 0.64 Methanol CH(CH3)2 H 0.46 Benzene C(CH3)3 H 0.79 Methanol C(CH3)3 H 0.51 Benzene CH3 CH3 0.39 0.08 0.47 Methanol CH3 CH3 0.09 0.24 0.33 Benzene CH(CH3)2 CH3 0.43 0. 10 0.53 Methanol CH(CH3)2 CH3 0. 10 0.28 0.38 Benzene C(CH3)3 CH3 0.53 0.22 0.75 Methanol C(CH3)3 CH3 0.09 0.32 0.41 Benzene CH3 Ph 0.56 0.12 0.68 Methanol CH3 Ph 0.21 0.47 0.68 Benzene CH(CH3)2 Ph 0.57 0. 17 0.74 Methanol CH(CH3)2 Ph 0.23 0.5 1 0.74 Benzene C(CH3)3 Ph 0.53 0.37 0.90 Methanol C(CH3)3 Ph 0.18 0.56 0.74 53 alkoxybenzophenone and suppress disproportionation of the biradical to starting ketone, resulting in an enhancement of the photocyclization quantum yield.50 For 2-alkoxy-3- alkylbenzophenones, it may be possible that solvation of the biradical reduces the rate constant for cyclization enough to make some other biradical process competitive. A possible pathway is outlined in Scheme 50. According to this mechanism, the biradical has two competitive cyclization reactions available to it: one leads to formation of the usual benzofuranol photoproducts, the other leads to formation of the quinoid structure a. Methanol would not affect the rate with which the biradical cyclizes to a, since such a cyclization does not involve the hydroxyl proton. Rearrangement of a to the starting ketone should be fast since it involves a rearomatization of the benzene ring. I RI J R‘ n o o o'OH 0 OH R “V R R 0 0 —“ —7 0 0 : Scheme 50. Proposed Mechanism for 2-Alkoxy-3-alkyl Benzophenones Methanol solvation of the biradical also results in a reverse Stereoselectivity for biradical cyclization. In benzene, cyclization of biradicals derived from 2-alkoxy-3- alkylbenzophenones clearly favors formation of the kinetically preferred product. That is, cyclization of these biradicals in hydrocarbon solvent favors the isomer in which the less bulky hydroxyl group is cis to the C-2 alkyl (cis-isomer). Solvation in methanol increases the steric bulk of the hydroxyl group, since methanol is now hydrogen bonded to the hydroxyl proton, the hydroxyl group is now comparable in size to a methyl (in 2- ethoxyl-3-alkylbenzophenone derived biradical) or a phenyl (in 2-benzyloxy-3- alkylbenzophenone derived biradical), cyclization proceeds with opposite stereochemical preference. Our temperature studies along with serniemperical calculations indicates that not only activation enthalpies, but also their entropies (the A factors in the Arrhenius equation, k = Ae'Ea/RT), which may reflect the intersystem crossing rates of the biradical rotamers, are responsible for the observed diastereoselectivities. Table 10. Arrhenius Data for 2-Alkoxy-3-alkyl Benzophenones Ketone Am/ ”a,” AEa, kcal/mol 4 10.3 0.44 5 10.7 0.51 5 88.3 2.1 7 16.6 0.75 8 10.8 0.70 9 15.7 1.46 Product ratios are influenced by the energies and hydrogen abstraction rates of reactive excited state conformer as well as interconversion and cyclization rates of biradical rotamers. Energies of reactive triplet conformers mirror those of reactive ground state minima since the only significant change in geometry due to n, 71'' excitation is a slight lengthening of the C-O bond.51 The hydrogen abstraction rates are dependent on the orientation of the abstractable hydrogen relative to the nodal plane of the carbonyl group52 and are assumed to be similar for various conformers. These factors control the 55 product ratio only when cyclization is faster than interconversion of biradical rotamers (ground state control). When biradicals interconvert faster than they cyclize, which is the case for most triplet biradicals due to their long lifetime, only energies and cyclization rates of various conformers influence product ratios (conformational control). Thus, in cases where the photocyclization is conformationally controlled, the product ratios can be calculated using,53 . (‘is trans 613/ tr ans = (Xcis/Xtrans)'(k cyc/k cyc) where Xa-s and Xmm are the population of the biradicals leading to cis and trans indanols, kfiscyc and "we” are the rates of the cyclizations for different conformers. The populations of different rotamers are determined by the difference in their free energies which are presumed to be dominated by enthalpies. There are several known mechanisms for ISC of biradicals.S4 In short biradicals, ISC is mainly driven by spin-orbit coupling, which is known to be very much dependent upon the distance and orientation of radical centers.55‘56‘57 The observed diastereoselectivities can be explained by the calculated energies, which reflects the conformational population, and cyclization rates which contain the intersystem crossing term. 2-Ethoxy-3-methylbenzophenone (4): Experimental results show the cis-benzofuranol to be the major cyclization product under all conditions. Ground state global minimizations indicate the presence of two reactive geometries, a low energy A (d=2.40 A, 00: 68°) in a pro—cis and a pro-trans geometry B (d: 2.51A, (0: 38°) 0.1 kcal/mol higher in energy. Arrhenius data for 4 indicate the pro-trans precursor to be enthalpically more stable 56 than the pro-cis one by 0.44 kcal/mol. Global minimization on the biradical from 4 show the presence of two minima within 0.42 kcal/mol of each other. The global minimum a is in a pro—trans geometry, and pro-cis (b) geometry is higher in energy than a by 0.41 kcal/mol, in good agreement with the experimental values. The difference in A factors can be attributed to a faster cyclization rate of the pro-cis precursor, due to its higher energy which in turn means a lower activation energy for cyclization. Therefore, the photocyclization of 4 is believed to be conforrnationally controlled which means that the biradical lives long enough to allow equilibration. Furthermore, the difference in the A factors indicates that there needs to be an activation energy for cyclization. 57 Table 11. Temperature Effect on 2-Alkoxy-3-alkylbenzophenones T 4 5 6 7 8 9 o C Solvent ( ) cisztrans cisztrans cisztrans cisztrans cisztrans cis:trans -78 Benzene 3.29:1 2.89:1 1:2.67 2.39:1 1.76:1 1:2.71 -20 Benzene 1.3: l 3.77:1 2.58:1 1:1.22 0 Benzene 4.53:1 4.22:1 1.87:1 4.04:1 2.89:1 1.03:1 25 Benzene 4.90:1 4.52:1 2.4:] 4.7:] 3.4:1 1.4:] 25 Crystal 1.76:1 25 Methanol 1:2.2 1:2.35 1:2.5 1:1.72 1:1.76 1:2.6 2-Ethoxy-3-isopropylbenzophenone (5): Global minimization (semiempirical- AMl level) with dihedral drivers around substituted benzene-acyl and ether oxygen-benzene bonds have shown that 5 has three energy minima within 0.5 kcal/mol of each other. In the lowest energy geometry A, the closest methylene hydrogen is 2.39 A away and makes a dihedral angle of 73° with the carbonyl 0 plane. The other minimum B is 0.45 kcal/mol higher in energy than the global minimum. B (d1=2.52 A, (01: 60°; d2=2.79 A, (02: 83°) has both methylene hydrogens close enough for abstraction. Another minimum C, which lies 0.47 kcal/mol above the global minimum, has a hydrogen 2.32 A (0): 56°) from carbonyl oxygen. 58 The Arrhenius plot is linear which indicates that the biradical conformers are equilibrated at all temperatures. Semiempirical minimizations reveal the presence of four minima within 2.2 kcal/mol of each other. Three of these (a, b and c) are in the pro-cis geometry and the other one ((1) is in a pro-trans geometry. Conforrnations b and c are respectively 1.5 and 1.8 kcal/mol higher in energy than a. The highest energy conformer (d) is 2.2 kcal/mol higher than a and will not contribute much to the overall yield of trans—benofuranol. Arrhenius data, however, indicate that the conformation leading to trans should be 0.51 kcal/mol more stable than the one leading to cis. The fact that the global minimum has a pro-cis geometry contrasts with the Arrhenius data. It was thought that ground state control might be operative. The rotational energy map for interconversion of a and (1 indicates a 6-7 kcal/mol barrier. This barrier is much too large for the interconversion of these biradical conformers to compete with cyclization. Thus, ground state control of reactivity must be operative. Semiempirical minimizations on the ground state of 5 revealed three minima within 0.5 kcal/mol of each other. If bond rotations are slow as expected and ground state control is operative, then these geometries should give the products in the correct ratios. Arrhenius data predict the two reactive geometries to be different in energy by 0.51 59 kcal/mol (good agreement with calculated results) with the lower energy geometry resulting in the trans-isomer. Indeed, the global ground state minimum is in the pro-trans geometry. The difference in the A factors is attributed to the difference in rotational entropies of the two conformers. The pro-cis conformer has a higher rotational freedom than the pro- trans conformer since in the latter phenyl and methyl are cis to each other. Thus, for the ground state control of reactivity, interconversion of the pro-cis conformer to the pro- trans one is entropically favored while the reverse is entropically disfavored. The fact that quantum yields of formation for the cis (0.43) and trans-benzofuranols (0.10) indicates that the pro-cis biradical is cyclizing more efficiently. 60 The lower cis/trans ratio in solid compared to solution reinforces our assumption that cyclization is faster than interconversion of biradical rotamers (ground state control). In solid, the observed selectivity always reflects a least-motion picture of biradical cyclization. The general conclusion is that low molecular flexibility in crystal may reduce but not totally prevent inversion by rotation. The fact that 5 yields relatively more trans- benzofuranol in the crystal confirms that pro-trans is the predominant initial biradical geometry. 3-t-Butyl-2-ethoxybenzophenone (6): Semiempirical calculations show that in the lowest energy geometry (A) of ground state 6, one of the methylene hydrogens (d: 2.36 A, (0: 71°) is close to carbonyl oxygen. Another minimum B (d1: 2.50 A, (01: 60°; d2=2.78 A, (02: 83°) higher in energy than A 61 by 0.35 kcal/mol, has both methylene hydrogens close enough for abstraction. C is another local minimum which lies 0.94 kcal/mol higher than the global minimum with one methylene hydrogen abstractable (d: 2.38 A, (0: 80°). The photobehavior of 6 is striking in that the trans-isomer, the minor benzofuranol formed at room temperature, is the predominant product at low temperatures in hydrocarbon solvent. The Arrhenius data would indicate the pro-trans biradical to be more stable than the pro-cis by 2.1kcal/mol. Global minimizations on the biradical of 6, however, show the global minimum (a) to have a pro-cis geometry, with the closest cyclizable pro-trans biradical (b) 0.35 kcal/mol higher in energy. Slow bond rotation in the biradical can not compete with cyclization, then the biradicals must react from the geometry in which it is formed and ground state control becomes operative. The lowest energy rotational map for interconversion of the ground state ketone conformers shows 8- 9 kcal/mol barriers. The cisztrans ratio at -78°C thus must be the result of the ground state control. Global minimizations on ground state of these ketones reveal the presence of three minima, with the lowest energy one being in the pro-trans geometry. It is thus believed that these three conformers are responsible for the observed cisztrans ratio at - 78°C. 62 2-Benzyloxy-3-methylbenzophenone (7): Global minimizations (AMl) with dihedral drivers around phenyl—acyl bond and phenyl-ether oxygen bond have revealed the presence of one distinct minimum on the energy surface of 2-BnO-3-MeBP. The lowest energy minimum has one of the methylene hydrogens (d: 2.41 A, 00: 63°) close enough for abstraction. The global minimum has a pro-cis geometry. The Arrhenius plot is linear which indicates that the biradical conformers are equilibrated at all temperatures. Semiempirical minimizations reveal the presence of two minima (a and b) within 0.4 kcal/mol of each other. The global minimum a is in the pro- trans geometry while b is in the pro-cis geometry. The calculated enthalpic difference between the two biradical rotamers is half of the measured value. It is believed that reactivity is rotationally controlled, with the discrepancy between the calculated and measured values attributed to over estimation of calculated pro-trans energy. The large difference in the A factors may be attributed to: 1) the pro-cis biradical cyclizing faster than the pro-trans biradical and 2) a larger entropic loss for the pro-trans relative to pro- cis biradical due to two phenyl groups ending up cis to each other in the trans —isomer. 63 2-Benzyloxy-3-isopropylbenzophenone (8): The lowest energy geometry of 8 A is in a pro-trans geometry. In this geometry, the closest methylene hydrogen is 2.36 A away and makes a dihedral angle of 69° with the carbonyl 0 plane. Global minimizations with dihedral drivers (15° increments) around benzene-acyl bond and benzene-ether oxygen bond reveal two other minima. B lies 0.19 kcal/mol above the global minimum with both methylene hydrogens (d1: 2.43 A, (01: 43°; d2: 2.53 A, (02: 85°) close enough for abstraction. Another minimum C 0.96 kcal/mol higher in energy than A has the closest methylene hydrogen 2.39 A from 64 Arrhenius data for 8 indicate that the conformation leading to trans-benzofuranol 65 should be 0.7 kcal/mol more stable than that one leading to cis-isomer. Our minimizations, however, reveal the presence of three minima within 1.3 kcal/mol of each other. Two of these (a and c) are in the pro-cis and the other one (b) is in a pro-trans geometry. Comforrnations b and c are 0.95 and 1.29 kcal/mol higher in energy than global minimum a, respectively. Conversion of a to conformer b suffers from relatively high barrier (10 kcal/mol). This means that at low temperature biradical interconversion can not compete with cyclization which in turn means that ground state control is operative. The difference in the A factors is attributed to a more efficient cyclization of the pro-cis conformer. 2-Benzyloxy-3-t-butylbenzophenone (9): The lack of stereoselectivity in photocyclization of 9 is similar to earlier results from our group. The two biradical geometries with phenyl tilted up or down are very similar in energy but have different orbital orientation which leads to different cyclization rates (Scheme 51). H H 30' p-Ph 30' p—Ph O O hv e —> $0 —— <9 0 «bog-j ph ’9 Ph 0” 17 l Bah? Bpfh’ U U ' fig?” ___—-_ e 89% ~ OH Ph 9 ° ’ 0H Scheme 51. Biradical Geometries of 9 66 B. Substituted Acetophenones Previous study showed that o-benzyloxybenzophenone is approximately fifty times more reactive than o-benzyloxyacetophenone.58 This difference in reactivity is directly attributable to the nature of the lowest excited triplet of each ketone. Electron-donating substituents at any ring position lower 7:, if and raise n, 112* transition energies; in phenyl alkyl ketones they cause an inversion of triplets such that the unreactive 7t, 7:“ state is lowest in energy.59 Careful analysis in our lab prompted the now widely accepted conclusion that in such cases hydrogen abstraction occurs from low equilibrium levels of the upper n, n‘ triplet;6 the observed reduced reactivities reflect the fractional population of that state. The two triplets also mix to a small extent, but this mixing does not affect reactivity significantly. 2-Alkoxy-3-alkylacetophenones, like o-benzyloxyacetophenone, have a 7:, n' lowest triplet. Since n, 7:,“ triplets are inherently more reactive than 7:, 76' triplets in hydrogen abstraction reactions, it is not surprising to find that 2-alkoxy-3-alkyl Table 12. Kinetic Results on 2-Ethoxy-3-alkyl Acetophenones in Benzene at 25°C O O ”(Y Ketone R kg", M'1 1'", ns 10 ‘ CH3 675.9 233.1 11 CH(CH3)2 511.8 176.5 12 C(CH3)3 304.7 105.1 “Value obtained by Stem-Volmer quenching of product formation. b16,: 2.9 x 109 M‘s". 67 acetophenones are less reactive than 2-alkoxy-3-alkylbenzophenones (Table 12, Table 13). Table 13. kg Values for 2-Alkoxy-3-alkyl Acetophenones in Benzene at 25°C R. OJ 0 “0* Ketone R R, (1,. 1611s:1 1651:“ 11051;" 10 CH3 CH3 0.085 4.29 2.69 0.36 11 CH(CH3)2 CH3 0.113 5.67 4.07 0.64 12 C(CH3)3 CH3 0.036 9.51 7.91 0.34 13 CH3 Ph 0.275 14 CH(CH3)2 Ph 0.324 15 C(CH3)3 Ph 0.272 aTotal quantum yield. bCalculated from l/r, assuming kd = 1.6 x 106 s". CProduct of (D and HI. Benzophenone 4 reacts in a 40-fold greater rate constant than acetophenone 10, the same trend has also been observed for other benzophenones and their corresponding acetophenones, apparently because of much different rotational barriers and rates of intersystem crossing in the two 1.5-biradical intermediates. 10 photocyclizes to a single benzofuranol isomer, but its major products are two isomeric hemiketals; under the same photochemical condition, 11 also gives single benzofuranol and two hemiketals with benzofuranol as the major product; for 12, 68 benzofuranol is the only observable product. Since the 7:, n‘ lowest triplet of substituted acetophenones is less reactive than the n, 7? lowest of substituted benzophenones, the low quantum yield of acetophenones could be partially due to radiationless decay competing with 8-hydrogen abstraction. However, the triplet life time ratio for acetophenone/benzophenone is the same as the ratio of rate constants for y-hydrogen abstraction for valerophenone/o-methoxyvalerophenone, models for n, n‘ and 7:, n‘ triplets undergoing the same internal reaction.60 There 5-hydrogen abstraction is concluded to be the major mode for triplet decay for both acetophenones and benzophenones, and the lower quantum yields for acetophenones must involve competing reactions of the 1,5-biradical formed from the triplet. The formation of the hemiketals indicate that the 1,5-biradicals also cyclize at the ortho position of the benzene ring (Scheme 52). This competitive cyclization is minor with 11 but major with 10. o9L9 OH 09%) o 9 0 OH H . H R“ slow = Fifi/k RE? 0 OH R 00H 15H HO O R / ’ >R ————> Scheme 52. Proposed Mechanism for 2-Ethoxy-3-alkyl Acetophenones The efficiency of benzofuranol formation apparently is directly related to the ease of rotation about the aryl-C1 bond. The n-system of a substituted benzoyl group is conjugated in the triplet state, hydrogen abstraction produces a triplet 1,5-biradical with a 69 fully conjugated benzyl radical center. A rotation of approximately 90° is required before cyclization can occur. In the acetophenone-derived biradical, such a rotation reduces the benzylic conjugation and thus is slow. The competing spirocyclization does not require rotation about the benzyl bond. The biradical from 10 has more time to undergo this reaction, which thus predominates. Increasing the size of 3-alkyl substituent changes the triplet conformation equilibrium, making the (syn, syn) conformer more favored. The presence of an isopropyl or a t-butyl group ortho to the alkoxy] group makes the 5- hydrogens more available to the carbonyl oxygen, hence, the 6-hydrogen abstraction is more efficient for 11 and 12. Scheme 53 outlined the preferred geometry of these 1,5- biradicals, as estimated by previous calculation on similar biradicals61 and as suggested by the stereoselective cyclization of such biradicals. The rotation about 01 and w required for benzofuranol formation allows the two nearly orthogonal p orbitals to develop strong overlap. Rotation about C and w, as required for spirocyclization, allows one p orbital to develop weaker overlap with the partial spin density at a carbon ortho to the hemipinacol radical site. 3-Isoprpyl and 3-t-butyl groups inhibits the rotation about w, so the acetophenones can not assume the proper geometry for hemiketal formation. It is this barrier that apparently favors cyclization to benzofuranol for 11 and 12. Scheme 53. Biradical Geometry of 2-Ethoxy-3-alkyl Acetophenones Wagner and coworkers have reported that photolysis of o-benzyloxyacetophenone produces the normal benzofuranol as well as 2-acetylbenzophenone.23 The mechanism 70 described in Scheme 54 provides a plausible and rather attractive explanation for the formation of both products. Ph Ph 00) (:4 6i —~ 68 9*; 5%” 69L Scheme 54. Proposed Mechanism for o-Benzyloxyacetophenone For 2-benzyloxy-3-alkylacetophenones, photolysis produces a complex mixture of products, which includes a single isomer of benzofuranol, two isomeric hemiketals, a benzyl transfer product, debenzylation product as well as its dimer (Scheme 55). Ph Ho 0 0 OH R + + Bn 0 R O Scheme 55. Photochemistry of 2-Benzyloxy-3-alkyl Acetophenones It has been known for some time that 13C chemical shifts of carbonyl groups in phenyl ketones are strongly sensitive to the degree of coplanarity of the benzoyl group62 and that the '3 C chemical shift of the methyl carbon in anisoles is sensitive to the geometry of the ring-methoxy bonding.63 In both cases, twisting of the carbonyl or alkoxy group out of 71 planarity with the benzene ring increases 6. Table 14 lists some NMR chemical shifts of the CO and OCHzPh carbons in 2-benzyloxy-3-alkylacetophenones and in model compounds. 1,3-Disubstitution, both alkyl and acyl, that prevents the alkoxy group from lying in the plane of the benzene ring increases the chemical shift of the methylene carbon. All the 3-alkyl substituted acetophenones show 8 values for the CHzPh carbom almost 7 to 8ppm larger than o-benzyloxyacetophenone, indicating a large degree of twisting out of plane. Substituted acetophenones show higher 5C=o values than acetophenone but not nearly as high as 2,4-tert—butylacetophenone. We therefore concluded that the benzoyl groups in these compounds are twisted but not nearly perpendicular. Table 14. 13 C Chemical Shifts for 2-Benzyloxy-3-alkyl Acetophenones“ R' O R R R’ 60-CH2-Ph9 PPm 6C=09 131”“ H H 197.0 H OCH2Ph 70.6 199.8 CH3 OCHzPh 76.7 201.4 CH(CH3)2 OCHzPh 78. 1 201 .9 C(CH3)3 OCHZPh 77.8 203.1 a In CDCI3. The quantum yields for various product formation of 2-benzyloxy-3- alkylacetophenones are listed in Table 15. The significantly lower k5-“ value observed for 72 o-benzyloxyacetophenone reflects its 7t, 7:3 lowest triplet configuration. Further 3 7r, 7:1 stabilizing 3-alkyl substituents would lower rate constants so much that hydrogen abstraction would occur only in very low quantum yield; while the incorporation of these 3-alkyl groups also enhances abstraction rate constants because of the decreased loss of rotational entropy in the transition state. Hence, the overall rate constant for the formation of benzofuranol does not change very much a lot by the additional 3-alkyl substituents. Table 15. Quantum Yields of 2-Benzyloxy-3-alkyl Acetophenones in Benzene at 25°C Ph OJ 0 “6* R (pcyc. (Dspim. (DBn-trans. q’coupt. (pdeBn H 0.023 CH3 0.026 0.039 0.095 0.085 0.030 CH(CH3)2 0.031 0.059 0.11 0.10 0.024 C(CH3)3 0.045 0.064 0.086 0.047 0.030 The formation of benzofuranol and hemiketals are due to the normal cyclization as well as the spirocyclization of the 1,5-biradical intermediate. This competition represents another unique example of conformational restrictions on a reactive intermediate. Since 71, 1!. is the lowest triplet for these 2-benzyloxy-3-alkylacetophenones, the efficiency of reaction is normally much smaller because reaction takes place from low equilibrium populations of the reactive upper triplet. The benzyl transfer products, debenzylation 73 products and their dimers probably are secondary products arising from the spiroepoxides (Scheme 56). R W R , R disprop. P h OH Scheme 56. Proposed Mechanism for 2-Benzyloxy-3-alkyl Acetophenones 2-Ethoxy-3-methylacetophenone (10): Semiempirical calculations at AMI level were performed on 10. The lowest energy geometry A has one methylene hydrogen at an abstractable distance (d: 2.64 A, 00: 77°) from the carbonyl oxygen. Minimizations (semiempirical-AMI level) were also performed with dihedral drivers (15° increments) for rotations around the benzene-acyl bond and the benzene-ether oxygen bond. The calculations reveal three other minima within 0.4 kcal/mol of each other. B is 0.26 kcal/mol higher in energy than the global minimum. In this geometry, however, the methylene hydrogens are too far to be abstracted. Another minimum C (0.32 kcal/mol higher than global minimum) has the closest methylene hydrogen 2.28 A (0): 38°) away from the carbonyl oxygen. Minimum D (0.37 kcal/mol higher in energy than global minimum) has an abstractable hydrogen 74 2.56 A ((0: 38°) away from the carbonyl oxygen. A is in a pro-cis geometry, C and D are in the pro-trans geometry. Global minimizations on the hydroxybiradical from 10 reveal the presence of 2 nrinima within 0.5 kcal/mol of each other. Global minimum a is in a pro-cis geometry, while conformer b (0.47 kcal/mol higher in energy than a) is in a pro-trans geometry. Given the short biradical lifetimes and the strong preference for a single benzofuranol isomer as product, it is tempting to speculate that the biradicals may be too short-lived to rotate out of their nascent geometries. It was thought that ground state control might be operative. 75 However, analysis of the lowest energy rotational path for the interconversion of the two biradical conformers did not reveal significant barriers (5 kcal/mol). Thus, biradical minima can interconvert and ground state control can not be operative. An extra feature of the photobehavior of 10 is the formation of hemiketal. The calculations reveal that neither cyclization mode can occur from the minimum energy conformation. Hemiketal formation requires that \y twist to 90°, which the calculations suggest costs 4.4 kcal/mol. Benzfuranol formation requires a significant increase in 01, a 60° twist costs about 4 kcal/mol. Since the rotational barriers for both cyclization modes are quite similar, there should be no significant differences in product ratio, which is in good agreement with the experimental results. 2-Ethoxy-3-isopropylacetophenone (11): Molecular mechanics and semiempirical calculations were performed on 11. In its lowest energy geometry A, one of the methylene hydrogens is close enough (d: 2.63 A, (0: 79°) for abstraction. Global minimizations with dihedral drivers (15° increments) around benzene-acyl bond and benzene-ether oxygen bond reveal 4 other minima within 0.3 kcal/mol of each other: B, which is 0.1 kcal/mol higher in energy than A, has one 76 abstractable hydrogen (d: 2.27 A, (0: 39°); conformer C (0.14 kcal/mol higher than global minimum) has one methylene hydrogen close enough for abstraction (d: 2.89 A, 00: 74°); in conformer D (0.26 kcal/mol higher than A), no hydrogens are close enough for abstraction; the other minimum E (0.27 kcal/mol higher in energy than global minimum) has one methylene hydrogen 2.52 A (0): 40°)away from the carbonyl oxygen. B, C and E are all in pro-trans geometries, while global minimum A is in a pro-cis geometry. The rotational energy map for interconversion of A to E does not indicate any significant barrier, the interconversion of biradical conformers can compete with cyclization. Thus, rotational control must be operative. Global minimizations on the biradical from 11 reveal the presence of 4 minima within 0.35 kcal/mol of each other, and all of them are in pro-cis geometries. None of the biradicals can cyclize directly, calculations suggest that it costs 5.8 kcal/mol for w to 77 twist to 90°, 3 50° twist of or costs 2.5 kcal/mol. Different product partitioning, which clearly reflects different barriers to rotation around bonds (1 and w, indicates that additional differentiation must occur. 3-t-Butyl-2-ethoxyacetophenone (12): In the lowest geometry of 12, the closest methylene hydrogen is 2.58 A away from and makes a dihedral angle of 82° with the carbonyl a plane. Another geometry, B, lies 1.82 kcal/mol above the global minimum. In this geometry the closest hydrogen is 2.36 A from the carbonyl oxygen and makes a dihedral angle of 78° with the carbonyl nodal 78 plane. Semiempirical minimizations on the biradical of 12 show the presence of four rrrinima within 1.6 kcal/mol of each other. Global minimum is in a pro-trans geometry, the other three minima b (0.07 kcal/mol higher than a), c (0.70 kcal/mol above the global minimum) and d (1.59 kcal/mol less stable than a) are all in pro-cis geometries. At room temperature, photolysis of 12 results in the formation of only cis-benzfuranol. 79 This high diastereoselectivity can not be ground state controlled, because 1) analysis of the lowest energy rotational path for the interconversion of the two biradical conformers a and d did not reveal significant barriers (5 kcal/mol) and 2) lowest energy ground state ketone is in a pro-trans geometry, while the pro-cis conformer B is 1.82 kcal/mol higher than A and will not contribute much to the overall yield of cis-benzfuranol if ground state control is operative. The efficiency of benzfuranol formation is directly related to the ease of rotation about the benzene-acyl bond. For biradical from 12, semiempirical calculations strongly suggest that the t—butyl group forces the biradical into a geometry in which one radical center is pointed directly at the other radical site, thus inviting cyclization. Spirocyclization, on the other hand, requires bond rotation which may be impeded by the t-butyl group. The minimized geometries of 12 lead to the minimum energy biradical geometries, which favor cyclization, as just noted. 2-Benzyloxy-3-t-butylacetophenone (15): Wagner reported a sharp contrast in the photobehavior of o-alkoxyacetophenones and benzophenones. Irradiation of benzophenones results in efficient formation of benzfuranols while that of acetophenones results mainly in diketones. Rotation of the 1,5— biradical produced by 6-hydrogen abstraction in these phenyl ketones is necessary for cyclization but destroy the benzylic conjugation. n-Conjugation is more important in excited states than in ground state. In the benzophenone derivatives, the benzylic radical center of the biradical can remain conjugated with the unsubstituted phenyl ring while the o-alkoxyphenyl ring rotates. The absence of the second phenyl ring in the acetophenone derivatives causes a retarded rotation. Thus, the difference in behavior was attributed to the retarded rotation of the benzylic center of the biradical which slows down the 80 benzfuranol formation and allows the biradical to undergo a less favored reaction, namely spirocyclization. The decrease in the quantum efficiencies of benzfuranol formation in the 2-benzyloxy- 3-alkylacetophenones as compared to 2-ethoxy-3-alkylacetophenones can be attributed to increasingly more efficient side reactions as the size of the 2—alkoxy group increases (which impedes cyclization due to increased strain during cyclization). The conformational factors involved in hydrogen abstraction of 2-benzyloxy-3- alkylacetophenones might be expected to be similar to those of 2-ethoxyacetophenones. 