mm:

‘f

. éafififia
,
.

rug:

.. . . I
.Juirfit VJ...
wi...s:...lx h n.
Fer-"rd. ...b.

Bx“:

In. 3....

1

I
..r

6.4..
3‘.‘

.... ...: a
.....wfifi...

8 n.

.4 a: .30
21331.1
. :c

... In
:umursxa.
:.
‘71.

B5213 I.

. ...... 4
1.59.0.

 

v... .....r

33.1..

.,

. ;

flu... .22!
1.7.2.3.

.I 1")-

! .
'3‘:

x

.l.
17“} .... .
11):}??? .
. Alixiy» ‘

'3

5.1,"??? :
..o‘lzixi...

: 9 4 I, “3.0.5... r.
i ... . ,
73.2.3:

I t.
. 1 ..
5.1;"...
. ...
.n >
a? a.
\I hush...“ .5
pristirv av 11..
...! x

91
‘ .‘Ls\¢ I . u
353‘}: |
. \K. .~ 9.

fits:
NP"

 

 

J
EU

T”il@/lllllllil

l TYuanAmEs u
l l I
3'ISK30104

ll

 

 

 

 

 

 

! .‘l'li'l ill/ll

3499

 

 

 

This is to certify that the

dissertation entitled

Stereoselectivity in the Intramolecular
Cycloaddition of Double Bonds
to Triplet Benzenes

presented by

Kung-Lung Cheng

has been accepted towards fulfillment
of the requirements for

Ph-D- degree in Organic Photochemistry

 

 

Wajor professor

 

Date NUD' (PA/yyv

MS U i: an Affirmative Action/Equal Opportunity Institution 0- 12771

 

 

 

 

LIBRARY
Michigan State
University

 

 

 

PLACE N RETURN BOXto romovothio ohockout‘lorn your rooord.
TO AVOID FINES return on or odor. m duo.

DATE DUE DATE DUE DATE DUE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MSU ioAn Afflnnotivo Action/Emu! Opportunity Institution
WI

 

STEREOSELECTIVITY IN THE INTRAMOLECULAR CYCLOADDITION
OF DOUBLE BONDS TO TRIPLET BENZENES

By

Kung-Lung Cheng

A DISSERTATION

submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY

Department of Chemistry

1994

ABSTRACT

STEREOSELECTIVITY IN THE INTRAMOLECULAR CYCLOADDITION
OF DOUBLE BONDS TO TRIPLET BENZENES

BY

Kung-Lung Cheng

The diastereoselectivty with which 0- and p-butenoxy acetophenones
undergo intramoiecular triplet [2 + 2] photocycloadditions has been measured.
Alkyl groups originally on the tether or the double bond show high selectivity with
regard to the configuration of the bridgehead stereocenters. The five- and four-
membered rings of the tricyclo[7.2.0.O5-9]undecadiene photoproducts are always
anti to each other and all-cis with respect to the six-membered ring. This fact
indicates that the photoinduced electrocyclization to a cyclobutene of one diene
unit of the bicyclo[6.3.0]undecatriene intermediate puckers in only one of two

possible ways.

The intermediacy of a 1,4-biradicai in this photocycloaddition was
confirmed by the means of a “Free Radical Clock“: the cyclopropylcarbinyl
radicals to aliylcarbinyl radicals rearrangement. Product analyses showed that
the biradicai cyclizes slowly but cleaves very rapidly, and undergoes a rare

tandem biradical cyclization process. Both the large cleavage/coupling rate ratio

and assistance by rearomatization may explain the modest quantum yields (<1) =

0.07 - 0.25) normally observed in this cyclization reaction.

The processes of photoreversion of cyclohexadienes and secondary
photoelectrocyclizations for cyclobutenes have also been examined. Efficient
photoreversion (<I> = 0.70 - 0.78) of the thermally stable cyclohexadiene to phenyl
ketone was observed. Low quantum efficiency of the cyclobutene formation (<b =
0.05 - 0.21) in secondary photoelectrocyclizations is probably due to an intensely

efficient cis and trans photoisomerization of cyclooctatrienes.

ACKNOWLEDGMENTS

I wish to thank Professor Peter J. Wagner for his guidance and
encouragement throughout the course of this research. i would like to thank the
Chemistry Department at MSU for financial support and use of its facilities and
the National Science Foundation and the National Institute of Health for the
research assistantships administrated by Professor Wagner. I would also like to
thank my friends in the Wagner group who made my stay at MSU an enjoyable
one.

i would like to thank Dr. Kevin McMahon for critically reading the
manuscript.

Most of all, I thank my wife, Wenchen, for her love, support, and
encouragement. i am also grateful to my parents, parents-in-law, and family for

their continuous support.

Table of Contents

INTRODUCTION ................................................................................................ 1
i. Preliminary Studies .............................................................................. 1
ll. Historical Perspective .......................................................................... 5
III. Mechanistic Considerations ............................................................... 21
iv. Quantum yields and kinetics .............................................................. 25
V. Research goals ................................................................................... 27

RESULTS ........................................................................................................... 28
l. Alkenoxyphenyl Ketones ...................................................................... 28
ll. Photocycioadditions and Identification of Photoproducts .................... 35

a. General ..................................................................................... 35
b. p-MOK ....................................................................................... 38
c. p-M1K ....................................................................................... 38
d. p-i1K ......................................................................................... 43
e. p-M1M3K .................................................................................. 45
f. p-l1M3K ..................................................................................... 47
g. p-M2M3K .................................................................................. 51
h. p-M3M4K .................................................................................. 53
i. p-M1M3M4K ............................................................................... 55
j. p-M4K ........................................................................................ 57
k. p-M3M4M5K .............................................................................. 58
l. p-M1M3M4M5K ........................................................................... 59
m. p-M4M5K ................................................................................. 61
n. o-I1K ......................................................................................... 62
o. o-i1M3K .................................................................................... 63
p. p-C4K ....................................................................................... 65
q. p-I4K ......................................................................................... 69

Ill. Diastereoselectivity and Chemical Yields of Photoproducts .............. 70

iV. Quantum Yields and Kinetic Results .................................................. 74
V. Conformation Analysis ........................................................................ 79
DISCUSSION ..................................................................................................... 1 08
l. Diastereoselectivity .............................................................................. 108
ll. Biradical Intermediacy ......................................................................... 122
Ill. Overall Mechanism ............................................................................. 131
IV. Conclusion ......................................................................................... 135
V. Suggestions of Further Research ....................................................... 136
EXPERIMENTAL ............................................................................................... 138
I. General Procedures ............................................................................. 138
ll. Purification of Chemicals ..................................................................... 139
A. Solvents ................................................................................... 139
B. Internal Standards .................................................................... 139
C. Column Chromatography ......................................................... 140
Ill. Equipment and Procedures ................................................................ 141
A. Photochemical Glassware ........................................................ 141
8. Sample Preparations ............................................................... 141
C. Degassing Procedures ............................................................ 141
D. Irradiation Procedures .............................................................. 142
E. Calculation of Quantum Yields ................................................. 143
N. Preparation of Starting Ketones ......................................................... 145
V. identification of Photoproducts ............................................................ 180
APPENDIX ......................................................................................................... 234
BIBLIOGRAPHY ................................................................................................ 258

List of Schemes

Scheme 1 Triplet intramoiecular [2+2] On‘ho Cycloaddition .............................. 1
Scheme 2 Mechanism of Triplet intramoiecular [2+2] Ortho Cycloaddition ....... 2
Scheme 3 Donor-Acceptor Conjugation ............................................................ 3

Scheme 4 Regioselectivity of Triplet Intramolecular [2+2] Ortho
Cycloaddition .................................................................................... 3