81 Ground state global rninirrrizations indicate the presence of three reactive geometries, a low energy A in a pro-trans geometry with an abstractable methylene hydrogen 2.57 A ((0: 81°) away from the carbonyl oxygen. B is 0.5 kcal/mol higher in energy (d1: 2.87 A, (01: 80°; d2: 2.91 A, (02: 62°) and C (0.92 kcal/mol higher than A) is also in a pro-trans geometry with one methylene hydrogen 2.71 A (0): 74°) away from the carbonyl oxygen. Semiempirical calculations have been performed on the conformational distribution of the hydroxybiradical from 15. There are only two minima within 0.9 kcal/mol of each other. Global minimum has a pro-trans geometry, the other conformer, which lies 0.90 kcal/mol above the global minimum, is in a pro-cis geometry. Analysis of the lowest energy rotational path for the interconversion of the two biradical conformers did not reveal significant barriers (4~5 kcal/mol). Thus, biradical minima can interconvert and ground state control can not be operative. It is believed that the formation of only the cis- benzfuranol is rotationally controlled, the pro-cis biraidcal cyclizes more efficiently. Both normal cyclization and spirocyclization require additional bond rotation: a 30° twist of or costs 1.3 kcal/mol and 50° twist costs 2.4 kcal/mol; while a 75° twist of w costs about 8 kcal/mol. 82 ‘ H abstraction OHO Scheme 57. Photochemistry of 15 15 also undergoes benzyl transfer, debenzylation as well as dimerization. Scheme 57 depicts the postulated mechanisms. Given its 7:, 7t* lowest triplet, we suspect some form 0f biradical process. There has been long-standing interest in the extent to which steric Congestion drives radical cleavage reactions.64 These reactions obviously demand steric Congestion. As for benzyl transfer reaction, the driving force for actual bonding of the benzyl group to oxygen is attributed to increased steric congestion; such bonding pulls the benzyl group away from the center of congestion. For the other two reactions, Cleavage of the benzylic carbon—ether oxygen bond forms a fully conjugated benzyl radical, which is also a compromise to relieve a good deal of built-in steric strain. 83 2-Benzyloxy-3-isopropylacetophenone (l4): Given that this ketone appears to be so sterically congested that bond rotations are relatively slow, we calculated various energy-minimized conformations of 14. Dihedral drivers were used for rotation about two key bonds: the benzene-acyl bond and the benzene-ether oxygen bond. Semiempirical (AMI level) calculations show that in the lowest energy geometry (A) of ground state 14 has one of the methylene hydrogen (d: 2.88 A, 0): 75°) close enough for abstraction, and it is in a pro-trans geometry. Global minimizations reveal three minima; in all, methylene hydrogens are abstractable. These 84 conformers are 0.03, 0.08 and 0.11 kcal/mol higher in energy than the global minimum. The lower energy conformer B (d: 2.25 A, (0: 41°) is in a pro-trans geometry; the middle energy conformer C has one methylene hydrogen 2.65 A ((0: 73°) away from the carbonyl oxygen and is in a pro-cis geometry; while in the higher energy conformer D, both methylene hydrogens are close enough for abstraction (d1: 2.32 A, (01: 28°; d2: 2.76 A, (1)2: 70°). The lowest energy biradical conformer a is in a pro-trans geometry, global minimization reveals another local minimum b 1.8 kcal/mol higher in energy than a and it is in a pro-cis geometry. As mentioned before, benzofuranol formation requires a significant increase in 01. For b, rotation of 30° costs only 1.6 kcal/mol, but rotation to 60° results in a 5 kcal/mol energy increase. It is this barrier that apparently inhibits cyclization to benzofuranol. Twisting of w to 90° which is required for spiroepoxide formation costs 10-13 kcal/mol, so few molecules can assume the proper geometry and the observed rate for spirocyclization is low. As described above, these 2-benzyloxy-3-alkylacetophenones undergo five reactions in varying proportions: cyclization to benzofuranol, spirocyclization to hemiketals, benzyl 85 transfer reaction, debenzylation and dimerization. l4 undergoes all these reactions competitively. The cyclization and spirocyclization are known to proceed by triplet-state 5-hydrogen abstraction that generates 1,5-biraidcal. 14 has 1:, 71* and n, 7t* lowest triplets, respectively, but it undergoes hydrogen abstraction only from its 11, 7t* triplet. The other three reactions involve triplet-state bond cleavage. In the absence of trapping agent, normal radical coupling and rearrangement products are formed. No mechanism has been postulated for these reactions; we suggest that it is initiated by 7t, 7t* lowest triplet, a reaction that we believe is common to acetophenones with electron-donating substituents. 2-Benzyloxy-3-methylacetophenone (13): Semiempirical calculations at AMI level were performed on 13. The lowest energy geometry was calculated to be the one (A) with one methylene hydrogen at an abstractable distance from the carbonyl oxygen ((1: 2.63 A, 00: 75°). Minimizations (semiempirical-AMI level) were also performed with dihedral drivers (15° increments) for rotation around benzene-acyl bond and benzene-ether oxygen bond to detect other conformations with methylene hydrogens aligned for abstraction. The calculations reveal another minimum 0.25 kcal/mol higher in energy than the global minimum. In this conformation (B), both methylene hydrogens are close enough for abstraction (d.= 2.26 A, (01: 30°; d2: 2.93 A, 62: 69°). Experimental results show the cis—benzofuranol to be the only cyclization product. Ground state global minimizations indicate the presence of two reactive geometries with the lower energy one in a pro-cis geometry. Furthermore, semiempirical minimizations on the biradical of 2-BnO—3-MeAP show the presence of two minima within 2.0 kcal/mol of each other. Lowest energy biradical conformer a is in a pro-trans geometry, the 86 - . o—v on- 1 '9‘ 1»— 4"... .:. ~ . fu‘fi'bWJu '-n - ' ‘. I ' ,1 «swat-1%.: ‘ I... . . - I or . ‘-. 4 ..- .Y - F .- _ -4 o ‘0‘... .. .I.~r.. "ft-i- :3 ii allul]. , . J. I 0.4 .‘l ‘50. ' '.I : .. ."' 3, l 1 ml..- _ 4.01 4. 2' 1T: '81:: (1349254111: v. . . 41.; W47: other local minimum b is 1.9 kcal/mol higher in energy than a and is in a pro-cis geometry. The rotational energy map for interconversion between a and b indicates 4-6 kcal/mol barrier. None of the minima can cyclize directly, both of them require additional rotation about a and v. For b a twist of a to 30° requires 1.3 kcal/mol of energy, a 50° twist costs 3 kcal/mol, while the twist of \l/ to 90° costs 5-9 kcal/mol. II. Photoinduced Carbon-Halogen Bond Cleavage A. Substituted Acetophenones 87 Irradiation of a-(bromoethoxy)acetophenone (17) produced a yellow solution, 01- (iodoethoxy)acetophenone (18) a red solution, while a-(chloroethoxy)acetophenone (16) remained water-white. The colors produced suggest the presence of the respective molecular halogen. What is unexpected is why loss of HX from parent haloketone did not generate terminal olefin. For 6-halovalerophenones, pyridine was added to trap any HX produced during irradiation. The quantum yield of B-elimination was maximized by 0.005-0.01 M pyridine. This corresponds to roughly the amount of HX that could be produced since conversion of the parent ketone (0.05 M) was limited to S 10%. Pyridine has been previously shown to maximize type H quantum yields by solvation of the biradical intermediate, thus preventing reverse hydrogen abstraction to give the ground state parent ketone.50 However, the concentration of pyridine necessary to maximize type H quantum yields by the solvation mechanism is typically 0.5—1.0 M. The maximization of elimination quantum yield at such low concentration of pyridine is consistent with the pyridine acting essentially as an HX trap, rather than by any biradical solvation mechanism. Sample of 17 and 18 containing pyridine gave white precipitates upon irradiation, presumably the pyridinium hydrohalide salt. No precipitate was formed with 16 under identical conditions. The solutions of the a-haloethoxyacetophenones remained water-white when irradiated in the presence of pyridine. The presence of pyridine did not affect the photochemical behavior of 16; while for 17 and 18, the major product became a-vinyloxyacetophenone (58). Table 16 lists the quantum yields for product formation of 01-(haloethoxy)acetophenones in various solvents. The quantum yields of a-(haloethoxy)acetophenones in benzene are quite high as 88 1"; 7‘ "6.1.; . ' 1113'?- .,..l N- , ‘fi, .. " “'r " ‘1 In, . l 1 1. r ' ' . 1 Q . “331‘“h y‘ml.‘ 0.. I. 5 "' it ,, — .9 ‘0 o- 3'“ {'5 ‘4 w . :1 35.: -2 T:. '4’ .1: w ," . v .‘3‘. - O .n- o o o o t '1." 1 ”11- In. 351.9111 "’1’ 7! ‘v-O"“ ‘5 r‘ g .0 no»; 3 .8“. . u A . ‘1' 7‘ 2... V‘" n 0' """O‘O‘h .2",- lttuiuuLfl .11; 436141434 tut-Wham .1 23,5. 2: '5" 943* ~ Table 16. Quantum Yields of a-(Haloethoxy)acetophenones at 25°C o ©2K/wa Ketone X (Du (Dem (Dcyc. (92.01111) 16" Cl 0.46 0.43 17" Br 0.041 0.49 18" I 0.29 16" Cl 0.45 0.43 17" Br 0.039 0.97 18" I 0.71 16c Cl 0.56 a Degassed benzene solutions containing 0.1 M ketone irradiated at 313 nm b In the presence of 0.1 M pyridine. ° In CH3CN. opposed to values of 8-halovalerophenones.32 High quantum yields are consistent with totally efficient biradical formation. Also, biradical reaction must be faster than reversal to starting ketone. Another intriguing aspect of the results in Table 16 is the decrease in total quantum yield in polar solvent. We believe the solvent effect on quantum yield is due to increased efficiency of return of the biradical intermediate to starting ketone in polar solvents. Wagner has suggested that hydrogen bonding of the biradical hydroxyl proton in polar solvents should impede back-transfer to the y-carbon and thus decrease k.r relative to kg and km? Hydrogen bonding is more complicated for the a- 89 (haloethoxy)acetophenones due to the presence of the internal ether oxygen. In nonpolar solvents the hydroxyl proton is internally hydrogen bonded to the ether oxygen, thus preventing back transfer to the y-carbon. Intramolecular hydrogen bonding in vicinal hydroxy ethers is moderately strong as long as geometrical restrictions do not prevent coplanarity. In polar solvents, intermolecular hydrogen bonding would compete with the intramolecular bonding to the ether oxygen as well as tie up hydroxyl protons and could thus occur with unpredictable results so that a different biradical solvent effect is not surprising. For 5-halovalerophenones type II elimination and B-elimination predominate, cyclobutanol formation only accounts for 12% of the biradical products. This determination of cyclobutanol yields together with the results in Table 10 clearly shows a relatively slow cyclization rate constant which could be due to steric considerations. In benzene, l6 preferentially forms the trans-cyclization product which indicates steric requirements are significant for cyclization. A small solvent effect resulting in less cyclization in polar solvents is observed: in methanol-d4, only trace amount of cyclization products were detected, while in acetonitrile acetophenone was the only detectable product. Also in methanol cyclization becomes less selective with a cisztrans ratio for the 3-oxetanols being 1.3:]. Both results are consistent with the interpretation that increased solvation or hydrogen bonding to the biradical makes cyclization more difficult because of steric factors. Previous experiment indicates that the carbon-halogen bonds are not broken by direct interaction with the excited triplet ketone.65 The best mechanism for product formation 90 I 1. w ‘ t ' | ' . n ' . ,n . . i '14v'tliuma . u. r" . :"‘ '—'l- .‘.. '- h‘ 3"."- - .a -o .1 -. .- 'o '- .c ...I .” .... 1. .- o .- o- ‘0. ~v ‘. II‘J.’ Ill,l ”1| “.‘r'; '13:.” " "V. o W'fiq" "‘5".ch .' .""‘ l‘ “I 36:11”? do . . .. . . ,1. ,, .. If _ d 109053151045 u- a. flar- 01!. AW 0- tr — 6'. o. ’ r’w'flafl involves competitive reactions of the biradicals formed by triplet state y-hydrogen abstraction (Scheme 58). ©/K/O\/\X "/ N OH O , 0% + X ©/”\ 1 .0 x ° W QM“ " Scheme 58. Proposed Mechanism for a-(Haloethoxy)acetophenones The formation of 2-hydroxyacetophenone (57) without pyridine is not totally unexpected since HX is capable of adding to olefins. In order to explore whether the addition process is an ionic or a free radical mechanism, we synthesized gem-dimethyl analog of 01-(bromoethoxy)acetophenone. The irridiation of a-(2-bromo-2- methylpropoxy)acetophenone (19) in benzene gave three detectable products (Scheme 59). With the presence of pyridine, photolysis gave the normal B-elimination product as ©/UVO\K’\ 0 Br O\>< Br 1'“) —’ O O 0606 . OH :0)“ - (3* Scheme 59. Photochemistry of 19 in Benzene Without Additive well as acetophenone. 91 We proposed an ionic addition mechanism for the formation of both 2- hydroxyacetophenone (57) and a-(1-bromo-2-methylpropoxy)acetophenone (60) Q/UVCDJ—H" waif: Scheme 60. Proposed Mechanism for 19 (Scheme 60): Triplet lifetimes were measured by a Stem-Volmer treatment using 2,5-dimethyl-2,4- hexadiene as a quencher for product formation. In the presence of 0.1 M pyridine the Stem-Volmer plots for a-(haloethoxy)acetophenones were linear (Table 17). It is well known that B-haloalkyl radicals eliminate halogen atoms readily.66 The relative rates of halogen cleavage from the biradical is apparent from the product distribution (type 11 products vs. halogen elimination products) and are in the expected order I>Br>Cl. Table 11 lists relative kx values for these ketones. Since carbon-halogen bonds do not quench the relatively long-lived triplet butyrophenone,67 it must be concluded that the III values represent the rate of y-hydrogen abstraction (kH, Table 17). The hydrogen abstraction rate constants for a-(haloethoxy)acetophenones are much faster than those for 8- halovalerophenones. A plausible explanation is that the ether oxygen lowers the entropy requirements for the formation of the six-membered ring transition state necessary for hydrogen abstraction. The substantial inductive effect of y-substituents on k“ values has been shown to follow a linear free energy relationship. The chlorine decreases kH to 1/29 92 its value in a-ethoxyacetophenone (8.4 x 109s‘1). The 01 values for I and Br are slightly lower than for C1, so that the k“ values for 17 and 18 should be respectively 15.5% and 90.4% greater than that for 16 if only inductive effects are important. The actual kH values suggest that B—bromo and iodo groups can participate in 'y-hydrogen abstraction (Scheme 61). This anchimeric assistance is known to be substantial for hydrogen abstraction by bromine atom, but minor for the more reactive alkoxy radical. The calculated rate enhancements, corrected for inductive effects are 146% and 122% for bromine and iodine respectively. As usual the n, n‘ mimics the behavior of alkoxy radicals and provides quantitative information not readily accessible from studies of radical reactions. Table 17. Kinetic Results of a—(Haloethoxy)acetophenones in Benzene with Pyridine at 25°C 0 ©2’y0wx Ketone X kq‘r‘, M‘1 1", ns kg, 107 s'1 k-x/k.3, 61 16 C] 17.2 3.44 29.1 <0.001 0.47 17 Br 10.2 2.04 49.0 1 0.45 18 I 7.4 1.48 67.6 >30 0.38 “Value obtained by Stem-Volmer quenching of product formation. "k,= 5 x 109 M's". Scheme 61. Anchimeric Assistance 93 B. Substituted Propiophenones Opposing to their a-(haloethoxy)acetophenone analogues, the photochemical behavior of B-(haloethoxy)propiophenones looks quite simple: in benzene with the presence of pyridine, photolysis of B-(haloethoxy)propiophenones gives a single B-elimination product. Table 18 lists steady state kinetic data for these ketones. Table 18. Kinetic Results of B-(Haloethoxy)propiophenones in Benzene with Pyridine at 25°C 0 Wow X Ketone X (Peri. kq‘r", M'1 1'", ns bf, 107 s'1 01 20 Cl 0.27 604.8 121.0 0.83 0.47 21 Br 0.26 450.8 90.2 1.11 0.45 22 I 0.26 85.4 17.1 5.85 0.38 aValue obtained by Stem-Volmer quenching of product formation. bkq= 5 x 109 M‘s". ckH = III. The reciprocal triplet lifetime of B-ethoxypropiophenone, presumably the rate constant for S-hydrogen abstraction by its 11, 7t* lowest triplet, is 2 x 107 3".” This value is large enough that no physical decay processes compete. Electron—withdrawing e-substituents such as halogen atoms should lower the observed rate constant sufficiently. We observed that a s-Cl deactivates 8-hydrogens by an order of magnitude. The effects of Br and I on triplet reactivity do not correlate well with their 01 values. We have suggested that they 94 provide anchimeric assistance to hydrogen abstraction, as is well known for the halogen atoms in free radical hydrogen abstraction. Comparing the data in Table 17 and Table 18, it can be seen clearly that 8-hydrogen abstractions have relatively low rate constants, which can be explained in terms of the well-known preference for 1,5-hydrogen transfers in radical chemistry. Our early studies indicated that 1,5-biradical efficiently disproportionates to form the enol of starting ketone, which rapidly tautomerizes; hydrogen bonding by the hydroxy group to solvent suppresses disproportionation to ketone but cannot suppress enolization. The low quantum yield of product formation for B-(haloethoxy)propiophenones also are caused by substantial 1,5-biradical disproportionation to enol of starting ketone (Scheme 62). Fortunately this competing enolization lowers only the quantum yield, not the chemical yield; the enols reketonize rapidly. V N OH O WON X ©/u\/\O/\ Scheme 62. Proposed Mechanism for fi-(Haloethoxy)propiophenones III. Triplet Biradical Behavior 95 1,5-Biradical cyclization is a ‘non-ionic’ process for five-membered ring formation, but the relatively large number of competitive reactions need to be taken into consideration from a synthetic standpoint. In order to determine the potential utility of photoinduced intramolecular hydrogen transfer for the synthesis of five-membered rings, we devised following experiment in which competitive reaction is used to determine the rate constant of 1,5-biradical cyclization. ©M / ..,. 0 0M 0 o/i \ + Ph 0 HO Scheme 63. Photochemistry of 69 Varsha Govardhan studied the reactivity of B-(cyclopropylmethoxy)propiophenone (69)}58 irradiation at low temperature provided both the cyclization and ring-opening products (Scheme 63), which indicated that normal cyclization and rearrangement were competitive. If krr at 20°C is ~7 x 107 s'1 as in the (Jr—cyclopropylethyl radical,69 then the life time of this 1,5-biradical is much longer than that of the 1,4-biradicals formed from 96 a-alkoxyacetophenones, as expected if the oxygen’s effect is mainly as a heavy atom rather than as a minimizer of eclipsing interactions. It might be expected that the oxygen in this 1,5-biradical, which is conjugated to the 8 radical site, would lower the krr value from that for cyclopropylethyl radical, as is the case for a-cyclopropylbenzyl radicals.7O Rate constant of 1,5-biradical cyclization can then be deduced from the observed product ratios and the rate constant for the cyclopropylmethoxy radical rearrangement. The measurement of rate constant for opening of cyclopropylmethoxy radical has been done in photolysis of a- cyclopropylmethoxyacetophenone (23) and based on the assumption that the rearrangement has identical rate constant in both B-(cyclopropylmethoxy)propiophenone (69) and a-cyclopropylmethoxyacetophenone (23). Table 19 lists the quantum yield of product formation for these two ketones. Table 19. Quantum Yields of Product Formation for 69 and 23 at 25°C O Ketone n (Du ‘Pcyc. 4’17 69a 2 0.41 0.09 23" 1 0.15 0.31 0.03 23° 1 0.28 0.43 a In toluene. b In methanol. C In benzene. Irradiation of 23 in benzene provided only the type II and cyclization products. No ring-opening product could be detected. Further work in methanol produced mainly 97 Jfl'D‘NOI I!" — 4 n '10 :0 1. .V 1,: - I "V v o . ' , l 3‘ T ‘1... '4‘3155'353 "'9‘“ .II' '|”-_'-.».” 'tgruhlin 1.! m .' -'-" 9”— ::-. up, w . . '<—. I... Jun”: d1:‘;fl~‘ile:.{:|r1ltlrnh‘-.’ .1190 . ~ _. .u ¢ -- ‘- ’. '. O ‘2 I T‘C: ." ”- li-fl.’ and It ”'40“. . acetophenone and oxetanols, the normal 1,4-biradical reactions, and very little ring- opening, indicating that krr is much slower than the 1,4-biradical decay rate (>108 5"). The lifetime of such a 1,4-biradical in methanol is 3 ns,71 which indicates a decay rate of 1,4-biradical to be 3.3X108 s". The rearrangement/(type II + cyclization) ratio is 1:15.3. Taking these numbers and the quantum yield of 0.49, i.e., 51% of the biradicals disproportionate to the starting ketone, the rate constant of cyclopropylmethoxy radical rearrangement is calculated to be 9.9x106 s”. For 69 we assume the rearrangement rate constant is the same as in 23. Given the assumption that 50% quantum yield reflects 50% biradical disproportionation, the product ratios indicate a 1,5-biradical cyclization rate constant to be 4.5x107 3". Solvent effect has also been studied for this 1,4-biradical, results are shown in Table 20. Several issues are of our interest. First, the cyclization/elimination ratio decreases with the increase of solvent polarity. In benzene the ratio is 1.8:1, while in acetonitrile it becomes 1.1:1. Hydrogen bonding seems to play an important role. It is possible that in non-polar solvents the hydroxyl proton is internally hydrogen bonded to the ether oxygen. Intramolecular hydrogen bonding in vicinal hydroxyl ethers is moderately strong as long as geometrical restrictions do not prevent coplanarity. Such an intermediate could accout for the relatively high ratio of cyclization products. In polar solvents, intermolecular hydrogen bonding would compete with the intramolecualr bonding to the ether oxygen, in this case the biradical prefers to exist in the stretched anti-conformation and give the observed result.72 Another important feature is the diastereoselectivity of cyclization. The cis/trans ratio depends on solvent polarity, showing little selectivity in polar solvents but favoring the isomer with the phenyl trans to the cyclopropyl group in 98 hydrocarbon solvents. Hydrogen bonding of the OH in 1,4-biradicals to solvent molecules increases the effective bulk of OH group, thus lowering the diastereoselectivity in cyclization. Table 20. Product Ratio for Photolysis of 23 Solvent cis-63 trans-63 55 Toluene 3.85 1 3.9 Benzene 3.57 1 2.57 Acetonitrile 2.19 l 2.85 t-Butanol 1.78 1 1.59 Another important feature of cyclization is the diastereoselectivity displayed when the prochiral carbonyl carbon becomes tetrahedral. Lewis reported years ago that two different types of selectivity arise,73 as demonstrated by valerophenone and a- methylbutyrophenone. They both form 1-phenyl-2-methylcyclobutanol; but the former gives a 35:1 cis/trans ratio while the latter gives only the cis-isomer. In a- methylbutyrophenone, the methyl and the phenyl groups assume anti orientations in the biradical before it cyclizes. Such steric preferences can involve several kcal/mol. In valerophenone, nonbonding interactions between methyl and phenyl are developed only as the two ends of the biradical begin to bond and obviously produce an energy differential of less than 1 kcal. Wagner and coworkers pointed out other examples of what may be a general rule, namely that pre-existing conformational preferences can be much larger than those developed only during cyclization. It seems to be the case for 23, the interaction between the phenyl and the cyclopropyl groups should be small until the 99 1,4 bond is almost completely formed, so at room temperature the photochemical cyclization of 23 shows a diastereoselectivity of 3.8:1, almost the same as that of valerophenone. Table 21. Temperature Effect on Cyclization Stereoselectivity of 23 in Toluene Temperature, °C cis-63 trans-63 -70 9.09 1 -15 5.30 1 25 3.85 l 80 2.81 1 Evans-Ed, (kcal/mol) 1.1 1 A,,a,,_,/Ac,-,. 1 .73 3 2.5 . w 2 ‘ I: 2 5 1.5 ~ '8 _=. 1 . 0.5 r 0 I r r T 2.5 3 3.5 4 4.5 5 1000/T Figure 3. Arrhenius plot of 23 An intriguing temperature effect was observed in our experiments. Table 21 lists product ratios in toluene as a function of temperature for 23. The corresponding 100 Arrhenius plot is shown in Figure 3, with the activation parameter differences listed in Table 21. Chandra’s group reported an investigation of the intramolecular y-hydrogen abstraction process in photoexcited alkyl ketones and diketones from their lowest 11, 1t* triplet states.45 In order to achieve hydrogen abstraction, the abstractable hydrogen atom must approach the oxygen atom of the carbonyl group to form a six-membered ring. Scheffer has reported several examples of ketones that undergo efficient intramolecular 7- hydrogen abstraction in the crystalline phase.‘6 He suggestes that, since the sum of the H and 0 van der Waals’ radii is 2.7 A, unless the abstractable hydrogen atom approaches to within 2.7 A of the carbonyl oxygen, reaction can not occur. Several ketones with separation distances between the H and O atoms of more than 2.7 A are found to be unreactive. The Norrish type H reactions generate 1,4-biradicals as intermediates which cyclize to oxetanols from alkoxy ketones. A B 23 can exist in a number of conformations defined by the dihedral angles a, B and y as shown in Scheme 64. Molecular mechanics and semiempirical calculations at AMI level were performed on 23. The lowest energy geometry A was calculated to be the one with one y-hydrogen at an abstractable distance from the carbonyl oxygen (d: 2.32 A, a: 164°, [3: 75°, 7: 70°). Minimizations (semiempirical-AMI level) were also performed with a 101 dihedral driver (15° increments) for rotation around B bond. The calculations revealed another minimum 1.49 kcal/mol higher in energy than the global minimum. In this conformation B, still only one of the methylene hydrogens is close enough for abstraction O (160% HfiHfi Scheme 64. Dihedral Angles of 23 (d: 2.30 A, 0): 18°). Experimental results show the cis-oxetanol to be the major cyclization product under all conditions. Ground state global minimizations indicate the presence of two reactive geometries, a low energy in a pro—trans and a pro-cis 1.49 kcal/mol higher in energy. Furthermore, semiempirical minimizations on the biradical of 23 show the presence of two minima within 3.3 kcal/mol of each other. The global minimum a is in a pro-cis geometry; b is higher in energy than a by 3.3 kcal/mol and in 'a pro—trans geometry. Cyclization processes, with their potential for ring strain, steric crowding and a loss of rotational entropy, are expected to produce barriers. The difference in A factors can be attributed to a faster cyclization rate of the pro-trans precursor, due to its higher energy 102 which in turn means a lower activation energy for cyclization. Therefore, the photocyclization of 23 is believed to be conformationally controlled which means that the triplet biradical lives long enough to allow equilibration. Furthermore, the difference in the A factors indicates that there needs to be an activation energy for cyclization. In their computational study of a-methoxyacetone, Chandra and coworkers found that in the nascent triplet biradical the two p orbitals on the carbon atoms at the radical sites are almost perpendicular to each other.45 This orientation is favorable for spin-orbit coupling, but the two-center spin-orbit coupling is enhanced as the distance between the radical sites decreases. This occurs as the cyclization process progresses. The height of the barrier for the cyclization process is estimaterd to be 53 kJ/mol. Another explanation for the observed diastereoselectivity is that ground state control is operative but the pro-trans biradical cyclizes less efficiently than the pro-cis biradical. This could be the case since the cyclization of the pro-trans biradical suffers from larger steric/non-bonded interactions during the closure than the pro-cis. Wagner pointed out that cleavage of 1,4-biradical can occur efficiently only in a conformation (anti) in which the two p orbitals are parallel to the C-C bond being broken.74 Hoffman’s calculations indicate such a conformation optimizes the mixing of 1! and 0 levels which promotes cleavage.75 Our considerations of steric and conformational effects in type 11 reactions suggests that the initial conformation of the biradical has the y p orbital almost parallel to the benzylic p orbital perpendicular to the B C-C bond. In order for the biradical to attain anti conformation, it must rotate about both the 01 and [3 bonds. Lewis has pointed out that cyclization of 1,4-biradical most likely produces a puckered cyclobutane ring,76 for which not as much bond rotation is necessary as for 103 cleavage. However, as mentioned above, the cyclization process suffers from the activation energy barrier, so for dialkyl and aryl alkyl ketones elimination is the predominant reaction. 3-oxetanol formation accounts for as much as 61% of the biradical products from a-alkoxyacetophenones, because the unfavorable eclipsing interaction in cyclobutane can be reduced with an oxygen in the skeleton. Actually, both Chandra45 and our calculation results reveal that 3-oxetanol is almost a planar four-membered ring. cis-oxetanol trans-oxetanol The preferential formation of cis-oxetanol in nonpolar solvents should be reconciled from the transition state structure for its formation, which should have less steric repulsion owing to the anti relationship between the sterically bulky phenyl and cyclopropyl groups at the 1,4 positions; since singlet biradicals are known to retain conformational memory of their precursor triplet biradicals before collapsing to the products, the low energy biradical a is pertinent for the observed trend. IV. Singlet vs. Triplet Behavior A. B-Cyclopropylmethoxybutanone (25) The main goal of this project was to determine the similarities and differences in 104 reactivity and selectivity of 1,5-singlet and triplet biradicals. From a mechanistic point of view, the difference in the reactivity of the singlet and triplet 1,5-biradicals and the role of environmental and conformational factors in determining the overall efficiency and chemical yield of tetrahydrofuranol formation must be addressed. 6 5 2 g 4 «~—— 0 cyclization g I rearrangement ‘E A total 3 3 . . u- —Poly. (cyclization) g —Po|y. (rearrangement) 2 2 —Po|y. (total) 2 flak 1 __I ._ . O I l T 1 1T 0 5 10 15 20 25 30 [Quencher] x 100 Figure 4. Stern-Volmer Quenching Plot of 25 As mentioned earlier, the reactive excited states for aliphatic ketones are both singlet and triplet states.”36 Thus, the excited states responsible for the observed photoreaction in 25, namely 8-hydrogen abstraction, have to be determined. Our study indicates that in benzene both cyclization and rearrangement can occur. Figure 4 shows plots of (Do/(D against the concentration of 2,5-dimethyl-2,4—hexadiene for the ketone. The simple Stem- Volmer relationship is obviously not followed in either case. Relatively low concentrations of quencher do a good deal of quenching, but at higher concentrations the quantum yields for both reactions level off to constant values. The most obvious interpretation of the results is that both reactions arise from both excited singlet and 105 triplet. If we take the quantum yield in 0.3 M quencher as a measure of the amount of singlet reaction, the mechanism is dissected as shown in Table 22. The overall quantum efficiency is low because of the well known highly efficient radiationless decay that accompanies singlet state hydrogen transfers. We have considered the possibility of enol formation for B-cycloprpopylmethoxybutanone. In our investigation, however, we were unable to detect any. The enol is expected to be much less stable with respect to ketone and if formed apparently is too short-lived to detect. Table 22. Quantum Yields for Product Formation of 25 at 25°C Ketone (pcyc.c (pcyc.-sd (pcycate (1)". (prr-sd (Drr-te 253 0.054 0.010 0.044 0.032 0.021 0.01 1 25" 0.068 //// a [Ketone] = 0.2 M in benzene. ” In methanol. c Quantum yield with no added quencher. C Quantum yield in 0.3 M 2,5-dimethyl-2,4-hexadiene. ° (I)t = (I) — (1),. The initial slope of the curve in Figure 4 should be equal to kq/kH, where kH is the rate constant of 5-hydrogen abstraction quenched by 2,5-dimethyl-2,4-hexadiene. The value is 25 M'l. We expect that energy transfer should be diffusion controlled, this would place the value of kq at about 5 x 109 M'ls". We therefore estimate the value of k“ as 2 x 108 s'1 for 25. The result was quite reasonable. The reactivity of excited singlet and triplet of unconjugated carbonyl compounds should be qualitatively similar since both states have the 11, 1t. configuration. Quenching of the formation of tetrahydrofuranols demonstrates that cyclization occurs dominantly from the triplet state. The Tl-spinisomer forms a long-lived triplet biradical which leads to low diastereoselectivity in cyclization (cis/trans = 2.9:1, Table 23). 106 The formation of rearrangement products is weakly quenched by 2,5-dimethyl-2,4- hexadiene, this result is consistent with the postulate that T; does not lead to significant amounts of E-67 and Z-67, i.e., rearrangement occurs mainly from S1. The model 1- 77 1. However, cyclopropylethyl radical opens to a 2.321 E/Z ratio of 2-penten-5-y photochemical rearrangement product is a 1:1 mixture of both E- and Z—alkenes (Table 17). There has been tendency to attribute ‘biradical’ character solely to triplet states.78 Our result indicates that singlet rearrangement could proceed concertedly. Consideration of bond energies indicates that the ring-opening is highly exothermic, so that the system has enough energy for the concerted formation of singlet alkenes. The absence of rearrangement products in methanol is another intriguing phenomenon. Since it is the singlet excited state that is mainly responsible for the ring-opening process and the following reaction rate constant may not be large enough that quenching by impurities or solvent would become competitive. Table 23. Product Ratio for Photolysis of 25a Solvent cis-68 trans-68 E -67 Z-67 Benzene 2.9 1 1.1 1.1 Methanol 1 . 1 1 a Product ratio without quencher. As mentioned before, the calculated triplet state 8-hydrogen abstraction rate constant of 25 is about 2 x 1088", which is comparable to the triplet 5-hydrogen abstraction rate constant of B—ethoxypropiophenone (2 x 107s'l).ll It is interesting that substitution of an oxygen atom for the y-methylene does not enhance the rate of 5-hydrogen abstraction. One might have expected the lone pairs on oxygen to cause less torsional strain than CH 107 bonds in the seven-membered ring transition state. But the presence of the ether oxygen does increase the percent cyclization as compared to simple alkyl ketones, which could be explained in terms of relief of strain energy due to the eclipsed conformation of vicinal hydrogens in a five-membered ring system. The cis/trans product ratio depends strongly on solvent (Table 23), as expected with hydroxybiradicals; but polar solvent only slightly raised the cyclization quantum efficiency. Combining this result with previous study on B-ethoxypropiophenone,79 we speculated that in the 1,5-biradicals a 1,4-hydrogen transfer might provide an alternative mode of internal disproportionation, one not affected by hydrogen bonding involving the OH group, although the resulting enol could not be detected. Studies of type H photocyclization reactions of dialkyl ketones are less common. The vast majority focus on the formation of cyclobutanols. Indeed, unless the 1,5-hydrogen abstraction pathway is blocked, it will be the predominant one. A limited study of five- membered ring formation was made by Descotes.80 His studies, which dealt largely with carbohydrate systems, showed that such cyclizations generally afforded stereoisomeric mixtures of tetrahydrofuranols. Additionally, Carless and coworkers noted the following cyclization with rather low stereoselectivity (Scheme 65).31 hv NOV \ 0 Scheme 65. Photochemistry of B-Allyloxybutanone The concerns of this investigation are both synthetic and mechanistic. At the synthetic level, we address the relationship of the structure to the yield of tetrahydrofuran products, as well as the possible means available to manipulate reaction conditions to enhance the 108 yield of THFs. At the mechanistic level, we identify the excited state responsible for THF formation, the role of conformational factors and environmental factors in determining the overall efficiency of THF formation. The rate constant of triplet 8-hydrogen abstraction for 25 has been estimated to be ca. 2 x 108 8". Since for triplet 2-pentanone kH is 0.16 x 108 s'1 and for singlet 2-pentanone is 1.8 x 108 s",82 we can estimate the rate constant of S-hydrogen abstraction given a rate for the triplet decay. By applying this factor to the rate constant for triplet B-hydrogen abstraction for 25, we estimate the rate constant of singlet 5-hydrogen abstraction for 25 to be ca. 2.2 x 109 s". This value is large enough to compete with intersystem crossing but not so fast as to completely dominate singlet deactivation, i.e., some intersystem crossing to produce a triplet that undergoes hydrogen abstraction is expected. For S-hydrogen transfer, rotation about the B, y C-C bond is also required. Since 8- hydrogen abstraction involves twice as many frozen rotation in its cyclic transition state as does y-hydrogen abstraction, part of the rate difference must reflect the differing entropy losses for the two processes. Global minimizations (semiempirical-AMI level) with dihedral drivers around [3 and 7 bonds have shown that the lowest energy geometry (A) of 25 has one of the S-hydrogens close enough for abstraction (d: 2.63 A, (0: 36°). Geometries B and C exist as local minima 1.45 kcal/mol and 1.60 kcal/mol higher than global minimum, respectively. In both B (d: 2.38 A, (0: 66°) and C (d: 2.52 A, to: 50°), one of the methylene protons is abstractable. The observed diastereoselectivity in benzene demands 0.6 kcal/mol energy differential 109 between the cis and trans modes of cyclization. As Lewis’ work first showed,73 the nonbonded interactions that cause such selectivity can either pre-exist in the biradicals or be created during cyclization as the methyl and cyclopropyl groups on the biradical ends approach each other. In the latter case, the energy differences between the two isomeric products would have to be even greater than the differential transition state energies for cyclization. The thermodynamic energy difference between the cis and trans products is not known, but molecular mechanics calculations suggest that puckering of the five- membered ring reduces the difference to near zero. Therefore the discrimination between the two modes of cyclization probably reflects pre-existing energy differences that persist during cyclization. We have tested this idea by performing MM2 calculations on the triplet biradical from 25. After minimization with respect to rotation about all acyclic C-C bonds, the two 110 cis-68 trans-68 minimum energy geometries were calculated to differ in energy by 0.64 kcal/mol. If the two biradical rotamers indeed differ by 0.64 kcal/mol, most of the observed selectivity simply reflects conformational equilibrium in the biradical before cyclization, provided that cyclization of both rotamers involves the same motion. This assumption seems reasonable here, since a simple disrotation around the two ortho C-C bonds is all that is required for coupling. When the OH group is solvated by hydrogen bonding in methanol, it is comparable in size to the methyl group, such that the two rotamers are nearly equal in energy and selectivity is lost. Scaiano postulated that the product composition from triplet biradicals is determined by variations in intersystem crossing rates of various biradical conformers.72 In short biradcials, ISC is mainly driven by spin-orbit coupling, which is known to be very much dependent upon the distance between radical centers. This means that ISC occurs most 111 — fast when the biradical ends are proximate, which is most likely to be at the moment of biradical coupling. Wagner has proposed the notion of coupled ISC and reaction.ll Both the singlet and triplet surfaces rise in energy with movement along the reaction coordinate, but the singlet surface is soon stabilized by the developing bond, such that the two surfaces cross at points that represent very low activation energy. The singlet biradical is then trapped in a conformational well that leads to reaction. The concept of reaction induced ISC has also been implied by Griesbeck’s explanation on stereoslectivity in [2+2] photocycloaddition of benzaldehyde to cyclic alkenes.83'84 He suggested that the observed stereoselectivity is caused by relative energy difference of two different conformers, which he interpreted as transient points through which stable 1,4-biradicals have to pass in order to invert spin and to overcome the spin barrier for bond formation. It is consistent with Wagner’ proposal in that ISC and product formation are induced by molecular motion along reaction coordinate. Our current results provide another example of the same phenomenon. As mentioned earlier, oxygen is said to have an effect on the 1,5-biradical, wherein the eclipsing effect is reduced when the carbon atom is replaced with oxygen, which facilitates bringing the two ends of the biradical together. This phenomenon has also been used to explain the high cyclization efficiency of the B-alkoxypropiophenones. On the other hand, it might be expected that an oxygen which is conjugated to the 8 radical center, would lower the krr value from that for cyclopropylethyl radical, as is the case for a-cyclopropylbenzyl radicals. Our study on 25 in benzene produced both the cyclization 112 and rearrangement products, indicating that cyclization and ring-opening were competitive. B. a-Cyclopropylmethoxyacetone (24) 1.35 1_3._____-__ -. -. .2--- _.._______, 1.25« -- ~-——- 1.2- --’ 1.15.- -, - e-*~--——-~ 1.1 W - ,rr,.rr,_-_______. 1.05~ —- — —- .._-_..._ 12* _-_ relative quantum yield 10WWW— - W— . W 0.95 —~ — W 0-9 I l l T 0 1 O 20 30 40 50 [O]x100 Figure 5. Stern-Volmer Quenching Plot of 24 The lowest energy excited state for aliphatic ketones is n, at state, both singlet and triplet 11, 1t* states undergo the Norrish type II photoreaction. Figure 3 shows plot of (Do/(D for 24 disappearance against quencher concentrations. The amount of nonquenchable reaction may reasonably be attributed to reaction through the excited singlet state with the remainder of the photochemical reaction occurring through the excited triplet state. The initial slope in Figure 5 can be equated to kq/kr (kr = sum of rate constants for reactions quenched). Our value of 4.4 indicates a kr value of 1.1 x 1098'1 for 24. Calculation done by Chandra and coworkers showed that the ether oxygen in the [3- position has no activating influence on the carbonyl oxygen for hydrogen abstraction.45 113 The increased rate constant of a-alkoxy acetone relative to aliphatic ketones may be due to a decrease in the bond dissociation energy of C-H homolysis in ethers relative to alkanes. It may be explained by the fact that the back lobe of the 0* orbital of the C-H bond overlaps with one of the two lone pair orbitals on the ether oxygen leading to a flow of electrons to the antibonding 0* orbital. This should cause a decrease in the C-H bond order of the bond containing the abstractable hydrogen. Irradiation of 24 in benzene resulted in the formation of both acetone and a single isomeric 3-oxetanol, identification of the excited state responsible for these reactions is of considerable interest. From the slight quenching of type H product formation, we conclude that excited singlet was primarily responsible for the photoelimination. This result does not, of course, establish the interrnediacy of a biradical. One might expect that excited singlet could undergo the elimination reaction by a completely concerted mechanism}8 Consideration of bond energies suggests a AH = 12 kcal/mol for type II elimination of a-CPMOA (Scheme 66).85 E31 of aliphatic ketones at room temperature in benzene is about 80.6 kcal/mol.86 Therefore, the type H reaction from singlet is 69 kcal/mol exothermic, not enough to produce aldehyde in its singlet state. 91 10\3‘ fir—r r 81 57 91 +81 -103-57=12 Scheme 66. Norrish Type 11 Reaction of 24 On the other hand, the formation of 3-oxetanol is almost unquenchable, which indicates that cyclization also occurs from the excited singlet, the formation of a single stereoisomer seems to confirm that: if triplet state is responsible for cyclization, then the 114 resulting triplet biradical would have enough time to equilibrate and a relatively low stereoselectivity would have been observed; when the cyclization occurs from singlet state, either the process is concerted, or the resulting singlet biradical is too short-lived to allow equilibration. The heteroatom reduces the distance between the biradical termini and reduces steric hindrance to the close approach of the termini because the number of H-H eclipsing interactions is reduced. Lifetime of this singlet biradical is short enough that bond rotation will not occur; that is, singlet biradical decay has to occur from a semi- frozen conformation. The cyclization process is observed in a-alkoxy acetophenones leading to the formation of 3-oxetanols. Experimental results have not been reported for a-alkoxy acetones. However, Chandra’s analysis shows that the singlet 1,4-biradical derived from a-methoxy acetone can cyclize readily to form 3-oxetanol.45 In the nascent triplet biradical, the distance between the radical sites is 3.0 A and the two p orbitals on the carbon atoms at the radical sites are almost perpendicular to each other. The mechanism suggested above is consistent with the solvent effect: in methanol photolysis of 24 gave only the type H elimination product. It is widely recognized that the effect is the result of the engagement of the OH group (from the ketyl center) in H- bonding,9 thus increasing the steric hindrance in cyclization. The model presented here provides a simple explanation: H-bonding solvent changes the conformational distribution, since singlet biradical will now be formed in somewhat different conformations the cyclization/fragmentation ratio can be expected to change. Our results indicate that the biradical intermediate from 24 undergoes cyclization and type H elimination before the cyclopropyl ring opening, so does the absence of 115 rearrangement product. In fact, it has been known that benzylic stabilization perturbs the equilibrium of the cyclopropylcarbinyl radical rearrangement and that the conjugation of oxygen lowers the rate even further down.70 The ring-opening rate of cyclopropylmethoxy radical is determined to be 9.9 x 106 from previous experiment. Table 24. Quantum Yields for Ketone Disappearence and Product Formation of 24 in Benzene at 25°C Ketone (bursa (Ddiswsb (bars-1c 0118 (1’1st (I’ll-rc d’cyea 24 0.29 0.22 0.07 0.25 0.19 0.06 0.034 a Quantum yield without quencher. b Quantum yield in 0.4 M quencher. c (1),: (b — (1),. The high yield of acetone would support Wagner’s suggestion that cyclization reactions have large barriers (due to lossof rotational freedom, ring strain and steric crowding around the forming bond) even on the singlet surface.87 Our calculations reveal that 24 has a similar conformation in the lowest 11, 1t* singlet and triplet states. Both of these states have a favorable conformation for hydrogen abstraction: lowest energy conformer on singlet surface has one methylene hydrogen close enough for abstraction (d: 2.17 A, 0: 156°, [3: 75°, 7: 72°); the lowest energy triplet state ketone also has only one of the y hydrogens abstractable (d: 2.15 A, a: 145°, [3: 75°, 7: 72°). It has been postulated that for y-hydrogen abstraction, once the reactive ketone conformer is reached, a further barrier is required to transfer the abstractable hydrogen to the carbonyl oxygen. Chandra’s computational study on a-alkoxyacetones confirmed the presence of such a barrier: for a-alkoxyacetone containing secondary C-H bonds in y-position, the barrier of y-hydrogen abstraction in the lowest triplet state is about 20 kJ/mor.45 116 Lowest energy singlet conformer Lowest energy triplet conformer Dialkyl ketones are known to undergo y-hydrogen abstraction in both T1 and 81.3637 Although studies of comparative processes are relatively few in number, in some cases the rate of y-hydrogen abstraction from 31 is much higher than from T1. For t-butyl alkyl ketones it was found that y-hydrogen abstraction arises predominantly from a singlet excited state. A more rapid rate for hydrogen abstraction from the singlet state may be rationalized on the basis of the higher energy of $1 and appear to the common relationship between rate and exothermicity in radical reactions. We conclude that an inherently faster rate of y-hydrogen abstraction in 81 leads to the selectivity observed. We now take the issue of an excited-state precursor of the products as settled and consider briefly some further mechanistic aspects of the results, particularly the effect of conformation on the chemical yield of products. cis-oxetanol 117 Singlet state type H reactions differ in many respects from the triplet reaction: cyclization/elimination ratio is smaller; radiationless decay/reaction ratio is higher; no polar solvent effect on singlet state quantum yield. In Table 18, we note that the quantum yield for cyclization is rather low as compared to that of 24. The act of hydrogen abstraction may produce a surface crossing along the singlet reaction surface that serves as a special ‘chemically assisted’ internal conversion.1‘36'37'38’82’88 This type of inefficiency is well documented and accepted in the case of singlet 1,4-biradicals from the experimental results of Wagner38 and Yang82 on the Norrish type H reaction and from the theoretical models of Salem89 and Michl.90 Based on these pioneering efforts, we interpret the inefficiency as resulting from a y-hydrogen-excited carbonyl interaction which either induces internal conversion or leads to formation of a singlet 1,4-biradical which efficiently disproportionates to the starting ketone. Since analogous triplet 1,4- biradical produced from 23 cyclizes efficiently to oxetanols, it is difficult to understand why the singlet 1,4—biradical produced from 24 would not cyclize efficiently. The singlet biradicals have very short lifetimes and the ground state control might be assumed to control their reactivity. However, our experimental result shows cis-oxetanol to be the only cyclization product. Global minimization on singlet excited state ketone indicates the presence of one reactive conformer which is in a pro-trans geometry. While semiempirical calculation on the singlet biraidcal shows the presence of two minima within 1.3 kcal/mol of each other. The global minimum a is in a pro-cis geometry, b is 1.21 kcal/mol higher in energy than a and is not in a good geometry to cyclize. Our results seem to indicate conformational control of reactivity in photocyclization of singlet biradicals. 118 119 Experimental Section I. General Procedures 1H and 13 C NMR spectra were obtained using either a 300 MHz Varian Gemini, a 300 MHz Varian UnityPlus, a 300 MHz Inova or a 500 MHz Varian UnityPlus instrument. IR spectra were recorded using solutions in CCl4 on a Nicolet IR-42 Fourier Transform R spectrometer. Compounds with low solubility in carbon tetrachloride were prepared as thin films on a NaCl plate by dissolving in an appropriate solvent then pipetting the solution on the salt plate. The solvent was allowed to evaporate and the cycle repeated until an acceptable film was achieved. UV spectra were recorded on a Shimadzu UV-160 spectrometer. Low resolution mass spectra were recorded on a Hewlett-Packard 5890 GC/MS Trio-1. The electron impact (E1) and direct probe methods were used. Gas chromatographic analysis were performed on a Varian 3400 machine with flame ionization detector, splitless capillary injector and a Megabore DB-210 capillary column. The GC was connected to a Hewlett-Packard 3393A integrating recorder. HPLC analyses were performed on a Rainin system equipped with Dynamax UV-D absorbance detector using a silica column. For the preparative TLC, Analtech Uniplate silica gel plates (20 x 20 cm, 1000 micron) were used. 120 a .‘1._ 7.40 5 ,I 0...“.4 '- ..’ . L 7- .. I . .- . _. 3- _I - . 'l' . : 6.- ‘ L1 . ‘- —.- .. -- . :J ._7 or- ’0' . - or,“ “.1- . 7 w u 9 ., , v... .-_.: w "-1. .. Q’W 15151.?37111‘w’i5 ‘_' ‘1 ‘,'1 g 1‘ 1"...1 v - Aorg-ga LR . f '[I‘ I. S nthesis: Pre aration of Startin Ketones I. Substituted 2-A1koxy-3-a1kyl Benzophenones ORO ”'W Ketone R R’ 1 CH3 CH3 2 CH3 CH(CH3)2 3 CH3 C(CH3)3 4 CH3CH2 CH3 5 CH3CH2 CH(CH3)2 6 CH3CH2 C(CH3)3 7 PhCHz CH3 8 PhCHz CH(CH3)2 9 PhCHz C(CH3)3 '- \ . 2-Methoxy-3-methylbenzophenone (1) a. » -v- t~4l. ‘1‘ .1 , -1 . - - .4: .._.. r 01 r , r ’- thflitl'fl 01140414. -'4’a‘d ’ .’ 0“ OCH" a. n-BuLi,TMEDA, CH3° 0” CH31, K2C03A Et201 00C"rt A acetone 7 b. benzaldehyde , 70 CH30 o 1 Scheme 67. Synthesis of 1 121 2-methylanisolegl To a 250 mL round-bottom flask were placed 2-cresol (8.7 g, 8.4 mL, 80 mmol) and 80 mL of acetone. Potassium carbonate (11.1 g, 80 mmol) was added followed by methyl iodide (28.4 g, 12.5 mL, 200 mmol). The mixture was allowed to reflux for about 12 hours and then cooled to room temperature. The white solid was filtered off, the filtrate was evaporated under reduced pressure. The residue was purified by $102 column chromatography with pure hexanes as the eluent to provide 2-methylanisole (5.8 g, 59% yield) as a colorless liquid. 2-meth0xy-3-methylbenzhydrol (70) To a vigorously stirred solution of 2-methylanisole (3.2 g, 26.2 mmol) and tetramethylethylenediamine (3.0 g, 26.2 mmol, 3.9 mL) in 80 mL of diethyl ether, was added n-butyl lithium (16.4 mL, 1.6 M in hexanes, 26.2 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (2.8 g, 26.2 mmol, 2.7 mL) was added to this solution. The reaction was quenched by addition of saturated NH4C1 aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSO4. Solvent was evaporated to yield crude product which was purified by column chromatography (hexanes: ethyl acetate 10: 1) to give 70 (3.9 g, 65% yield) as a colorless oil. 1H NMR (CDC13, 300MHz), 5 ppm: 2.28 (s, 3H), 3.51 (s, 3H), 3.84 (s, 1H), 6.03 (s, 1H), 7.01 (t, J: 7.5 Hz, 1H), 7.14 (dd, J: 7.8, 13.5 Hz, 2H), 7.34 (m, 5H). 2-methoxy-3-methylbenzophen0ne (1)92 122 Pyridinium chlorochromate (5.5 g, 16.4 mmol) was suspended in 60 mL of anhydrous CHzClz. 70 (2.5 g, 11.0 mmol) in 10 mL of CHzClz was added in one portion to the magnetically stirred solution.93 After 3 hours 30 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotoevaporation. The crude product was purified by column chromatography (hexanes: ethyl acetate 50:1) to give 1 (1.7 g, 69% yield) as a colorless oil. IH NMR (CDC13, 300MHz), 8 ppm: 2.32 (s, 3H), 3.60 (s, 3H), 7.07 (t, J: 7.5 Hz, 1H), 7.17 (dd, J: 1.8, 7.5 Hz, 1H), 7.31 (dd, J: 0.9, 7.5 Hz, 1H), 7.45 (t, J: 7.8 Hz, 2H), 7.55 (tt, J: 1.5, 7.5 Hz, 1H), 7.81 (dt, J: 1.5, 7.8 Hz, 2H). 13C NMR (75 MHz, CDC13), 8 ppm: 16.02, 61.81, 123.44, 127.21, 128.30, 129.94, 131.71, 132.87, 133.15, 133.47, 137.47, 156.45, 196.84. IR (neat, cm'l): 2941.82 (w), 1668.64 (s), 1597.26 (m), 1466.09 (m), 1317.55 (m), 1288.61 (m), 1226.88 (m), 1006.97 (m), 966.46 (w). MS, m/z: 226.1 (100.0%), 208.4 (100.0%), 181.1 (100.0%), 148.8 (100.0%), 134.5 (98.9%), 104.9 (100.0%), 76.9 (100.0%). Anal. Calcd C15H14Oz: C, 79.65; H, 6.19. Found: C, 79.84; H, 6.15. UV (path: lcm, 1m, nm (em,x M")): Benzene, 282 (3,019), 313 (449). 2. 3-Isopropyl-2-methoxybenzophenone (2) 2-isopr0pylanisole91 123 0” OCH" a. n-BuLi, TMEDA, CH3° OH CH3I,K2003L Et20.0°C~rt _ acetone , b. benzaldehyde v 71 CH3O 0 Scheme 68. Synthesis of 2 To a 250 mL round-bottom flask were placed 2-isopropylphenol (8.2 g, 8.1 mL, 60 mmol) and 60 mL of acetone. Potassium carbonate (8.3 g, 60 mmol) was added followed by methyl iodide (17.0 g, 7.5 mL, 120 mmol). The mixture was allowed to reflux for about 12 hours and then cooled to room temperature. The white solid was filtered off, the filtrate was evaporated under reduced pressure. The residue was purified by SiOz column chromatography with pure hexanes as the eluent to provide 2-isopropylanisole (5.6 g, 62% yield) as a colorless liquid. 3-isopropyl-2-meth0xybenzhydrol (71) To a vigorously stirred solution of 2-isopropylanisole (4.4 g, 29.0 mmol) and tetramethylethylenediamine (3.5 g, 29.0 mmol, 4.5 mL) in 80 mL of diethyl ether, was added n-butyl lithium (18.2 mL, 1.6 M in hexanes, 29.0 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (2.8 g, 26.0 mmol, 2.7 mL) was added to this solution. The reaction was quenched by addition of saturated NH4C1 aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous Na2504. Solvent was evaporated to yield crude product which was purified by column chromatography 124 (hexanes: ethyl acetate 10: 1) followed by recrystallization from hexanes to give 71 (4.0 g, 60% yield) as a white crystalline solid. 1H NMR (CDC13, 300MHz), 8 ppm: 1.20 (d, J: 6.9 Hz, 3H), 1.22 (d, J: 6.9 Hz, 3H), 2.89 (s, broad, 1H), 3.29 (heptet, J: 6.9 Hz, 1H), 3.56 (s, 3H), 6.07 (s, 1H), 7.11 (m, 2H), 7.23 (m, 2H), 7.32 (tt, J: 1.2, 7.5 Hz, 2H), 7.39 (dd, J: 1.8, 7.5 Hz, 2H). m.p.: 75.3~76.5°C 3-isopropyl-2-meth0xybenz0phen0ne (2)92 Pyridinium chlorochromate (7.5 g, 22.0 mmol) was suspended in 80 mL of anhydrous CHzClz. 71 (3.8 g, 15.0 mmol) in 15 mL of CHzClz was added in one portion to the magnetically stirred solution.93 After 4 hours 40 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotoevaporation. The crude product was purified by column chromatography (hexanes: ethyl acetate 50:1) to give 2 (3.6 g, 96% yield) as a white solid. 1H NMR (CDC13, 300MHz), 8 ppm: 1.25 (d, J: 6.9 Hz, 6H), 3.36 (heptet, J: 6.9 Hz, 1H), 3.60 (s, 3H), 7.17 (m, 2H), 7.43 (m, 3H), 7.56 (tt, J: 1.5, 7.2 Hz, 1H), 7.83 (dd, J: 1.2, 6.9 Hz, 2H). 13C NMR (75 MHz, CDC13), 6 ppm: 23.61, 26.33, 62.90, 123.76, 127.13, 128.31, 129.10, 129.98, 132.76, 133.19, 137.42, 142.32, 155.50, 197.00. H1 (neat, cm'l): 2964.97 (m), 1670.57 (8), 1597.26 (w), 1290.54 (s), 1006.97 (m). MS, m/z: 253.9 (37.7%), 238.8 (19.4%), 195.1 (20.2%), 177.0 (50.6%), 161.0 (43.5%), 125 105.0 (100.0%), 91.0 (100.0%), 76.8 (100.0%). Anal. Calcd C17H1802: C, 80.31; H, 7.09. Found: C, 80.21; H, 7.13. UV (path: 1cm, 7.4m nm (emM M")): Benzene, 281 (3,289), 313 (497). m.p.: 69.6~70.3°C 3. 3-t-Butyl-2-methoxybenzophenone (3) 0H OCH" a. n-BuLi,TMEDA, CH3° OH *6 *0 - acetone b. benzaldehyde 72 CH30 0 FCC, CHZCIZ : 3 Scheme 69. Synthesis of 3 2-t-but‘ylanisole91 To a 250 mL round-bottom flask were placed 2-t-butylphenol (9.0 g, 9.2 mL, 60 mmol) and 60 mL of acetone. Potassium carbonate (8.3 g, 60 mmol) was added followed by methyl iodide (17.0 g, 7.5 mL, 120 mmol). The mixture was allowed to reflux for about 12 hours and then cooled to room temperature. The white solid was filtered off, the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography with pure hexanes as the eluent to provide 2-t-butylanisole (6.0 g, 61% yield) as a colorless liquid. 3—t-butyl-2-meth0xybenzhydr0l (72) 126 To a vigorously stirred solution of 2-t-butylanisole (5.3 g, 32.0 mmol) and tetramethylethylenediarrune (3.7 g, 32.0 mmol, 4.8 mL) in 80 mL of diethyl ether, was added n-butyl lithium (20.0 mL, 1.6 M in hexanes, 32.0 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (3.4 g, 32.0 mmol, 3.3 mL) was added to this solution. The reaction was quenched by addition of saturated NH4C1 aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSO4. Solvent was evaporated to yield crude product which was purified by column chromatography (hexanes: ethyl acetate 15:1) followed by recrystallization from hexanes to give 72 (5.4 g, 63% yield) as a white crystalline solid. lH NMR (CDC13, 300NH12), 8 ppm: 1.38 (s, 9H), 2.58 (s, broad, 1H), 3.57 (s, 3H), 6.06 (s, 1H), 7.01 (t, J: 7.5 Hz, 1H), 7.18 (dd, J: 1.8, 7.5 Hz, 1H), 7.41 (m, 2H), 7.52 (tt, J: 1.5, 7.5 Hz, 2H), 7.80 (dd, J: 1.8, 7.8 Hz, 2H). m.p.: 78.2~79.1°C. 3 -t-butyl-2-meth0xybenzophenone (3)92 Pyridinium chlorochromate (10.1 g, 30.0 mmol) was suspended in 100 mL of anhydrous CHzClz. 72 (5.4 g, 20.0 mmol) in 15 mL of CH2C12 was added in one portion to the magnetically stirred solutionf”3 After 3 hours 40 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotoevaporation. The crude product was purified by column chromatography (hexanes: 127 ethyl acetate 50: 1) to give 3 (5.4 g, 100% yield) as a white solid. ’H NMR (CDCl3, 300MHz), 8 ppm: 1.39 (s, 9H), 3.55 (s, 3H), 7.07 (t, J: 7.8 Hz, 1H), 7.22 (dd, J: 2.1, 7.8 Hz, 1H), 7.44 (m, 3H), 7.56 (tt, J: 1.2, 7.5 Hz, 1H), 7.84 (dd, J: 1.8, 8.4 Hz, 2H). 13C NMR (75 MHz, CDC13), 8 ppm: 30.47, 35.10, 62.10, 122.71, 128.33, 128.43, 129.44. 130.03, 132.37, 133.23, 137.16, 142.75, 158.39, 197.26. IR (neat, cm'l): 2959.18 (m), 1684.78 (s), 1583.70 (w), 1412.07 (m), 1290.54 (m), 1230.74 (m), 1008.90 (w). MS, m/z: 268.8 (26.7%), 267.9 (26.7%), 252.9 (42.0%), 235.2 (30.6%), 175.0 (21.4%), 105.0 (100.0%), 91.0 (100.0%), 76.9 (100.0%). Anal. Calcd C13H20022 C, 80.60; H, 7.46. Found: C, 80.63; H, 7.33. UV (path: 1cm, 11m, nm (em, M")): Benzene, 280 (3,662), 313 (803). mp: 54.0~54.8°C 4. 