Scheme 5 Modes of Addition in Photocycioaddition of Benzene with an

alkene ............................................................................................... 6
Scheme 6 Synthesis of (i)-Cedrene .................................................................. 14
Scheme 7 Synthesis of (i)-Silphinene ............................................................... 14
Scheme 8 Synthesis of (i)-Subergorgic acid ..................................................... 15
Scheme 9 Synthesis of (-)-Retigeranic acid ....................................................... 15
Scheme 10 Synthesis of Grayanotoxin ll ........................................................... 16
Scheme 11 Synthesis of p-M1K ......................................................................... 30
Scheme 12 Synthesis of p-I1K, p-M1M3K, p-I1M3K, o-I1K and 041M3K ........... 30
Scheme 13 Synthesis of p-M2M3K .................................................................... 31
Scheme 14 Synthesis of p-M3M4K and p-M1M3M4K ......................................... 32
Scheme 15 Synthesis of 4-Hydroxy-3-methylacetophenone ............................. 32
Scheme 16 Synthesis of p-C4K and p-I4K ......................................................... 33
Scheme 17 Synthesis of 4'-(3-Butyn-1-oxy)acetophenone Derivatives ............. 34

Scheme 18 Observations of Triplet Intramolecular [2+2] Ortho

Cycloaddition ................................................................................. 37
Scheme 19 Chair-like and Boat-like Transition States ...................................... 110
Scheme 20 Transition State TS-1 and Biradical BR-1 ....................................... 110
Scheme 21 Transition States TS-1, TS-2, TS-3 and T84 ................................ .111

Scheme 22 Transition State of Substituted Hex-5-enyl radicals in

intramoiecular Free-Radical Cyclization ........................................ 113

vii

Scheme 23 Biradicals BR-1 and BR—2 ............................................................... 115

Scheme 24 Conformation Preference of Biradicals BR-1 and BR-2 ................. 115
Scheme 25 Biradicals 811-3 and BR-4 ............................................................... 116
Scheme 26 Stereoselectivity of Ring Opening and Photociosure ...................... 117

Scheme 27 Valence Tautomerism between Bicyclo[4.2.0]octa-2,4-diene

and Cycloocta-1,3,5-triene ............................................................. 118
Scheme 28 Zwitterionic Intermediate with Donor-Acceptor Property ................. 119
Scheme 29 Synthesis of Isocomene .................................................................. 120
Scheme 30 Stereoselectivity of Subergorgic Acid ............................................. 120
Scheme 31 Stereoselectivity of Grayanotoxin ll ................................................ 121
Scheme 32 Mechanism of [2+2] Photocycioaddition of Dienone ....................... 123
Scheme 33 Photochemistry of p-C4K ................................................................ 123
Scheme 34 Photochemical Reactions of Benzene with Furans ........................ 124
Scheme 35 Mechanism of Photochemical Reaction of p—C4K ........................... 126
Scheme 36 Biradical Tandem Cyclization ......................................................... 127
Scheme 37 Photochemistry of y-cyclopropylbutyrophenone .............................. 128
Scheme 38 Photochemistry of B-cyclopropylstyrene ......................................... 128
Scheme 39 Biradical Tandem Cyclization of Crinipellin A ................................ .129
Scheme 40 Mechanism of Photochemical Reaction of p-M3M 4K ...................... 133
Scheme 41 Photoisomerization of Cycloocta-1,3-diene .................................... 134

viii

List of Tables
Table 1 Intramolecular Cycloadditions of Arenes to Aikenes ............................. 13
Table 2 Alkenoxyphenyl Ketones ....................................................................... 28
Table 3 Diastereomeric Excess and Chemical Yields of Various 1-Acetyl-
8-oxatricyclo-[7.2.0.05v9]undeca-2,1O-dienes ....................................... 70
Table 4 Diastereomeric Excess of Various 9-AcetyI-4-oxatricyclo-
[7.2.0.03v7]undeca-2,10-dienes ............................................................ 71
Table 5 Diastereomeric Excess of Various 4- or 6-AcetyI-11-
oxabicyclo[6.3.0]undeca-1 ,3,5-triene ................................................... 72

Table 6 Diastereomeric Excess of Various 4-Acetyl-11-

oxatricyclo[6.3.0.01v6] undeca-2,4-diene ............................................. 73
Table 7 Quantum Yields of Various Cyclooctatrienes or Cyclohexadienes ....... 74
Table 8 Quantum Yields of Various Cyclobutenes ............................................. 75
Table 9 Quantum Yields and Kinetic Data of Starting Ketones .......................... 76
Table 10 Coupling Constants of Polycyclic Ketone ............................................ 80
Table 11 Coupling Constants of p-I4CB ............................................................. 82
Table 12 Coupling Constants of p-M1CB ........................................................... 83
Table 13 Coupling Constants of p-M1M3CB ...................................................... 84
Table 14 Coupling Constants of p-I1M3CB ........................................................ 85
Table 15 Coupling Constants of p-M 2M3CB ...................................................... 87
Table 16 Coupling Constants of p-M 3M4CB ...................................................... 88
Table 17 Coupling Constants of p-M1M3M4CB .................................................. 89
Table 18 Coupling Constants of p-M 4GB ........................................................... 90
Table 19 Coupling Constants of p-M 3M4MscB .................................................. 91
Table 20 Coupling Constants of p—M1M3M4M5CB ............................................. 92
Table 21 Coupling Constants of p-M4MscB ...................................................... 94
Table 22 Coupling Constants of o-l1CB ............................................................. 95

Table 23 Coupling Constants of o-I1M3CB ........................................................ 96

Table 24 Coupling Constants of p-M 2M3CH ...................................................... 97

Table 25 Coupling Constants of p-M3M4CH ...................................................... 98

Table 26 Coupling Constants of p-M1M3M4CH .................................................. 99

Table 27 Coupling Constants of p-MOCOT ........................................................ 100
Table 28 Coupling Constants of p-M1COT ........................................................ 101
Table 29 Coupling Constants of p-M1M3COT .................................................... 102
Table 30 Coupling Constants of p-I1M3COT ...................................................... 103
Table 31 Coupling Constants of o—I1COT .......................................................... 105
Table 32 Coupling Constants of o-I1M3COT ...................................................... 106
Table 33 Cis Olefinic Coupling Constants in Cyclic Systems ............................ 107
Table 34 Rate Constants for Cyclizations of Substituted ................................... 132

Table 35 Nuclear Overhauser Effect (nOe) on the Major Product of

Various 1 -AcetyI-8-oxatricyclo-[7.2.0.05:9lundeca-2, 10-dienes

(CB) ..................................................................................................... 227
Table 36 Nuclear Overhauser Effect (nOe) on the Major Product of

Various 4- or 6-Acetyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-trienes

(COT) ................................................................................................... 228
Table 37 Nuclear Overhauser Effect (nOe) on the Major Product of

Various 4-AcetyI-1 1-oxatricyclo[6.3.0.01-6] undeca-2,4-dienes

(CH) ..................................................................................................... 229
Table 38 G0 Response Factors of Various Acetophenones (K) and
Cyclooctatrienes (COT) ....................................................................... 230

Table 39 HPLC Response Factors of Acetophenones (K) and
Cyclohexadienes (CH) ........................................................................ 231
Table 40 Quantum Yield Determination of 1-Acetyl-8-oxatricyclo-

[7.2.0.05-9jundeca-2,10-diene at 313 nm in Methanol ......................... 235

Table 41 Quantum Yield Determination of 4-Acetyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol .............. 236
Table 42 Quantum Yield Determination of 1-Acetyl-7-methyl-8-oxatricycio-
[7.2.0.05v9jundeca-2,10-diene at 313 nm in Methanol ......................... 237
Table 43 Quantum Yield Determination of 4-AcetyI-10-methyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol .............. 238
Table 44 Quantum Yield Determination of 1-Acetyl-7-isopropyI-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene at 313 nm in Methanol
(1) ........................................................................................................ 239
Table 45 Quantum Yield Determination of 1-Acetyl-7-isopropyl-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene at 313 nm in Methanol
(2) ........................................................................................................ 240
Table 46 Quantum Yield Determination of 4-AcetyI-10-isopropyI-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol .............. 241
Table 47 Quantum Yield Determination of 1-Acetyl-7-isopropyl-5-methyl-8-
oxatricyclo[7.2.0.05.9]undeca-2,10-diene at 313 nm in Methanol ........ 242
Table 48 Quantum Yield Determination of 1-Acetyl-7-isopropyl-5-methyl-8-
oxatricyclo[7.2.0.05v9]undeca-2,10-diene at 366 nm in Methanol ........ 243
Table 49 Quantum Yield Determination of 4-Acetyl-10-isopropyl-8-methyl-
11-oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol ......... 244
Table 50 Quantum Yield Determination of 9-AcetyI-5-isopropyl-4-
oxatricyclo[7.2.0.03v7lundeca-2,10—diene at 313 nm in Methanol ........ 245
Table 51 Quantum Yield Determination of 6-Acetyl-10-isopropyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol .............. 246
Table 52 Quantum Yield Determination of 9-Acetyl-5-isopropyl-7-methyl-4-
oxatricyclo-[7.2.0.03-7]undeca-2,10-diene at 313 nm in Methanol ....... 247