2-Ethoxy-3-methylbenzophenone (4) OH 05‘ a. n-BuLi, TMEDA, 5’0 0” a. NaOCH3 _ 512010°C~fl A b. EtBr b. benzaldehyde , 73 E10 0 4 Scheme 70. Synthesis of 4 1 2-ethoxytoluenez" 128 2-Cresol (8.6 g, 8.2 mL, 800 mmol) was added to sodium methoxide (4.3 g, 80.0 mmol) in 60 mL of methanol and stirred under nitrogen for about 1 hour. Ethyl bromide (21.8 g, 14.9 mL, 200.0 mmol) in 15 mL of methanol was added dropwise; the solution was refluxed overnight. The methanol was removed on a rotary evaporator and residue taken up into 80 mL of diethyl ether. The ether was washed with saturated sodium bicarbonate. The aqueous layers were combined and washed with ether. The ether extracts were combined, washed with brine and dried over anhydrous NaZSO4. The solvent was removed in vacuo to afford a yellow oil. This oil was purified by column chromatography (hexanes) to give 2-ethoxytoluene (6.6 g, 61% yield) as a colorless liquid. 2-ethoxy-3-methylbenzhydrol (73) To a vigorously stirred solution of 2-ethoxytoluene (4.8 g, 35.0 mmol) and tetramethylethylenediamine (4.1 g, 35.0 mmol, 5.3 mL) in 80 mL of diethyl ether, was added n-butyl lithium (22.0 mL, 1.6 M in hexanes, 35.0 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (3.4 g, 32.0 mmol, 3.3 mL) was added to this solution. The reaction was quenched by addition of saturated NH4C1 aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSO4. Solvent was evaporated to yield crude product which was purified by column chromatography (hexanes: ethyl acetate 20: 1) to afford 73 (6.4 g, 83% yield) as a pale yellow oil. 1H NMR (CDC13, 300NH-Iz), 8 ppm: 1.29 (t, J: 7.2 Hz, 3H), 2.27 (s, 3H), 2.96 (s, broad, 1H), 3.61 (dq, J: 7.2, 9.3 Hz, 1H), 3.74 (dq, J: 7.2, 9.3 Hz, 1H), 6.05 (s, 1H), 6.99 (dd, 129 J: 6.9, 8.1 Hz, 1H), 7.10 (d, J: 7.5 Hz, 2H), 7.34 (stack, 5H). 2-eth0xy~3-methylbenzophen0ne (4) Pyridinium chlorochromate (13.3 g, 40.0 mmol) was suspended in 80 mL of anhydrous CHzClz. 73 (6.4 g, 26.4 mmol) in 15 mL of CH2C12 was added in one portion to the magnetically stirred solution.93 After 3 hours 50 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotoevaporation. The crude product was purified by column chromatography (hexanes: ethyl acetate 50:1, then hexanes: dichloromethane 2:1) to afford 4 (3.6 g, 56% yield) as a colorless oil. 1H NMR (CDC13, 300NH-Iz), 8 ppm: 1.06 (t, J: 7.2 Hz, 3H), 2.31 (s, 3H), 3.75 (q, J: 7.2 Hz, 2H), 7.06 (t, J: 7.5 Hz, 1H), 7.21 (dd, J: 1.8, 7.5 Hz, 1H), 7.32 (dd, J: 1.8, 7.5 Hz, 1H), 7.42 (tt, J: 1.8, 7.8 Hz, 2H), 7.54 (tt, J: 2.1, 7.2 Hz, 1H), 7.82 (m, 2H). 13C NMR (75 MHz, CDC13), 8 ppm: 15.27, 16.21, 70.37, 123.32, 127.39, 128.23, 129.93, 131.91, 133.00, 133.02, 133.46, 137.58, 155.56, 197.02. IR (neat, cm"): 3067.21 (w), 2978.47 (w), 2924.46 (w), 1670.57 (8), 1597.26 (m), 1448.73 (m), 1317.55 (m), 1288.61 (m), 1219.17 (m), 1087.99 (w), 1032.05 (m), 966.46 (w), 848.79 (w). MS, m/z: 240.2 (12.4%), 210.9 (26.7%), 134.6 (100.0%), 104.5 (27.9%), 76.9 (91.6%), 50.8 (41.6%). Anal. Calcd for C16H1602: C, 80.00; H, 6.67. 130 ‘r . 1 ' . . . 1 "w - .wa" """' "In. ."' "‘- 1M. .“ ' " I. t l‘-.'.; . . '9' '0 .4 r 1 . > ,1 "'1'""0.~q31"001u|q..' '1'; "-30 u u. .'. ' ..Nf - ‘1'11 ”1.1.1.741 1. ~ 1 0- - ‘ '.' 249.1.“ "5: . _. ..v: 41“,“;- - ' 10.1-. .i‘ 'I” ...p-_' . U ‘ II ‘ -| 5 u I “.1“ ..n.'—-s' o --.-_,‘, .- - Kata-'2 . 4...... l l 9"” r, :1... ,1. u-Ip—J ‘.4‘,-"'_F5‘ ,1! 1."... r' m1=*1"‘1.1.41. ..,:, H _‘ I";Q¢‘ a o_ .1 ' . II '... 13‘451. 111! 'l 97"“ -o-"'!;.'a'ni .L‘: " .‘ “'. 4.181.131- 3111341113161. Found: C, 79.82; H, 6.37. UV (path: 1cm, 2...... nm (em, M")): Benzene, 281 (3,212), 313 (529). 5. 2-Ethoxy-3-isopr0pylbenzophenone (5) OH a. n-BuLi, TMEDA, 5'0 O” a. NaOCHa E120,0°C~rt A b. EtBr b. benzaldehyde V 74 EtO 0 Scheme 71. Synthesis of 5 Z-ethoxycumenez‘? 2-Isopropylphenol (8.2 g, 8.1 mL, 60.0 mmol) was added to sodium methoxide (3.3 g, 60.0 mmol) in 60 mL of methanol and stirred under nitrogen for about 1 hour. Ethyl bromide (13.1 g, 9.0 mL, 120.0 mmol) in 15 mL of methanol was added dropwise; the solution was refluxed overnight. The methanol was removed on a rotary evaporator and residue taken up into 80 mL of diethyl ether. The ether was washed with saturated sodium bicarbonate. The aqueous layers were combined and washed with ether. The ether extracts were combined, washed with brine and dried over anhydrous Nasta. The solvent was removed in vacuo to afford a yellow oil. This oil was purified by column chromatography (hexanes) to give 2-ethoxycumene (6.3 g, 64% yield) as a colorless liquid. 2-eth0xy-3-isopropylbenzhydrol (74) 131 To a vigorously stirred solution of 2—ethoxycumene (3.2 g, 20.0 mmol) and tetramethylethylenediamine (2.3 g, 20.0 mmol, 3.0 mL) in 60 mL of diethyl ether, was added n-butyl lithium (12.5 mL, 1.6 M in hexanes, 20.0 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (1.9 g, 18.0 mmol, 1.9 mL) was added to this solution. The reaction was quenched by addition of saturated NHaCl aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSO4. Solvent was evaporated off to yield crude product which was purified by column chromatography (hexanes: ethyl acetate 20:1) to afford 74 (4.1 g, 84% yield) as a pale yellow oil. ‘H NMR (CDC13, 300MHz), 8 ppm: 1.20 (d, J: 6.9 Hz, 3H), 1.22 (d, J: 6.9 Hz, 3H), 1.34 (t, J: 6.9 Hz, 3H), 2.99 (s, broad, 1H), 3.26 (heptet, J: 6.9 Hz, 1H), 3.46 (q, J: 6.9 Hz, 2H), 3.68 (stack, 2H), 6.08 (s, 1H), 7.06 (stack, 2H), 7.22 (stack, 2H), 7.32 (t, J: 7.8 Hz, 2H), 7.40 (dd, J: 1.2, 9.0 Hz, 2H). 2-eth0xy-3-isoprOpylbenzophenone (5) Pyridinium chlorochromate (7.7 g, 23.0 mmol) was suspended in 60 mL of anhydrous CH2C12. 74 (4.1 g, 15.2 mmol) in 15 mL of CHzClz was added in one portion to the magnetically stirred solution.93 After 3 hours 50 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotaevaporation. The crude product was purified by column chromatography (hexanes: ethyl acetate 60: 1) to afford 5 (3.5 g, 85% yield) as a colorless oil. 132 1H NMR (CDC13, 300MHz), 8 ppm: 1.05 (t, J: 7.2 Hz, 3H), 1.24 (d, J: 6.9 Hz, 6H), 3.72 (heptet, J: 6.9 Hz, 1H), 3.74 (q, J: 7.2 Hz, 2H), 7.13 (dt, J: 0.3, 7.5 Hz, 1H), 7.20 (dd, J: 2.1, 7.5 Hz, 1H), 7.42 (stack, 3H), 7.57 (tt, J: 1.5, 7.5 Hz, 1H), 7.82 (m, 2H). 13C NMR (75 MHz, CDCl3), 8 ppm: 15.29, 23.69, 26.22, 71.43, 123.67, 127.23, 128.24, 129.09, 129.98, 132.95, 133.02, 137.50, 142.52, 154.43, 197.15. R (neat, cm’l): 3065.28 (w), 2964.97 (m), 2930.24 (w), 2870.44 (w), 1672.50 (8), 1597.26 (w). 1446.80 (m), 1388.92 (w), 1288.61 (m), 1217.24 (m), 1030.12 (w). MS, m/z: 268.2 (23.4%), 238.8 (14.3%), 224.8 (7.9%), 163.4 (53.0%), 147.0 (29.8%), 105.0 (100.0%), 77.0 (84.0%). Anal. Calcd for ClgHzoOZI C, 80.60; H, 7.46. Found: C, 80.71; H, 7.35. UV (path: 1cm, km, nm (emax M")): Benzene, 280 (3,637), 313 (545). 6. 3-t-Butyl-2-ethoxybenzophenone (6) a. n-BuLi,TMEDA, 5'0 O” a. NaOCHl: E120.0°C~rl ‘ b. EtBr b. benzaldehyde V 75 E10 0 FCC. CH2C|2 : Scheme 72. Synthesis of 6 2-t-butyleth0xybenzene23 2-t-Butylphenol (9.0 g, 9.2 mL, 60.0 mmol) was added to sodium methoxide (3.3 g, 60.0 mmol) in 60 mL of methanol and stirred under nitrogen for about 1 hour. Ethyl 133 bromide (16.4 g, 11.2 mL, 150.0 mmol) in 15 mL of methanol was added dropwise; the solution was refluxed overnight. The methanol was removed on a rotary evaporator and residue taken up into 80 mL of diethyl ether. The ether was washed with saturated sodium bicarbonate. The aqueous layers were combined and washed with ether. The ether extracts were combined, washed with brine and dried over anhydrous Na2SOa. The solvent was removed in vacuo to afford a yellow oil. This oil was purified by column chromatography (hexanes) to give 2-t—butylethoxybenzene (7.2 g, 67% yield) as a colorless liquid. 3-I-butyl-2-eth0xybenzhydr0l (75) To a vigorously stirred solution of 2-t-butylethoxybenzene (4.6 g, 26.0 mmol) and tetramethylethylenediamine (3.0 g, 26.0 mmol, 3.9 mL) in 60 mL of diethyl ether, was added n-butyl lithium (16.3 mL, 1.6 M in hexanes, 26.0 mmol) slowly at 0°C under nitrogen.92 The lithiation mixture was stirred overnight and benzaldehyde (2.5 g, 24.0 mmol, 2.4 mL) was added to this solution. The reaction was quenched by addition of saturated N114C1 aqueous solution at 0°C. Water layer was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSO4. Solvent was evaporated off to yield crude product which was purified by column chromatography (hexanes: ethyl acetate 20:1) to afford 75 (4.7 g, 69% yield) as a pale yellow oil. 1H NMR (CDCl3, 300MHz), 8 ppm: 1.47 (t, J: 7.8 Hz, 3H), 1.47 (s, 9H), 2.74 (s, 1H), 3.91 (dq, J: 6.9, 9.3 Hz, 1H), 4.04 (dq, J: 6.9, 9.3 Hz, 1H), 6.25 (s, 1H), 7.06 (t, J: 7.5 Hz, 1H), 7.12 (dd, J: 2.1, 7.5 Hz, 1H), 7.43 (stack, 4H), 7.47 (dd, J: 1.5, 7.5 Hz, 2H). 134 ;::..[?.r -lf¢.&~1-. .lu-‘Io‘ - . .t'itcLI-‘Jfin‘fimfil Altair: '3 .3 39.6" 1' o . . a 0 . b .o . .. 3.7 .- o ’1' ;. .— ..' ‘- u..- .- ..- a» " -- _. o -‘ no»- . 1'0 .O'Jp” .‘ ' | .w. 0 ' 011.513...” d.nj;5,"_;', . . I 1 “1.3"" "1 «that. .‘l .._.]: 9.2-:6; 11:116.- ‘ {,7-9‘. d l _ . . .. .’... .' 3-t-butyl-2-eth0xybenz0phenone (6) Pyridinium chlorochromate (8.3 g, 25.0 mmol) was suspended in 70 mL of anhydrous CHZClz. 75 (4.7 g, 16.5 mmol) in 15 mL of CHzClz was added in one portion to the magnetically stirred solution.93 After 3.5 hours 50 mL of dry ether was added and the supernatant decanted from the black gum. The insoluble residue was washed thoroughly with anhydrous ether whereupon it became a black granular solid. The combined organic layer was passed through a short pad of silica gel, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography (hexanes: ethyl acetate 60: 1) to afford 6 (2.9 g, 62% yield) as a colorless oil. 1H NMR (CDC13, 300MHz), 8 ppm: 0.96 (t, J: 6.9 Hz, 3H), 1.40 (s, 9H), 3.73 (q, J: 6.9 Hz, 2H), 7.06, (t, J: 7.8Hz, 1H), 7.23 (dd, J: 1.8, 7.8 Hz, 1H), 7.42 (tt, J: 1.8, 7.5 Hz, 2H), 7.46 (dd, J: 2.1, 7.8 Hz, 1H), 7.54 (tt, J: 1.2, 7.5 Hz, 1H), 7.82 (dd, J: 2.1, 7.8 Hz, 2H). 13C NMR (75 MHz, CDC13), 8 ppm: 14.98, 30.48, 35.08, 70.76, 122.67, 128.19, 128.46, 129.46, 130.07, 132.70, 133.03, 137.11, 142.79, 157.05, 197.32. IR (neat, cm"): 2963.04 (m), 2876.23 (w), 1666.71 (8), 1583.76 (m), 1429.43 (8), 1387.00 (m), 1317.55 (m), 1290.54 (8), 1265.46 (m), 1224.95 (8), 1033.98 (m), 964.53 (m), 912.45 (w). MS, m/z: 282.0 (65.5%), 267.0 (63.5%), 249.0 (53.7%), 238.9 (48.2%), 177.0 ( 100.0%), 161.0 (100.0%), 132.9 (69.0%), 104.9 (100.0%), 76.8 (100.0%). Anal. Calcd for C|9H22022 C, 80.85; H, 7.80. Found: C, 80.87; H, 7.77. UV (path: 1cm, kmxnm (am M")): Benzene, 281 (3,375), 313 (818). 135 7. 2-Benzyloxy-3-methylbenzophenone (7) 0H OCH" a. n-BuLi, TMEDA, CHSO OH CH31, K2003; EtZO! 000"” _ PCC: CHZCIZ - acetone 7 b. benzaldehyde ' ' CH3O 0 HO 0 Bno o BBI'3, CH2C12 _ BnCI, K2003 _ e e , e o e e 7 1 76 Scheme 73. Synthesis of 7 2-hydr0xy-3-methylbenzophenone (76)94'95 A solution of 1 (2.6 g, 11.5 mmol) in 40 mL of dichloromethane cooled to -78°C was treated with boron tribromide (23 mL, 1 M in CHzClz, 23.0 mmol). After 30 mins the reaction was warmed to -10°C, where stirring was continued for another 2 hours. The reaction was quenched at -10°C by the addition of 10 mL of ether. The reaction mixture was warmed to room temperature and was stirred an additional 30 mins followed by addition of water. Isolation of the product by dichloromethane extraction gave a dark red liquid, which was chromatographed (hexanes: ethyl acetate 30: 1) to afford 76 (2.1 g, 87% yield) as a yellow liquid. 1H NMR (CDC13, 300MHz), 8 ppm: 2.31 (s, 3H), 6.76 (t, J: 7.5 Hz, 1H), 7.44 (stack, 3H), 7.56 (tt, J: 1.8, 7.5 Hz, 1H), 7.66 (dd, J: 1.5, 7.8 Hz, 2H), 12.32 (s, 1H). 2-benzyloxy-3-methylbenz0phenone (7)23 To a 250 mL round-bottom flask were added 76 (2.1 g, 10.0 mmol), benzyl chloride (1.3 g, 10.0 mmol, 1.2 mL), potassium carbonate (0.7 g, 5.0 mmol) and 30 mL of absolute ethanol. The mixture was refluxed overnight then cooled to room temperature. 136 Vacuum filtration gave a clear pale yellow solution, which was concentrated under reduced pressure. The residue was partitioned between diethyl ether and water. Aqueous phase was extracted with ether, combined organic layer was washed with brine and dried over anhydrous Na2304. The crude product was purified by column chromatography (hexanes: ethyl acetate 60:1) to afford 7 (2.7 g, 90% yield) as a pale yellow oil. 1H NMR (CDCl3, 300NH-Iz), 8 ppm: 2.36 (s, 3H), 4.80 (s, 2H), 7.19 (stack, 3H), 7.29 (stack, 4H), 7.39 (dd, J: 1.2, 7.5 Hz, 1H), 7.46 (tt, J: 1.5, 7.2 Hz, 2H), 7.61 (tt, J: 1.2, 7.2 Hz, 1H), 7.90 (dd, J: 1.5, 7.8 Hz, 2H). 13C NMR (75 MHz, CDC13), 8 ppm: 16.33, 76.45, 123.76, 127.62, 127.94, 127.97, 128.26, 128.29, 130.12, 132.15, 133.12, 133.24, 133.64, 136.74, 137.54, 155.06, 196.78. IR (neat, cm"): 3063.35 (w), 2922.53 (w), 1666.71(s), 1597.26 (m), 1448.73 (m), 1317.55 (m), 1215.31 (m), 1087.99 (w). MS, m/z: 302.2 (7.8%), 134.8 (21.6%), 91.0 (100.0%), 76.9 (34.5%), 65.0 (26.3%). Anal. Calcd for CZIHISOZ: C, 83.44; H, 5.96. Found: C, 83.32; H, 6.00. UV (path: 1cm,)t1mm nm (em, M")): Benzene, 280 (3,547), 313 (525). 8. 2-Benzyloxy-3-isopropylbenzophenone (8) 2-hydroxy-3-isopropylbenzophenone (77)”?5 A solution of 2 (3.3 g, 13.0 mmol) in 40 mL of dichloromethane cooled to -78°C was treated with boron tribromide (26 mL, 1 M in CHzClz, 26.0 mmol). After 30 mins the reaction was warmed to -10°C, where stirring was continued for another 2 hours. The reaction was quenched at -10°C by the addition of 10 mL of ether. The reaction mixture 137 OH OCH3 a. n-BuLi, TMEDA, CH3O 0” /k© CH31,K2C03;/l\© Et20.0°C~rt _/l\‘/‘\. PCC,CHZCI2A acetone b. benzaldehyde CH30 O HO O BnO 0 Wk. BBrLCH2C|2 _ J“ BnCI, K2C03_ /’\‘/u\. Q 0 , O Q O O 2 77 8 Scheme 74. Synthesis of 8 was warmed to room temperature and was stirred an additional 30 mins followed by addition of water. Isolation of the product by dichloromethane extraction gave a dark red liquid, which was chromatographed (hexanes: ethyl acetate 35: 1) to afford 77 (2.7 g, 87% yield) as a yellow liquid. 1H NMR (CDC13, 300MHz), 8 ppm: 1.27 (d, J: 7.2 Hz, 6H), 3.44 (heptet, J: 7.2 Hz, 1H), 6.82 (t, J: 7.5 Hz, 1H), 7.46 (stack, 4H), 7.56 (tt, J: 1.8, 7.5 Hz, 1H), 7.64 (dd, J: 1.5, 7.8 Hz, 2H), 12.20 (s, 1H). 2-benzyloxy-3-isopropylbenzophenone (8)23 To a 250 mL round-bottom flask were added 77 (2.7 g, 11.3 mmol), benzyl chloride (1.4 g, 11.3 mmol, 1.3 mL), potassium carbonate (0.8 g, 6.0 mmol) and 30 mL of absolute ethanol. The mixture was refluxed overnight then cooled to room temperature. Vacuum filtration gave clear pale yellow solution which was concentrated under reduced pressure. The residue was partitioned between diethyl ether and water. Aqueous phase was extracted with ether, combined organic layer was washed with brine and dried over anhydrous NaZSOa. The crude product was purified by column chromatography (hexanes: ethyl acetate 60:1) to afford 8 (3.2 g, 87% yield) as a pale yellow oil. 138 1H NMR (c1303, 300MHz), 8 ppm: 1.28 (d, J: 6.9 Hz, 6H), 3.45 (heptet, J: 6.9 Hz, 1H), 4.80 (s, 2H), 7.13 (stack, 2H), 7.27 (stack, 5H), 7.47 (stack, 3H), 7.63 (tt, J: 1.5, 7.5 Hz, 1H), 7.93 (dd, J: 1.5, 7.8 Hz, 2H). 13C NMR (75 MHz, cool.) 8 ppm: 23.69, 26.22, 77.50, 124.15, 127.39, 127.84, 127.91, 128.24, 128.29, 129.26,130.14, 133.13, 133.18, 136.70,137.47,142.75,153.83,l96.95. IR (neat, cm"): 3065.28 (w), 2946.97 (8), 2868.51 (m), 1662.85 (8), 1597.26 (m), 1439.68 (8), 1298.54 (8), 1253.89 (m), 1213.38 (8), 1163.22 (m), 1093.78 (w). MS, m/z: 330.4 (20.4%), 239.3 (100.0%), 225.3 (28.6%), 162.8 (40.8%), 104.9 (100.0%), 90.8 (100.0%), 76.9 (100.0%), 65.0 (100.0%). Anal. Calcd for C23H2202: C, 83.64; H, 6.67. Found: C, 83.69; H, 6.66. UV (path: 1cm, 1m, nm (em: M”)): Benzene, 280 (3,580), 313 (555). 9. 2-Benzyloxy-3-t-butylbenzophenone (9) OH OCH" a. n-BuLi, TMEDA, CH3O 0“ c11;,1,1 ©/u\/O\/\:Ts LiCl, THF ©2K/O\/\CI reflux 90 16 Scheme 82. Synthesis of 16 sodium bicarbonate solution and saturated brine. The organic phase was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. Purification by flash chromatography (hexanes: ethyl acetate 1:1) gave 88 (13.5 g, 74.0 mmol, 45% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.52 (m, 6H), 4.68 (s, broad, 1H), 4.90 (dd, J: 3.0, 9.0 Hz, 1H), 7.23 (m, 5H). toluene-4-sulf0nic acid 2-(2-hydr0xy-2-phenyl—eth0xy)-ethyl ester (89) To a 100 mL round-bottom flask were added 88 (2.0 g, 11.0 mmol), pyridine (3.5 g, 44.3 mmol, 3.6 mL) and 30 mL of CHzClz. p-Toluenesulfonyl chloride (2.3 g, 12.0 mmol) was added in portions at 0°C.97 The reaction mixture was allowed to warm to room temperature and stirred for additional 10 hours. Water was added to this mixture, organic phase was separated and aqueous layer was extracted with CHzClz . Combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. Solvent was removed under vacuum, column chromatography (hexanes: ethyl acetate 4:1) gave 89 (3.4 g, 10.1 mmol, 92% yield) as a colorless oil. 1H NMR (300 MHz, CDC13), 6 ppm: 2.43 (s, 3H), 2.71 (s, 1H), 3.40 (t, J: 9.6 Hz, 1H), 157 3.54 (dd, J: 3.3, 9.6 Hz, 1H), 3.70 (m, 2H), 4.18 (t, J: 5.1 Hz, 2H), 4.79 (dd, J: 3.0, 9.0 Hz, 1H), 7.31 (m, 7H), 7.80 (d, J: 8.4 Hz, 2H). toluene-4-sulf0nic acid 2-(2-0x0-2-phenyl-eth0xy)-ethyl ester (90) A solution of 89 (8.9 g, 26.5 mmol) in 10 mL of methylene chloride was added to a solution of Dess—Martin periodinane (12.4 g, 29.2 mmol) in 50 mL of methylene chloride with stirring.98 After 2 hours the homogeneous reaction mixture was diluted with 20 mL of methylene chloride and 30 mL of 1 M NaOH aqueous solution. After the mixture was stirred for 30 mins, organic phase was separated and water layer was extracted with methylene chloride. Combined organic layer was washed with saturated brine and dried over anhydrous NazSO4. Solvent was removed under reduced pressure and flash chromatography (hexanes: ethyl acetate 3:1) gave 90 (7.3 g, 21.9 mmol, 82% yield) as a white solid. 1H NMR (300 MHz, CDC13), 6 ppm: 2.41 (s, 3H), 3.82 (t, J: 4.5 Hz, 2H), 4.22 (t, J: 4.5 Hz, 2H), 4.73 (s, 2H), 7.30 (d, J: 8.1 Hz, 2H), 7.45 (t, J: 7.8 Hz, 2H), 7.58 (t, J: 7.5 Hz, 1H), 7.77 (d, J: 8.1 Hz, 2H), 7.85 (d, J: 7.5 Hz, 2H). m.p.: 58.1~59.0°C a-(ch10r0ethoxy)acet0phenone (16) A solution of 90 (0.9 g, 2.7 mmol) and lithium chloride (0.46 g, 10.8 mmol) in 30 mL of tetrahydrofuran was refluxed for 14 hours.99 The reaction mixture was cooled to room temperature and water was added. Water layer was extracted with ether. Combined organic layer was washed with saturated brine, dried over anhydrous NazSO4 and 158 concentrated under reduced pressure. Purification by flash chromatography (hexanes: ethyl acetate 30:1) gave 16 (0.45 g, 2.3 mmol, 85% yield) as a colorless oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.70 (t, J: 5.7 Hz, 2H), 3.87 (t, J: 5.7 Hz, 2H), 4.84 (s, 2H), 7.46 (t, J: 7.8 Hz, 2H), 7.58 (t, J: 7.5 Hz, 1H), 7.90 (d, J: 7.8 Hz, 2H). l3C NMR (75 MHz, CDC13), 6 ppm: 42.78, 71.67, 74.04, 127.86, 128.77, 133.72, 134.61, 195.96. IR (CHC13, cm'l): 3063.35 (w), 2872.37 (w), 1701.43 (s), 1597.26 (w), 1448.73 (w), 1228.81 (m), 1145.86 (8), 968.39 (w). MS, m/z: 162.0 (27.4%), 105.0 (100.0%), 76.9 (66.2%), 50.7 (31.0%). Anal. Calcd for CIOHHCIOZ: C, 60.45; H, 5.54. Found: C, 60.52; H, 5.59. UV (path: 1cm, Mm nm (emax M")): Benzene, 282 (944), 313 (47). 2. a-(Bromoethoxy)acetophenone (17) OH OH 0ethylene glycol O\/\0H TsCl. pyridine y O\/\oTs 130°C CHZCIZ, 0°C 88 89 O O DMP, CH2C|2 _ O\/\OTS nBu4NBr O\/\ Br ' THF, reflux 90 17 Scheme 83. Synthesis of 17 a-(bromoethoxy)acet0phenone (17) A solution of 90 (3.0 g, 9.0 mmol) and nBuzNBr (4.3 g, 13.5 mmol) in 50 mL of dry THF was heated to reflux under N2.99 After 24 hours, the reaction mixture was cooled, 159 diluted with 10 mL of ether, and washed with water and brine. The organic layer was dried with N azSO4 and concentrated under vacuum. Purification by flash chromatography (hexanes: ethyl acetate 40: 1) gave 17 (1.8 g, 7.4 mmol, 82% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.53 (t, J: 6.0 Hz, 2H), 3.92 (t, J: 6.0 Hz, 2H), 4.83 (s, 2H), 7.46 (t, J: 7.5 Hz, 2H), 7.58 (t, J: 7.5 Hz, 1H), 7.90 (d, J: 7.2 Hz, 2H); 13C NMR (75 MHz, CDCl3), 6 ppm: 30.14, 71.53, 73.93, 127.88, 128.79, 133.74, 134.61, 195.94; IR (CHCl3, cm'l): 3063.35 (w), 2872.37 (w), 1699.50 (3), 1597.26 (m), 1448.73 (m), 1282.83 (w), 1226.88 (m), 1140.08 (3), 966.46 (w); MS, m/z: 162.0 (27.5%), 105.0 (100.0%), 76.9 (67.6%), 50.7 (32.0%). Anal. Calcd for CloHnBrOzz C, 49.38; H, 4.53. Found: C, 49.47; H, 4.53. UV (path: 1cm, 1mm nm (emax M")): Benzene, 282 (937), 313 (48.4). 3. a-(Iodoethoxy)acetophenone (18) a-(i0d0eth0xy)acet0phen0ne ( 18) A solution of 90 (3.0 g, 9.0 mmol) and nBuaNI (5.0 g, 13.5 mmol) in 50 mL of dry THF was heated to reflux under N2.99 After 24 hours, the reaction mixture was cooled, diluted with 10 mL of ether, and washed with water and brine. The organic layer was dried with Na2804 and concentrated under vacuum. Purification by flash chromatography (hexanes: ethyl acetate 30: 1) gave 18 (2.3 g, 7.9 mmol, 88% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.32 (t, J: 6.9 Hz, 2H), 3.87 (t, J: 6.9 Hz, 2H), 4.82 (s, 2H), 7.46 (t, J: 7.8 Hz, 2H), 7.58 (t, J: 7.5 Hz, 1H), 7.91 (d, J: 7.8 Hz, 2H); 160 0ethylene glycol HO\/\OH TsCl, pyridine ‘ O\/\0Ts 130°C 01-12012, 0°C 89 O O DMP, CH2C|2> ©/u\/O\/\:TS ”BU4Nl OK/o\/\| THF, reflux 90 18 Scheme 84. Synthesis of 18 13C NMR (75 MHz, CDC13), 6 ppm: 2.19, 72.28, 73.62, 127.90, 128.77, 133.72, 134.61, 195.93; IR (CHCl3, cm'l): 2918.67 (w), 2868.51 (w), 1699.50 (8), 1597.26 (w), 1448.73 (w), 1228.81 (m), 1124.64 (111), 974.18 (w); MS, m/z: 162.0 (27.5 %), 105.0 (100.0%), 76.9 (69.8%), 50.7 (36.0%). Anal. Calcd for CloHnIOz: C, 41.38; H, 3.79. Found: C, 41.26; H, 3.78. UV (path: 1cm, 1m, nm (em, M")): Benzene, 282 (1,057), 313 (140.4). 4. a-(2-Bromo-2-methylpropoxy)acetophenone (19) 2 -( 2-methylallyloxy )-I -phenylethanol (91) To a 250 mL three—neck round-bottom flask, equipped with a condenser, were added NaH (1.0 g, 25.0 mmol, 60% dispersion in mineral oil), 40 mL of THF and 20 mL of HMPA.100 2—Methyl-2-propen-1-ol (1.8 g, 25.0 mmol) was added dropwise over a 20 mins period under dry nitrogen. The resulting yellowish solution was refluxed for 30 mins and cooled to room temperature, and styrene oxide (3.0 g, 25.0 mmol) was added dropwise over 15 mins. After 30 mins of stirring at room temperature, the mixture was 161 O OH 0\/J\ %/ NaH THF + 0” —_'__’HMPA, reflux 91 ° ° 9< fl. °v1\__H_Br_. 0 Br CHZCIZ' n CH3COQH 92 19 Scheme 85. Synthesis of 19 boiled under reflux for 4 hours. The cooled reaction mixture was quenched with H20, acidified with aqueous 3 M HCl, and extracted with ether. The extracts were combined, washed with water, aqueous NaHCO3 and saturated aqueous NaCl solution, and finally dried over NaZSO4.»The solvent was removed under vacuum, purification of the crude product by column chromatography (hexanes: ethyl acetate 10:1) afforded 91 (3.6 g, 18.8 mmol, 75% yield) as a pale yellow oil. lH NIVIR (300 MHz, CDC13), 6 ppm: 1.73 (s, 3H), 2.76 (s, broad, 1H), 3.41 (dd, J: 9.3, 9.9 Hz, 1H), 3.56 (dd, J: 3.3, 9.9 Hz, 1H), 3.96 (s, 2H), 4.91 (stack, 3H), 7.34 (stack, 5H). a-(2-methylallyloxy)acet0phenone (92) PCC (5.2 g, 21.8 mmol) was dispersed in 50 mL of CH2C12, 91 (2.6 g, 13.3 mmol) was added dropwise to this solution at 0°C and the reaction mixture was allowed to warm to room temperature.93 After 6 hours of stirring at room temperature, sticky solid was filtered off and organic phase was washed with saturated brine, dried over NaZSO4. Solvent was removed under reduced pressure, the residue was purified by column chromatography (hexanes: ethyl acetate 20:1) to give 92 (1.8 g, 9.5 mmol, 71% yield) as 162 a colorless oil. 1H NMR (300 MHz, CDC13), 6 ppm: 1.75 (s, 3H), 4.04 (s, 2H), 4.70 (s, 2H), 4.93 (d, J: 1.2 Hz, 1H), 4.99 (d, J: 1.2 Hz, 1H), 7.47 (t, J: 7.8 Hz, 2H), 7.57 (t, J=8.7 Hz, 1H), 7.92 (d, J: 7.8 Hz, 2H). a-(2-br0m0-2-methylpr0p0xy)acet0phen0ne (19) 92 (1.6 g, 8.4 mmol) was dissolved in 20 mL of acetic acid, dry HBr gas was bubbled into this solution.'0' Water was added to quench the reaction, this reaction mixture was neutralized by saturated NaHCO3 aqueous solution. Organic layer was then washed with brine and dried over NaZSO4. Concentration of solvent under vacuum followed by column chromatography (hexanes: ethyl acetate 40:1) gave 19 (1.0 g, 3.7 mmol, 44% yield) as a yellow liquid. 1H NMR (300 MHz, CDC13), 6 ppm: 1.77 (s, 6H), 3.67 (s, 2H), 4.85 (s, 2H), 7.45 (t, J: 7.5 Hz, 2H), 7.56 (t, J: 7.2 Hz, 1H), 7.91 (d, J: 7.2 Hz, 2H); 13C NMR (75 MHz, CDC13), 6 ppm: 30.85, 63.37, 74.41, 81.42, 127.95, 128.72, 133.63, 134.73, 196.43; R (CHC13, cm'l): 2972.68 (w), 2926.39 (w), 1703.36 (3), 1599.19 (w), 1450.65 (w), 1228.81 (s), 1128.50 (s), 993.47 (w); MS, m/z: 190.1 (2.2%), 105.0 (100.0%), 85.0 (10.3%), 76.9 (51.1%), 57.0 (28.0%), 50.8 (30.2%). Anal. C31Cd for C12H15Br02: C, 53.14; H, 5.54. Found: C, 53.32; H, 5.77. 163 D. B-(Haloethoxy)propiophenones O ©/U\AO/\/ X Ketone R 20 Cl 21 Br 22 I 1. ,B-(Chloroethoxy)propiophenone (20) O CHjcozk / ethylene glycol o/\/OH CICHaCHZOH, reflux CHQCIZ 0 o TsCl, pyridine O/\/0Ts LiCl O/VCI CH2012 THF, reflux 95 20 Scheme 86. Synthesis of 20 phenyl vinyl ketone (93)]02 3-Chloropropiophenone (8.4 g, 50.0 mmol) was dissolved in 30 mL of absolute ethanol. The solution was heated and potassium acetate (5.0 g, 51.0 mmol) was added slowly with vigorous stirring. The solution was filtered, 50 mL of chloroform was added, the alcohol was then removed by washing with water. The chloroform was removed on a rotary evaporator and the residue was distilled under vacuum to give 93 (4.8 g, 36.4 mmol, 73% yield) as a colorless liquid. 'H NMR (300 MHz, CDC13), 8 ppm: 5.92 (dd, J: 1.5, 10.5 Hz, 1H), 6.42 (dd,J: 1.5, 17.1 164 Hz, 1H), 7.18 (dd, J: 10.5, 17.1 Hz, 1H), 7.47, (t, J: 7.5 Hz, 2H), 7.55 (d, J: 6.9 Hz, 1H), 7.92 (d, J: 6.9 Hz, 2H). ,8-(2-hydroxy)eth0xypr0piophenone (94) Sodium (0.9 g, 37.8 mmol) was dissolved in 2.7 mL of ethylene glycol, this solution was then introduced to the methylene chloride solution of 93 (1.0 g, 7.6 mmol) in 10 mins at 0°C.103 This mixture was allowed to warm to room temperature and stirred for another 4 hours. Water was added to quench the reaction, and the solution was acidified by addition of 3 M hydrochloric acid. Aqueous layer was extracted with methylene chloride. Organic layer was combined, washed with saturated brine and dried over Na2804. Solvent was removed under vacuum and flash chromatography (hexanes: ethyl acetate 3: 1) gave 94 (0.8 g, 4.1 mmol, 54% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.26 (t, J: 6.0 Hz, 2H), 3.60 (t, J=5.1Hz, 2H), 3.72 (t, 1251 Hz, 2H), 3.92 (t, J: 6.0 Hz, 2H), 7.45 (t, J: 7.8 Hz, 2H), 7.55 (t, J: 7.8 Hz, 1H), 7.96 (d, J: 8.4 Hz, 2H). Ioluene-4-sulfonic acid 2 -( 3 -0x0-3 -phenyl-pr0p0xy )-ethyl ester (95) 94 (0.8 g, 3.9 mmol) and pyridine (1.3 mL, 15.5 mmol) were dissolved in 20 mL of CH2C12.97 At 0°C, p-toluenesulfonyl chloride (0.8 g, 4.3 mmol) was added in portions to this solution. The mixture was allowed to warm to room temperature and stirred for another 5 hours. Water was added and the solution was acidified to pH 6-7. Aqueous layer was extracted with CHzClz. Combined organic layer was washed with brine and dried over NaZSO4. Removal of solvent under reduced pressure and flash chromatography 165 (hexanes: ethyl acetate 3: 1) gave 95 (1.2 g, 3.5 mmol, 89% yield) as a white solid. 1H NMR (300 MHz, CDCl3), 6 ppm: 2.39 (s, 3H), 3.17 (t, J: 6.6 Hz, 2H), 3.66 (t, J: 4.8 Hz, 2H), 3.82 (t, J: 6.6 Hz, 2H), 4.13 (t, J: 4.8 Hz, 2H), 7.27 (d, J: 8.4 Hz, 2H), 7.45 (t, J: 7.5 Hz, 2H), 7.56 (tt, J: 1.5, 7.5 Hz, 1H), 7.76 (d, J: 8.4 Hz, 2H), 7.91 (d, J: 7.5 Hz, 2H). m.p.: 65.0~65.9°C ,B-(chloroethoxy)pr0pi0phen0ne (20) A solution of 95 (1.4 g, 4.0 mmol) and lithium chloride (0.7 g, 16.0 mmol) in 30 mL of tetrahydrofuran was refluxed for 24 hours.99 The reaction mixture was cooled to room temperature and water was added. Water layer was extracted with ether. Combined organic layer was washed with saturated brine, dried over anhydrous NaZSO4 and concentrated under reduced pressure. Purification by flash chromatography (hexanes: ethyl acetate 30: 1) gave 20 (0.8 g, 3.7 mmol, 92% yield) as a colorless oil. 'H NMR (300 MHz, CDC13), 8 ppm: 3.27 (t, J: 6.6 Hz, 2H), 3.60 (t, J: 6.0 Hz, 2H), 3.74 (t, J: 6.0 Hz, 2H), 3.93 (t, J: 6.6 Hz, 2H), 7.45 (t, J: 7.8 Hz, 2H), 7.55 (t, J: 7.2 Hz, 1H), 7.95 (d, J: 7.8 Hz, 2H); 13C NMR (75 MHz, CDC13), 6 ppm: 38.69, 42.72, 66.38, 71.23, 128.10, 128.62, 133.23, 136.89, 198.10; IR (CHCI3, cm"): 2876.23 (w), 1684.07 (s), 1597.26 (w), 1448.73 (m), 1369.63 (m), 1215.31 (m), 1122.71 (s), 748.48 (w); MS, m/z: 214.2 (0.8%), 212.1 (2.7%), 149.0 (12.1%), 132.0 (15.6%), 105.0 (100.0%), 77.0 (100.0%), 50.6 (63.1%). 166 Anal. Calcd for CHH13C102: C, 62.12; H, 6.12. Found: C, 62.16; H, 6.16. UV (path: 1cm, 1",... nm (em, M")); Benzene, 282 (680), 313 (45.8). 2. fi-(Bromoethoxy)propiophenone (21) 0 o CH3002K / ethylene glycol; O/\/0H ClCH30H20H, reflux: CH2C|2 94 0 o TsCl, pyridine O/\/OTS nBugNBr O/\/ Br CHZCIZ THF, reflux 95 21 Scheme 87. Synthesis of 21 fl-(bromoethoxy)pr0pi0phenone (21) A solution of 95 (1.4 g, 4.0 mmol) and nBuaNBr (1.9 g, 6.0 mmol) in 35 mL of dry THF was heated to reflux under N2.99 After 6 hours, the reaction mixture was cooled, diluted with 10 mL of ether, and washed with water and brine. The organic layer was dried with NaZSO4 and concentrated under vacuum. Purification by flash chromatography (hexanes: ethyl acetate 20: 1) gave 21 (0.9 g, 3.6 mmol, 89% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 3.27 (t, J: 6.6 Hz, 2H), 3.44 (t, J: 6.0 Hz, 2H), 3.80 (t, J: 6.0 Hz, 2H), 3.93 (t, J: 6.6 Hz, 2H), 7.45 (t, J: 7.5 Hz, 2H), 7.56 (t, J: 6.9 Hz, 1H), 7.95 (d, J: 6.9 Hz, 2H); 13C NMR (75 MHz, CDC13), 6 ppm: 30.33, 38.68, 66.24, 71.05, 128.12, 128.63, 133.26, 136.87, 171.83; IR (neat, cm'l): 2874.30 (w), 1682.14 (5), 1597.26 (w), 1448.73 (m), 1367.70 (w), 167 1215.31 (m), 1120.78 (8), 748.48 (m); MS, m/z: 258.2 (0.3%), 256.2 (0.3%), 149.0 (6.8%), 133.2 (7.7%), 105.0 (100.0%), 77.0 (52.1%), 50.8 (29.6%). Anal. Calcd for CnngBrOz: C, 51.36; H, 5.06. Found: C, 51.63; H, 5.14. UV (path: 1cm, km, nm (emax M")): Benzene, 281 (1,099), 313 (69.7). 3. fl-(Iodoeth0xy)prapiophenone (22) 0 o CH3C02K / ethylene glycol o/\,OH ClCHaCH2OH, reflux: CH2CI2 94 0 o TsC|,pyridine_ O/\/OTS "BU4NI : o/\/' 01-12012 a THF, reflux 95 22 Scheme 88. Synthesis of 22 fl-(i0d0eth0xy)pr0pi0phen0ne (22) A solution of 95 (1.4 g, 4.0 mmol) and nBuaNI (2.2 g, 6.0 mmol) in 35 mL of dry THF was heated to reflux under N2.” After 4 hours, the reaction mixture was cooled, diluted with 10 mL of ether, and washed with water and brine. The organic layer was dried with NaZSO4 and concentrated under vacuum. Purification by flash chromatography (hexanes: ethyl acetate 20: 1) gave 22 (1.1 g, 3.6 mmol, 90% yield) as a white solid. 