Table 53 Quantum Yield Determination of 6-AcetyI-10-isopropyl-8-methyl-

11-oxabicycio[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol ......... 248
Table 54 Quantum Yield Determination of Polycyclic Ketone and 1,2-

Adduct from 4'-(4-Cyciopropyl-3—buten-1-oxy)acetophenone at

313 nm in Methanol (1) ........................................................................ 249
Table 55 Quantum Yield Determination of Polycyclic Ketone and 1,2-

Adduct from 4'-(4-Cyciopropyl-3-buten-1-oxy)acetophenone at

313 nm in Methanol (2) ........................................................................ 250
Table 56 Quantum Yield Determination of Polycyclic Ketone and 1,2-

Adduct from 4'-(4-Cyclopropyl-3-buten-1-oxy)acetophenone at

313 nm in Methanol (3) ........................................................................ 251
Table 57 Quantum Yield Determination of 4-Acetyl-7,8-dimethyl-11-

oxatn'cyclo[6.3.0.0l-Gjundeca-2,4-diene at 313 nm in Methanol .......... 252
Table 58 Quantum Yield Determination of 4'-(3,4-Dimethyl-3-buten-1 -

oxy)acetophenone at 313 nm in Methanol and Quenching Study

by 2,5-Dimethyl-2.4-hexadiene ............................................................ 253
Table 59 Quantum Yield Determination of 4'-(3,4-Dimethyl-3-buten-1-

oxy)acetophenone at 313 nm in Methanol and Quenching Study

by Sorbic Acid ..................................................................................... 254
Table 60 Quantum Yield Determination of 4-Acetyl-7-isopropyl-11-

oxabicycio[6.3.0.01v6]undeca-2,4-diene at 313 nm in Methanol .......... 255
Table 61 Chemical Yield Determination of 4-AcetyI-10-isopropyl-11-

oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol .............. 256
Table 62 Chemical Yield Determination of Polycyclic Ketone and 1,2-

Adduct from 4'—(4—Cyclopropyl-3-buten-1-oxy)acetophenone at

313 nm in Methanol ............................................................................. 257

xii

List of Figures

Figure 1. Frontier molecular orbitals (FMO) and excited states of benzene

(mirror plane) .................................................................................... 23
Figure 2. Orbital energies of triplet electron-deficient benzene with

electron ............................................................................................. 24
Figure 3. 1H-NMR spectrum of 4-acetyl-10-methyl-11-

oxabicycio[6.3.0]undeca-1,3,5-triene (p-M1COT) in 00013 .............. 41
Figure 4. 1H-NMR spectrum of 1-acety|-7-methyl-8-oxatricyclo-

[7.2.0.05»9]undec-2,10-dienes (p-M1CB) in CD300, obtained by

irradiation of p-M1COT ..................................................................... 42
Figure 5. 2D COSY spectrum of the equilibrium of 4-acetyl-10-isopropyl-8-

methyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-triene (p-I1M300T)

and 4-acetyl-10-isopropyl-8-methyl-1 1-

oxatricyclo[6.3.0.01-6]undeca-2,4-diene (p-I1M3CH) in CDCI3 .......... 49
Figure 6. Time-resolved UV-Visible spectra of 4-acetyl-10-isopropyl-8-

methyl-1 1~oxabicyclo[6.3.0]undeca-1,3,5-triene (p-i1M3COT) at

313 nm irradiation in methanol . ....................................................... 50
Figure 7. Before and after irradiation 1H-NMR spectra of 4'-(2,3-dimethyl—

3-buten-1-oxy)acetophenone (p-MzMaK) and its chemical yield

determination .................................................................................... 52
Figure 8. Before and after irradiation of 1H-NMR spectra of cis+trans 4'-(4-

cyclopropyI-3-buten-1-oxy)acetophenone (p-C4K) in C0300. ........ 67
Figure 9. DEPT spectra of polycyclic ketone in CDCI3. ..................................... 68
Figure 10. Stem-Volmer plots of 4'-(3-methyl-3-penten-1-

oxy)acetophenone (p-M3M4K) with 2,5-dimethyl-2,4-hexadiene

in methanol ....................................................................................... 77

xiii

Figure 1 1.

Figure 12.
Figure 13.
Figure 14.
Figure 15.
Figure 16.
Figure 17.
Figure 18.
Figure 19.
Figure 20.
Figure 21.
Figure 22.
Figure 23.
Figure 24.
Figure 25.
Figure 26.
Figure 27.
Figure 28.
Figure 29.
Figure 30.
Figure 31.
Figure 32.
Figure 33.
Figure 34.
Figure 35.

Stem-Voimer plots of 4'-(3-methyI-3-penten-1-

oxy)acetophenone (p-M3M4K) with sorbic acid in methanol ............ 77
Best geometry of polycyclic ketone ................................................... 80
Best geometry of p-I4CB ................................................................... 81
Best geometry of p-M1CB ................................................................. 83
Best geometry of p-M1MacB ............................................................ 84
Best geometry of p—I1M3CB .............................................................. 85
Best geometry of p-M 2M3CB ............................................................ 87
Best geometry of p-M 3M4CB ............................................................ 88
Best geometry of p-M1M3M4CB ........................................................ 89
Best geometry of p-M 4GB ................................................................. 90
Best geometry of p-M 3M4M5CB ........................................................ 91
Best geometry of p-M1M3M4MSCB ................................................... 92
Best geometry of p-M4M5CB ............................................................ 94
Best geometry of o-I1CB ................................................................... 95
Best geometry of o-I1M3CB .............................................................. 96
Best geometry of p-M2M3Cl-i ............................................................ 97
Best geometry of p-M3M4CH ............................................................ 98
Best geometry of p-M1M3M4CH ........................................................ 99
Best geometry of p-M oCOT .............................................................. 100
Best geometry of p-M1COT .............................................................. 101
Best geometry of p-M1M3COT .......................................................... 102
Best geometry of p-I1M3COT ............................................................ 103
Best geometry of o-I1COT ................................................................ 104
Best geometry of o-I1MacOT ............................................................ 106
1H-NMR spectrum of Cis/trans 3-methyl-1-tosy|-3-pentene in

CDCIg. ............................................................................................... 158

Figure 36.
Figure 37.

Figure 38.

Figure 39.

Figure 40.

Figure 41.

Figure 42.

Figure 43.

Figure 44.

Figure 45.

1H-NMR spectrum of cisxtrans p—M3M4K in CDCI3. ......................... 159
1H-NMR spectrum of Cis/trans 4-cyclopropyl-3-buten-1—ol in

CDCI3. ............................................................................................... 1 72
1H-NMR spectrum of Cis/trans p-I4K in 00013. ............................... 176
NOE experiments of rec-(1S,5R,7S,9R)-1-acetyI-5,7-dimethyl-

8-oxatricyclo-[7.2.0.05-9]undeca-2,10-diene (p-M1M3CB) in

00300 .............................................................................................. 189
NOE experiments of rec-(7R,8R)-4-acetyl-7,8-dimethyl-11-
oxatricyclo—[6.3.0.01.6]undeca-2,4-diene (p-M3M4CH) in 00013. ...... 199
NOE experiments of rac-(1S,4R,5R,7S,9R)-1-acetyl-4,5,7-
trimethyl-8-oxatricyclo-[7.2.0.05:9]undeca-2,10-diene (p-

M1M3M4CB) in 00300. .................................................................... 202
NOE experiments of rac-(1S,4R,5R,9R)-1-acety|-4-methyl-8-
oxatricyclo-[7.2.0.05v9]undeca-2,10-diene (p-M4CB) in 00300. ...... 204
NOE experiments of rec-(1S,4R,5R,7S,9R)-1-acetyl-3,4,5,7-
tetramethyl-8-oxatricyclo-[7.2.0.05:9]undeca-2,10-diene (p-
M1M3M4M5CB) in 00300. ............................................................... 211
NOE experiments of rec-(1S,SS,7R,9R)-9-acetyI-5-isopropyI-7-
methyl-4-oxatricyclo-[7.2.0.03'7]undeca-2,10-diene (041M3CB)

in CDaOD. ......................................................................................... 220
NOE experiments of rac-(8R,1OS)-6-acetyl-10-isopropyl-8-

methyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-triene (o-I1M3COT) in

CDCl3. ............................................................................................... 221

INTRODUCTION

1. Preliminary Studies

Wagner and Nahm reported the first intramoiecular [2+2] ortho
cycloaddition of ortho- and para-alkenoxyphenyl ketones via 1r,1r* lowest triplets.
Addition to the remote double bond yields bicyclo[4.2.0]octadienes that quickly
convert thermally to cyclooctatrienes. The cyclooctatrienes undergo subsequent
photochemical diene-to-cyclobutene interconversion to form linear or angular

bicyclooctadienes different from the initial photoadducts (Scheme 1).‘v2

Scheme 1

 

 

 

O
WON». 3::— O sit—>06
O O

The mechanism of this reaction was proposed to proceed via a triplet state
in contrast to an excited singlet. The 1:, rc“ lowest triplet state of the p-
alkoxyphenyi ketone undergoes intramoiecular charge transfer with the donor
double bond to generate an exciplex, followed by 1,4-biradical formation. This

biradicai may either give cis-trans isomerization or couple to produce the

2

cycloadducts. Facile Cis-trans isomerization of the remote double bond (<I> = 0.27)

strongly implicates a biradicai intermediate (Scheme 2).

Scheme 2

H o 03—» °§7

triplet exciplex

ihv I
. \ - \
«WP--.

l

cycloadduct

The suprafacial [2+2] cycloadduct containing a cyclohexadiene subunit,
undergoes rapid thermal disrotatory opening to give the all cis-cyclooctatriene.
Secondary photolysis of the cyclooctatriene gives a photostable cyclobutene, by
disrotatory closure in accordance with orbital-symmetry rules.3

Cyclobutenes, which are thermally unstable, open easily to
cyclooctatrienes. This ring opening is proposed to occur, not via a concerted
electrocyclic reaction, but by cleavage of the weakened central C-C bond due to

donor-acceptor conjugation (Scheme 3).4

Scheme 3

 

High regioselectivity promoted by ring substituents ortho to the tether has
also been reported.“ This selectivity appears to reflect inductive effects by the
ring substituents on the triplet state cycloaddition. Strong electron-donating
substituents, e.g., OMe and SMe, favor cycloaddition away from the ortho
substituents. In contrast, strong electron-withdrawing substituents, e.g., CN and
CONH2, favor cycloaddition toward the substituents. Ketones containing an ortho
methyl group also favor cycloaddition toward the allql substituent. Exciplex
orientational preferences cannot totally explain the observed regioselectivity

(Scheme 4).

 

   

4

Irradiation of the above acylbenzenes generated either angular or linear
cyclobutenes, except for the methoxy-substituted case. Irradiation to 20 °/o
conversion of the latter gave only methoxy-substituted cyclohexadiene in >80 °/o
yield even after workup. Irradiation of the methoxy-substituted cyclohexadiene
produced mainly starting acylbenzene. The same behavior has been observed
for a derivative in which the anchoring oxygen is replaced with a methylene

group.7 This suggests that back photocleavage of the cyclohexadiene is efficient.

II. Historical Perspective

Photochemistry covers all processes by which chemical change occurs by
the action of visible or ultraviolet radiation. These processes normally involve
direct participation of an electronically excited state. Excited states are produced
by electron movement from the lower to higher energy levels. Excited states have
properties and electron distribution which are very different from ground states,
and therefore exhibit reactions not accessible from the ground states.8

Benzene can be used as an example. With few exceptions, benzene is
structurally rigid in the ground state but becomes extremely flexible and
chemically labile when irradiated with light. Since the discovery of benzene's
photoisomerization to fulvene, its unexpected photolability has aroused
considerable research interest.9 During the last three decades, there has been
great progress made on its versatile transformations, such as isomerization,

addition, substitution and cycloaddition.10'13

041:, ..=

The first reports of photocycloaddition, reactions of double bonds with
aromatic rings, appeared soon after the discovery of benzene
photorearrangements. Angus and Bryce-Smith attempted to trap fulvene by
addition of a dienophile, maleic anhydride.14 Product analysis indicated the
reaction proceeded via initial [2+2] photocycloaddition of maleic anhydride to

benzene, followed by a Diels-Alder cycloaddition.

 

Photocycioaddition between benzene and a double bond has become a
versatile and synthetically useful reaction. There are three modes of addition in
photocycloaddition of benzene with an alkene; 1,2 ( ortho ), 1,3 ( meta ) and to a
lesser extent 1,4 ( para ) to form bicyclo-[4.2.0]octa-2,4-dienes, tricyclo-
[3.3.0.04.6]oct-2-enes and bicyclo-[2.2.2]octa-2,5-dienes, respectively (Scheme
5).

Scheme 5
C] 1,2-addition
+ II ___>hv 1,3—addition
1 ,4-addition

Such a bichromophoric reaction may proceed inter- or intramoiecularly. In
intramoiecular systems, the addition pattern and the efficiency of the reaction is
dependent on chain length and type of tether. Generally, intramoiecular

interactions are more efficient. The stereoselectivity of intramoiecular reactions,

7

as a consequence of geometric restriction, will be discussed in greater detail

later.
lntennolecular

The earliest example of intermolecular ortho photocycloaddition was
discovered by Gilbert et. al.15 Direct irradiation of benzene in the presence of 1,1-
dimethoxyethylene provided 7.7-dimethoxybicyclo-[4.2.0]octa-2,4-diene; acid
treatment gave the cyclooctatrienone. Ortho photocycloadditions were also
observed in irradiation of benzene with maleimide,16 methyl vinyl ketone,17

methyl vinyl sulfide,11 methacrylonitrile, methyl acrylate,18 or 1,4-dioxene.‘5

M90 0M9
+ _h_>v C. kOM: —->
254nm

Irradiation of benzonitrile and 2-methyl-2-butene produced a 1:1 adduct
which was identified as 7,7,8-trimethylbicyclo[4.2.0]octa-2,4-diene-1-carbonitrile.
This compound is not stable to ultraviolet light and readily reverted to benzonitrile
and olefin. Dialkylacetylenes could also added to benzonitrile photochemically

and cyclooctatetraene-carbonitrile was isolated. ‘9

CN

CN
hv —H
+ l ——’
O 254 nm —-

 

8
Similar reactions have also been reported in the photochemistry of
naphthalene derivatives. Photocycioaddition of 2-naphthol with acrylonitrile in a
1:1 isopropyl alcohol-tert-butyl alcohol mixture afforded the head-to-head
cyclobutanol product, 7-cyano-2,3-benzobicyclo[4.2.0]octa-2,4-dien-6-ol. Further
treatment with NaOH gave 1-(2-cyanoethyI)-2-naphthol, via a retroaldol

reaction.20

 

Irradiation of hexafluorobenzene and phenylacetylene gave phenyl-
hexafluorobicyclo[4.2.0]octatriene which was thermally converted to

hexafluorocycloc'ictatetraene.21

 

F F F
+ III
F F Ph F P“
F F F
intramoiecular

Wagner and Nahm discovered that phenyl ketones with 1:, 1r* lowest
triplets undergo intramoiecular [2+2] ortho cycloaddition to remote double bonds
to generate tricycloundecadienes, and this are thermally converted to an isomeric

cyclobctatriene.1 Such cyclooctatrienes underwent a subsequent photochemical

9
diene-to-cyciobutene interconversion to form isomeric tricycloundecadienes

which are different from the initial photoadducts.2

O

 

 

The first example of intramoiecular 1,2-addition of simple alkenes to triplet
naphthalenes was achieved by Wagner and Sakamoto.22 Both 1-butenoxy-2-
acetonaphthones and 2-butenoxy-1-acetonaphthones undergo [2+2]
cycloadditions from their triplet states with high chemical yield. The results were
similar to the [2+2] photocycloadditions of 2-, 4- and 6-(2-oxa-4,5-dimethyl-4-
hexenyl)-1-cyanonaphthalenes but the latter are known to proceed from singlet

exciplexes with high quantum yield (0.69).”