1H NMR (300 MHz, CDC13), 6 ppm: 3.23 (t, J: 6.6 Hz, 2H), 3.26 (t, J: 6.6 Hz, 2H), 3.73 (t, J: 6.6 Hz, 2H), 3.92 (t, J: 6.6 Hz, 2H), 7.45 (t, J: 7.5 Hz, 2H), 7.55 (t, J: 7.2 Hz, 168 1H), 7.96 (d, J: 7.2 Hz, 2H); 13C NMR (125 MHz, CDCl3), 8 ppm: 2.91, 38.65, 65.91, 71.70, 128.10, 128.60, 133.22, 136.84, 198.11; 1R (CHC13, em"): 2874.54 (w), 1684.87 (3), 1448.73 (w), 1367.70 (w), 1209.52 (w), 1105.35 (5), 746.55 (m); MS, m/z: 304.1 (0.3%), 154.8 (11.9%), 133.0 (34.9%), 105.0 (100.0%), 77.0 (84.7%), 50.8 (43.5%), 42.7 (10.8%). Anal. Calcd for C. 1H13IOZ: C, 43.42; H, 4.28. Found: C, 43.68; H, 4.53. UV (path: 1cm, 2...... nm (em... M")): Benzene, 281 (1,048), 313 (55.3). m.p.: 36.5~37.2°C E. a/B-Cyclopropylmethoxy Ketones .5140» Ketone R n 23 Ph 1 24 CH3 1 25 CH3 2 1. a-(Cyclopropylmethoxy)acetophenone (23) 2-(cyclopropylmeth0xy)- I -phenylethanol (96) Sodium hydride (3.2 g, 80.0 mmol, 60% dispersion in mineral oil) was added to a dry three-neck round—bottom flask, 80 mL of THF and 40 mL of HMPA were then 169 OH O a. NaH, HMPA O\/A 3- 100002» DMSO of 1.40/V THF, reflux _ CHzclz. -78°C _ b. styrene oxider b. Et3N, -78°C~rt , 96 23 Scheme 89. Synthesis of 23 introduced.100 Cyclopropylmethanol (5.8 g, 80.0 mmol, 6.5 mL) was added dropwise during a 20 mins period under dry argon. The resulting solution was refluxed for 1 hour and then cooled to room temperature. Styrene oxide (9.6 g, 80.0 mmol, 9.1 mL) was then added to the reaction mixture. After 30 mins of stirring at room temperature, the mixture was refluxed for 2 hours and cooled to room temperature. The reaction mixture was quenched with water, acidified with 3 M HCl, and then extracted with ether. The extracts were combined, washed with water, aqueous NaHCO3 solution and brine, and finally dried over anhydrous NaZSO... The solvent was removed under reduced pressure, crude product was purified by column chromatography (hexanes: ethyl acetate 6: 1) to afford 96 (9.9 g, 64% yield) as a pale yellow oil. 1H NMR (300 MHz, CDC13), 6 ppm: 0.19 (m, 2H), 0.54 (m, 2H), 1.08 (m, 1H), 2.69 (s, broad, 1H), 3.37 (stack, 3H), 3.61 (dd, J: 3.0, 9.9 Hz, 1H), 4.89 (dd, J: 3.0, 9.3 Hz, 1H), 7.33 (stack, 5H). a—(cyclopr0pylmeth0xy)acet0phenone (23) A solution of oxalyl chloride (1.5 g, 12.0 mmol, 1.0 mL) in 50 mL of dichloromethane was added to a 100 mL round-bottom flask. DMSO (1.9 g, 24.1 mmol, 1.7 mL) was dissolved in dichloromethane and then added dropwise to the reaction mixture at - 78°C.104 After 5 mins stirring, 96 (2.1 g, 10.9 mmol) was added. 15 mins later, 170 triethylamine was introduced and the reaction mixture was allowed to warm to room temperature. Water was used to quenched reaction, aqueous layer was extracted with dichloromethane, combined organic layer was washed with brine and dried over anhydrous Na2S04. Removal of the solvent afforded an orange oil, the crude product was purified by column chromatography (hexanes: ethyl acetate 15:1) to afford 23 (1.6 g, 79% yield) as a pale yellow oil. lH NMR (300 MHz, CDC13), 6 ppm: 0.22 (m, 2H), 0.54 (m, 2H), 1.12 (m, 1H), 3.43 (d, J: 8.4 Hz, 2H), 4.76 (s, 2H), 7.45 (tt, J: 1.8, 7.8 Hz, 2H), 7.56 (dt, J: 1.8, 7.5 Hz, 1H), 7.94 (dd, J: 1.8, 7.5 Hz, 2H). 13C NMR (125 MHz, CDC13), 6 ppm: 2.96 (2 lines), 10.42, 72.05, 73.86, 127.72, 128.67, 133.55, 134.64, 195.87. IR (CHC13, cm"): 3082.64 (w), 3007.41 (w), 2866.59 (w), 1701.43 (s), 1599.19 (w), 1448.73 (w), 1226.88 (m), 1132.36 (m), 756.19 (w). MS, m/z: 189.5 (5.0%), 121.6 (5.0%), 119.8 (100.0%), 105.1 (100.0%), 90.8 (21.6%), 77.8 (95.3%), 65.2 (14.5%), 55.4 (100.0%), 51.5 (49.4%), 50.4 (32.6%). Anal. Calcd for C12H1402: C, 75.79; H, 7.37. Found: C, 75.91; H, 7.21. UV (path: 1cm, 1...... nm (9...... M")): Benzene, 274 (927), 313 (54.5). 2. a-(Cyclopropylmethoxy)acetone (24) a. NaH, HMPA OH 3- (C0004 DMSO 0 HO THF. reflux 47 0 CH2CI2. 78°C : O /\v b. propylene oxide A/ \A b. Et3N, -78°C~rt /U\/ \/A 97 24 Scheme 90. Synthesis of 24 171 I ~(cyclopr0pylmeth0xy)~2-pr0panol (97) To a 500 mL three-neck round-bottom flask were added NaH (10.0 g, 253.0 mmol), 70 mL of THF and 35 mL of HMPA.100 Then cyclopropylmethanol (18.3 g, 253.0 mmol, 20.0 mL) was added dropwise to this solution at such a rate that mild refluxing is maintained. Upon completion of the addition, the reaction mixture was refluxed additional 30 mins and then cooled to room temperature. At this point, propylene oxide (14.8 g, 253.0 mmol, 17.6 mL) was added dropwise to the solution, the mixture was then allowed to stir overnight at approximately 30~40°C. After about 2 days’ reaction, water was added and the solution was acidified to pH~7 by addition of 1 M HCl at 0°C, water layer was extracted with ether, combined organic layer was washed with water, saturated NaHCO3 solution, brine and then dried over anhydrous NazSO4. Vaccum distillation afforded 97 (13.0 g, 40% yield) as a colorless liquid. lH NMR (300 MHz, CDC13), 6 ppm: 0.19 (m, 2H), 0.51 (m, 2H), 1.07 (m, 1H), 1.12 (d, J: 7.8 Hz, 3H), 2.27 (s, broad, 1H), 3.22 (t, J: 9.9 Hz, 1H), 3.28 (d, J: 6.9 Hz, 2H), 3.44 (dd, J: 3.0, 9.9 Hz, 1H), 3.95 (m, 1H). a-(cyclopr0pylmeth0xy)acetone (24) Dess-Martin Periodinane (45.2 g, 1.1 mol) was dissolved in 80 mL of dichloromethane, at room temperature a solution of 97 (9.2 g, 708.0 mmol) in dichoromethane was added dropwise to this oxidant.98 Upon completion of the addition, the reaction mixture was allowed to stir at room temperature. After 48 hours’ reaction, water and 2.5 M NaOH solution were added and the mixture was stirred for additional 30 mins. Water layer was extracted with dichloromethane, combined organic layer was 172 washed with brine and dried over anhydrous NaZSOa. Solvent was removed under reduced pressure, vacuum distillation gave 24 (7.0 g, 77% yield) as a colorless liquid. 1H NMR (300 MHz, CDC13), 6 ppm: 0.20 (m, 2H), 0.54 (m, 2H), 1.06 (m, 1H), 2.14 (s, 3H), 3.31 (d, J: 7.2 Hz, 2H), 4.05 (s, 2H). 13C NMR (75 MHz, CDC13), 6 ppm: 2.99 (2 lines), 10.31, 26.31, 75.88, 76.23, 207.26. IR (neat, cm'l): 3084.57 (m), 3007.41 (m), 2872.37 (8), 1720.72 (8), 1415.93 (m), 1356.13 (m), 1122.71 (s), 1020.47 (m), 831.43 (w). MS, m/z: 127.1, 96.0, 82.9, 71.0, 58.0, 55.0, 43.0. Anal. Calcd for C7H1202: C, 65.63; H, 9.38. Found: C, 65.58; H, 9.27. UV ( ath: 1cm, 1...... nm (a... M“)): Benzene, 284 (20.6), 313 (7.7). p 3. ,6-(Cyclopropylmethoxy)butanone (25) o i/ + HOW Na. 014.01. = MON 25 Scheme 91. Synthesis of 25 ‘ [3-(cyclopropylmethoxy)butanone (25) Sodium (0.3 g, 13.0 mmol) was dissolved in cyclopropylmethanol (14.4 g, 200.0 mmol, 16.2 mL), this solution was then added to a solution of methyl vinyl ketone (17.5 g, 250.0 mmol, 20.8 mL) in dichloromethane at 0°C.103 After 2 hours, water was added to quench the reaction, the mixture was acidified to pH 6~7 by adding 1 M HCl. Organic phase was rinsed with brine and dried over anhydrous NaZSOa. Removal of the solvent followed by vacuum distillation afforded 25 (12.5 g, 44% yield) as a colorless liquid. 173 1H NMR (300 MHz, CDC13), 6 ppm: 0.16 (m, 2H), 0.51 (m, 2H), 1.01 (m, 1H), 2.16 (s, 3H), 2.68 (t, J: 6.6 Hz, 2H), 3.23 (d, J: 6.9 Hz, 2H), 3.67 (t, J: 6.6 Hz, 2H). 13C NMR (75 MHz, CDCl3), 6 ppm: 2.92 (2 lines), 10.45, 30.44, 43.78, 65.32, 75.84, 207.40. IR (neat, cm"): 3082.64 (m), 3005.48 (s), 2868.51 (s), 1713.01 (s), 1369.99 (111), 1169.01 (m), 1107.28 (s), 1020.47 (111), 933.67 (w). MS, m/z: 141.0, 112.0, 85.0, 70.9, 57.1, 43.0. Anal. Calcd for CngaOzz C, 67.61; H, 9.86. Found: C, 67.57; H, 10.03. UV (path: 1cm, 7...... nm (a... M")): Benzene, 277 (183), 313 (3.8). 174 [11. Identification of Photoproducts Preparative photochemistry was carried out in either a Rayonet reactor equipped with 300 nm lamps or a Pyrex, water-cooled immersion well with a 450 W medium pressure mercury arc light source. The temperature in the Rayonet reactor averaged 35°C. Submerging the immersion well in deionized water in a mirrored dewar maintained the temperature between l7~23°C, which fluctuated with the temperature of the cooling water. The immersion well was fitted with a Pyrex (>290 nm) sleeve. Quantum yields and Stem-Volmer quenching studies were measured with filtered light at 313 nm. The 313 nm band was isolated from a medium pressure 450 W Hanovia mercury arc lamp using a solution of alkaline potassium chromate (0.002 M K2Cr04 in 1% aqueous potassium carbonate). All samples were degassed by purging with argon for twenty minutes prior to irradiation with a continuous stream of oxygen free argon. The outlet needle was then be removed to maintain a positive pressure. After removal of the argon source the septum was wrapped several times with Teflon tape to ensure an air tight seal. If irradiation took longer than 24 hours, the samples were degassed at each 24 hour interval in case oxygen had leaked in through the speta. Products from 2-meth0xy-3—methylbenz0phen0ne (1) CH30 O hv DO “—370 1 Scheme 92. Photoproduct from 1 175 NMR experiment A 0.75 mL benzene-d6 solution of 1 (8.1 mg, 0.036 mmol, 0.048 M) was degassed and irradiated in a NMR tube. Irradiation gave only one product. The reaction was monitored by 1H NMR and was complete (100% conversion) after 20 minutes of irradiation with Pyrex filtered light (medium pressure mercury arc lamp). The ]H NMR spectra showed the disappearence of the 2-methoxy group (singlet at 3.36ppm) with the simultaneous growth of two doublets at 4.27ppm (J: 10.2 Hz) and 4.42ppm (J: 9.9 Hz). The product was identified as 26. Preparative experiment A preparative scale reaction was carried out in 60 mL of benzene with 1 (650 mg, 2.9 mmol, 0.048 M). The reaction was complete after 16 hours of irradiation in a Rayonet reactor equipped with 300 nm lamps. The benzene was removed by rotoevaporation and the residue was purified by column chromatography (hexanes: ethyl acetate 20:1) to afford a single product. 3-hydr0xy-7-methyl-3-phenyl—2,3-dihydrobenz0furanol (26) IH NMR (500 MHz, C6D6), 6 ppm: 1.74 (s, 1H), 2.26 (s, 3H), 4.27 (d, J: 10.0 Hz, 1H), 4.42 (d, J: 10.0 Hz, 1H), 6.68 (t, J: 7.5 Hz, 1H), 6.75 (d, J: 6.5 Hz, 1H), 6.92 (d, J: 7.0 Hz, 1H), 7.04 (t, J: 7.0 Hz, 1H), 7.09 (t, J: 7.5 Hz, 2H), 7.41 (d, J: 7.0 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 15.18, 82.84, 86.27, 120.84, 121.46, 122.17, 126.42, 127.40, 128.27, 131.55, 132.34, 143.78, 159.67. IR (neat, cm’l): 3418.30 (8, broad), 3059.49 (w), 3028.63 (w), 2945.68 (w), 1599.19 (8), 176 1448.73 (s), 1313.69 (m), 1190.23 (s), 1068.70 (8), 987.68 (m). MS, m/z: 208.3 (100.0%), 207.4 (72.6%), 178.3 (44.7%), 165.2 (47.5%), 152.2 (13.0%), 89.4 (52.9%), 76.2 (20.2%). Anal. Calcd for C15H1402: C, 79.65; H, 6.19. Found: C, 79.79; H, 6.09. Product from 3-isopropyl-2-methoxybenz0phen0ne (2) CH30 O 0 OH hv, rex O O O O 2 27 Scheme 93. Photoproduct from 2 NMR experiment A 0.75 mL benzene-d6 solution of 2 (7.3 mg, 0.029 mmol) was degassed in 8 NMR tube. Within 20 minutes of irradiation through Pyrex with a mercury arc lamp, most of the 2 had disappeared with the formation of only one photostable product. The product possessed a 1H NMR spectrum consistent with 27 . Preparative experiment A preparative reaction was carried out with 2 (500 mg, 2.0 mmol, 0.033 M) in 60 mL of benzene. The preparatory scale reaction gave an identical result as the NMR scale reaction. Silica gel column chromatography with hexanes gave a single product. 3-hydr0xy-7-is0pr0pyl-3-phenyl-2,3-dihydrobenz0furanol (27) IH NMR (300 MHz, C6D6), 6 ppm: 1.32 (d, J: 6.6 Hz, 3H), 1.33 (d, J: 6.9 Hz, 3H), 1.69 177 (s, 1H), 3.32 (heptet, J: 6.9 Hz, 1H), 4.29 (d, J: 10.2 Hz, 1H), 4.38 (d, J: 10.2 Hz, 1H), 6.76 (dd, J: 0.6, 4.5 Hz, 2H), 7.08 (stack, 4H), 7.40 (dt, J: 1.8, 6.9 Hz, 2H). 13C NMR (75 MHz, C6D6), 6 ppm: 22.43, 22.57, 28.79, 82.70, 86.24, 121.75, 122.18, 126.45, 127.39, 127.49, 128.26, 131.75, 132.71, 143.81, 158.78. IR (neat, cm'l): 3418.30 (m), 2961.11 (3), 1672.50 (m), 1595.33 (m), 1441.01 (3), 1302.12 (w), 1186.37 (m), 1066.77 (w), 964.53 (w). MS, m/z: 236.4 (100.0%), 221.4 (100.0%), 177.8 (42.0%), 164.8 (42.4%), 114.7 (20.8%), 94.7 (24.0%). Anal. Calcd for CnngOz: C, 80.31; H, 7.09. Found: C, 80.30; H, 7.01. Product from 3-t-butyl-2-methoxybenzophenone (3) CH3O O O OH —”~ 3 28 Scheme 94. Photoproduct from 3 NMR experiment A 0.75 mL benzene-d6 solution of 3 (7.8 mg, 0.029 mmol, 0.039 M) was degassed in a NMR tube. Within 15 minutes of irradiation through Pyrex with a mercury arc lamp all of the 3 had disappeared, with the formation of only one product. The photostable product possessed a 1H NMR spectrum consistent with 28. Preparative experiment 178 A preparative scale reaction was carried out in 60 mL of benzene with 3 (800 mg, 3.0 mmol, 0.050 M). The reaction was complete after 6 hours of irradiation in a Rayonet reactor equipped with 300 nm lamps. The benzene was removed by rotoevaporation and the residue was purified by column chromatography (hexanes: ethyl acetate 20:1) to afford a single product. 7 -t-butyl -3 -hydroxy-3 phenyl -2,3 dihydrobenzofuranol (28) 1H NMR (300 MHZ, C(,D(,), 6 ppm: 1.50 (s, 9H), 1.66 (s, 1H), 4.28 (d, J: 10.2 Hz, 1H), 4.44 (d, J: 10.2 Hz, 1H), 6.78 (stack, 2H), 7.08 (stack, 3H), 7.17 (dd, J: 2.4, 6.9 Hz, 1H), 7.41 (dd, J: 1.8, 7.8 Hz, 2H). 13C NMR (75 MHz, C6136), 5 ppm: 29.57, 34.42, 82.25, 85.88, 121.58, 122.60, 126.46, 127.22, 127.37, 128.25, 133.59, 134.10, 143.90, 159.13. IR (neat, cm’l): 3414.44 (m, broad), 2957.25 (8), 1589.55 (w), 1429.43 (8), 1207.59 (w), 1068.70 (w). MS, m/z: 250.3 (44.6%), 235.3 (100.0%), 207.2 (33.8%), 165.0 (34.1%), 103.3 (38.3%), 76.5 (16.6%). Anal. Calcd for C13H2002: C, 80.60; H, 7.46. Found: C, 80.81; H, 7.28. Products from 2-ethoxy-3-methylbenzo_p_henone (4) 4 (7.5 mg, 0.030 mmol) in 0.75 mL of deuterated toluene was irradiated until no trace of starting material could be observed by NMR. The signals for two isomeric benzofuranols (cis-29 and trans-29) were detected upon analysis of the NMR spectrum of 179 EtO 0 DO 0606 4 cis-29 trans-29 Scheme 95. Photoproducts from 4 the photolysis mixture. In our investigation, photochemistry was conducted at various temperatures to ascertain the effect of temperature on product ratios. The diastereometric ratio of benzofuranols was determined by NMR integration of the methine quartet signals corresponding to each isomer. In order to separate the two benzofuranols, large scale irradiation using 4 (0.9 g, 3.8 mmol) in 80 mL of benzene was performed. Solvent was evaporated to leave a yellow oil which was chromatographed by column using 2% ethyl acetate in hexanes solution. The cis-isomer was the first compound eluted. cis-3—hydroxy-2, 7-dimethyl-3-phenyl-2,3-dihydrobenzofuranol (cis-29) 'H NlVIR (500 MHZ, CpDn), 5 ppm: 1.28 (s, 1H), 1.31 (d, J: 7.0 Hz, 3H), 2.29 (s, 3H), 4.44 (q, 1: 6.5 Hz, 1H), 6.70 (t, J: 7.5 Hz, 1H), 6.75 (d, J: 6.5 Hz, 1H), 6.93 (d, J: 7.5 Hz, 1H), 7.06 (dt, J: 1.5, 7.5 Hz, 1H), 7.12 (t, J: 7.5 Hz, 2H), 7.45 (d, J: 7.0 Hz, 2H). 13C NMR (125 MHz. C6D6), 6 ppm: 12.03, 15.31, 82.76, 90.64, 120.65, 121.40, 122.62, 126.90, 127.40, 127.95, 131.57, 133.23, 143.33, 159.40. IR (neat, cm'l): 3547.54 (m, broad), 3028.63 (w), 2934.10 (w), 1599.19 (8), 1446.73 (5), 1381.21 (m), 1213.36 (5), 1064.84 (m), 1022.40 (w). MS, m/z: 239.9 (62.8%), 222.1 (91.4%), 221.0 (60.8%), 177.9 (49.0%), 134.9 (100.0%), 104.9 (38.0%), 76.3 (58.0%). Anal. Calcd for C16H1602: C, 80.00; H, 6.67. 180 Found: C, 80.04; H, 6.48. m.p.: 75.0~75.8°C trans-3-hydroxy-2, 7 -dimethyl-3 phenyl-2,3-dihydr0benz0furanol (trans-29) 1H NMR (500 MHZ, C6D6). 6 ppm: 0.82 (d, J: 7.0 Hz, 3H), 1.72 (s, 1H), 2.28 (s, 3H), 4.60 (q, J: 7.0 Hz, 1H), 6.75 (t, J: 7.5 Hz, 1H), 6.82 (d, J: 6.5 Hz, 1H), 6.96 (dd, J: 1.0, 7.5 Hz, 1H), 7.02 (tt, J: 1.5, 7.5 Hz, 1H), 7.08 (t, J: 6.5 Hz, 2H), 7.31 (d, J: 6.5 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 15.22, 17.61, 85.48, 90.85, 121.38, 122.65, 127.30, 127.51, 127.96, 128.04, 131.54, 132.28, 141.72, 159.02. IR (neat, cm'l): 3418.30 (8, broad), 2980.40 (m), 2932.17 (w), 1599.19 (3), 1458.85 (m), 1379.28 (w), 1192.18 (111), 1055.30 (m). MS, m/z: 239.9 (0.3%), 222.2 (93.3%), 221.1 (100.0%), 179.1 (29.8%), 177.9 (99.2%), 144.9 (52.9%), 114.9 (30.6%), 95.9 (27.5%). Anal. Calcd for C 161—11602: C, 80.00; H, 6.67. Found: C, 79.79; H, 6.57. Products from 2-ethoxy-3- isoprolebenzophenone (5) EtO O by P rex 00—41%: 5 ale-30 trans-30 Scheme 96. Photoproducts from 5 5 (7.5 mg, 0.028 mmol) in 0.75 mL of deuterated benzene was irradiated until starting material could not be observed by NMR. The signals corresponding to two isomeric 181 benzofuranols (cis-30 and trans-30) were detected in the NMR spectrum of the mixture. The effect of temperature on product ratios was investigated by conducting the photochemistry in acetone-dry ice, NaCl—ice, ice water and silicon oil (66°C) baths. Solid state irradiation was performed by packing a melting point capillary tube with the compound and irradiating it through Pyrex-filtered UV light for 30 minutes. The diastereomeric ration of the products was determined by NMR integration of the methine quartet peaks corresponding to each isomer. Large scale irradiation using 5 (0.45 g, 1.7 mmol) in 60 mL of benzene was performed until 100% conversion (GC). Solvent was removed to leave a yellow oil which was separated by column chromatography (hexanes: ethyl acetate 40: 1). The cis-isomer was eluted before the trans-isomer. The products were recovered as oils. cis-3 -hydroxy— 7 -isopropyl-2-methyl -3 phenyl -2,3 -dihydrobenzofi4ranol (cis-30) 1H NMR (500 MHz, C6D6). 6 ppm: 1.29 (s, 1H), 1.32 (d, J: 11.5 Hz, 6H), 1.33 (d, J: 11.0 Hz, 3H), 3.37 (heptet, J: 11.5 Hz, 1H), 4.48 (q, J: 11.0 Hz, 1H), 6.77 (d, J: 6.0 Hz, 1H), 6.78 (d, J: 9.0 Hz, 1H), 7.11 (stack, 4H), 7.44 (dd, J: 2.5, 11.0 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 12.12, 22.62, 28.60, 82.63, 90.61, 121.71, 122.64, 126.91, 127.37, 127.42, 128.17, 131.56, 133.57, 143.40, 158.47. IR (neat, cm'l): 3549.47 (m, broad), 2961.11 (3), 1597.26 (m), 1442.94 (8), 1383.14 (w), 1201.81 (w), 1064.84 (m). 1 MS, m/z: 268.0 (38.0%), 250.0 (12.9%), 235.0 (16.8%), 163.0 (100.0%), 104.9 (47.8%), 76.9 (36.9%). Anal. Calcd for ClgHzoOZZ C, 80.60, H, 7.46. 182 Found: C, 80.60; H, 7.34. trans-3-hydroxy-7-isopr0pyl-2-methyl-3-phenyl-2,3-dihydrobenzofitranol (trans-30) 1H NMR (500 MHz, C613,), 8 ppm: 0.82 (d, J: 11.0 Hz, 3H), 1.33 (d, J: 11.5 Hz, 6H), 1.72 (s, 1H), 3.33 (heptet, J: 11.5 Hz, 1H), 4.62 (q, J: 11.0 Hz, 1H), 6.84 (stack, 2H), 7.09 (stack, 4H), 7.31 (dd, J: 2.5, 11.5 Hz, 2H). 13C NMR (125 MHz, C6136). 6 ppm: 17.61, 22.49, 28.69, 85.34, 90.77, 121.63, 122.66, 127.32, 127.36, 127.50, 131.72, 132.54, 137.89, 141.70, 158.12. IR (neat, cm’l): 3426.01 (m), 2963.04 (m), 1445.66 (8), 1190.23 (m), 1059.05 (s), 939.45 (w). MS, m/z: 250.0 (100.0%), 234.9 (100.0%), 206.9 (25.9%), 191.0 (25.9%), 188.9 (24.7%), 177.9 (36.5%), 164.9 (33.7%), 114.9 (28.6%), 102.8 (34.9%), 90.9 (22.1%), 77.0 (18.0%), 43.0 (24.7%). Anal. Calcd for ClgHzoozi C, 80.60; H, 7.46. Found: C, 80.81; H, 7.26. Products from 3-t-butyl-2-ethoxybenzophenone (6) W60 0 4: *é“. O + *9“. cis-31 trans-31 Scheme 97. Photoproducts from 6 6 (8.0 mg, 0.028 mmol) in 0.75 mL of deuterated benzene was irradiated until starting material could not be observed by NMR. The signals corresponding to two isomeric 183 benzofuranols (cis-31 and trans-31) were detected in the NMR spectrum of the mixture. The effect of temperature on product ratios was investigated by conducting photochemistry in acetone-dry ice, NaCl-ice, ice water and silicon oil (66°C) baths. The diastereometric ratio of benzofuranols was determined by NMR integration of the methine quartet signals corresponding to each isomer. Large scale irradiation using 6 (0.6 g, 2.1 mmol) in 60 mL of benzene was performed until 100% conversion by NMR. The products were separated by column chromatography (hexanes: ethyl acetate 50:l~35:1) and characterized. cis-7-t-butyl-3 -hydroxy-2-methy1-3-phenyl-2,3 -dihydrobenzofi4ranol (cis-31) 1H NMR (500 MHz, C6D6), 6 ppm: 1.29 (s, 1H), 1.32 (d, J: 10.5 Hz, 3H), 1.52 (s, 9H), 4.47 (q, J: 10.5 Hz, 1H), 6.78 (stack, 2H), 7.11 (stack, 3H), 7.20 (dd, J: 4.5, 10.5 hz, 1H), 7.43 (dt, J: 3.0, 11.0 Hz, 2H). 13C NMR (125 MHZ, CeDo), 6 ppm: 12.16, 29.62, 34.48, 82.18, 90.24, 121.52, 123.08, 126.93, 127.21, 127.35, 128.16, 133.88, 134.46, 143.51, 158.88. IR (neat, cm'l): 3456.88 (m), 2957.25 (m), 1591.48 (w), 1431.36 (3), 1072.56 (m), 885.44 (m). MS, m/z: 282.0 (56.1%), 267.0 (40.8%), 249.0 (51.4%), 177.0 (100.0%), 161.0 (33.3%), 132.9 (32.6%), 104.9 (88.6%), 90.9 (24.6%), 76.8 (62.8%), 57.0 (28.6%). Anal. Calcd for C19H2202: C, 80.85; H, 7.80. Found: C, 80.80; H, 7.99. trans-7-t-butyl-3-hydroxy-2-methyl-3-phenyl-2,3-dihydrobenzofuranol (trans-31) 184 1H NMR (500 MHz, C6D6), 6 ppm: 0.81 (d, J: 11.5 Hz, 3H), 1.50 (s, 9H), 1.71 (s, 1H), 4.60 (q, J: 11.0 Hz, 1H), 6.81 (t, J: 12.0 Hz, 1H), 6.87 (dd, J: 3.0, 12.5 Hz, 1H), 7.06 (stack, 3H), 7.21 (dd, J: 3.0, 12.5 Hz, 1H), 7.32 (dt, J: 2.5, 11.5 Hz, 2H). 13(2 NMR (125 MHz, C.D.), 8 ppm: 17.55, 29.53, 34.39, 84.89, 90.41, 121.44, 123.07, 127.09, 127.35, 127.49, 127.85, 133.34, 134.07, 141.67, 158.51. IR (neat, cm'l): 3383. 57 (m, broad), 2959.18 (m), 1591.48 (w), 1431.38 (s), 1213.38 (w), 1057.13 (m). MS, m/z: 264.0 (100.0%), 250.3 (35.7%), 249.0 (100.0%), 221.1 (65.5%), 178.0 (44.7%), 164.9 (31.4%), 110.0 (60.8%), 102.9 (33.7%), 77.1 (14.6%). Anal. Calcd for ClszzIOZ: C, 80.85; H, 7.80. Found: C, 80.81; H, 7.71. m.p.: 74.8~75.5°C Products from 2-benzyloxy-3-methylbenzophenone (7) BnO O POH POH hv P rex DO w—L'O 7 cis-32 trans-32 Scheme 98. Photoproducts from 7 NMR experiment A 0.75 mL benzene-d6 solution of 7 (8.2 mg, 0.027 mmol) was degassed in a NMR tube. The reaction was monitored by 1H NMR and was complete (100% conversion) after 10 minutes of irradiation with Pyrex filtered light (medium pressure mercury arc lamp). The lH NMR spectra showed the disappearence of the methylene group (singlet at 185 4.80ppm) with the simultaneous growth of two singlets at 5.57ppm and 5.61ppm corresponding to two isomeric benzofuranols (cis-32 and trans-32). The effect of temperature on product ratios was investigated by conducting photochemistry in acetone- dry ice, NaCl-ice, ice water and silicon oil (66°C) baths. The diastereometric ratio of benzofuranols was determined by NMR integration of the methine singlet signals corresponding to each isomer. Preparative experiment A preparative reaction was canied out with 7 (800 mg, 2.7 mmol) in 60 ml. of benzene. The preparatory scale reaction gave a identical results as the NMR scale reaction. Silica gel column chromatography (hexanes: ethyl acetate 30:1~20:1) gave two products. cis-3 -hydroxy- 7 -methyl -2,3-diphenyl -2,3 -dihydrobenzofuranol (cis-32) ‘H NMR (500 MHz. C6D6), 8 ppm: 1.53 (s, 1H), 2.36 (s, 3H), 5.57 (s, 1H), 6.74 (t, J: 7.0 Hz, 1H), 6.83 (d, J: 7.0 Hz, 1H), 6.98 (d, J: 7.5 Hz, 1H), 7.13 (stack, 8H), 7.34 (dd, J: 1.5, 7.0 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 15.30, 83.57, 95.57, 120.80, 121.94, 123.14, 127.15, 127.42, 127.48, 128.22, 128.25, 128.41, 131.60, 132.92, 134.80, 143.55, 159.15. IR (neat, cm"): 3545.61 (111), 3030.56 (m), 2918.67 (w), 1599.19 (5), 1446.73 (5), 1207.59 (s), 1064.84 (m), 947.17 (m). MS, m/z: 284.1 (100.0%), 268.4 (13.5%), 255.3 (17.8%), 239.3 (22.1%), 140.9 (34.5%), 134.4 (42.0%), 119.8 (35.3%), 113.2 (19.3%). 186 Anal. Calcd for CZIngOZ: C, 83.44; H, 5.96. Found: C, 83.10; H, 5.79. m.p.: 89.0~89.6°C trans-3-hydroxy-7-methyl-2,3-diphenyl-2,3-dihydrobenzofuranol (trans-32) 1H NMR (500 MHz, C6D6), 6 ppm: 2.00 (s, 1H), 2.36 (s, 3H), 5.61 (s, 1H), 6.84 (stack, 8H), 7 .03 (stack, 5H). 13C NMR (125 MHz, C6D6), 6 ppm: 15.22, 87.32, 96.44, 121.94, 122.80, 123.43, 126.54, 127.11, 127.40, 127.45, 127.55, 127.77, 131.68, 132.35, 137.68, 141.38, 159.45. IR (neat, cm'l): 3424.08 (m, broad), 3032.48 (m), 1597.26 (3), 1446.76 (5), 1263.54 (m), 1005.01 (8), 956.81 (m). MS, m/z: 284.2 (100.0%), 255.2 (27.1%), 239.2 (29.8%), 140.5 (38.0%), 119.4 (42.4%), 76.8 (20.6%). Anal. Calcd for C21H1302: C, 83.44; H, 5.96. Found: C, 83.57; H, 5.79. Products from 2-benzyloxv-3-isopropylbenzophenonefi) Ph \Ph 8110 o O OH 0 " OH hv, rex 0 o —"L~ 0 0+ 0 0 8 cis-33 trans-33 Scheme 99. Photoproducts from 8 NMR experiment A 0.75 mL toluene-d8 solution of 8 (7.7 mg, 0.023 mmol) was prepared in an NMR 187 tube. The ketone was irradiated through Pyrex. The reaction was monitored by 1H NMR analysis. The two products had 1H NMR spectra consistent with cis-33 and trans-33. The effect of temperature on product ratios was investigated by conducting photochemistry in acetone-dry ice, NaCl-ice, ice water and silicon oil (66°C) baths. The diastereometric ratio of two benzofuranols was determined by NMR integration of the methine singlet signals corresponding to each isomer. Preparative experiment The preparative photolysis of 8 was carried out in 25 mm x 250 mm pyrex tube irradiated in a Rayonet reactor equipped with 300 nm lamps. 8 (0.85 g, 2.6 mmol) was dissolved in 60 mL of benzene and degassed. The tube was irradiated for 12 hours and the solvent removed. TLC analysis (SiOz, hexanes: ethyl acetate 40:1) revealed two major products. The photoproducts were isolated using column chromatography (hexanes: ethyl acetate 40: 1). The first compound eluted had spectral data consistent with cis-33. The second compound eluted had spectral data consistent with trans-33. cis-3-hydroxy-7-isopropyl-2,3-diphenyl-2,3-dihydrobenzofi4ranol (cis-33) 1H NMR (500 MHz, C6D6), 6 ppm: 1.38 (d, J: 7.0 Hz, 3H), 1.40 (d, J: 7.0 Hz, 3H), 1.53 (s, 1H), 3.39 (septet, J: 7.0 Hz, 1H), 5.61 (s, 1H), 6.81 (t, J: 7.5 Hz, 1H), 6.84 (dd, J: 2.0, 7.5 Hz, 1H), 7.10 (stack, 7H), 7.17 (m, 2H), 7.34 (dt, J: 2.0, 8.0 Hz, 2H). 13C NMR (125 MHz, Cer), 6 ppm: 22.50, 22.68, 29.04, 83.44, 95.55, 122.21, 123.21, 127.17, 127.37, 127.46, 127.56, 128.22, 128.29, 128.41, 131.65, 133.18, 134.99, 143.67, 158.24. 188 IR (neat, cm"): 3545.61 (rn, broad), 3063.35 (w), 2963.04 (m), 1444.37 (8), 1197.95 (m), 1010.83 (m), 952.96 (m), 860.36 (w). MS, m/z: 330.4 (11.0%), 239.3 (35.7%), 163.2 (56.5%), 105.1 (53.7%), 91.0 (100.0%), 77.0 (34.1%). Anal. Calcd for C23H2202: C, 83.64; H, 6.67. Found: C, 83.58; H, 6.62. trans-3-hydroxy—7-isopropyl-2,3-diphenyl-2,3-dihydrobenzofuranol (trans-33) 1H NMR (500 MHZ, C6D6), 6 ppm: 1.38 (d, J: 7.0 Hz, 3H), 1.40 (d, J: 7.0 Hz, 3H), 1.96 (s, 1H), 3.38 (septet, J: 7.0 Hz, 1H), 5.62 (s, 1H), 6.83 (stack, 8H), 7.04 (stack, 4H), 7.14 (m, 1H). 13C NMR (125 MHz, C6D6), 6 ppm: 22.47, 22.61, 29.06, 87.15, 96.40, 122.21, 122.85, 126.52, 127.08, 127.39, 127.45, 127.54, 127.68, 127.79, 131.58, 132.62, 137.85, 141.44, 158.59. IR (neat, cm'l): 3406.72 (m, broad), 3034.41 (w), 2961.11 (m), 1595.33 (w), 1448.80 (3), 1005.04 (m), 837.21 (w). MS, m/z: 312.0 (100.0%), 297.4 (72.9%), 296.5 (40.8%), 269.3 (16.1%), 239.3 (16.9%), 191.3 (21.4%), 165.2 (25.1%), 141.2 (23.4%), 105.0 (28.2%), 91.2 (14.3%), 77.2 (20.7%). Anal. Calcd for C23H2202: C, 83.64; H, 6.67. Found: C, 83.48; H, 6.37. m.p.: 84.1~84.5°C 189 Products from 2-benzyloxy-3-t-butylbenzophenone (9) Ph Ph BnO o 0 OH 0 '° OH hv, rex 9 cis-34 trans-34 Scheme 100. Photoproducts from 9 NMR experiment A 0.75 mL toluene-d8 solution of 9 (8.2 mg, 0.024 mmol) was degassed in a NMR tube. The reaction was monitored by 1H NMR and was complete (100% conversion) after 10 minutes of irradiation with Pyrex filtered light (medium pressure mercury arc lamp). The 1H NMR spectra showed the disappearence of the methylene group (singlet at 4.67ppm) with the simultaneous growth of two singlets at 5.53ppm and 5.59ppm corresponding to two isomeric benzofuranols (34). The effect of temperature on product ratios was investigated by conducting photochemistry in acetone-dry ice, NaCl-ice, ice water and silicon oil (66°C) baths. The diastereometric ratio of benzofuranols was determined by NMR integration of the methine singlet signals corresponding to each isomer. Preparative experiment A preparative reaction was carried out with 7 (750 mg, 2.2 mmol) in 60 mL of benzene. The preparatory scale reaction gave a identical results as the NMR scale reaction. Silica gel column chromatography (hexanes: ethyl acetate 30:1~20:1) gave two products. 190 cis-7-t-butyl-3-hydroxy-2,3-diphenyl-2,3-dihydr0benzofuranol (cis-34) 'H NMR (500 MHz, C6D6), 8 ppm: 1.56 (s, 10H), 5.63 (s, 1H), 6.80 (t, J: 7.5 Hz, 1H), 6.86 (dd, J: 1.5, 7.5 Hz, 1H), 7.10 (stack, 6H), 7.19 (dd, J: 2.0, 7.5 Hz, 2H), 7.22 (dd, J: 1.5, 8.0 Hz, 1H), 7.35 (dd, J: 1.5, 8.5 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 29.70, 34.50, 83.02, 95.32, 122.04, 123.62, 127.20, 127.27, 127.32, 127.45, 128.22, 128.34, 128.40, 133.97, 134.03, 135.09, 143.75, 158.56. IR (neat, cm'l): 3547.54 (m), 2959.18 (m), 1431.30 (s), 1361.92 (w), 1010.83 (m), 949.10 (w). MS, m/z: 344.1, 329.1, 239.4, 177.0, 165.0, 133.0, 118.4, 91.0, 76.9, 57.1. Anal. Calcd for C24Hz402: C, 83.72; H, 6.98. Found: C, 83.50; H, 6.77. m.p.: 81.9~82.5°C trans-7-t-butyl-3-hydroxy-2,3-diphenyl-2,3-dihydrobenzofuranol (trans-34) 1H NMR (500 MHz, C6D6), 6 ppm: 1.57 (s, 9H), 1.86 (s, 1H), 5.60 (s, 1H), 6.84 (stack, 8H), 7.07 (stack, 4H), 7.26 (dd, J: 2.0, 7.0 Hz, 1H). 13C NMR (125 MHz, C6D6), 6 ppm: 29.65, 34.47, 86.66, 96.14, 122.03, 123.20, 126.52, 127.06, 127.29, 127.33, 127.46, 127.54, 127.81, 133.49, 133.93, 137.83, 141.57, 158.84. IR (neat, cm"): 3399.01 (m, broad), 3065.28 (w), 2961.11 (m), 1591.48 (m), 1431.38 (3), 1228.81 (m), 1006.97 (m), 960.67 (m). MS, m/z: 326.2 (100.0%), 311.0 (100.0%), 283.4 (36.1%), 282.5 (35.3%), 165.0 (34.9%), 141.3 (100.0%), 134.2 (55.7%), 126.1 (47.5%), 119.5 (37.7%), 76.8 (29.4%). Anal. Calcd for C24H2402: C, 83.72; H, 6.98. 191 Found: C, 84.08; H, 6.75. Products from 2-eth0xv-3-methylacet0phen0ne (10) E10 0 hVC606ex 10 cis-35 Scheme 101. Photoproducts from 10 10 (4.4 mg, 0.025 mmol) in 0.75 mL of deuterated benzene was irradiated. The signals for three products were detected in the NMR spectrum of the mixture. Two of these products, the hemiketals (36), disappear as the irradiation time (percent conversion) increases. The signal for one product was detected at 100% conversion in the NMR spectrum of the photolysis mixture. This product was a benzofuranol (cis-35). The hemiketal/benzofuranol ratio was determined by NMR integration of the methine quartet signal of the hemiketals and the methine quartet signal of the benzofuranol. Large scale irradiation using 10 (0.5 g, 2.8 mmol) in 60 mL of benzene was performed until 40% conversion (GC). Solvent was removed to leave a yellow oil which was chromatographed by deactivated silica gel (hexanes: ethyl acetate 20:1) to separate the products. The starting ketone was the first fraction eluted followed by benzofuranol and the two hemiketals. The two hemiketals were obtained as a 1:1 mixture. The structural assignment of the benzofuranol was accomplished by performing nOe experiment: irradiation of the methine signal caused an enhancement of the methyl signal (singlet at 1.26ppm). This suggests that the benzofuranol has a cis—stereochemistry. 