R1
R1
0 0 R2 j R2
I I hv go— o
R1=R2=H or
R1=Me, R2=H or
R1=H,R2=Et

CN

300 —“—v—» 30

10

Irradiation of N-benzylstyrylacetamides provides tricyclic amide products
via cycloaddition between the styryl and benzene groups. The photoproducts

quantitatively revert to starting material on heating or photolysis.24

Pr... H

  

ll

”1),

 

heat or hv

0“»

Morrison and coworkers had previously examined the intramoiecular ortho

photocycloaddition of benzene to triple bonds.“ The initial cycloadducts

rearranged inefficiently to cyclooctatetraenes. Placement of a trimethylsilyl group

on the triple bonds provides cyclooctatetraenes in high chemical yield.26

 

X: H or OH
Y= Me or TMS
Intermolecular

Wilzbach and Kaplan reported the first meta photocycloaddition in 1966.
Photolysis of a solution of cis-but-2-ene in benzene at 254 nm provided 6,7-

dimethyl-tricyclo[3.3.0.02.3]oct-3-ene.27 In addition, Bryce-Smith, Gilbert and

11
Orger also reported that irradiation of an equimolar mixture of benzene and cis-

cyclooctene led to a 1:1 adduct , identified as tetracyclo[6.6.0.02-4-03.7]tetradec-s-

hv
+ | —»
( 254nm ®
+ ——>
254 nm
‘7

Different combinations of benzene and various alkenes have been

ene.28

photolyzed and the observed isomeric adducts of meta addition isolated; for
example, mono-, di-, tri-, tetra- alkyl-substituted alkenes, cycloalkenes17 (3-, 4-,
5-, 6-, 7-, 9-membered ring) and alkenes with electron donating groups (-Ot-Bu)
or withdrawing groups (-Cl, -OAc).12 Minor ortho cycloadducts are also obtained

in some of the above examples.

OAc

.+r

azbzczd = 20:1 :1 :6

h OAc

v _, a @ b @OAC

OAc
OAc

Meta photocycloadditions of mono-, di-, tri- and hexa-substituted

benzenes to various alkenes have been studied. Substituents on the benzene

12
ring appear to have a pronounced directing effect (regioselectivity) on the
addition, but complicate product analysis. in general, ortho cycloaddition
involving charge transfer between an electron poor benzene and electron rich
double bond has been predicted by Bryce-Smith. However, an exception, the
photocycloaddition of an electron poor benzene (benzonitrile) and electron rich

double bond (1 ,3-dioon-2-one) yields exclusively meta adducts.29

O O
C N 0% N c 0%
/ o O O
o + r >=o 4»
O N C
a b
azb = 45 : 55
Intramolecular

Morrison and Ferree reported that photolysis of trans-6-phenylhex-2-ene
leads to the formation of 2,6 and 1,3 diastereomeric cycloadducts via a singlet

process.30

0 .
_._v, on.

254 nm V
a (2,6) b (1,3) 0 (1,3)

a:(b+c)=91 :9

13

Other intramoiecular meta cycloadditions of benzenes with various alkyl-

substituted tether are summarized in Table 1.

Table 1 Intramolecular Cycloadditions of Arenes to Aikenes

starting material

Ph(CH2)30H=CH2
Ph(CH2)30H=CHMe (cis)

Ph(CH 2)30Me=CH 2
Ph(CH2)30H=CM62
PhCHMe(CH2)20H=CH2
PhCHZCHMeCHZCH=CH2
Ph(CH2)20HMeCH=CH2
PhO(CH2)ZCH=CH2
o-MePh(CH2)3CH=CH2
o-MePh(CH2)3CH=CHMe (trans)
o-MePh(CH2)3CH=CHMe (cis)
o-MePhCHMe(CH2)2CH=CMe2
o-MePhCHMe(CH2)2CMe=CHMe
p—AcPh(CH2)30H=CH2

a. 0 not determined.

orientation

2,6/1,3
1,3

2,5 / 1,3
1,3
2,6/1,3
2,6
2,6/ 1,3 / 2,4
2,4
1,3/1,4
2,6/1,3
1,3

1,3

1,3

product ratio and <1)

(D25 = 0.11, (1313 = 0.04

51,3 = 0.26
1 : 1.6, 510F055

a
1.7: 1, ¢rot=0-055
(blot = 0.035

2.2: 1.3: 1, (11.050055

very inefficient

5.9 2 1, d’ror = 0.60

1 : 1 (with other isomers)

a
1 : 1 isomers
1 : 1 isomers

no meta cycloaddition

ref.

31
30
11
12
11

11

31

32

12

34

14
The versatility of meta cycloaddition has led to the development of very
elegant synthetic approaches to a wide variety of natural products. Wender and
Howbert reported the first application of an arene-alkene photocycloaddition as

the key step in the total synthesis of (i)-cedrene (Scheme 6).35

Scheme 6

    

H .
(i)Cedrene

 

Exo / endo selectivity in photocycloaddition for the synthesis of (i)-
silphinene is controlled by steric hindrance; orbital overlap leading to the endo
complex can not be achieved without introducing strain, resulting in an exo-
selective reaction. Formation of the B-methyl stereoisomer is a consequence of
non-bonding interactions in the transition state (Scheme 7).33

Scheme 7

 

 

U, MeNHg: .6.

’1’,“

(1)-Silphinene

Me Me

e Me H
exo favored

15

Recently, meta cycloaddition has been used to synthesize (i)-subergorgic
acid,36 (-)-retigeranic acid,37 and grayanotoxin II.11 The stereospecificity, Induced
by ortho-substituents on benzene, has been obtained by pro-existing stereogenic
centers on the tethers at the benzylic, allylic, homobenzylic position or
combinations of all three. (Scheme 8-10) Less attention has been paid to the
diastereoselectivity exhibited by the tether itself during cyclization. This topic
forms the central core of the research discussed in this thesis, and will be

expanded upon later.

Scheme 8

   

I—\
00
\ /

Scheme 9

 

 

(-)-retigeranic acid

16
Scheme 10

MeO
TBSO M60

‘1, grayanotoxin ll

 

lntennolecular

Para photocycloaddition occurs primarily when benzene rings are
photolyzed in the presence of dienes or allenes. Irradiation of isoprene and
benzene gave the initial 1:1 photoadduct which undergoes a 1,3-hydrogen shift to

afford the observed product; 3-methylenebicyclo[4.2.0]deca-7,9-diene.38

O <44 I)

Yang extended the para photocycloaddition to naphthalene with

cyclohexadiene and isolated the polycyclic hexaprismanes in moderate yield.39

w
(:3 . 254 nm 0 \

Intramolecular

Not many examples have been reported for intramolecular para
photocycloaddition, due largely to the ring strain in the photoproducts. An
interesting example, reported by Gilbert and coworkers, is that photolysis of the
enol ether below afford the tricyclic ether in high chemical yield and quantum

yield.38
0

Becker has investigated the stereochemistry of intramolecular
photocycloaddition of enones with tethered alkenes. The identical low
stereoselectivity (around 1 : 1) of the cycloadducts was found when 8-
alkenylcyclopentenones (either cis or trans) were irradiated. It was concluded

that steric effects might not influence the course of reaction.”41

 

 

ORH
0
HR
hv 3’
01' ——-—> +
0H8

 