192 cis-3-hydr0xy-2,3, 7 -trimethyl-2,3 -dihydr0benzofuranol (cis-35) 1H NMR (500 MHz, C6D6), 6 ppm: 1.01 (s, 1H), 1.26 (s, 3H), 1.28 (d, J: 6.5 Hz, 3H), 2.24 (s, 3H), 4.03 (q, J: 6.5 Hz, 1H), 6.77 (t, J: 7.5 Hz, 1H), 6.92 (dd, J: 1.5, 7.5 Hz, 1H), 6.98 (d, J: 7.0 Hz, 1H). 13C NMR (125 MHz, C6D6), 6 ppm: 13.22, 15.24, 23.96, 77.45, 87.65, 120.58, 120.93, 121.02, 131.25, 132.72, 158.25. IR (neat, cm"): 3404.79 (m, broad), 2976.54 (m), 1601.12 (m), 1442.94 (m), 1217.24 (3), 1059.05 (3). MS, m/z: 177.9 (16.5%), 163.2 ((49.7%), 145.1 (26.7%), 135.2 (100.0%), 119.0 (26.1%), 91.1 (38.0%), 77.1 (33.2%). Anal. Calcd for C11H1402: C, 74.16; H, 7.87. Found: C, 74.30; H, 7.80. 1 , 3 -dihydr0- 1 , 3,4 -trimethylisobenz0furan-1 -01 (36) 'H NMR (500 MHz, C6D6), 6 ppm: 1.30 (d, 6.5 Hz, 3H), 1.37 (d, J: 6.5 Hz, 3H), 1.70 (s, 3H), 1.77 (s, 3H), 1.89 (s, 3H), 1.92 (s, 3H), 2.26 (s, 1H), 2.35 (s, 1H), 5.06 (q, J: 6.5 Hz, 1H), 5.18 (q, J: 6.5 Hz, 1H), 6.85 (d, J: 7.5 Hz, 2H), 7.02 (dt, .12 3.0, 7.5 Hz, 2H), 7.07 (d, J: 7.5 Hz, 2H). 13C NMR (125 MHz, C6D6), 6 ppm: 18.18, 18.48, 21.31, 22.90, 27.60, 28.56, 77.49, 78.02, 106.90, 107.04, 119.86, 119.92, 128.33, 128.37, 130.17. 130.26, 131.26, 131.33. 142.02, 142.39, 142.93, 143.38. IR (neat, cm'l): 3416.37 (m, broad), 2988.12 (m), 2937.96 (m), 1787.02 (3), 1699.50 (m), 1684.07 (m), 1479.59 (w), 1437.15 (w), 1275.11 (m), 1096.71 (m), 1057.13 (m). 193 MS, m/z: 176.3 (1.0%), 161.2 (100.0%), 105.1 (49.1%), 77.2 (16.6%), 43.2 (47.1%). Products from 2-eth0xy-3-isopropylacetophenone (11) BO 0 0 OH O OH hv, Pyrex C606 + 11 38 cis-37 Scheme 102. Photoproducts from 11 11 (3.7 mg, 0.018 mmol) in 0.75 mL of deuterated benzene was irradiated. The signals for three products were detected in the NMR spectrum of the mixture. Two of these products, the hemiketals (38), disappear as the irradiation time (percent conversion) increases. The signal for one product was detected at 100% conversion in the NMR spectrum of the photolysis mixture. This product was a benzofuranol (cis-37). The structural assignment of the benzofuranol was accomplished by performing nOe experiment: irradiation of the methine signal (quartet at 4.05ppm, J: 7.0 Hz) caused an enhancement of the methyl signal (singlet at 1.26ppm). This suggests that the benzofuranol has a cis-stereochemistry. The hemiketal/benzofuranol ratio was determined by NMR integration of the methine quartet signal of the hemiketals and the methine quartet signal of the benzofuranol. The hemiketals were difficult to isolate because of a rapid decomposition on silica gel. The spectroscopic data given are from the NMR mixture of photoproducts in benzene. The large scale irradiation using 0.5 g (2.4 mmol) of 11 in 60 mL of benzene was performed until 100% conversion (GC). Solvent was removed to leave a yellow oil which was chromatographed by column chromatography (hexanes: ethyl acetate 15: 1~10: 1) to separate the product. 194 cis-3-hydr0xy-7-isopr0pyl-2,3-dimethyl-2,3-dihydr0benz0furanol (cis-37) 1H NMR (500 MHz, C6136), 6 ppm: 0.96 (s, 1H), 1.26 (s, 3H), 1.29 (d, J: 7.0 Hz, 6H), 1.31 (d, J: 7.0 Hz, 3H), 3.30 (septet, J: 7.0 Hz, 1H), 4.05 (q, J: 7.0 Hz, 1H), 6.84 (t, J: 7.5 Hz, 1H), 7.01 (dd, J: 1.5, 7.5 Hz, 1H), 7.06 (dd, J: 1.5, 7.5 Hz, 1H). l3C NMR (125 MHz, C6D6), 6 ppm: 13.30, 22.53, 22.63, 24.07, 28.58, 77.30, 87.61, 121.04,121.24,127.11, 131.49,133.04, 157.30. IR (neat, cm'l): 3391.29 (m, broad), 2964.97 (s), 1559.19 (w), 1442.94 (3), 1209.52 (m), 1062.91 (m). MS, m/z: 188.0 (100.0%), 173.1 (100.0%), 158.0 (29.0%), 145.1 (52.6%), 127.7 (76.1%), 115.1 (55.7%), 105.2 (20.1%), 91.1 (30.2%), 79.1 (38.4%), 43.2 (100.0%). Anal. Calcd for C13H1302: C, 75.73; H, 8.74. Found: C, 76.07; H, 8.76. m.p.: 35.2~35.8°C 1 , 3 -dihydr0-4-isopropyl - I , 3 -dimethylisobenzofitran- 1 -0l (38) 1H NMR (300 MHz, C6D6), 6 ppm: 1.36 (d, J: 6.3 Hz, 3H), 1.43 (d, J: 6.6 Hz, 3H), 1.70 (s, 3H), 1.77 (s, 3H), 2.63 (septet, J: 6.6 Hz, 2H), 5.22 (q, J: 6.6 Hz, 1H), 5.34 (q, J: 6.6 Hz, 1H). Product from 3-t-butyl-2-ethoxyacetophenone (1;) NMR experiment Irradiation of 12 (4.1 mg, 0.019 mmol) in 0.75 mL of benzene-d6 gave only one product. The reaction was monitored by 1H NMR analysis periodically. The quartet at 195 EtO O O OH hv, Pyrex 0606 12 cis-39 Scheme 103. Photoproduct from 12 3.52ppm for the methylene group disappeared at the same rate as the growth of a quartet at 4.04ppm in benzene-d6. The product was determined to be cis-7-t-buty1-3-hydroxy-2,3- dimethyl—2,3-dihydrobenzofuranol (cis-39) based on its 1H and 13C NMR spectra. Preparative experiment A preparative reaction was carried out with 0.5 g (2.3 mmol) of 12 in 60 mL of benzene. The preparatory scale reaction gave an identical results as the NMR scale reaction. Silica gel column chromatography (hexanes: ethyl acetate 20:1) gave a single product. cis-7-t-butyl-3-hydr0xy-2,3-dimethyl-2,3-dihydr0benz0furanol (cis-39) lH NMR (300 MHz, C6D6), 6 ppm: 0.89 (s, 1H), 1.19 (s, 3H), 1.22 (d, J: 6.6 Hz, 3H), 1.42 (s, 9H), 3.98 (q, J=6.6 Hz. 1H), 6.78 (t, J: 7.5 Hz, 1H), 6.97 (dd, J: 1.5, 7.5 Hz, 1H), 7.11 (dd, J: 1.5, 7.5 Hz, 1H). 13C NNIR (125 MHz, C6D6), 6 ppm: 13.29, 24.15, 29.56, 34.39, 76.84, 87.27, 121.05, 121.44, 126.85, 133.78, 133.87, 157.72. IR (neat, cm'l): 3379.72 (m, broad), 2959.18 (8), 1595.33 (w), 1431.36 (5), 1209.52 (m), 1062.91 (m), 893.16 (m). MS, m/z: 202.0 (100.0%), 188.5 (26.7%), 187.0 (100.0%), 159.3 (54.5%), 158.6 (55.7%), 196 127.7 (72.9%), 114.9 (52.2%), 90.9 (39.2%), 79.0 (43.5%), 71.5 (45.9%), 42.9 (73.7%). Anal. Calcd for CMHZOOZ: C, 76.36; H, 9.09. Found: C, 76.51; H, 9.20. m.p.: 32.5~32.9°C Products from 2-benzyloxy-3-methylacetophenone (13) ,5: fire: BnO 0 0,940 {EA—LL. 0606“ :5?“ +10%“? Scheme 104. Photoproducts from 13 Irradiation of a 0.019 M benzene—d6 solution of 13 gave a complex mixture of products. The NMR tube was irradiated with Pyrex filtered light from a medium pressure mercury arc lamp. The progress of the reaction was monitored by 1H NMR analysis. The reaction was approximately 50% complete after 10 hours. The preparative reaction sample was prepared using the same technique that was applied to the NMR scale sample except with 0.38 g (1.58 mmol) of 13. The solvent was removed by rotoevaporation and a yellow oil remained. The crude product was purified by column chromatography (hexanes: ethyl acetate 30:1~15:1): the first fraction eluted had the spectral data consistent with 42; the second fraction was recrystallized from hexanes to afford a yellow crystal which was determined by 1H and 13C NMR to be 41; 197 the third compound eluted was recovered starting material; the fourth fraction was purified again by crystallization from hexanes to give yellow powder, this compound was determined to be 44 based on spectral data; the last fraction was purified again by column chromatography (hexanes: ethyl acetate 30:1~20:1), it was assigned to be cis-40 based on spectral data. The two hemiketals (43) were unable to isolate due to quick decomposition on silica gel, NMR spectrum of the photoproducts mixture shows two singlets at 5.84ppm and 5.96ppm corresponding to the methine protons of the two hemiketals. 5-benzyl-2~hydroxy-3-methylacetophenone (41) 1H NMR (500 MHz, C6D6), 6 ppm: 1.88 (s, 3H), 2.16 (s, 3H), 3.62 (s, 2H), 6.90 (d, J: 1.5 Hz, 1H), 6.97 (d, J: 1.5 Hz, 1H), 7.05 (stack, 3H), 7.15 (stack, 211), 13.11 (1H). 13C NMR (125 MHz, C6D6), 6 ppm: 15.59, 26.00, 41.19, 119.10, 126.53, 127.91, 128.25, 128.82, 128.99, 130.51, 138.19, 141.50, 160.17, 204.52. IR (neat, cm'l): 2920.60 (w), 1633.91 (8), 1429.43 (m), 1369.63 (m), 1292.47 (m), 1128.50 (w). MS, m/z: 240.2 (88.3%), 225.2 (100.0%), 197.1 (70.7%), 178.0 (31.8%), 165.0 (24.5 %), 151.8 (33.9%), 91.0 (54.8%), 43.1 (77.4%). Anal. Calcd for C16H1602: C, 80.00; H, 6.67 . Found: C, 80.05; H, 6.59. m.p.: 89.1~89.7°C I -( 3 '-acetyl-4,4 ’-dihydroxy-5,5 ’-dimethyl-biphenyl-3-yl)-ethanone (44) 198 1H NMR (300 MHz, CDC13), 6 ppm: 2.32 (s, 3H), 2.69 (s, 3H), 7.50 (d, J=2.1 Hz, 1H), 7.65 (d, J: 2.1 Hz, 1H), 12.56 (s, 1H). 13C NMR (125 MHz, CDC13), 6 ppm: 15.69, 26.92, 119.03, 126.10, 128.14, 130.75, 135.83, 160.21, 204.72. IR (neat, cm'l): 2933.53 (w), 1637.77 (m), 1425.58 (5), 1278.97 (8), 1207.59 (3), 1174.80 (m). MS, m/z: 281.1 (23.0%), 207.1 (100.0%), 187.2 (17.2%), 147.1 (19.9%), 135.1 (26.1%), 73.1 (56.0%). Anal. Calcd for C13H1304: C, 72.48; H, 6.04. Found: C, 72.55; H, 5.98. m.p.: 240.5~241.3°C cis—3-hydroxy-3, 7-dimethyl-2-phenyl-2,3-dihydrobenzofuranol (cis-40) lH NMR (500 MHz, C6D6), 6 ppm: 0.96 (s, 1H), 1.39 (s, 3H), 2.30 (s, 3H), 5.00 (s, 1H), 6.83 (t, J: 8.0 Hz, 1H), 6.97 (d, J: 8.0 Hz, 1H), 7.08 (d, J: 7.5 Hz, 1H), 7.14 (stack, 3H), 7.25 (dd, J: 2.0, 8.5 Hz, 2H). 13C NMR (125 MHZ, C6D6), 6 ppm: 15.24, 25.11, 78.44, 92.93, 120.73, 121.44, 121.50, 127.56, 127.91, 128.39, 131.32, 132.15, 135.91, 158.27. IR (neat, cm'l): 3439.52 (m, broad), 2924.46 (w), 1599.19 (m), 1454.51 (3), 1207.59 (3), 1093.78 (w). MS, m/z: 222.4 (100.0%), 178.1 (43.4%), 145.1 (32.1%), 115.0 (31.3%), 76.9 (31.3%). Anal. Calcd for C16H1602: C, 80.00; H, 6.67. Found: C, 80.06; H, 6.85. 199 Products from 2-benzyloxy-3-isopropylacetophenone (14) %H-F J\©/M\+ W BnO O ”-9.45 hv, P rex C606 14 %4 Ho 0 O OH Scheme 105. Phot0products from 14 Irradiation of a 0.020 M benzene-d6 solution of 14 gave a complex mixture of products. The NMR tube was irradiated with Pyrex filtered light from a medium pressure mercury arc lamp. The progress of the reaction was monitored by 1H NMR analysis. The reaction was approximately 60% complete after 12 hours. The preparative reaction sample was prepared using the same technique that was applied to the NMR scale sample except with 0.90 g (3.36 mmol) of 14. The solvent was removed by rotoevaporation and a yellow oil remained. The crude product was purified by column chromatography (hexanes: ethyl acetate 30:1~15:1): the first fraction eluted had the spectral data consistent with 47; the second fraction was recrystallized from hexanes to afford a yellow crystal which was determined by 1H and 13C NMR to be 46; the third compound eluted was recovered starting material; the fourth fraction was purified again by crystallization from hexanes to give yellow powder, this compound was determined to be 49 based on spectral data; the last fraction was purified again by column chromatography (hexanes: ethyl acetate 30:1~20:1), it was assigned to be cis-45 based on spectral data. The two hemiketals (48) were unable to isolate due to quick 200 decomposition on silica gel, NMR spectrum of the photoproducts mixture shows two singlets at 5.92ppm and 6.05ppm corresponding to the methine protons of the two hemiketals. 5-benzyl-2-hydroxy-3-isopropylacetophenone (46) 'H NMR (300 MHz, Con). 6 ppm: 1.28 (d, J: 6.9 Hz, 6H), 1.97 (s, 3H), 3.60 (septet, J: 6.9 Hz, 1H), 3.76 (s, 2H), 7.07 (d, J: 2.1 Hz, 1H), 7.13 (stack, 3H), 7.24 (stack, 3H), 13.32 (1H). 13C NMR (75 MHz, C6D6), 6 ppm: 22.38, 26.10, 27.04, 41.39, 119.36, 126.53, 128.23, 128.82, 128.96, 130.72, 133.96, 138.03, 141.48, 159.43, 204.73. IR (neat, cm'l): 3026.70 (w), 2963.04 (m), 1635.84 (3), 1454.51 (5), 1389.63 (m), 1250.03 (m), 1167.08 (m), 979.96 (w). MS, m/z: 268.2 (45.5%), 253.2 (52.9%), 165.1 (13.0%), 115.0 (14.1%), 91.1 (100.0%), 76.5 (27.1%), 43.0 (87.5 %). Anal. Calcd for C lgHzoOzI C, 80.60; H, 7.46. Found: C, 80.72; H, 7.15. 1 -( 3 ’-acetyl-4,4 '-dihydroxy-5,5 ’-diisopropyl-biphenyl-3-yl)-ethanone (49) lH NMR (300 MHz, CDC13), 6 ppm: 1.33 (d, J: 6.9 Hz, 6H), 2.03 (s, 3H), 3.63 (septet, J: 6.9 Hz, 1H), 7.40 (d, J: 2.4 Hz, 1H), 7.61 (d, J: 2.1 Hz, 1H), 13.37 (s, 1H). 13C NMR (75 MHz, CDC13), 5 ppm: 22.40, 26.18, 27.41, 119.62, 126.56, 131.78, 131.92, 138.53, 160.27, 204.84. IR (neat, cm'l): 2963.04 (w), 1633.91 (8), 1433.29 (m), 1317.55 (3), 1236.53 (m), 201 1169.01 (w), 979.96 (w). MS, m/z: 354.2 (60.2%), 339.1 (16.1%), 297.1 (6.6%), 165.0 (6.8%), 43.3 (100.0%). Anal. Calcd for C22H26O4: C, 74.58; H, 7.34. Found: C, 74.53; H, 7.19. m.p.: 182.8~183.5°C cis—3-hydroxy-7-isopropyl-3-methyl-2-phenyl-2,3-dihydrobenzofuranol (cis-45) 1H NMR (300 MHz, C6D6), 5 ppm: 1.02 (s, 1H), 1.32 (d, J: 6.9 Hz, 3H), 1.34 (d, J: 6.9Hz, 3H), 1.38 (s, 3H), 3.31 (septet, J: 6.9 Hz, 1H), 5.04 (s, 1H), 6.88 (t, J: 7.5 Hz, 1H), 7.12 (stack, 5H), 7.27 (dd, J: 1.8, 7.5 Hz, 2H). 13C NMR (75 MHz, C6D6), 6 ppm: 22.48, 22.57, 25.27, 28.96, 78.28, 92.88, 121.58, 121.70, 127.27, 127.47, 128.32, 128.38, 131.55, 132.39, 136.10, 157.32. IR (neat, cm'l): 3437.59 (m, broad), 3032.48 (w), 2963.04 (m), 1597.26 (w), 1442.94 (5), 1203.73 (m), 1080.27 (w), 993.47 (m). MS, m/z: 250.4 (100.0%), 249.1 (65.5%), 234.8 (36.9%), 207.2 (49.0%), 177.9 (33.3%), 173.1 (52.2%), 157.2 (34.5%), 151.5 (21.3%), 114.9 (60.8%), 91.0 (56.5%). Anal. Calcd for C18H2002Z C, 80.60; H, 7.46. Found: C, 80.68; H, 7.68. Products from 42-benzyloxy-3-t-butylacetophenone (15) Irradiation of a 0.018 M benzene-d6 solution of 15 gave a complex mixture of products. The NMR tube was irradiated with Pyrex filtered light from a medium pressure mercury arc lamp. The progress of the reaction was monitored by 1H NMR analysis. The 202 reaction was approximately 90% complete after 10 hours. Ph 8:10 0 cis-50 hv, Pyrex CGDG ' Ph .. X694 Ho 0 00 OH Scheme 106. Photoproducts from 15 The preparative reaction sample was prepared using the same technique that was applied to the NMR scale sample except with 0.30 g (1.06 mmol) of 15. The solvent was removed by rotoevaporation and a yellow oil remained. The crude product was purified by column chromatography (hexanes: ethyl acetate 30:1~10:1): the first fraction eluted had the spectral data consistent with 52; the second fraction was purified again by column chromatography (hexanes: ethyl acetate 80:1) to afford a yellow solid which was determined by 1H and 13C NMR to be 51; the third compound eluted was recovered starting material; the fourth fraction was purified again by crystallization from hexanes to give yellow powder, this compound was determined to be 54 based on spectral data; the last fraction was purified again by crystallization from hexanes, it was assigned to be cis- 50 based on spectral data. The two hemiketals (53) were unable to isolate due to quick decomposition on silica gel, NMR spectrum of the photoproducts mixture shows two singlets at 5.85ppm and 5.98ppm corresponding to the methine protons of the two hemiketals. 203 5-benzyl-3-t-butyl-2-hydroxyacetophenone (51) 1H NMR (300 MHz, C6D.) 5 ppm: 1.43 (s, 9H), 1.83 (s, 3H), 3.65 (s, 2H), 7.01 (stack, 4H), 7.10 (stack, 2H), 7.28 (d, J: 2.1 Hz, 1H), 13.46 (1H). 13C NMR (75 MHz, C6D6), 5 ppm: 26.30, 29.47, 35.13, 41.51, 119.74, 126.54, 128.68, 128.85, 128.99, 130.28, 134.54, 139.03, 141.43, 161.24, 205.05. IR (neat, cm'l): 2959.19 (m), 1631.99 (s), 1433.29 (5), 1363.85 (m), 1331.05 (m), 1238.46 (8), 1105.35 (w). MS, m/z: 282.3 (51.3%), 267.3 (100.0%), 266.5 (38.4%), 178.0 (8.2%), 91.0 (73.7%), 43.0 (61.0%). Anal. Calcd for cszzoz: c, 80.85; H, 7.80. Found: C, 80.69; H, 7.46. I -( 3 '-acetyl-5,5 ’-di-t-butyl-4,4 ’-dihydroxy-biphenyl-3-yl)-ethanone (54) lH NMR (300 MHz, CDC13), 6 ppm: 1.46 (s, 9H), 2.70 (s, 3H), 7.58 (d, J: 2.1 Hz, 1H), 7.67 (d, J: 2.1 Hz, 1H), 13.11 (s, 1H). 13C NMR (75 MHz, CDC13), 6 ppm: 27.21, 29.27, 35.11, 119.50, 126.69, 131.00, 132.59, 139.36, 161.46, 205.18. IR (neat, cm"): 2951.46 (m), 1630.06 (8), 1427.51 (8), 1361.92 (m), 1319.48 (m), 1205.66 (m), 1103.42 (w). MS, m/z: 382.8 (87.1%), 381.7 (68.2%), 367.8 (47.1%), 366.7 (41.6%), 176.0 (25.1%), 165.0 (14.4%), 130.6 (34.9%), 57.3 (49.4%), 43.0 (100.0%). Anal. Calcd for C24H3004: C, 75.39; H, 7.85. Found: C, 75.34; H, 7.84. 204 m.p.: 219.5~219.8°C cis-7-t-butyl-3-hydroxy-2,3-dimethyl-2,3-dihydrobenzofuranol (cis-50) 1H NMR (500 MHz, C6136), 6 ppm: 0.94 (s, 1H), 1.38 (s, 3H), 1.50 (s, 9H), 5.06 (s, 1H), 6.88 (t, J: 7.5 Hz, 1H), 7.14 (stack, 4H), 7.21 (dd, J: 1.0, 7.5 Hz, 1H), 7.29 (dd, J: 1.5, 7.5 Hz, 2H). 13C NMR (125 MHz, C6D6). 6 ppm: 25.28, 29.62, 34.40, 77.83, 92.70, 121.55, 121.96, 126.97, 127.41, 127.77, 128.46, 133.13, 133.93, 136.21, 157.69. IR (neat, cm'l): 3433.73 (m, broad), 2959.18 (s), 1593.40 (w), 1431.38 (8), 1361.92 (w), 1205.66 (m), 1066.77 (w). MS, m/z: 264.3 (100.0%), 249.2 (100.0%), 221.2 (67.1%), 178.0 (45.5%), 110.2 (94.9%), 102.6 (24.2%), 76.7 (66.7%). Anal. Calcd for C19H2202: C, 80.85; H, 7.80. Found: C, 80.84; H, 7.62. m.p.: 112.2~112.9°C Products from a-(chloroethoxflacetophenone (16) NMR experiment in benzene-d6 O O\/\ C' benzevne-da 16 cis-56 Scheme 107. Photoproducts from 16in Benzene A 0.75 mL of benzene-d6 solution of 16 (7.1 mg, 0.036 mmol, 0.048 M) was degassed in a NMR tube. Irradiation gave two major products. The reaction was monitored by 1H 205 NMR and was nearly complete after 30 minutes of irradiation with Pyrex filtered light (medium pressure mercury arc lamp). One of the products had a 1H NMR spectrum consistent with acetophenone (55). The NMR solution was also injected into the gas chromatograph and had a peak with an identical retention time as 55. The other product was determined to be cis-56 based on its 1H and 13C NMR spectra. This reaction was repeated with the presence of pyridine which gave identical result as the one without pyridine. NMR experiment in methanol-d4 0 HO HO O O (2* (2% o)? 0 Cl \c O 55 cis-56 trans-56 Q)“ W “" > methanol-d4 O O 16 G/u\/OH (DA/OJ + + 57 58 Scheme 108. Photoproducts from 16in Methanol A 0.75 mL methanol-d4 solution of 16 (8.1 mg, 0.041 mmol, 0.055 M) was degassed. The sample was irradiated with Pyrex filtered light. After 30 minutes of irradiation, a mixture of several products including two isomeric oxetanols, acetophenone, 2— hydroxyacetophenone and a trace amount of a-vinyloxyacetophenone were detected, by their signals, upon analysis of the NMR spectrum of the photolysis mixture. The reaction was complete (100% conversion) after 1.5 hours of irradiation, 1H NMR spectrum showed the disappearence of a doublet of doublet at 6.54ppm corresponding to the vinylidene proton of a-vinyloxyacetophenone (58). 206 Preparative experiment A preparative reaction was carried out with 0.2 g (1.01 mmol, 0.025 M) of 16 in 40 mL of benzene. The preparatory scale reaction gave identical results as the NMR scale reaction. Silica gel column chromatography (hexanes: ethyl acetate 40:1~20:1) gave two major products: the first fraction eluted had the spectral data consistent with 55, the second fraction eluted was the cyclization product cis-56. The structural assignment of the oxetanol was accomplished by performing nOe experiment: irradiation of the methine signal (octet at 5.05ppm) caused an enhancement of one of the aryl proton signals (dt at 7.53ppm). This suggests that the oxetanol has a cis-stereochemistry. cis-2-chloromethyl-3-phenyl-oxetan-3-ol (cis-56) 1H NMR (500 MHz, CDC13), 6 ppm: 2.51 (s, broad, 1H), 3.77 (dd, J: 5.0, 11.0 Hz, 1H), 4.10 (dd, J: 8.0, 11.0 Hz, 1H), 4.77 (dd, J: 1.0, 7.0 Hz, 1H), 4.87 (d, J: 7.0 Hz, 1H), 5.05 (ddd, J: 1.0, 5.0, 8.0 Hz, 1H), 7.34 (tt, J: 1.0, 7.5 Hz, 1H), 7.43 (tt, J: 2.0, 7.5 Hz, 2H), 7.53 (dt, J: 1.0, 7.5 Hz, 2H). 13C NMR (75 MHz, CDCl3), 6 ppm: 41.67, 76.15, 82.48, 89.16, 124.90, 128.27, 128.83, 142.25. IR (neat, cm'l): 3375.86 (8, broad), 2966.90 (w), 1448.73 (m), 1176.73 (m), 1057.13 (m), 984.53 (s), 850.72 (m). MS, m/z: 162.0 (100.0%), 147.0 (51.9%), 105.0 (96.1%), 89.1 (71.2%), 77.0 (41.7%), 51.1 (17.5%). Anal. Calcd for CloHnClOz: C, 60.45; H, 5.54. Found: C. 60.47; H, 5.56. 207 Products from a-(bromoethoxy)acetophenone (17) NMR experiment in benzene-d6 (without pyridine) O O O HO benzene-d; 1" + 55 57 59 17 Scheme 109. Photoproducts from 17 in Benzene A 0.75 mL benzene-d6 solution of 17 (7.1 mg, 0.029 mmol, 0.039 M) was degassed in a NMR sample tube. The sample was irradiated with Pyrex filtered light in an immersion well setup. The well was submerged in deionized water and the reaction temperature was maintained between l7~20°C during the reaction period. The reaction was continued for 30 minutes, the starting ketone had been completely consumed and the solution had turned yellow. The 1H NMR spectrum showed a mixture of 55, 57 and trace amount of 2- methyl-3-phenyl-oxetan-3-ol (59). NMR experiment in benzene-d6 ( with pyridine) O O\/\ 8 ©/“\/ r benzhene'ds> dk... OKZ/k/ pyridine 17 Scheme 110. Photoproducts from 17 in Benzene With Pyridine A 0.75 mL benzene-d6 solution of 17 (6.7 mg, 0.027 mmol, 0.037 M) and a drop of pyridine was degassed and irradiated in an immersion well setup. The sample gave white precipitates upon irradiation, presumably the pyridinium bromide salt. After 20 minutes of reaction, 40% of the starting ketone had been consumed, the IH NMR spectrum showed the formation of two products: 55 and 58. 208 NMR experiment in toluene-d8 A solution of 17 (8.5 mg, 0.035 mmol, 0.047 M) in 0.75 mL of toluene-d8 was degassed in a NMR tube. The sample was irradiated with Pyrex filtered light in a acetone-dry ice bath. 50% of the starting ketone had been consumed after 40 minutes of irradiation and the solution had turned yellow. 1H NMR spectrum showed the formation of 55, 57 and 59. NMR experiment in methanol-d4 A solution of 17 (7.4 mg, 0.032 mmol, 0.045 M) in 0.70 mL of methanol-d4 was degassed and irradiated. The reaction was complete after 30 minutes of irradiation. The NMR spectrum of the crude reaction sample was virtually uninterpretable due to overlapping peaks. No attempt was made to isolate the products. Preparative experiment (without pyridine) A preparative reaction was carried out with 0.40 g (1.65 mmol, 0.027 M) of 17 in 60 mL of benzene. The preparatory scale reaction gave an identical result as the NMR scale reaction. Silica gel column chromatography (hexanes: ethyl acetate 8:1) gave two major products: the first fraction eluted had the spectral data consistent with 55, the second fraction eluted was 57 based on 1H and 13 C NMR spectral data as well as the comparison with authentic sample of 57 purchased from Aldrich. 2-hydroxyacetophenone (57) 1H NMR (500 MHz, CDC13), 6 ppm: 3.47 (t, J: 5.0 Hz, 1H), 4.86 (d, J: 5.0 Hz, 2H), 209 7.49 (t, J: 7.5 Hz, 2H), 7.61 (tt, J: 1.0, 7.5 Hz, 1H), 7.91 (dd, J: 1.0, 7.5 Hz, 2H). 13C NMR (125 MHz, coc13), 5 ppm: 65.46, 127.69, 128.98, 133.43, 134.28, 198.39. Preparative experiment (with pyridine) A preparative reaction was carried out with 0.60 g (2.47 mmol, 0.031 M) of 17 and 0.39 g (5.0 mmol, 0.062 M) of pyridine in 80 mL of benzene. The reaction was nearly complete after 6 hours of irradiation. The white precipitate was filtered and solvent was removed under reduced pressure. The crude product was purified by column chromatography (hexanes: ethyl acetate 20: 1) to afford 0.1 g of 58 as white solid. a-vinyloxyacetophenone (58) lH NIVIR (300 MHz, CDC13), 6 ppm: 4.13 (dd, J: 3.0, 6.9 Hz, 1H), 4.25 (dd, J: 3.0, 14.4 Hz, 1H), 4.97 (s, 2H), 6.54 (dd, J: 6.9, 14.4 Hz, 1H), 7.47 (t, J: 7.5 Hz, 2H), 7.59 (t, J: 7.5 Hz, 1H), 7.93 (d, J: 7.5 Hz, 2H). 13C NMR (125 MHz, CDCl3), 6 ppm: 70.24, 88.02, 127.99, 128.80, 133.81, 134.58, 150.94, 194.14. IR (neat, cm'l): 1693.72 (s), 1599.19 (m), 1450.65 (m), 1230.74 (m), 1095.71 (m). MS, m/z: 105.0 (100.0%), 77.1 (71.4%), 51.2 (15.5%). Anal. Calcd for CloHloOZ: C, 74.07; H, 6.17. Found: C, 73.97; H. 6.31. Products from a-(iodoethoxy)acetophenone (18) NMR experiment (without pyridine) 210 O O O\/\l hv : OH benzene-d6 18 57 Scheme 111. Photoproduct from 181n Benzene A 0.75 mL benzene-d6 solution of 18 (9.0 mg, 0.031 mmol, 0.041 M) was degassed. The sample was irradiated with Pyrex filtered light in an immersion well setup. The well was submerged in deionized water and the reaction temperature was maintained between l7~20°C during the reaction period. After 50 minutes of irradiation the sample had become dark red in color. The major product had 1H NMR consistent with 57. NMR experiment (with pyridine) O O ()\/\l hv : 0% benzene-d6 pyridine 18 58 Scheme 112. Photoproduct from 18 in Benzene With Pyridine A solution of 18 (8.4 mg, 0.029 mmol, 0.039 M) and a drop of pyridine in 0.75 mL of benzene-d6 was degassed and irradiated. The reaction was complete after 5 hours of irradiation and gave one major product although the reaction solution gave white precipitates. The product had a 1H NMR spectrum consistent with 58. Productsfrom a-(2-bromo-2-methylpropoxymcetophenone (19) NMR experiment in benzene—d6 A solution of 19 (7.6 mg, 0.028 mmol, 0.038 M) in 0.75 mL of deuterated benzene was degassed in a NMR tube. The sample was irradiated with Pyrex filtered light in an 211 O O ©/‘J\/O\>
©jK/O\'/|\ + OK + ©/fi\/OH benzene-d6 Br 19 60 55 57 Scheme 113. Photoproducts from 19 in Benzene immersion well setup. The reaction gave three major products: 55, 57 and the third product had the 1H NMR spectrum consistent with a-(l-bromo-2- methylpropoxy)acetophenone (60). No attempt was made to isolate the products. The spectroscopic data given are from the N1VIR mixture of photoproducts in benzene. a-(I -bromo-2-methylpropoxy)acetophenone (60) 1H NMR (300 MHZ, C6D6), 6 ppm: 1.07 (d, J: 6.6 Hz, 3H), 1.13 (d, J: 6.6 Hz, 3H), 2.20 (ds, J: 3.3, 6.6 Hz, 1H), 4.53 (d, J: 16.0 Hz, 1H), 4.54 (d, J: 16.0 Hz, 1H), 5.83 (d, J: 3.6 Hz, 1H), can’t identify aryl protons due to the peak overlap. NMR experiment in toluene-d3 (with pyridine) ° x ° 3k ° 0 Br hv : O / + toluene-d8 pyridine 19 61 55 Scheme 114. Photoproducts from 19in Benzene With Pyridine A solution of 19 (8.0 mg, 0.030 mmol, 0.040 M) and a drop of pyridine in 0.75 mL of toluene-d8 was degassed and irradiated. The sample gave white precipitates upon irradiation. After 2 hours of irradiation the 1H NMR showed the formation of two major products: 55 and 61. No attempt was made to isolate the products. The spectroscopic data given are from the NMR mixture of photoproducts in toluene. 212 a—( 2-methyl -1 -propenoxy)acetophenone (61) 1H NMR (300 MHz, toluene-d3), 6 ppm: 1.45 (s, 3H), 1.71 (s, 3H), 4.35 (s, 2H), 5.66 (t, J: 1.5 Hz, 1H), can’t identify aryl protons due to the peak overlap. Products from B-(chloroethoxy)propiophenone (2_0) NMR experiment in benzene-d6 ( with pyridine) O O O/\/Cl hv > O/\ benzene-d6 pyridine 20 62 Scheme 115. Photoproduct from 20 A 0.75 mL benzene-d6 solution of 20 (6.9 mg, 0.032 mmol, 0.043 M) and a drop of pyridine was degassed and irradiated. The reaction was monitored by 1H NMR analysis periodically. The reaction was nearly complete after 2 hours of irradiation. The product was determined to be B-vinyloxypropiophenone (62) based on its 1H and 13C NMR spectra. The formation of 62 was independent of the light source employed. 62 was formed by irradiation with a medium pressure mercury arc lamp (Pyrex filtered) and 300 nm lamps in a Rayonet reactor. Each reactor gave identical results. NMR experiment in methanol-d4 (with pyridine) A 0.75 mL methanol-d4 solution of 20 (7.0 mg, 0.033 mmol, 0.044 M) and a drop of pyridine was degassed and irradiated. After 30 minutes of irradiation 1H NMR spectrum showed the formation of one major product: 62. After one hour of irradiation, the NMR spectrum of the crude reaction sample was virtually uninterpretable due to overlapping peaks. 213 Products from B-(bromoethoxv)propiophenone (21) O O O/\/ Br hv : O/\ benzene-d5 pyridine 21 62 Scheme 116. Photoproduct from 21 NMR experiment (with pyridine) A 0.75 mL benzene-d6 solution of 21 (6.8 mg, 0.026 mmol, 0.035 M) and a drop of pyridine was degassed and irradiated. The reaction was monitored by 1H NMR analysis periodically. The reaction was nearly complete after 2 hours of irradiation. The product was determined to be B-vinyloxypropiophenone (62) based on its 1H and 13C NMR spectra. Preparative experiment ( with pyridine) A preparative reaction was carried out with 0.50 g (1.95 mmol, 0.039 M) of 21 and 0.15 g (1.90 mmol, 0.038 M) of pyridine in 50 mL of benzene. The reaction was nearly complete after 5 hours of irradiation. The white precipitate was filtered and solvent was removed under reduced pressure. The crude product was purified by column chromatography (hexanes: ethyl acetate 30: 1~20: 1) to afford 62. ,B-vinyloxypropiophenone (62) 1H NMR (300 MHz, CDC13), 6 ppm: 3.33 (t, J: 6.6 Hz, 2H), 4.02 (dd, J: 2.1, 6.9 Hz, 1H), 4.13, (t, J: 6.6 Hz, 2H), 4.24 (dd, J: 2.1, 14.4 Hz, 1H), 6.45 (dd, J: 6.9, 14.4 Hz, 1H), 7.46 (t, J: 7.8 Hz, 2H), 7.56 (t, J: 7.2 Hz, 1H), 7.97 (d, J: 7.2 Hz, 2H). l3c NMR (125 MHz, CDC13). 5 ppm: 37.83, 63.18, 86.96, 128.09, 128.64, 133.31, 214 136.78, 151.53; IR (film, cm'l): 3067.21 (w), 2926.39 (w), 2853.08 (w), 1674.43 (s), 1616.55 (w), 1448.73 (w), 1196.02 (m), 817.92 (w). MS, m/z: 176.2 (3.4%), 133.2 (22.6%), 105.0 (100.0%), 76.9 (72.7%), 50.8 (38.3%). Anal. Calcd for C1 1H1202: C, 75.00; H, 6.82. Found: C, 75.21; H, 7.01. Products from B-(iodoethoxymropiophenone (22) O O/\/' by = O/\ benzene-d5 pyridine 22 62 Scheme 117. Photoproduct from 22 NMR experiment (with pyridine) A 0.75 mL benzene-d6 solution of 22 (8.1 mg, 0.027 mmol, 0.036 M) and a drop of pyridine was degassed and irradiated. The reaction was monitored by 1H NMR analysis periodically. The reaction was nearly complete after 2 hours of irradiation. The product was determined to be B-vinyloxypropiophenone (62) based on its 1H and 13C NMR spectra. Products from a-cyclopropylmethoxyacetophenone (2_3) NMR experiment in benzene-d6 A 0.8 mL benzene-d6 solution of 23 (6.6 mg, 0.035 mmol, 0.043 M) was irradiated until starting material could not be observed by NMR. The signals for three products were detected in the NMR spectrum of the mixture. These products included two 215 0 0 HO HO O\/A hv, Birex _ O O benzene-d; + + g 55 23 cis-63 trans-63 Scheme 118. Photoproducts from 23 in Benzene isomeric oxetanols (cis-63 and trans-63) and 55. The effect of temperature on product ratios was also investigated by conducting the photochemistry in ice water and silicon oil (60°C) baths. The product ratios were determined by NMR integration of the methine doublet signals of the oxetanols and the methyl singlet signal of acetophenone. The structural assignments of the oxetanols was accomplished by performing nOe experiments. Irradiation of the methine doublet at 4.08ppm in the minor isomer caused an enhancement of the OH signal, irradiation of the methine doublet at 4.30ppm in the major isomer caused an enhancement of one of the aryl proton signals. These data strongly suggest that the minor isomer has a trans-stereochemistry. NMR experiment in toluene-d3 23 (6.8 mg, 0.036 mmol, 0.048 M) in 0.75 mL of deuterated toluene was irradiated through Pyrex filter until no trace of starting material could be observed by NMR. The signals of two isomeric oxetanols (63) and acetophenone were detected upon analysis of the NMR spectrum of the photolysis mixture. In our investigation, photochemistry was conducted at various temperature to acertain the effect of temperature on product ratios. The diastereomeric ratio of oxetanols was determined by NMR integration of the methine doublet signals corresponding to each isomer. 