R = Me, t-Bu \/

18
A 1,4-biradicai intermediate was found to be involved in this reaction. The
enone with a cyclopropyl group at the end of the double bond was photolyzed
and gave the normal [2+2] cycloadducts as well as rearrangement products in a

ratio of 2:1.42

 

Photosensitized cycloaddition of 1-(co -alkenyl)-2-pyridone afforded an
intramolecular [2+2] cycloadduct across the 5,6-bond of the 2-pyridone to give a
tricyclic lactam which contains a cis-ring junction in 95 % yield. The addition was

regio- and stereospecific.43

 

The intramolecular [4+4] photocycloaddition of tethered bis-pyridone
provides an 8-5 bicyclic carbon skeleton. It is interesting that the stereoselectivity
of the hydroxy group is reversed in dichloromethane. This solvent effect on
stereoselectivity for the hydroxy-substituted tethers was explained by hydrogen

bonding of the hydroxy group to the solvent, methanol.“46

19

 

Ethanol 11 : 1
Dichloromethane 3 : 4

 

 

1,3,5-Cyclooctatriene has been found to exist in equilibrium with its
valence tautomer, bicyclo[4.2.0]octa-2,4-diene.47 Such an equilibrium was also
observed in our system. From orbital symmetry rules, bicyclo[4.2.0]octa-2,4-
diene should be converted thermally to 1,3,5-cyclooctatriene by a disrotatory
process.48 This was observed at 100 °C experimentally. However, direct
photolysis of bicyclo[4.2.0]octa—2,4-diene in the gas phase at 280-300 nm

produced mainly 1,3,5-cyclooctatriene and benzene plus ethylene.49

20
Warrener and co—workers offered another example of photoisomerization
of a bicyclo[4.2.0]octa-2,4-diene. Irradiation of compound X generated a
cyclooctatriene, benzene plus ethylene and tricyclo[4.2.0.02-5]octene in either

THF or benzene.50

 

 

 

 

CI
Cl
CI CF3 Cl CF3
_ 0 ,_> "’ @
Cl
hv Cl
Cl CF3 hv Cl / CF3 Cl CF3
11 .— .. :2 Om
CI CF3 CI \ CF3 A CI CF 3
Cl

 

 

 

 

 

 

21
III. Mechanistic Considerations

The mechanisms of photocycloadditions between benzene and double
bonds and the various factors influencing the modes of cycloaddition have been
subjects of longstanding interest. The first question that arises is, does the
reaction proceed in a concerted or stepwise fashion, from the singlet or triplet
state. Previously reported cycloadditions involved the singlet excited states of
benzene except the examples using phenyl ketones recently found by the
Wagner group.1

Due to deuterium labeling studies51 and regio- and stereo-selectivity
analysis of products,17 the mechanism for photocycloadditions between benzene
and double bonds is proposed to proceed via the formation of an exciplex
followed by bond formation. Mattay has reported long wavelength emission
attributable to an exciplex. Quenching of this emission and of product formation
have identical rate constants (kq'r).52

Bryce-Smith and Longuet-Higgins provided the first theoretical treatment.
From an orbital symmetry viewpoint, they proposed that ortho and para
cycloadditions of double bonds to benzene are forbidden from the 1B2u (S1) state,
unless they involve charge transfer.53 Meta cycloadditions are considered to be
symmetry allowed from this state. The ionization potential difference rule (A I.P.
between benzene and double bond) can be used to predict the modes of
cycloaddition. Reactions of benzene (IF. = 9.24 eV) with alkenes having I.P.
between 8.6 and 9.6 eV generally proceed with meta-mode selectivity. On the
other hand, when the A LP. is larger than this range (i 0.5 eV), charge transfer
and ortho-modes are favored.17

Since the ionization potential difference rule (A LP.) is based solely on the

energies of filled orbitals, the consideration of both energies of filled orbitals and

22

singly occupied molecular orbitals was further studied. Houk provided a frontier
molecular orbital (FMO) analysis for rationalizing the partitioning of these
photocycloaddition modes.54 The actual frontier orbitals of benzene are the
combinations of configurations: the lowest excited singlet B2,, (SA*-AS*); the
lowest triplet B1u (SS*+AA*). The analysis indicated that the alkene's HOMO can
mix with the benzene S orbital to stabilize 3 meta cycloaddition and with the
benzene A orbital to stabilize an ortho cycloaddition. Alkene 1t* orbital mixing with
the benzene A‘ is possible in both cases. A para-approach is only weakly
stabilized by interaction of the benzene S and alkene 1t orbital. From this
analysis, it could be predicted that ortho cycloaddition is stabilized by an A -> 8*
transition, but meta cycloaddition is stabilized by an S -> A* transition (Figure 1).

However, substituents on the benzene and/or the double bond would
remove the degeneracy of the HOMOs and of the LUMOs. An electron
withdrawing group, such as acetyl or cyano, would stabilize both the S and S“
orbitals of benzene, so that the HOMO is the A orbital and LUMO the S* orbital.
Ortho cycloaddition is favored over the meta mode due to stabilization of the A ->

8* transition (Figure 2).55

23
Figure 1. Frontier molecular orbitals (FMO) and excited states of benzene (mirror

plane)

Benzene FMO's Alkene FMO's

+1.15 eV -1.78 eV

1t* (LUMO)

-9.24 eV -10.52 eV

   

s A n (HOMO)

B2,, (SA* - AS*) lowest excited singlet state

B1,, (88* + AA*) lowest triplet state

24
Figure 2. Orbital energies of triplet electron-deficient benzene with electron

withdrawing groups, such as acetyl or cyano group, and alkene for ortho addition

Benzene FMO's Ortho addition

 

 

 

s A A

 

25
IV. Quantum yields and kinetics

Equation 1 describes the rate of a photochemical reaction as a function of
la, the total light intensity (photons/s or einsteins/s) absorbed by the sample
during photolysis. It is important to distinguish among light incident upon the
sample, total absorbed light, and light absorbed by the reacting compound. Most
actinometry determines light incident upon the sample. When the optical density
(A) of the sample, as described by Beer's law, is 2 or larger, then effectively all of

the incident light (>99°/o) is absorbed.
Rate = (b x l a (1)

The proportionality constant (b that relates rate to light intensity is the

observed quantum yield. It can also be defined independently as the ratio of

molecules reacted to photons absorbed, in equation 2.

no. of molecules of product formed
(bproduct =
no. of photons absorbed

 

(2)

The triplet lifetimes of the ketones in this thesis were measured by the
Stem-Volmer quenching technique.56 2,5-Dimethyl-2,4-hexadiene or sorbic acid
was used to quench the triplet ketones by energy transfer. The mathematical

expression of this process is given in equation 3.

 

(D0: d’rsckrTT
(I) k
(I) = 9" '
l/TT +kq[Q]
(D
71,9- =1+kth[O] (3)

26

where (ho, <1) = quantum yield in the absence and the
presence of a quencher, respectively

17 = 1 IE ki , triplet lifetime

kq : rate constant for quenching by the quencher

k,: rate constant for the product formation

[Q] : concentration of a quencher

A plot of <1>ol (I) vs. [Q] provides a straight line with an intercept of 1 and a
slope of quT. The quenching rate of either 2,5-dimethyl-2,4-hexadiene or sorbic
acid is usually close to the diffusion controlled rate 7.5 x109 M:1 s:1 in methanol at

25 °C.62 The triplet lifetime can be calculated from the slope of the Stern-Volmer

plot.

27

V. Research goals

In this dissertation, the stereochemistry of intramolecular cycloaddition of
double bonds to triplet benzenes will be discussed. Since there are four potential
stereocenters on the tether and at least two more stereocenters generated from
the secondary photochemical electrocyclic rearrangement, the
diastereoselectivity of thermally stable cycloadducts and photostable
cyclobutenes were explored. The biradicai intermediacy of this
photocycloaddition was confirmed by incorporating a radical clock
(cyclopropylcarbinyl radical rearranging to allylcarbinyl radical).57 Quantum yields

for each process were measured independently.