216 NMR experiment in acetonitrile-d3 A solution of 23 (7.0 mg, 0.037 mmol, 0.046 M) in 0.8 mL of acetonitrile-d3 was degassed in an NMR tube. The sample was irradiated with Pyrex filtered light. The reaction was complete after 2 hours of irradiation and gave three major products including two isomeric oxetanols (63) and acetophenone. The diastereomeric ratio of oxetanols was determined by NMR integration of the methine doublet signals corresponding to each isomer. NMR experiment in methanol-d4 O O ©/il\ (DA/OW + 55 64 O O\/A hv, Pyrex _ methanol-d; HO HO O O 23 + + i A cls-63 trans-63 Scheme 119. Photoproducts from 23 in Methanol 23 (7.6 mg, 0.040 mmol, 0.053 M) in 0.75 mL of deuterated methanol was degassed and irradiated until no starting ketone could be observed by NMR analysis. The signals for two isomeric oxetanols (63), 55 and 64 were detected upon analysis of the NMR spectrum of the photolysis mixture. The diastereomeric ratio of oxetanols was determined by NMR integration of the methine doublet signals corresponding to each isomer. Preparative experiment in t-butanol 217 0.5 g (2.6 mmol, 0.044 M) of 23 was dissolved in 60 mL of t-butanol, degassed and irradiated with Pyrex filtered light. The reaction was complete after 1.5 hours of irradiation and a pale yellow color persisted. The solvent from a small fraction of the reaction solution was removed by rotary evaporation; the residue was dissolved in CDC13 and the 1H NMR analysis revealed a mixture of two isomeric oxetanols and acetophenone. The crude reaction mixture was separated by deactivated silica gel column chromatography (CH2C12: ethyl acetate 10:1). The first fraction eluted had the spectral data consistent with acetophenone, its NMR solution was also injected into the gas chromatograph and had a peak with an identical retention time as acetophenone, the NMR solution was also spiked with authentic acetophenone and reinjected into the gas chromatograph, only one peak was visible in the chromatogram. The 1H NMR spectrum of the second product was consistent with the structure of cis-63; the last fraction eluted was determined to be trans-63 based on spectral data. cis-2—cyclopropyl—3-phenyl-oxetan-3-ol (cis-63) 1H NMR (500 MHz, CDC13), 6 ppm: 0.25 (m, 1H), 0.52 (m, 1H), 0.62 (m, 1H), 0.74 (m, 1H), 1.40 (m, 1H), 2.79 (s, 1H), 4.30 (d, J: 7.5 Hz, 1H), 4.64 (dd, J: 1.0, 7.0 Hz, 1H), 4.84 (d, J: 7.0 Hz, 1H), 7.30 (tt, J: 1.5, 7.0 Hz, 1H), 7.40 (m, 2H), 7.55 (m, 2H). 13C NMR (125 MHz, CDC13), 6 ppm: 0.83, 2.28, 10.30, 48.70, 82.82, 96.16, 124.60, 127.76, 128.62, 142.91. IR (film, cm'l): 3383.57 (8, broad), 2920.60 (w), 1495.02 (w), 1448.73 (w), 1170.94 (111), 1026.26 (w), 962.60 (m). MS, m/z: 190.4 (0.3%), 172.3 (0.2%), 136.3 (7.0%), 105.2 (100.0%), 91.3 (11.2%), 77.3 218 (35.3%), 54.3 (60.3%). Anal. Calcd for C12H1402: C, 75.79; H, 7.37. Found: C, 75.68; H, 7.39. trans-2-cyclopropyl-3-phenyl-oxetan-3-ol (trans-63) IH NMR (500 MHz, CDCl3), 6 ppm: 0.21 (stack, 2H), 0.32 (m, 1H), 0.46 (m, 2H), 2.21 (s, 1H), 4.09 (d, J: 8.5 Hz, 1H), 4.68 (d, J: 7.5 Hz, 1H), 4.99 (dd, J: 1.0, 7.0 Hz, 1H), 7.34 (m, 1H), 7.42 (m, 2H), 7.59 (m, 2H). 1H NMR (500 MHz, CD3OD), 6 ppm: 0.18 (m. 2H), 0.26 (m, 1H), 0.43 (m, 1H), 0.47 (m. 1H), 4.08 (d, J: 9.5 Hz, 1H), 4.64 (dd, J: 0.5, 7.0 Hz, 1H), 4.95 (dd, J: 1.0, 7.0 Hz, 1H), 7.30 (tt, 12 1.5, 7.0 Hz, 1H), 7.40 (m 2H), 7.61 (m, 2H). 13C NMR (125 MHz, CDC13), 6 ppm: 1.41, 3.15, 12.25, 78.94, 79.69, 98.81, 126.00, 127.98, 128.41, 139.69. IR (film, cm'l): 3383.57 (8, broad), 3086.50 (w), 2882.02 (m), 1448.73 (w), 1153.58 (m), 1074.49 (m), 1026.26 (m), 954.89 (8). MS, m/z: 172.3 (7.3%), 128.0 (7.3%), 105.3 (100.0%), 77.3 (77.6%), 51.1 (47.3%). Anal. Calcd for C12H1402: C, 75.79; H, 7.37. Found: C, 75.78; H, 7.29. Preparative experiment in methanol A preparative reaction was carried out with 0.55 g (2.89 mmol, 0.048 M) of 23 in 60 mL of methanol. The preparatory scale reaction gave an identical result as the NMR scale reaction. Deactivated silica gel column chromatograph (dichloromethane: ethyl acetate 219 10:1) gave four products: 55, 64 and two isomeric oxetanols (63). a-(I -butenoxy)acetophenone (64) 1H NMR (500 MHz, CDC13), 6 ppm: 0.95 (t, J: 7.5 Hz, 3H), 1.93 (dq, J: 1.5, 7.5 Hz. 2H), 4.89 (stack, 3H), 6.31 (dt, .1: 1.5, 12.5 Hz, 1H), 7.46 (t, J: 8.0 Hz, 2H), 7.57 (tt, J: 1.5, 7.0 Hz, 1H), 7.92 (d, J: 7.5 Hz, 2H). l3C NMR (125 MHz, CDC13), 6 ppm: 14.99, 20.90, 71.42, 107.72, 128.02, 128.73, 133.65, 134.75, 144.75, 194.79. IR (film, cm'l): 2970.75 (w), 1689.86 (3), 1452.58 (w), 1290.54 (m), 1101.49 (w), 975.25 (w). MS, m/z: 188.3 (5.9%), 160.3 (13.4%), 105.3 (94.6%), 83.3 (65.8%), 77.3 (88.7%), 55.4 (100.0%), 50.4 (32.4%). Anal. Calcd for C12H1402: C, 75.79; H, 7.37. Found: C, 75.62; H, 7.19. Products from a-cyclopropylmethoxvacetone (24) NMR experiment in benzene-d6 A 0.6 mL benzene-d6 solution of 24 (3.7 mg, 0.029 mmol, 0.048 M) was degassed and irradiated through Pyrex with a 450 W medium pressure mercury arc lamp. The sample HO O O hv, Pyrex O /u\/0\/A benzene-d; A + 24 cis-65 Scheme 120. Photoproducts from 24 in Benzene 220 was hung outside the immersion well setup. The progress of the reaction was monitored by 1H NMR and was complete after 12 hours. The 1H NMR of the photolysis mixture showed two major products: acetone and oxetanol (cis-65). The product ratio was determined by NMR integration of the methine doublet signal of the oxetanol and the methyl singlet signal of acetone. The structural assignments of the oxetanol was accomplished by performing nOe experiments. Irradiation of the methine doublet at 3.89ppm caused an enhancement of the methyl signal, this suggests that this oxetanol has a cis-stereochemistry. NMR experiment in methanol-d4 0 hv, Pyrex _ 0 H CO OCH A/Ofi methanol-d; /u\ + 3 k8 24 66 Scheme 121. Photoproducts from 24 in Methanol A solution of 24 (4.4 mg, 0.034 mmol, 0.046 M) in 0.75 mL of deuterated methanol was degassed in an NMR tube. The sample was irradiated with Pyrex filtered light and the reaction was monitored by NMR analysis. After 13 hours of irradiation 50% of the starting ketone had been consumed, the 1H NMR showed the formation of two major products. One of them has the 1H NMR spectrum consistent with acetone, the other one was determined to be the acetal (66) of the starting ketone based on its 1H and 13C NMR spectral data. NMR experiment in acetonitrile-d3 A solution of 24 (5.2 mg, 0.041 mmol, 0.054 M) in 0.75 mL of acetonitrile-d3 was 221 degassed and irradiated with Pyrex filtered light. After 84 hours of irradiation 1H NMR spectrum showed the formation of acetone and oxetanol (65). However, it took almost 10 days for the starting ketone to be completely consumed. Preparative experiment in benzene A preparative reaction was canied out with 0.34 g (2.66 mmol, 0.044 M) of 24 in 60 mL of benzene. The preparatory scale reaction gave an identical result as the NMR scale reaction. Solvent was removed under reduced pressure, the residue was purified by column chromatography (hexanes: ethyl acetate 5:1). The first fraction eluted was recovered starting material, the second fraction eluted had the 1H and 13C NMR spectra consistent with oxetanol (cis-65). cis-2-cyclopropyl-3-methyl-oxetan-3-ol (cis-65) 1H NMR (300 MHz, CDC13), 6 ppm: 0.21 (m, 1H), 0.42 (m, 1H), 0.61 (stack, 2H), 1.19 (m, 1H), 1.46 (s, 3H), 2.61 (s, broad, 1H), 3.89 (d, J: 7.5 Hz, 1H), 4.35 (d, J: 10.5 Hz, 1H), 4.39 (d, J: 10.5 Hz, 1H). 13C NMR (125 MHz, CDC13), 6 ppm: 0.48, 1.78, 10.11, 25.44, 73.38, 82.60, 95.80. IR (film, cm'l): 3410.58 (8, broad), 2966.90 (8), 2876.23 (8), 1377.35 (m), 1221.10 (m), 1116.93 (m), 1026.26 (m), 964.53 (8). MS, m/z: 128.5 (0.1%), 111.4 (0.1%), 101.3 (4.1%), 87.3 (17.7%), 57.3 (45.4%), 55.4 (100.0%), 41.4 (15.4%). Anal. Calcd for C7H1202: C, 65.63; H, 9.38. Found: C, 65.62; H, 9.11. 222 Preparative experiment in methanol A preparative reaction was carried out with 0.60 g (4.69 mmol, 0.059 M) of 24 in 80 mL of methanol. The sample was degassed and irradiated in a Rayonet reactor equipped with 300 nm lamps. Periodically a small aliquot of the reaction solution was taken out and analyzed by GC. The chromatogram gave a peak (~87%) with a retention time of 2.74 minutes after 20 hours of irradiation, the peak grew to ~90% of total area after 54 hours of irradiation. This compound had been isolated by column chromatography (hexanes: ethyl acetate 10:1), it was determined to be the acetal (66) of the starting ketone based on its 1H NMR spectral data. (2,2-dimethoxy-propoxymethyl)—cyclopropane (66) 'H NMR (500 MHz, CDC13), 5 ppm: 0.17 (m, 2H), 0.49 (m, 2H), 1.03 (m, 1H), 1.33 (s, 3H), 3.20 (s, 6H), 3.31 (d, J: 7.0 Hz, 2H), 3.41 (s, 2H). 13C NMR (75 MHz, CDC13), 5 ppm: 100.24, 76.06, 71.46, 48.21, 20.18, 10.31, 2.97. IR (film, cm"): 2943.75 (m), 2868.51 (m), 1462.23 (w), 1375.42 (111), 1251.96 (m), 1120.78 (3), 1055.20 (s). MS, m/z: 142.0 (8.1%), 87.0 (23.3%), 71.9 (27.1%), 59.0 (36.4%), 55.1 (100.0%), 42.9 (36.4%). Products from B-cyclopropylmethovautanone (25) NMR experiment in benzene-d6 A 0.75 mL benzene-d6 solution of 25 (4.0 mg, 0.028 mmol, 0.038 M) was degassed. Irradiation was conducted with a Pyrex filtered light from a mercury arc lamp. Progress 223 cis-68 Scheme 122. Photoproducts from 25 in Benzene of the reaction was followed by 1H NMR. The reaction was approximately 50% complete after 30 hours. Four products were detected in the NMR spectrum of the mixture and were identified as two 4-butenyloxybutanones (E-67 and Z-67) and two isomeric tetrahydrofurans (cis-68 and trans-68). Product ratio was determined by NMR integration of the vinyl proton signals of the 4-butenyloxybutanones and the methine signals (doublet) of the tetrahydrofurans. NMR experiment in toluene-d8 A solution of 25 (6.5 mg, 0.046 mmol, 0.057 M) in 0.8 mL of toluene-d3 was irradiated with Pyrex filtered light at room temperature. The progress of the reaction was monitored by 1H NMR analysis. After 100 hours of irradiation 70% of the starting ketone had been consumed. Four products were detected in the NMR spectrum of the photolysis mixture and were identified as E-67, Z-67, cis-68 and trans-68. The effect of temperature on product ratios had also been investigated. However, at 0°C and -78°C irradiation of 25 in toluene did not give any product after 75 hours of irradiation. NMR experiment in methanol-d4 224 25 (6.6 mg, 0.046 mmol, 0.062 M) in 0.75 mL of deuterated methanol was degassed in trans-68 Scheme 123. Photoproducts from 25 in Methanol an NMR tube and irradiated with Pyrex filtered light from a medium pressure mercury arc lamp at room temperature. The reaction was monitored by 1H NMR and it was approximately 50% complete after 48 hours of irradiation. Two products were detected in the NMR spectrum of the photolysis mixture and were identified as two isomeric tetrahydrofurans. The diastereomeric ratio of tetrahydrofurans was determined by NMR integration of the methine doublet signals corresponding to each isomer. Preparative experiment Large scale irradiation using 0.85 g (6.0 mmol, 0.060 M) of 25 in 100 mL of benzene was performed. Solvent was evaporated to leave a colorless liquid which was purified by column chromatography (hexanes: ethyl acetate 4:1). The first fraction eluted was a mixture of E-67 and Z-67 which could not be further separated. The stereochemistry of the double bonds was determined based on coupling constant of the vinyl protons. The second fraction eluted was recovered starting ketone. The third fraction was a mixture of two THFs, they were separated by column chromatography (chloroform: acetone 10:1). The structural assignments of the THFs was accomplished by performing nOe experiments. Irradiation of the methine doublet at 2.75ppm in the major isomer caused an enhancement of the methyl signal, irradiation of the methine signal at 2.94ppm in the 225 minor isomer caused an enhancement of the OH signal. These data suggest that the major isomer has a cis-stereochemistry and the minor isomer has a trans-stereochemistry. cis-2-cyclopropyl-3—methyl-tetrahydrofitran-3-ol (cis-68) IH NMR (500 MHz, CDC13), 6 ppm: 0.27 (m, 1H), 0.35 (m, 1H), 0.56 (m, 2H), 0.95 (m, 1H), 1.35 (s, 3H), 1.85 (s, broad, 1H), 2.02 (stack, 2H), 2.75 (d, J: 8.5 Hz, 1H), 3.75 (dt, J: 4.5, 9.0 Hz, 1H), 3.96 (q, J: 8.5 Hz, 1H). l3C NMR (125 MHz, CDC13), 6 ppm: 1.23, 1.50, 8.32, 23.79, 41.32, 65.16, 78.36, 90.38. IR (film, cm'l): 3437.59 (8, broad), 2974.61 (3), 2880.09 (m), 1373.49 (w), 1124.64 (m), 1043.62 (8), 999.25 (m). MS. m/z: 114.3 (5.9%), 72.5 (34.9%), 71.4 (54.1%), 57.4 (36.6%), 43.4 (100.0%). trans-2-cyclopropyl-3-methyl-tetrahydrofuran-3-ol (trans-68) 1H NMR (500 MHz, CDCl3), 6 ppm: 0.30 (m, 2H), 0.52 (m, 2H), 0.70 (m, 1H), 1.43 (s, 3H), 1.70 (s, broad, 1H), 1.97 (stack, 2H), 2.94 (d, J: 8.5 Hz, 1H), 3.91 (stack, 2H). l3C NMR (125 MHz, CDC13), 6 ppm: 1.55, 2.21, 12.00, 23.08, 40.59, 65.52, 79.82, 91.91. IR (film, cm'l): 3416.37 (m, broad), 2922.53 (8), 2851.15 (5), 1462.23 (m), 1379.28 (m), 1099.56 (m), 1028.19 (m). MS, m/z: 114.0 (4.0%), 72.2 (29.6%), 71.1 (46.4%), 57.1 (27.3%), 43.1 (100.0%). E-4-but-1-enyloxy-2-butanone (E-67) and Z-4-but-1-enyloxy-2-butanone (Z-67) 1H NMR (500 MHz, CDC13), 5 ppm: 0.93 (two triplets overlap, J: 7.5 Hz), 1.90 (qintet, J: 7.2 Hz), 2.01 (qintet, J: 7.5 Hz), 2.16 (s), 2.17 (s), 2.71 (two triplets overlap), 3.87 (t, 226 J: 6.3 Hz), 3.95 (t, J: 6.3 Hz), 4.34 (q, J: 6.9 Hz), 4.79 (sextet, J: 6.9, 12.6 Hz), 5.85 (dd, J: 1.5, 6.3 Hz), 6.17 (d, J: 12.6 Hz). 13C NMR (125 MHz, CDC13), 6 ppm: 14.36, 15.17, 17.31, 21.00, 30.42, 30.53, 43.02, 43.48, 63.81, 66.89, 106.70, 109.83, 143.88, 145.16, 206.49, 206.59. IR (film, cm'l): 2972.68 (w), 1710.88 (8), 1452.58 (m), 1290.54 (m), 1099.56 (w). 227 IV. Measurement of Quantum Yields Solvents Benzene- 3.5 L of reagent grade benzene was mixed with 500 mL concentrated sulfuric acid and the mixture was stirred for 2-3 days. The benzene layer was separated and was washed with 100 mL portions of concentrated sulfuric acid several times until the sulfuric acid layer did not turn yellow. The benzene was then washed with distilled water and saturated sodium bicarbonate solution. The benzene was separated, dried over magnesium sulfate and filtered into a 5 L round-bottom flask. Phosphorus pentoxidc (100 g) was added and the solution was refluxed for 48 hours. After refluxing, the benzene was distilled through a one meter column packed with stainless steel helices. The first and last 10% were discarded. (b.p.: 78°C) Benzene-d6- The benzene-d6 was purchased from Aldrich chemical in 5g quantities. The purity used was 99+ atom %D and was used without purification. Methanol- Reagent grade absolute methanol was refluxed over magnesium tumings for 2 hours, and distilled through a half meter column packed with glass helices. The first and last 10% were discarded. Pyridine- Pyridine (Mallinkrodt) was refluxed over barium oxide for 12 hours and distilled through a half meter column packed with glass helices. The first and last 10% were discarded. Internal standards Eicosane (C20)- Eicosane (Aldrich) was purified by recrystallization from ethanol. Methyl benzoate (MB)— Methyl benzoate was purified by fractional distillation. 228 n-Octyl benzoate (OB)- n-Octyl benzoate was purified by Dr. Peter J. Wagner and used without further purification. Methyl 4-methoxybenzoate (MMOB)- Methyl 4-methoxybenzoate was prepared by methylation of methyl 4-hydroxybenzoate and purified by fractional distillation. 1H NMR (300 MHz, CDCl3), 6 ppm: 3.84 (s, 3H), 3.86 (s, 3H), 6.89 (d, J: 9.0 Hz, 2H), 7.97 (d, J: 9.3 Hz, 2H). 13C NMR (75 MHz, CDCl3), 6 ppm: 166.82, 163.31, 131.55, 122.61, 113.56, 55.36, 51.78; IR (film, cm’l): 2968.83 (w), 1713.01 (s), 1610.77 (m), 1288.61 (8), 1107.28 (m), 1022.40 (m). MS, m/z: 166.2 (100.0%), 135.2 (100.0%), 107.2 (44.3%), 92.2 (60.8%), 77.3 (100.0%), 70.3 (29.8%), 43.1 (100.0%). Quencher 2,5-Dimethyl-2,4-hexadiene- 2,5—Dimethyl-2,4-hexadiene was allowed to sublime in the refrigerator. Actinometer Valerophenone (VP)- Valerophenone (Aldrich Chemical) was purified by fractional distillation. Glassware All new glassware (syringes, volumetric flasks and pipettes) used in quantitative 229 measurements were rinsed with reagent grade acetone, deionized water and boiled in an Alconox (laboratory detergent) and deionized water solution for 24 hours. The glassware was rinsed and boiled in deionized water for 24 hours, this cycle was repeated 3 times. After the final rinse with deionized water, the glassware was dried at 140°C in a dedicated oven for photolysis glassware and cooled to room temperature prior to use. If the glassware was previously used, the glassware was rinsed thoroughly with HPLC grade acetone and oven dried, this cleaning (rinsing) procedure limits the inaccuracy due to glass degradation with constant Alconox washings. Ampoules used for the irradiation were made from Alconox washed 13 x 100mm Pyrex culture tubes by flame heating approximately 2,5cm from the top with an oxygen- natural gas torch and drawing them to a uniform 150m length. The NMR sample tubes were prepared by the Michigan State University Glass Shop. High resolution model 535pp (pyrex, ID: 4.000mm 1- 3 0.005”) from Wildmad Glass were fused to a 2 inch Pyrex extension and attached to a 10/30 ground glass joint. The tubes were cleaned by rinsing thoroughly with HPLC grade acetone and then oven dried. The tubes were recycled by scoring and breaking the Pyrex extension and reattaching the ground glass joint. Preparation of samples Solution Preparation The solutions were prepared by weighing the desired material directly into a volumetric flask. Dilutions were made with the minimum number of transfers by volumetric pipettes. The ketone/intemal standard solutions were divided equally into four 230 2.8 mL portions by a 5.0 mL Hamilton syringe with 20 gauge lure lock needle and placed into the pre-drawn ampoules. In the case for NMR solutions, four 0.7 mL portions were syringed by a 1.0 mL Hamilton syringe with 20 gauge, 10 in. luer lock needle which limited the ketone solution beading to the wall of the NMR tube. In order to obtain accurate results we adapted our merry-go-round method, which was constructed for standardized test tubes. Degassing Procedure Previously filled irradiation ampoules were attached to a vacuum line that was evacuated for at least one hour. These tubes were arranged on a circular manifold equipped with twelve vacuum stopcocks each fitted with size 00 one hole rubber stoppers. The sample tubes were frozen in liquid nitrogen and evacuated for at least 20 minutes. The stopcocks were closed and the tubes were allowed to warm to room temperature. The freeze-pump-thaw cycle was conducted four times and the tubes sealed with an oxygen-natural gas torch while still under vacuum. In the degassing of NMR samples, it was necessary to facilitate the thawing procedure by rinsing the tubes with 95% ethanol from the top of the sample level to the bottom of the tubes. If this was not done the thawing solution would expand and crack the thin walled NMR sample tubes. Photochemical Reaction Setup The quantum yield measurements were conducted at 313 nm with filtered light. The 313 nm light was isolated using a solution of alkaline potassium chromate (0.002 M KzCrO4 in 1% aqueous potassium carbonate). Irradiation was conducted with the light 231 source mounted in the center of a merry-go-round setup. For NMR tubes, the 14 mm merry-go-round hole size was adapted with Teflon disk adapters (1 mm x 12 Teflon wafer with a 5 mm centered bore) to ensure the NMR tube fit snug inside of the standardized test tube. The portion of the NMR tube above the merry-go-round was wrapped with black electrical tape since the 0.7 mL volume was above this level and would have absorbed reflected light. The use of the Teflon adapter ensure the NMR sample tubes were equal distance from the light source which was mounted in the center. Actinometry The quantum yields for product formation were measured by irradiating ketone solutions parallel to valerophenone as an actinometer. The quantum yields were calculated using Equation 1, Equation 1. <1>=[PP]/I where [PP] is the concentration of photoproduct and I is the intensity of light absorbed by the sample. The value of I was determined by parallel irridiation to valerophenone which forms acetophenone with a quantum yield of (PAP: 0.33 at 313 nm. The acetophenone concentration was determined from Equation 2, Equation 2. [AP]: Rf* [IS]* AAp/ A13 where, [AP] is the concentration of acetophenone, [IS] is the concentration of internal standard, Rf is the instrument response factor, A Ap is the integrated area of acetophenone, 232 AIS is the integrated area of the internal standard. The intensity of light, I, was determined from Equation 3 since [AP] is known. Equation 3. 1: [AP]/ 0.33 The concentration of photoproduct, [PP] was calculated from Equation 4. Equation 4. [PP]: prp* [IS]* (AAp/ A15) where, [PP] is the concentration of photoproduct, [IS] is the concentration of internal standard, prp is the instrument response factor, App is the integrated area of product, A13 id the integrated area of the internal standard. Quenching studies Stem-Volmer quenching studies were performed with the appropriate triplet quencher. The Stem-Volmer expression (Equation 5) is: Equation 5. (Do/(D: 1+ deho where, (D0 is the quantum yield in the absence of quencher, (1) is the quantum yield in the presence of quencher, [Q] is the concentration of quencher, kq is the bimolecular rate constant for quenching. To is the life time of the excited state being quenched. There is a linear relation between (Do/(D and the quencher concentration. When (Do/CD is 233 plotted versus [Q], the slope is kw). The quenching is assumed to be diffusion controlled with a rate constant of 5 x 109 M'ls'l. 234 Quantum Yield Measurement for 2-Methoxy-3-methylbenzophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 25. Product Quantum Yield of 2-Methoxy-3-methy[benzophenone in Benzene Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 26 7003 53328 0.0008323 0.51 2 26 7797 54728 0.0009029 0.55 3 26 7388 51444 0.0009102 0.56 4 26 6122 52813 0.0007347 0.45 5 26 6353 53952 0.0007463 0.46 Average 26 6933 53253 0.0008253 0.51 ACT: VP, [VP]: 0.1008 M; ISACT= C20, [ISAcr]= 0.004014 M; [ketone]: 0.01127 M, ISKET= C20, [1810”]: 0.003986 M. Irradiation time 3 hours. Conversion: 7.3 %. Irradiation wavelength: 313 nm. 235 Quantum Yield Measurement for 2-Methoxy-3-methylbenzophenone in Methanol GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 26. Product Quantum Yield of 2-Methoxy-3-methylbenzophenone in Methanol Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 26 3938 17347 0.0006285 0.32 2 26 3319 15093 0.0006088 0.31 3 26 5105 17970 0.0007865 0.39 4 26 4620 17536 0.0007294 0.37 5 26 4242 17380 0.0006757 0.34 6 26 4201 16441 0.0007074 0.35 Average 26 4238 16961 0.0006894 0.35 ACT: VP, [VP]: 0.1002 M; ISACT= C20, [ISAcr]= 0.003177 M; [ketone]: 0.01005 M, 18mm: MB, [18mm]: 0.005324 M. Irradiation time 3 hours. Conversion: 6.9 %. Irradiation wavelength: 313 nm. 236 Quantum Yield Measurement for 3-Isopropyl-2-methoxybenzophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 27. Product Quantum Yield of 3-Isopropyl-2-methoxybenzophenone in Benzene Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 27 7365 55933 0.0008654 0.64 2 27 7198 54226 0.0008724 0.65 3 27 7069 54996 0.0008448 0.63 Average 27 721 1 55052 0.0008609 0.64 ACT: VP, [VP]: 0.1008 M; ISACT= C20, [18mm]: 0.004071 M; [ketone]: 0.01020 M, 181031: C20, [ISKET]= 0.004057 M. Irradiation time 3.5 hours. Conversion: 8.4 %. Irradiation wavelength: 313 nm. 237 Quantum Yield Measurement for 3-Isopropyl-2-methoxybenzophenone in Methanol GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 28. Product Quantum Yield of 3-Isopropyl-2-methoxybenzophenone in Methanol Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 27 6702 16695 0.0008955 0.45 2 27 6443 16764 0.0008674 0.44 3 27 7365 17266 0.0009516 0.48 4 27 7018 16365 0.0009567 0.48 5 27 6573 16245 0.0009026 0.45 Average 27 6820 16667 0.0009128 0.46 ACT = VP, [VP]: 0.1002 M; ISAcr= C20, [ISAcr]= 0.003177 M; [ketone]: 0.01014 M, ISKET= MB, [18mm]: 0.005441 M. Irradiation time 3 hours. Conversion: 9.0 %. Irradiation wavelength: 313 nm. 238 Quantum Yield Measurement for 3-t-Butyl-2-methoxybenzophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 29. Product Quantum Yield of 3-t-Butyl-2-methoxybenzophenone in Benzene Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 28 12439 48878 0.001249 0.74 2 28 12823 47354 0.001308 0.78 3 28 11982 43425 0.001354 0.81 4 28 14383 48778 0.001447 0.86 5 28 12412 48787 0.001248 0.74 Average 28 12808 47444 0.001321 0.79 ACT: VP, [VP]: 0.1043 M; ISAcr= C20, [ISAcr]= 0.003887 M; [ketone]: 0.01021 M, ISKETz C20, [ISKET]= 0.003957 M. Irradiation time 2 hours. Conversion: 12.9 %. Irradiation wavelength: 313 nm. 239 Quantum Yield Measurement for 3-t-Butyl-2-methoxybenzophenone in Methanol GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 30. Product Quantum Yield of 3-t-Butyl-2-methoxybenzophenone in Methanol Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 28 6492 14324 0.0009704 0.49 2 28 8415 16578 0.001087 0.55 3 28 7684 16143 0.001019 0.51 4 28 7425 15797 0.001006 0.50 Average 28 7504 15711 0.001021 0.51 ACT: VP, [VP]: 0.1002 M; ISAC]: C20, [ISAcrlz 0.003177 M; [ketone]: 0.01015 M, ISKE1~= MB, [18mm]: 0.005353 M. Irradiation time 3 hours. Conversion: 10.1 %. Irradiation wavelength: 313 nm. 240 Quantum Yield Measurement for 2-Ethoxy-3-methylbenzophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mL/min Loop: 20 uL Detection wave length: 270nm Table 31. Products Quantum Yield of 2-Ethoxy-3-methylbenzophenone in Benzene Sample # thg’gdua Area (PP) Area (IS) [PP] ch 1 cis-29 1654025 3069857 0.001503 0.39 2 cis-29 1768669 3349770 0.001473 0.38 3 cis-29 1867995 3265381 0.001596 0.41 4 cis-29 1985509 3889244 0.001424 0.37 Average cis-29 1819050 3393563 0.001499 0.39 Sample # Ph°‘?1§’1§‘)’°“°‘ Area (PP) Area (IS) [PP] <1) 1 trans-29 270285 3069857 0.0002949 0.08 2 trans-29 332009 3349770 0.0003320 0.09 3 trans-29 360276 3265381 0.0003696 0.10 4 trans-29 357911 3889244 0.0003083 0.08 Average trans-29 330120 3393563 0.00031 17 0.08 ACT: VP, [VP]: 0.1003 M; ISACp= OB, [BAG]: 0.01051 M; [ketone]: 0.01145 M, ISKE1~= OB, [18mm]: 0.01077 M. Irradiation time 3 hours. Conversion= 15.8 %. Irradiation wavelength: 313 nm. 241 Quantum Yield Measurement for 2-Ethoxy-3-methylbenzophenone in Methanol Table 32. Products Quantum Yield of 2-Ethoxy-3-methylbenzophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mUrnin Loop: 20 (AL Detection wave length: 270nm Sample # thggdua Area (PP) Area (IS) [PP] (D 1 cis-29 2093021 15402006 0.0003586 0.11 2 cis-29 1664169 15379874 0.0002856 0.09 3 cis-29 1709047 15706222 0.0002872 0.09 4 cis-29 1915236 15164859 0.0003333 0.10 5 cis-29 1678344 15227359 0.0002909 0.09 Average cis-29 181 1963 15376064 0.00031 11 0.09 Sample # Ph°tfl§1§‘)’°“°‘ Area (PP) Area (IS) [PP] cl> 1 trans-29 4099983 15402006 0.0008436 0.25 2 trans-29 3667472 15379874 0.0007557 0.23 3 trans-29 4046209 15706222 0.0008164 0.24 4 trans-29 4099182 15164859 0.0008566 0.26 5 trans-29 3546696 15227359 0.0007381 0.22 Average trans-29 3891908 15376064 0.0008021 0.24 ACT: VP, [VP]: 0.1009 M; ISAcr-c OB, [ISACT]= 0.01068 M; [ketone]: 0.01017 M, ISKET= OB, [ISKET]= 0.01019 M. Irradiation time 3 hours. Conversion= 10.9 %. Irradiation wavelength: 313 nm. 242 Quantum Yield Measurement for 2-Ethoxy-3-isopropylbenzophenone in Benzene Table 33. Products Quantum Yield of HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mL/min Loop: 20 11L Detection wave length: 270nm 2-Ethoxy-3-isopropylbenzophenone in Benzene Sample # thaggdua Area (PP) Area (IS) [PP] <1) 1 cis-30 1375177 2884559 0.001250 0.43 2 cis-30 1613032 3226327 0.001311 0.45 3 cis-30 1486168 3209472 0.001215 0.42 Average cis-30 1491459 3106786 0.001259 0.43 Sample # Phag‘g‘lw Area (PP) Area (IS) [PP] (b 1 trans-30 285140 2884559 0.0002880 0.10 2 trans-30 331223 3226327 0.0002991 0.10 3 trans-30 292018 3209472 0.0002651 0.09 Average trans-30 302794 3106786 0.0002841 0.10 ACT: VP, [VP]: 0.100 M; ISA”: OB, [ISACT]= 0.01060 M; [ketone]: 0.01012 M, ISKET= OB, [18mm]: 0.01075 M. Irradiation time 2.5 hours. Conversion= 15.2 %. Irradiation wavelength: 313 nm. 243 Quantum Yield Measurement for 2-Ethoxy-3-isopropylbenzophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mIJmin Loop: 20 11L Detection wave length: 270nm Table 34. Products Quantum Yield of 2-Ethoxy-3-isopropylbenzophenone in Methanol Photoproduct Sample # (PP) Area (PP) Area (IS) [PP] (D 1 cis-30 1583316 12108302 0.0003331 0.10 2 cis-30 1664169 12260621 0.0003378 0.10 3 cis-30 1625855 12261861 0.0003358 0.10 4 cis-30 1597101 12083135 0.0003367 0.10 Average cis-30 1617610 12178480 0.0003359 0.10 Sample # Ph°tfg1§°du°t Area (PP) Area (IS) [PP] <1) 1 trans-30 3859434 12108302 0.0009018 0.27 2 trans-30 4040158 12260621 0.0009323 0.28 3 trans-30 3992653 12261861 0.0009213 0.28 4 trans-30 3940246 12083135 0.0009226 0.28 Average trans-30 3958123 12178480 0.0009195 0.28 ACT = VP, [VP]: 0.1009 M; ISAcr= OB, [ISAcr]= 0.01068 M; [ketone]: 0.01016 M, ISKE1~= OB, [ISKET]= 0.01044 M. Irradiation time 3 hours. Conversion= 12.4 %. Irradiation wavelength: 313 nm. 244 Quantum Yield Measurement for 3-t-Butyl-2-ethoxybenzophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mIJmin Loop: 20 11L Detection wave length: 270nm Table 35. Products Quantum Yield of 3-t-Butyl-2—ethoxybenzophenone in Benzene Sample # Ph°t$lfi°°°°t Area (PP) Area (IS) [PP] CD 1 cis-31 960284 2944582 0.0009005 0.53 2 cis-31 970943 3006415 0.0008915 0.53 3 cis-31 1084304 3087089 0.0009695 0.57 4 cis-31 1001763 3202002 0.0008640 0.51 5 cis-31 1 140364 3486913 0.0000903 0.53 Average cis-31 1031532 3145400 0.0009055 0.53 Sample # Ph°t°lfl§°°u°t Area (PP) Area (IS) [PP] o 1 trans-31 378139 2944582 0.0003713 0.22 2 trans-31 383823 3006415 0.0003692 0.22 3 trans-31 415431 3087089 0.0003891 0.23 4 trans-31 389030 3202002 0.0003513 0.21 5 trans-31 448683 3486913 0.0003721 0.22 Average trans-31 403021 3145400 0.0003706 0.22 ACT: VP, [VP]: 0.101 M; Isaac OB, [18mm]: 0.01075 M; [ketone]: 0.009943 M, [Sm-r: OB, [1893]: 0.01087 M. Irradiation time 4.5 hours. Conversion= 12.9 %. Irradiation wavelength: 313 nm. 245 Quantum Yield Measurement for 3-t-Butyl-2-ethoxybenzophenone in Methanol Table 36. Products Quantum Yield of 3-t-Butyl-2-ethoxybenzophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 97:3 Flow rate: 1.0 mUmin Loop: 20 11L Detection wave length: 270nm Sample # Ph°t°§gdu°t Area (PP) Area (IS) [PP] o 1 cis-31 1268137 11040178 0.0003011 0.09 2 cis-31 1463886 11175273 0.0003433 0.10 3 cis-31 1189772 10541632 0.0002959 0.09 4 cis-31 1322986 11111558 0.0003121 0.09 5 cis-31 1249445 10507371 0.00031 17 0.09 Average cis-31 1298845 10875202 0.0003128 0.09 Sample # thgg’dua Area (PP) Area (IS) [PP] (D 1 trans-31 4064690 11040178 0.001011 0.30 2 trans-31 4741536 11175273 0.001165 0.35 3 trans-31 3738846 10541632 0.0009736 0.29 4 trans-31 4403951 11111558 0.001088 0.33 5 trans-31 4084107 10507371 0.001067 0.32 Average trans-31 4206626 10875202 0.001061 0.32 ACT: VP, [VP]: 0.1009 M; ISAC]: OB, [ISACle 0.01068 M; [ketone]: 0.01010 M, ISKET= OB, [ISKET]= 0.01032 M. Irradiation time 3 hours. Conversion= 13.6 %. Irradiation wavelength: 313 nm. 246 Quantum Yield Measurement for 2-Benzyloxy-3-methylbenzophenone in Benzene Table 37. Products Quantum Yield of 2-Benzyloxy-3-methylbenzophenone in HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mL/min Loop: 20 11L Detection wave length: 270nm Benzene Sample # 13mg?“ Area (PP) Area (IS) [PP] o 1 cis-32 1749775 3005008 0.001736 0.58 2 cis-32 1541765 2887493 0.001592 0.53 3 cis-32 1851426 3020190 0.001828 0.61 4 cis-32 1642339 2919449 0.001678 0.56 5 cis-32 1638892 3007432 0.001625 0.54 Average cis-32 1684839 2967914 0.001692 0.56 Sample # Phagggdua Area (PP) Area (IS) [PP] (D l trans-32 376496 3005008 0.0003732 0.12 2 trans-32 349804 2887493 0.0003616 0.12 3 trans-32 425434 3020190 0.0004201 0.14 4 trans-32 359641 2910450 0.0003685 0.12 5 trans-32 341804 3007432 0.0003389 0.11 Average trans-32 370636 2967914 0.0003725 0.12 ACT = VP, [VP]: 0.1006 M; ISAC]: OB, [ISAcr]= 0.01258 M; [ketone]: 0.01036 M, ISKE1~= OB, [18mm]: 0.01039 M. Irradiation time 2.5 hours. Conversion= 19.9 %. Irradiation wavelength: 313 nm. 247 Quantum Yield Measurement for 2-Benzyloxy-3-methylbenzophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mIJmin Loop: 20 11L Detection wave length: 270nm Table 38. Products Quantum Yield of 2-Benzyloxy-3-methylbenzophenone in Methanol Sample # P “0:331:39“ Area (PP) Area (IS) [PP] o 1 cis-32 1 152349 25940834 0.0003156 0.20 2 cis-32 1225125 25273562 00003444 0.21 3 cis-32 1316578 26460580 0.0003535 0.22 4 cis-32 957385 23924716 0.0002843 0.18 5 cis-32 1 160469 25942198 0.0003178 0.20 Average cis-32 1162381 25508378 0.0003328 0.21 Sample # Ph°‘°§1§‘)’°“°t Area (PP) Area (IS) [PP] o 1 trans-32 2737374 25940834 0.0007495 0.46 2 trans-32 2694473 25273562 0.0007575 0.47 3 trans-32 2875658 26460580 0.0007720 0.48 4 trans-32 2585594 23924716 0.0007675 0.48 5 trans-32 2804635 25942198 0.0007680 0.48 Average trans-32 2739547 25508378 0.0007630 0.47 ACT: VP, [VP]: 0.1001 M; ISAC]: OB, [ISAcr]= 0.01017 M; [ketone]: 0.01032 M, ISK5T= MMOB, [18mm]: 0.001157 M. Irradiation time 3 hours. Conversion= 10.6 %. Irradiation wavelength: 313 nm. 248 Quantum Yield Measurement for 2-Benzyloxy-3-isopropylbenzophenone in Benzene Table 39. Products Quantum Yield of 2-Benzyloxy-3-isopropylbenzophenone in HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mIJmin Loop: 20 11L Detection wave length: 270nm Benzene Sample # thal’gm“ Area (PP) Area (IS) [PP] o 1 cis-33 1 131561 3449442 0.0009265 0.56 2 cis-33 1081801 3175337 0.0009625 0.58 3 cis-33 1088479 3216579 0.0009560 0.57 4 cis-33 1086314 3228100 0.0009505 0.57 5 cis-33 972562 2974809 0.0009255 0.56 Average cis-33 1072143 3208853 0.0009440 0.57 Sample # Ph°‘:’l§’§)’°“°t Area (PP) Area (IS) [PP] o 1 trans-33 338735 3449442 0.0002733 0.16 2 trans-33 322351 3175337 0.0002825 0.17 3 trans-33 321365 3216579 0.0002780 0.17 4 trans-33 318791 3228100 0.0002748 0.17 5 trans-33 266595 2974809 0.0002494 0.15 Average trans-33 313567 3208853 0.0002771 0.17 ACT: VP, [VP]: 0.1011 M; ISACT= OB, [18mm]: 0.01053 M; [ketone]: 0.01021 M, 18K“: OB, [18mm]: 0.0105 M. Irradiation time 2 hours. Conversion= 12.0 %. Irradiation wavelength: 313 nm. 249 Quantum Yield Measurement for 2-Benzyloxy-3-isopropylbenzophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mL/min Loop: 20 11L Detection wave length: 270nm Table 40. Products Quantum Yield of 2-Benzyloxy-3-isopropylbenzophenone in Methanol Photoproduct Sample # (PP) Area (PP) Area (IS) [PP] (D 1 cis-33 14081 13 26469996 0.0003834 0.24 2 cis-33 1357258 26315792 0.0003717 0.23 3 cis-33 1361312 27249610 0.0003600 0.22 4 cis-33 1456114 28132438 0.0003730 0.23 Average cis-33 1395699 27041959 0.0003720 0.23 Sample # Phaggdw Area (PP) Area (IS) [PP] o 1 trans-33 2959210 26469996 0.0007975 0.49 2 trans-33 2991773 26315792 0.0008110 0.50 3 trans-33 3141865 27249610 0.0008225 0.51 4 trans-33 3275875 28132438 0.0008305 0.51 Average trans-33 3092181 27041959 0.0008155 0.51 ACT: VP, [VP]: 0.1001 M; ISACp= OB, [ISACT]= 0.01017 M; [ketone]: 0.01057 M, ISKET= MMOB, [ISKET]= 0.001205 M. Irradiation time 3 hours. Conversion= 11.2 %. Irradiation wavelength: 313 nm. 250 Quantum Yield Measurement for 2-Benzyloxy-3-t-butylbenzophenone in Benzene Table 41. Products Quantum Yield of 2-Benzyloxy-3-t-butylbenzophenone in HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mIJmin Loop: 20 [IL Detection wave length: 270nm Benzene Sample # Phaal’gdua Area (PP) Area (IS) [PP] <1) 1 cis-34 1099732 3438742 0.0008805 0.51 2 cis-34 1151723 3305121 0.0009595 0.55 3 cis-34 1040958 3145707 0.0009110 0.52 4 cis-34 1027819 2844583 0.0009950 0.57 5 cis-34 940908 2950084 0.0008780 0.51 Average cis-34 1052228 3136847 0.0009250 0.53 Sample # Ph°‘:’§l§‘)’°“°t Area (PP) Area (IS) [PP] (D 1 trans-34 737148 3438742 0.0005990 0.34 2 trans-34 788226 3305121 0.0006665 0.38 3 trans-34 715326 3145707 0.0006355 0.37 4 trans-34 694686 2844583 0.0006825 0.39 5 trans-34 620733 2950084 0.0005880 0.34 Average trans-34 71 1224 3136847 0.0006345 0.37 ACT: VP, [VP]: 0.1013 M; [Sacra OB, [ISACT]= 0.01044 M; [ketone]: 0.01076 M, 181051: OB, [18m]: 0.01039 M. Irradiation time 1.5 hours. Conversion= 14.5 %. Irradiation wavelength: 313 nm. 251 Quantum Yield Measurement for 2-Benzyloxy-3-t-butylbenzophenone in Methanol 1 Table 42. Products Quantum Yield of 2-Benzyloxy-3-t-butylbenzophenone in HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mL/min L00p: 20 [LL Detection wave length: 270nm Methanol Sample # Phaggdua Area (PP) Area (IS) [PP] <1) 1 cis-34 997494 28165682 0.0002750 0.17 2 cis-34 1089359 29196418 0.0003040 0.19 3 cis-34 1057382 29269584 0.0002944 0.18 4 cis-34 927860 25673770 0.0002945 0.18 Average cis-34 1018024 28076364 0.0002918 0.18 Sample # Photfggduct Area (PP) Area (IS) [PP] <1) 1 trans-34 3058267 28165682 0.0008715 0.54 2 trans-34 3363677 29196418 0.0009245 0.57 3 trans-34 3278290 29269584 0.0008990 0.56 4 trans-34 2852610 25673770 0.0008920 0.55 Average trans-34 313821 1 28076364 0.0008970 0.56 ACT: VP, [VP]: 0.1001 M; ISAC-r: OB, [ISACT]= 0.01017 M; [ketone]: 0.01045 M. ISKE-rz MMOB, [ISKET]= 0.001349 M. Irradiation time 3 hours. Conversion= 11.4 %. Irradiation wavelength: 313 nm. 252 Quantum Yield Measurement for 2-Ethoxy-3-methylacetophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mUmin Loop: 20 [LL Detection wave length: 270nm Table 43. Product Quantum Yield of 2-Ethoxy-3-methylacetophenone in Benzene Sample # Phaggdw Area (PP) Area (IS) [PP] <1) 1 cis-35 1 189901 1 1943471 0.0004312 0.040 2 cis-35 1220458 11655668 0.0004531 0.042 3 cis-35 1177504 12002069 0.0004245 0.039 4 cis-35 1300661 12121396 0.0004644 0.043 5 cis-35 1151178 11994237 0.0004154 0.038 Average cis-35 1207940 11943368 0.0004377 0.040 ACT: VP, [VP]: 0.1051 M; ISAC]: OB, [ISACT]= 0.01115 M; [ketone]: 0.01045 M, ISKET= MB, [ISKET]= 0.01104 M. Irradiation time 14 hours. Conversion= 8.5 %. Irradiation wavelength: 313 nm. 253 Quantum Yield Measurement for 2-Ethoxy-3-isopropylacetophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mIJmin Loop: 20 11L Detection wave length: 270nm Table 44. Product Quantum Yield of 2-Ethoxy-3-isopropylacetophenone in Benzene Sample # 13mg?” Area (PP) Area (IS) [PP] <1) 1 cis-37 3179575 10646218 0.001067 0.084 2 cis-37 3263724 10980159 0.001062 0.084 3 cis-37 2866382 10478002 0.0009775 0.077 4 cis-37 2789153 10899856 0.0009144 0.072 Average cis-37 3024709 10751059 0.001005 0.079 ACT: VP, [VP]: 0.0996 M; ISAC]: OB, [ISAcr]= 0.01055 M; [ketone]: 0.01045 M, ISKE-rz MB, [Isles—F]: 0.01021 M. Irradiation time 16.5 hours. Conversion= 14 %. Irradiation wavelength: 313 nm. 254 Quantum Yield Measurement for 3-t-Butyl-2-ethoxyacetophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mI/min Loop: 20 [L Detection wave length: 270nm Table 45. Product Quantum Yield of 3-t-Butyl-2-ethoxyacetophenone in Benzene Sample # thggdua Area (PP) Area (IS) [PP] <1) 1 cis-39 1 192035 10805872 0.0003751 0.033 2 cis-39 1390991 1051 1478 0.0004500 0.040 3 cis-39 1292224 10158638 0.0004325 0.038 4 cis-39 1084126 10231688 0.0003605 0.032 5 cis-39 1192798 10301271 0.0003937 0.035 Average cis-39 1230435 10401789 0.0004024 0.036 ACT: VP, [VP]: 0.1002 M; ISAC]: OB, [ISACT]= 0.01067 M; [ketone]: 0.01038 M, ISKET= MB, [ISKET]= 0.01003 M. Irradiation time 13 hours. Conversion= 4 %. Irradiation wavelength: 313 nm. 255 Quantum Yield Measurement for 2-Benzyloxy-3-methy1acetophenone in Benzene lHNMR analysis: Varian Unity+__500 Relaxation time (d1): 10 sec Table 46. Products Quantum Yield of 2-Benzyloxy-3-methylacetophenone in Benzene Sample # P“°‘f§;§’°“° Area (PP) Area (IS) [PP]x104 <1) 1 cis-40 0.31 100.00 2.995 0.027 2 cis-40 0.27 100.00 2.602 0.023 3 cis-40 0.26 100.00 2.504 0.022 4 cis-40 0.29 100.00 2.848 0.025 5 cis-40 0.30 100.00 2.946 0.026 Average cis-40 0.29 100.00 2.929 0.026 Sample # Phaflfi’gdua Area (PP) Area (IS) [PP]x104 <1) 1 43 0.43 100.00 4.222 0.038 2 43 0.45 100.00 4.369 0.039 3 43 0.43 100.00 4.222 0.038 4 43 0.47 100.00 4.615 0.041 Average 43 0.45 100.00 4.357 0.039 Sample # wags?” Area (PP) Area (IS) [PP]x103 <1) 1 41 2.14 100.00 1.048 0.094 2 41 2.09 100.00 1.024 0.091 3 41 2.12 100.00 1.039 0.093 4 41 2.33 100.00 1.144 0.10 Average 41 2.17 100.00 1.064 0.095 Sample # Photfggduct Area (PP) Area (IS) [PP]x104 <1) 1 44 3.04 100.00 9.935 0.089 2 44 2.79 100.00 9.115 0.081 3 44 2.67 100.00 8.740 0.078 4 44 3.19 100.00 10.425 0.093 Average 44 2.92 100.00 9.554 0.085 Sample # Ph°tafgdu°t Area (PP) Area (IS) [PP]x104 <1) 1 42 0.78 100.00 2.537 0.023 2 42 0.92 100.00 2.995 0.027 256 3 42 1.15 100.00 3.764 0.033 4 42 1.06 100.00 3.469 0.031 Average 42 0.98 100.00 3.409 0.030 ACT: VP, [VP]: 0.1012 M; ISACT= MB, [18mm]: 0.01147 M; [ketone]: 0.02067 M, ISKE-p: TMS, [13m]: 0.008182 M. Irradiation time 72 hours. Conversion= 14.9 %. Irradiation wavelength: 313 nm. 257 Quantum Yield Measurement for 2-Benzyloxy-3-isopropy[acetophenone in Benzene Table 47. Products Quantum Yield of 2-Benzyloxy-3-isoprpopylacetophenone in lHNMR analysis: Varian Unity+_500 Relaxation time (d1): 10 sec Benzene Sample # Ph°tfl§l§°°u°t Area (PP) Area (IS) [PP]x104 <1) 1 cis-45 0.46 100.00 3.475 0.031 2 cis-45 0.42 100.00 3.208 0.029 3 cis-45 0.46 100.00 3.475 0.031 4 cis-45 0.51 100.00 3.895 0.035 Average cis-45 0.46 100.00 3.513 0.031 Sample # Photplpgduct Area (PP) Area (IS) [PP]x104 (1) 1 48 0.88 100.00 6.680 0.060 2 48 0.71 100.00 5.420 0.048 3 48 0.88 100.00 6.670 0.060 4 48 1.01 100.00 7.675 0.068 Average 48 0.87 100.00 6.610 0.059 Sample # Ph°‘3§’l§‘)’°“°t Area (PP) Area (IS) [PP]x103 <1) 1 46 3.22 100.00 1.230 0.11 2 46 2.70 100.00 1.029 0.092 3 46 3.24 100.00 1.237 0.11 4 46 3.53 100.00 1.346 0.12 Average 46 3.17 100.00 1.211 0.11 Sample # thggdua Area (PP) Area (IS) [PP]x103 <1) 1 49 4.41 100.00 1.123 0.10 2 49 4.20 100.00 1.069 0.095 3 49 4.62 100.00 1.175 0.10 4 49 5.50 100.00 1.399 0.12 Average 49 4.41 100.00 1.122 0.10 Sample # thggdua Area (PP) Area (IS) [PP]x104 <1) 1 47 0.90 100.00 2.279 0.020 2 47 1.24 100.00 3.157 0.028 3 47 1.00 100.00 2.533 0.023 258 4 47 1.15 100.00 2.915 0.026 Average 47 1.07 100.00 2.721 0.024 ACT: VP, [VP]: 0.1012 M; ISAC]: MB, [ISAC—r]: 0.01147 M; [ketone]: 0.02037 M, ISKET= TMS, [ISKET]= 0.006364 M. Irradiation time 72 hours. Conversion= 17.8 %. Irradiation wavelength: 313 nm. 259 Quantum Yield Measurement for 2-Benzyloxy-3-t-butylacetophenone in Benzene lHNMR analysis: Varian Unity+_500 Relaxation time (d1): 10 see Table 48. Products Quantum Yield of 2-Benzyloxy-3-t-butylacetophenone in Benzene Sample # 13mg?” Area (PP) Area (IS) [PP]x104 <1) 1 cis-50 0.81 100.00 4.86 0.043 2 cis-50 0.87 100.00 5.19 0.046 3 cis-50 0.87 100.00 5.22 0.047 Average cis-50 0.85 100.00 5.09 0.045 Sample # Ph°1°§g°°°t Area (PP) Area (IS) [PP]x104 <1) 1 53 1.17 100.00 6.990 0.062 2 53 1.27 100.00 7.590 0.068 3 53 1.16 100.00 6.960 0.062 Average 53 1.20 100.00 7. 180 0.064 Sample # Ph°ta§1§°°U°t Area (PP) Area (IS) [PP]x103 q) 1 51 3.34 100.00 1.000 0.089 2 51 3.64 100.00 1.092 0.097 3 51 2.68 100.00 0.804 0.072 Average 51 3.22 100.00 0.966 0.086 Sample # Ph°‘°§1§‘)’°"“ Area (PP) Area (IS) [PP]x104 <1) 1 54 2.72 100.00 5.440 0.049 2 54 2.95 100.00 5.900 0.053 3 54 2.20 100.00 4.400 0.039 Average 54 2.62 100.00 5.245 0.047 Sample # thfggduct Area (PP) Area (IS) [PP]x104 <1) 1 52 1.50 100.00 3.000 0.027 2 52 1.68 100.00 3.350 0.030 3 52 1.87 100.00 3.730 0.033 Average 52 1.68 100.00 3 .360 0.030 260 ACT = VP, [VP]: 0.1012 M; ISAsz MB, [18.1”]: 0.01147 M; [ketone]: 0.02028 M, ISKET= TMS, [ISKET]= 0.005 M. Irradiation time 72 hours. Conversion= 15.1 %. Irradiation wavelength: 313 nm. 261 Quantum Yield Measurement for a-(Chloroethoxy)acetophenone in Benzene with Pyridine GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 49. Products Quantum Yield of a-(Chloroethoxy)acetophenone in Benzene with Pyridine Sample # Ph°‘?§1§‘)’°“°t Area (PP) Area (IS) [PP] <1) 1 55 8409 52070 0.001922 0.42 2 55 9975 51628 0.002300 0.50 3 55 8490 52033 0.001942 0.42 Average 55 8958 51910 0.002054 0.45 Sample # thal’g‘iua Area (PP) Area (IS) [PP] <1) 1 cis-56 8352 52070 0.002009 0.44 2 cis-56 7731 51628 0.001876 0.41 3 cis-56 8538 52033 0.002056 0.45 Average cis-56 8205 51910 0.001980 0.43 ACT: VP, [VP]: 0.1222 M; ISACT= C20, [ISACT]= 0.005191 M; [ketone]: 0.1227 M, ISKE1~= C20, [18mm]: 0.005220 M; [Py]= 0.1246 M. Irradiation time 1.5 hours. Conversion= 3.3 %. Irradiation wavelength: 313 nm. 262 Quantum Yield Measurement for a-(Chloroethoxy)acetophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 50. Products Quantum Yield of a-(Chloroethoxy)acetophenone in Benzene l Sample # Ph°‘f§1§°°“°‘ Area (PP) Area (IS) [PP] <1) 1 55 7248 52157 0.001578 0.48 2 55 6885 53322 0.001466 0.44 3 55 7840 52797 0.001686 0.51 4 55 6598 51039 0.001468 0.44 5 55 6698 52848 0.001439 0.43 6 55 7415 55856 0.001507 0.45 Average 55 7114 53003 0.001524 0.46 Sample # Ph°tfggdu°t Area (PP) Area (IS) [PP] <1) 1 cis-56 5900 52157 0.001352 0.41 2 cis-56 6148 53322 0.001378 0.42 3 cis-56 6345 52797 0.001436 0.43 4 cis-56 5823 51039 0.001363 0.41 5 cis-56 5965 52848 0.001349 0.41 6 cis-56 7005 55856 0.001499 0.45 Avegge cis-56 6198 53003 0.001396 0.43 ACT: VP, [VP]: 0.1165 M; ISACT= C20, [ISAC-r]: 0.004964 M; [ketone]: 0.1003 M, 181037: C20, [181037]: 0.004979 M. Irradiation time 1.5 hours. Conversion= 2.9 %. Irradiation wavelength: 313 nm. 263 Quantum Yield Measurement for a-(Chloroethoxy)acetophenone in Acetonitrile GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 51. Product Quantum Yield of a-(Chloroethoxy)acetophenone in Acetonitrile Sample # Ph°tfl§1§°du°t Area (PP) Area (18) [PP] <1) 1 55 8965 22643 0.002180 0.51 2 55 10393 23053 0.002482 0.59 3 55 10828 24210 0.002462 0.58 Average 55 10062 23302 0.002375 0.56 ACT: VP, [VP]: 0.1002 M; ISAC]: C20, [18am]: 0.005020 M; [ketone]: 0.09963 M, ISKET= MB, [18mm]: 0.005735 M; [Py]= 0.1001M. Irradiation time 2 hours. Conversion= 2.4 %. Irradiation wavelength: 313 nm. 264 Quantum Yield Measurement for a-(Bromoethoxy)acetophenone in Benzene with Pyridine HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 92:8 Flow rate: 1.0 mUmin Loop: 20 [IL Detection wave length: 270nm Table 52. Products Quantum Yield of a—(Bromoethoxy)acetophenone in Benzene with Pyridine Sample # 13mg?” Area (PP) Area (IS) [PP] <1) 1 58 2845141 6599028 0.001969 0.98 2 58 2634157 6273533 0.001917 0.96 3 58 2818302 6623554 0.001943 0.97 4 58 2836361 6738881 0.001922 0.96 Average 58 2783490 6558749 0.001938 0.97 Sample # Ph°tf§1§°°w Area (PP) Area (18) [PP] <1) 1 55 88950 6599028 0.0000786 0.039 2 55 84609 6273533 0.0000786 0.039 3 55 88625 6623554 0.0000780 0.039 4 55 88321 6738881 0.0000764 0.038 Average 55 87673 6558749 0.0000779 0.039 ACT = VP, [VP]: 0.1003 M, ISAcrz MB, [ISAC-r]: 0.02159 M, Rf (AP): 0.270; [ketone]: 0.09988 M, 181051: MB, [18mm]: 0.02468 M, Rf (PP): 0.185; [Py]= 0.09924 M. Irradiation time: 1.5 hours. Conversion= 2.0 %. Irradiation wavelength: 313nm. 265 Quantum Yield Measurement for a-(Bromoethoxy)acetophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 53. Products Quantum Yield of a-(Bromoethoxy)acetophenone in Benzene Sample # Ph°tfggdu°t Area (PP) Area (IS) [PP] <1) 1 55 2039 56603 0.0003341 0.10 2 55 1661 52909 0.0002911 0.09 3 55 1719 54163 0.0002944 0.09 4 55 1665 59203 0.0002609 0.08 Average 55 1771 55720 0.0002951 0.09 Sample # Ph°tfggdu°t Area (PP) Area (IS) [PP] <1) 1 57 8200 56603 0.001567 0.48 2 57 8016 52909 0.001640 0.50 3 57 7825 54163 0.001564 0.48 4 57 8745 59203 0.001598 0.49 Average 57 8197 55720 0.001592 0.49 ACT: VP, [VP]: 0.1112 M; ISAC]: C20, [ISACT]= 0.005065 M; [ketone]: 0.1118 M, ISKET= C20, [ISKET]= 0.004068 M. Irradiation time 2.5 hours. Conversion= 1.7 %. Irradiation wavelength: 313 nm. 266 Quantum Yield Measurement for a-(Iodoethoxy)acetophenone in Benzene with Pyridine HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 92:8 Flow rate: 1.0 mUInin Loop: 20 [IL Detection wave length: 270nm Table 54. Product Quantum Yield of a-(Iodoethoxy)acetophenone in Benzene with Pyridine Sample # Phaggdua Area (PP) Area (IS) [PP] <1) 1 58 2016267 6677598 0.001379 0.69 2 58 2037322 6575789 0.001415 0.71 3 58 2077216 6666886 0.001423 0.71 4 58 2141342 6701123 0.001459 0.73 Average 58 2068409 6655349 0.001419 0.71 ACT = VP, [VP]: 0.1003 M, ISAC]: MB, [ISAcr]= 0.02159 M, Rf (AP): 0.270; [ketone]: 0.09888 M, 181031: MB, [18mm]: 0.02468 M, Rf (PP): 0.185; [Py]= 0.09924 M. Irradiation time: 1.5 hours. Conversion= 1.4 %. Irradiation wavelength: 313nm. 267 Quantum Yield Measurement for a-(Iodoethoxy)acetophenone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 55. Product Quantum Yield of a-(Iodoethoxy)acetophenone in Benzene Photoproduct Sample # (PP) Area (PP) Area (IS) [PP] <1) 1 57 8116 59848 0.001888 0.30 2 57 6943 56753 0.001703 0.27 3 57 6750 56131 0.001674 0.26 4 57 8959 59235 0.002106 0.33 Average 57 7692 57992 0.001843 0.29 ACT: VP, [VP]: 0.1083 M; ISACF= C20, [18.1”]: 0.005050 M; [ketone]: 0.09956 M, ISKET= C20, [18m]: 0.005234 M. Irradiation time 2 hours. Conversion= 1.9 %. Irradiation wavelength: 313 nm. 268 Quantum Yield Measurement for B-(Chloroethoxy)propiophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 92:8 Flow rate: 1.0 mIJmin Loop: 20 [IL Detection wave length: 270nm Table 56. Product Quantum Yield of B-(Chloroethoxy)propiophenone in Benzene Sample # thfil’g’dum Area (PP) Area (IS) [PP] <1) 1 62 8583762 6173298 0.005688 0.30 2 62 8148468 6506156 0.005123 0.27 3 62 8913927 8026826 0.004542 0.24 4 62 9423810 7709031 0.005000 0.26 Average 62 8767492 7103828 0.005088 0.27 ACT = VP, [VP]: 0.09990 M, ISACT= MB, [ISAcr]= 0.02003 M, Rf (AP): 0.270; [ketone]: 0.1006 M, ISKET= MB, [ISM]: 0.02035 M, Rf (PP): 0.201; [Py]= 0.09808 M. Irradiation time: 18 hours. Conversion=5.1 %. Irradiation wavelength: 313nm. 269 Quantum Yield Measurement for [3-(Bromoethoxy)propiophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mUmin Loop: 20 [IL Detection wave length: 270nm Table 57. Product Quantum Yield of B-(Bromoethoxy)propiophenone in Benzene Photoproduct Sample # (PP) Area (PP) Area (IS) [PP] <1) 1 62 3668457 7741138 0.002351 0.26 2 62 3549309 8071273 0.002181 0.25 3 62 424301 1 8842783 0.002380 0.27 4 62 3645366 7640597 0.002367 0.27 Average 62 3776536 8073948 0.002366 0.26 ACT = VP, [VP]: 0.1003 M, ISACT= MB, [IS/Icy]: 0.02159 M, Rf (AP): 0.270; [ketone]= 0.09888 M, ISKET= MB, [ISKE-r]: 0.02468 M, Rf (PP): 0.201; [Py]= 0.09924 M. Irradiation time: 5 hours. Conversion= 2.4%. Irradiation wavelength: 313nm. 270 Quantum Yield Measurement for B-(Iodoethoxy)propiophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mIJmin Loop: 20 [IL Detection wave length: 270nm Table 58. Product Quantum Yield of B-(Iodoethoxy)propiophenone in Benzene Sample # thE’Ifi’gdw Area (PP) Area (IS) [PP] <1) 1 62 6756031 6355221 0.003972 0.30 2 62 6024549 6610510 0.003405 0.26 3 62 4786325 6308394 0.002959 0.22 4 62 5578600 6781218 0.003074 0.23 5 62 5763102 6151670 0.003501 0.27 Average 62 5781721 6441403 0.003488 0.26 ACT = VP, [VP]: 0.09059 M, ISAC]: MB, [ISACT]= 0.01909 M, Rf (AP): 0.270; [ketone]: 0.08896 M, ISKET= MB, [18mm]: 0.01859 M, Rf (PP): 0.201; [Py]= 0.1002 M. Irradiation time: 8 hours. Conversion=3.9 %. Irradiation wavelength: 313nm. 271 Quantum Yield Measurement for a-Cyclopropylrnethoxyacetophenone in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 ml/min Loop: 20 [IL Detection wave length: 270nm Table 59. Products Quantum Yield of a-Cyclopropylmethoxyacetophenone in Benzene Photoproduct Sample # (PP) Area (PP) Area (IS) [PP] (D l 55 1692273 6527340 0.001575 0.27 2 55 1819823 6503191 0.001700 0.29 3 55 1964772 6820565 0.001750 0.30 4 55 1627440 6179187 0.001600 0.27 Average 55 1773916 6507571 0.001656 0.28 Sample # Photaplquuct Area (PP) Area (IS) [PP] (D l cis-63 1889955 6527340 0.001954 0.33 2 cis-63 1886644 6503191 0.001958 0.33 3 cis-63 1867755 6820565 0.001848 0.31 4 cis-63 187481 1 6179187 0.002048 0.35 Average cis-63 1881893 6507571 0.001952 0.33 Sample # Ph°ta§gdu°t Area (PP) Area (IS) [PP] <1) 1 trans-63 579996 6527340 0.0005998 0.10 2 trans-63 558407 6503191 0.0005796 0.10 3 trans-63 590623 6820565 0.0005845 0.10 4 trans-63 553421 6179187 0.0006045 0.10 Average trans-63 570834 6507571 0.0005921 0.10 ACT = VP, [VP]: 0.1050 M, ISACT= MB, [ISAcr]= 0.02074 M; [ketone]: 0.09630 M, ISKE1~= MB, [18mm]: 0.02250 M. Irradiation time: 4.5 hours. Conversion= 4.4 %. Irradiation wavelength: 313nm. 272 Quantum Yield Measurement for a-Cyclopropylmethoxyacetophenone in Methanol HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mIJmin Loop: 20 [IL Detection wave length: 270nm Table 60. Products Quantum Yield of a—Cyclopropylmethoxyacetophenone in Methanol Sample # Ph°ta§1§°°u°t Area (PP) Area (IS) [PP] <1) 1 55 1299578 6018519 0.001217 0.15 2 55 1440367 6221134 0.001305 0.16 3 55 1335558 6199573 0.001214 0.15 4 55 1246666 6058796 0.001160 0.14 Average 55 1329714 6124506 0.001224 0.15 Sample # Ph°t°§1§°°w Area (PP) Area (IS) [PP] <1) 1 cis-63 1705567 6018519 0.001775 0.22 2 cis-63 1821082 6221134 0.001834 0.22 3 cis-63 1765544 6199573 0.001784 0.22 4 cis-63 1728459 6058796 0.001787 0.22 Average cis-63 1755222 6124506 0.001795 0.22 Sample # thggdw Area (PP) Area (IS) [PP] <1) 1 trans-63 708966 6018519 0.0007379 0.09 2 trans-63 725663 6221134 0.0007307 0.09 3 trans-63 719996 6199573 0.0007275 0.09 4 trans-63 717209 6058796 0.0007415 0.09 Average trans-63 718046 6124506 0.0007344 0.09 Sample # thgg‘lua Area (PP) Area (IS) [PP] <1) 1 64 678886 6018519 0.0006595 0.08 2 64 692001 6221 134 0.0006503 0.08 3 64 680024 6199573 0.0006413 0.08 4 64 684081 6058796 0.0006601 0.08 Average 64 683853 6124506 0.0006528 0.08 273 ACT = VP, [VP]: 0.1005 M, ISM: MB, [ISAcr]= 0.02046 M; [ketone]: 0.1027 M, ISKE1~= MB, [181(51): 0.02088 M. Irradiation time: 4 hours. Conversion= 4.3 %. Irradiation wavelength: 313nm. 274 Quantum Yield Measurement for a-Cyclopropylmethoxyacetone in Benzene 'HNMR analysis: Varian Unity+_500 Relaxation time (d1): 10 see Table 61. Products Quantum Yield of a-Cyclopropylmethoxyacetone in Benzene Sample # thggdua Area (PP) Area (IS) [PP] <1) 1 Acetone 302.97 100.00 0.06550 0.19 2 Acetone 422.62 100.00 0.09137 0.27 3 Acetone 378.02 100.00 0.08173 0.24 4 Acetone 413.18 100.00 0.08933 0.26 5 Acetone 368.86 100.00 0.07975 0.24 Average Acetone 377.13 100.00 0.08555 0.25 Sample # Photapgduct Area (PP) Area (IS) [PP] (D 1 cis-65 48.85 100.00 0.01056 0.031 2 cis-65 58.40 100.00 0.01263 0.037 3 cis-65 51.25 100.00 0.01108 0.033 4 cis-65 59.26 100.00 0.01281 0.038 5 cis-65 51.21 100.00 0.01107 0.033 Average cis-65 53.79 100.00 0.01 163 0.034 ACT: VP, [VP]: 0.1057 M; ISAC1= MB, [ISAcr]= 0.02051 M; [ketone]: 0.624 M, ISKET= MB, [Ism]: 0.02162 M. Irradiation time 353.3 hours. Conversion= 15.2 %. Irradiation wavelength: 313 nm. 275 Quantum Yield Measurement for B-Cyclopropylmethoxybutanone in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 70°C Hold time: 3min. Final temperature: 220°C Rate: 7°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 62. Products Quantum Yield of B-Cyclopropylmethoxybutanone in Benzene Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 cis-68 1 l 159 36457 0.002193 0.042 2 cis-68 8390 30202 0.001984 0.038 3 cis-68 7410 26547 0.002000 0.038 4 cis-68 9048 30063 0.002157 0.041 5 cis-68 7980 26002 0.002200 0.042 6 cis-68 8274 28450 0.002084 0.040 Average cis-68 8710 29620 0.002103 0.040 Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (I) 1 trans-68 3958 36457 0.0007833 0.015 2 trans-68 3108 30202 0.0007400 0.014 3 trans-68 2574 26547 0.0006995 0.013 4 trans-68 2580 30063 0.0006192 0.012 5 trans-68 2630 26002 0.0007297 0.014 6 trans-68 2951 28450 0.0007483 0.014 Average trans-68 2967 29620 0.0007200 0.014 Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 67 14787 36457 0.001682 0.032 2 67 1 1690 30202 0.001660 0.031 3 67 1 1522 26547 0.001800 0.034 4 67 l 1 167 30063 0.001541 0.029 5 67 12227 26002 0.001950 0.037 6 67 10599 28450 0.001545 0.029 Average 67 1 1999 29620 0.001697 0.032 ACT: VP, [VP]: 0.1004 M; ISAC]: C20, [ISACT]= 0.002780 M; [ketone]: 0.145 M, ISKET= C20, [18mm]: 0.002454 M. Irradiation time 156 hours. Conversion= 3.1 %. Irradiation wavelength: 313 nm. 276 Quantum Yield Measurement for B-Cyclopropylmethoxybutanone in Methanol Table 63. Products Quantum Yield of fl-Cyclopropylmethoxybutanone in Methanol GC analysis: Varian 3400 Column: DB-210 Initial temperature: 70°C Hold time: 3min. Final temperature: 220°C Rate: 7°C/min. Injector temperature: 200°C Detector temperature: 220°C Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (I) 1 cis-68 18704 33583 0.004416 0.037 2 cis-68 16752 34512 0.003 849 0.032 3 cis-68 16902 32057 0.004181 0.035 4 cis-68 16885 29678 0.00451 1 0.038 5 cis-68 18865 341 19 0.004384 0.037 Average cis-68 17622 32790 0.004268 0.036 Sample # Photoproduct (PP) Area (PP) Area (IS) [PP] (D 1 trans-68 15833 33583 0.003767 0.032 2 trans-68 16542 345 12 0.003830 0.032 3 trans-68 15530 32057 0.003871 0.033 4 trans-68 13912 29678 0.003746 0.032 5 trans-68 16037 341 19 0.003756 0.032 Average trans-68 15568 32790 0.003794 0.032 ACT: VP, [VP]: 0.1087 M; ISAcr: C20, [18mm]: 0.005333 M; [ketone]: 0.2035 M, ISKET= MB, [ISKET]= 0.006147 M. Irradiation time 64 hours. Conversion= 4.0 %. Irradiation wavelength: 313 nm. 277 Quenching of the Product Formation in 2-Methoxy-3-methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/rnin. Injector temperature: 200°C Detector temperature: 220°C Table 64. Quenching of the Product Formation in 2-Methoxy-3- methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene [Q] A(PP)/A(IS) 0.00 0.766 1.00 0.00098 0.722 1.06 0.0020 0.676 1.13 0.0029 0.671 1.19 0.010 0.462 1.66 [ketone]: 0.01011 M, ISKET= OB, [18m]: 0.01049 M, Rf (cis-31): 0.254, Rf (trans-31): 0.266; Q: 2,5-dimethyl-2,4-hexadiene. Irradiation time: 7 hours. Irradiation wavelength: 313 nm. qu : 65.7 M" 283 Quenching of the Products Formation in 2-Benzyloxy-3-methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mL/min Loop: 20 [IL Detection wave length: 270nm Table 70. Quenching of the Products Formation in 2-Benzyloxy-3- methylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene IQ] A(PP)/A(IS) (D°/(D 0.00 0.226 1.00 0.0057 0.203 1.12 0.0114 0.184 1.23 0.0171 0.171 1.33 [ketone]: 0.01025 M, ISK5T= OB, [ISKET]= 0.0111 M, Rr(cis-32)= 0.287, Rf (trans-32): 0.287; Q: 2,5—dimethyl-2,4-hexadiene. Irradiation time: 3 hours. Irradiation wavelength: 313 nm. qu= 19.1 M" 284 Quenching of the Products Formation in 2-Benzyloxy-3-isopropylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene Table 71. Quenching of the Products Formation HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mIJmin Loop: 20 uL Detection wave length: 270nm in 2-Benzyloxy-3— isopropylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene [Q] Amp/~15) 0.00 0.278 1.00 0.0020 0.248 1.12 0.0040 0.224 1.24 0.0060 0.204 1.36 0.010 0.174 1.60 [ketone]: 0.01015 M, 18m: OB, [ISKET]= 0.01022 M, Rf (cis-33): 0.269, Rf (trans- 33)= 0.265; Q= 2,5-dimethyl-2,4-hexadiene. Irradiation time: 3 hours. Irradiation wavelength: 313 nm. W = 60 M" 285 Quenching of the Products Formation in 2—Benzyloxy-3-t-butylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 30:1 Flow rate: 1.0 mIJmin Loop: 20 1.1L Detection wave length: 270nm Table 72. Quenching of the Products Formation in 2-Benzyloxy-3-t- butylbenzophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene [Q1 Amp/Am) 0.00 0.199 1.00 0.0057 0.187 1.06 0.011 0.176 1.13 0.017 0.168 1.19 [ketone]: 0.01095 M, 18m: OB, [13m]: 0.01046 M, Rf (cis-34): 0.265, Rf (trans- 34)= 0.269; Q: 2,5-dimethyl-2,4-hexadiene. Irradiation time: 2 hours. Irradiation wavelength: 313 nm. qu=11M‘l 286 Quenching of the Products Formation in 2-Ethoxy-3-methylacetophenone with 2,5- Dimethyl-2,4-hexadiene at 313 nm in Benzene HPLC analysis: Rainin with Dynamax Column: Dynamax normal phase Solvent system: Hexanes: Ethyl Acetate Solvent ratio: 95:5 Flow rate: 1.0 mIJmin Loop: 20 uL Detection wave length: 270nm Table 73. Quenching of the Products Formation in 2-Ethoxy-3-methy[acetophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene [Q1 Amp/A05) ¢°I°/(D 0.00 0.063 1.00 0.0059 0.024 2.63 0.012 0.015 4.27 0.024 0.0077 8.19 [ketone]: 0.01 M, ISKET= MB, [15m]: 0.01 M, Rf (cis-39): 0.339; Q: 2,5-dimethyl- 2,4-hexadiene. Irradiation time: 21 hours. Irradiation wavelength: 313 mm. m = 304.7 M" 289 Quenching of the Products Formation in a-(Chloroethoxy)acetophenone with 2,5- Dimethyl-2,4-hexadiene at 313 nm in Benzene GC analysis: Varian 3400 Column: DB-210 Initial temperature: 80°C Hold time: 1min. Final temperature: 220°C Rate: 8°C/min. Injector temperature: 200°C Detector temperature: 220°C Table 76. Quenching of the Products Formation in a-(Chloroethoxy)acetophenone with 2,5-Dimethyl-2,4-hexadiene at 313 nm in Benzene Adm/Am) <1>°l°l