RESULTS

I. Alkenoxyphenyl Ketones

In order to investigate the stereoselectivity of the [2+2] photocycloaddition
of triplet benzene to double bonds, alkyl-substituted alkenoxyphenyl ketones
were employed as reactants. These ketones were prepared by the 8N2 reaction
between the phenolates of para- or ortho- hydroxyacetophenones and alkyl-
substituted alkenyl tosylates in dry dimethyl formamide ( DMF ) or acetone. Alkyl-
substituted alkenyl tosylates were prepared from the corresponding alcohols by
standard tosylation in pyridine. Alcohols were purchased from the Aldrich

Company or made by either Grignard or Wittig reactions.

Table 2 Alkenoxyphenyl Ketones

 

* para- or ortho- alkenoxyacetophenones
* M = methyl, I = isopropyl, C = cyclopropyl group and K = ketone
* The shorthand is also applied to CH = cyclohexadiene, COT = cyclooctatriene

and C8 = cyclobutene

28

P'MoK

Mr K

P4 1 K
P'M1M3K
I"l 1M3K
P'MzMaK
P'MaMrrK
P'M1M3M4K
p-M4K
P-M3M4M5K
W1M3M4M5K
P'McMsK
PC4K

P44K

(H 1 K

(H 1M3K

29

para butenoxyacetophenone without substituent
para R1 = Me

para R1 = i-Pr

para R1: R3 = Me

para R1 = i-Pr, R3 = Me

para R3 = R3 = Me

para R3 = R4 = Me
paraR1=R3=R4=Me
para R4 = Me

para R3 = R4 = R5 = Me
paraR1=R3=R4=R5=Me
para R4 = R5 = Me

para R4 = cyclo-Pr

para R4 = iso-Pr

ortho R1 = iso-Pr

ortho R1 = iso-Pr, R3 = Me

The synthesis of p-M1K is outlined in Scheme 11.

Alcohols used to make p-I1K, p-M1M3K, p-I1M3K, o—l1K and o-I1M3K were

prepared by reaction between acetaldehyde or isobutyraldehyde and allyl

Grignard reagents, followed by tosylation at 0°C in pyridine. The standard

coupling method was carried out in DMF (Scheme 12).

Scheme 11

 

 

 

 

 

 

Scheme12
R2
1_M ,l , O
R1CHO + X\/K 9 2 \I V) HOW
2. NH4CI (aq) 1 2
R1=Me,iPr R R
R’- = H, Me
X=Cl, Br

 

TsO ,ll\ 0“
——->Tf‘:' W Q *0“) W

R1 R2 K2CO3, DMF

ortho- or para

   
 

 

1-Hydroxy-2-methyl-3-butanone was used as the precursor of p-M2M3K.
After protection using the methylthiomethyl group (MOM), a Wittig reaction using

methyl triphenylphosphonium bromide, followed by removal of the MOM group by

31
mercury chloride, gave the corresponding alcohol. Tosylation and coupling

provided the ketone p-M2M3K (Scheme 13).

Scheme 13

 

 

O
O
1: I
OH 9 OAS/
\‘rOH
O
PhaP+ CH3 - Br HgCl2
> OAS/ >

n-BuLi, THF MeCN

O

The alcohols for p-M3M4K and p-M1M3M4K were prepared by reaction of

  
   

 

 

 

ethylene oxide or propylene oxide and vinyl cuprate reagents (Scheme 14).

 

 

 

Scheme 14
O 1_ Mg, l ,Cul, THF
+ Br 2 > HO /
AR‘ 2. Acetic acid (aq) R1
R1 = M6, H
(Be-Gm
TsCl TsO / O)—<;>—— N
, A, O /
0 F11 K2003, DMF R1

 

The methyl-substituted hydroxyacetophenones were prepared by a

thermal Fries rearrangement method. The hydroxyl group of o-cresol was
protected by an acetyl group. Stirring in the presence of aluminum chloride in
nitrobenzene at room temperature generated the rearranged 4-hydroxy-3-
methylacetophenone (Scheme 15). This compound was used for the syntheses
0i P'MaMcMsK. P'M1M3M4M5K and P'McMsK-

Scheme 15

 

OH

\
’

Acetyl chloride, GIN Arc:3

 

 

 

 

 

33
Alcohols used to prepare p-C4K and p-I4K were prepared by Wittig
reaction between 3-hydroxypropyltriphenylphosphonium chloride and

cyclopropane-carboxaldehyde or isobutyraldehyde (Scheme 16).

Scheme 16

 

n-BuLi, THF

> Ph3P+WOH )
Cl - R1CHO

 

 

———’

O
OM91 R1 = cyclo- or iso- propyl

R1 M0” ___, R, Mo“

 

 

4'-(3-Butyn-1-oxy)acetophenone was prepared by the coupling method

and then protected by ethylene glycol. A trimethylsilyl group was added to the
end the triplet bond, and final deprotection was performed in aqueous HCI

solution (Scheme 17).

Scheme 17

 

 

 

 

35
ll. Photocycioadditions and Identification of Photoproducts

a. General

All photoproducts were identified by nuclear magnetic resonance
spectroscopy (IH-NMR and 13C-NMR).

For small scale photolysis, 0.7 mL argon-bubbled methanol solutions of
various alkyl-substituted alkenoxyacetophenones (0.01 to 0.03 M) were irradiated
with a medium pressure mercury arc filtered so as to isolate the 313 nm band or
filtered only by Pyrex glass filter (> 290 nm). Time-resolved NMR analysis
indicated clean conversion of each reactant into a mixture of two diastereomers
of 1-acetyl-8-oxatricyclo—[7.20.05-9]undeca-2,10-dienes (from para ketones) or 9-
acetyl-4—oxatricyclo-[7.2.0.03-7]undeca-2,10-dienes (from ortho ketones).
Diastereomeric product ratio was determined by integration of oiefinic and/or
methyl group signals observed in high resolution 1H-NMR spectra. Chemical
yields were measured by integration of methyl group signals in the 1H-NMR
spectra relative to an internal standard (methyl benzoate). The stereochemistry of
photoproducts was determined by nuclear Overhauser effect experiments (nOe).

These 1-acetyi-8-oxatricyclo-[7.2.0.05-9]undec-2,10-dienes (henceforth
abbreviated as CB, cyclobutenes) were then converted thermally (either standing
at room temperature for a few days or heated at 40°C overnight) to equilibrium
mixtures of 4-acetyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene (henceforth
abbreviated as COT, cyclooctatriene) and/or 4-acetyl-11-oxatricyclo[6.3.0.0]
undeca-2,4-diene (refer to the CH, cyclohexadiene). Similarly, 9-acetyl-4-
oxatricyclo-[7.2.0.03-7]undeca-2,10-dienes were converted to 6-acetyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene (refer to the COT, cyclooctatriene). Again,
isomer ratios were determined by 1H-NMR, while the stereochemistry was

confirmed by nOe experiments of isolated products .

36

For the purpose of isolation, large scale photolyses were performed in
100 mL Pyrex test tubes or Pyrex reactors. Argon-bubbled methanol solutions
0.01-0.02 M in various alkyl-substituted alkenoxyacetophenones (ca. 0.2 g in
120 mL methanol) were irradiated above 290 nm and the progress of irradiation
was checked with TLC, G0 or HPLC by removal of a small aliquot by syringe.
After > 95% conversion, the solvent was evaporated and the residue was purified
by alumina or silica gel column chromatography. The isolated products were re-
identified as cyclohexadienes, cyclooctatrienes or cyclobutenes, depending on
how stable the cyclobutenes are after chromatography at room temperature. The
isolated yield was also measured and the isolated products (COT or CH) could
be used for quantum yield determination. Also, the isolated products (COT or
CH) were irradiated again to confirm the formation of cyclobutenes (CB). Scheme
18 describes briefly the observed photoreactions and subsequent thermal
rearrangements.

The diastereoselectivity of the reaction is characterized by the
diastereomeric excess (de) as defined in eq. (4); where c and c' are the
concentration of the major and minor isomers ,respectively, of cyclohexadienes,

cyclooctatrienes or cyclobutenes in the mixture.58

°/ode=(c-c'/c+c')x100 (4)

37

Scheme 18

 

b. p-MoK

An NMR tube containing 2.0 x 10-2 M p-IllloK in CD3OD was irradiated with
a Pyrex-filtered mercury arc, following Nahm's procedures.59 1-Acetyl-8-
oxatricyclo-[7.2.0.05.9]undeca-2,10-diene and a small amount of 4-acetyl-10-
methyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene were identified by 1H-NMR
spectroscopy at low conversion but only 1-acetyI-8-oxatricyclo-[7.2.0.05-9]undeca-
2,10-diene was obtained after completion. NOe showed the bridgehead proton
H5 and cyclobutene ring cis to each other. The 1-acetyl-8-oxatricyclo-
[7.2.0.05-91undeca-2,10-diene converted totally to 4-acetyl-10-methyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene in 2 days at room temperature, whereas

Nahm performed the conversion at 200°C.59

C. p-M1K

 

O
HWV’ -""-’-'->Py II

00300

 

 

An NMR tube containing 3.4 x 10‘2 M p-M1K and 3.3 mg methyl benzoate
in 00300 was degassed with argon and irradiated by Pyrex-filtered mercury arc.
After 100 % conversion, two photoproducts were identified by 1H-NMR as
diastereomers of 1-acetyl-7-methyl-8-oxatricyclo-[7.2.0.05.9]undeca-2,10-diene.

The chemical yield was 85%, which was measured by NMR integration of the

39

methyl group of methyl benzoate (8 3.99) and the products' acetyl groups ( 6
2.183 and 8 2.185). A diastereomeric excess (de) of 41% was determined by
integration of the 7-Me doublets (6 = 1.05 vs. 5 1.14 in a ratio 2.5 : 1). Two AB
quartet patterns at 5 6.29, 6.42 (J = 2.8 Hz) and 6 6.28, 6.34 (J = 2.9 Hz)
represent the isomeric pair of cyclobutene hydrogens. It is interesting that H4, is
coupled to H 2 through allylic coupling (J = 2.3 Hz) in this rigid structure but H45
isn‘t, The stereochemistry of H40, and H43 was assigned from the nOe
experiments.

The nOe results indicated that the major photoproduct has the bridgehead
proton H5 and 7-Me trans to each other, but H5 and cyclobutene ring cis to each
other. The minor photoproduct also has H5 and the cyclobutene ring cis to each
other, but the bridgehead proton H5 and 7-Me are also cis to each other.

When the reaction was performed at 313 nm, it gave identical results. In
addition, there were only slight differences in diastereomeric excess (de) when

this compound was irradiated in either benzene or acetonitrile.

 

 

 

A dry methanol solution (210 mL) of p-M1K (a x 10-3 M) was bubbled with
argon and monitored by TLC or 60 during irradiation (Pyrex filter) until 100 %

conversion. The solvent was evaporated at 45°C and the residue changed from

4o

colorless to yellow. The product mixture was passed through a silica gel column
and the isolated yield was 63 °/o. The structures were identified as diastereomers
of 4-acetyl-10-methyI-11-oxabicyclo[6.3.0]undeca-1,3,5-triene from the following
spectroscopic data: Pairs of resonances were observed in both the oiefinic and
aliphatic regions of 1H-NMR spectra, 10-Me (6 1.33 vs. 8 1.34) and COMe (8 2.31
vs. 6 2.35). The well-resolved pattern of oiefinic peaks was assigned to two
cyclooctatriene skeletons; the major has 8 5.36 (dd), 6.02 (dt), 6.36 (d), 6.99 (d),
and the minor has 5 5.41 (dd), 5.89 (dt), 6.25 (dt), 7.06 (d), with only slight
difference in coupling constants: J23 = 8.0 Hz, J53 = 11.3 Hz (major) and J33 =
6.3 Hz, J53 = 13.1 Hz (minor). A diastereomeric excess (de) of 56 % was
determined by integration of H10 signals (8 = 4.41 vs. 4.71 in a ratio of 3.2 : 1 in
Figure 3). The discrepancy in the ratio of diastereoselectivity between COT
(56%) and CB (41%) is probably due to limitations in the integration of NMR
spectroscopy. Another possibility is a little decomposition of COT during the
interconversion from CB to CDT.

The UV-Visible spectrum showed a Amax at 344 nm and IR spectrum had a
peak at 1682 cm'1 indicative of a highly conjugated carbonyl compound. An
identical molecular ion peak to the starting ketone was found in the mass
spectrum.

The cyclooctatriene diastereomers were irradiated in methanol to gave
the same 3.2:1 ratio of diastereomeric 1-acetyl-7-methyl-8-oxatricyclo-
[7.2.0.05u91undec-2,10-dienes. (Figure 3,4) The cyclooctatriene diastereomers
were separated by neutral alumina chromatography. Since the stereoselectivity
observed for the cyclooctatrienes is the same as for cyclobutene formation, the
bridgehead proton H3 and Mew are assigned trans to each other in the major

cyclobctatriene and cis in the minor. This was confirmed by nOe experiments.

41

 

m.000 c. c.0055. 9533.3
-wompcao.m.o_o_o>o_nmxo-F 73565073893 .0 =55QO $22-7: .0 2:9".

«.wm o.m _ c.m ~.m «.oq o.w«

 

22 ms.

.53 ..54

 

42

 ., 3117....

m.« o.m

P——-P——~—p__

 

_

 

_

m.m
__

o.m mm.

 

 

o.v

m4»

592
.d .o 55.59.. .3 8528 .858 5 80.2.5 $55-25
-823.e...o.o.NE-o_o>oEexo-m-_§o5-5-285-F .o 525on $22-1. .4 2:94.

 

o.m

 

 

m.m

 

d. p-I1K

 

4.
4.

hv, Pyrex
———>

00300

III
I
0.
all
I

o
i
o
it
., i.“-
Q
Q

 

 

A mixture of 2.0 mg of p-l1K and 4.3 mg internal standard (methyl
benzoate) in a 0.6 mL CD3OD (0.015 M) was degassed and irradiated by
mercury arc with a Pyrex filter. Photoreactions were followed by 1H-NMR
spectroscopy from 100 % of reactant to 0 %. Photoproducts were characterized
as a pair of 1-acetyl-7-isopropyl-8-oxatricyclo[7.2.0.05.9]undeca-2,10-diene
diastereomers, as in the previous example. Two sets of peaks were obtained in
1H-NMR spectrum. A pair of AB quartets at 5 6.25, 6.45 and 6 6.27, 6.35 were
assigned to two cyclobutenes. Two multiplets (dd) at 8 0.47, 0.88 and 6 0.83,
0.90 represented two non-equivalent methyls in each isopropyl group due to an
adjacent chiral center. Integration of the two H13 signals (6 6.45 vs. 8 6.35)
indicated 90% chemical yield and 67% diastereomeric excess.

The major diastereomer has the bridgehead proton H5 and i-Pr7 trans to
each other, and H5 is cis to the cyclobutene ring. The minor product had the

bridgehead proton H5 and i-Pr7 cis to each other and the cyclobutene ring.

 

 

 

A solution of 0.10 g p-l1K in a MeOH (60 mL), was degassed and
irradiated at >290 nm. The reaction was monitored by TLC or GC to 100 %
conversion. After removal of solvent, the residue was purified by silica gel column
chromatography to give two products in 68% isolated yield. The structures were
identified as the two diastereomers of 4-acetyl-10-isopropyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene from the following spectroscopic results: 1H-
NMR spectrum showed two sets of four vinyl protons; 8 5.37 (dd, J = 8.4, 2.2 H2,
H2), 6.05 (dt, J = 10.8, 8.1 H2, H5), 6.32 (d, J = 10.8 H2, H5) and 7.09 (d, J = 8.4
Hz, H3) for the major and 8 5.40 (d, J = 6.3 Hz, H2), 5.86 (dt, J = 13.2, 4.3 H2,
H5), 6.20 (cit, J = 13.2, 2.2 H2, H5) and 7.17 (d, J = 6.3 H2, H3) for the minor. The
diastereomeric excess, determined by integration of the two H3 signals , is 65%.
In addition, there are two acetyl groups at 5 2.31 and 2.34 and two sets of
doublets (6 0.90, 1.00 and 8 0.89, 0.99) representing the isopropyl group of each
diastereomer. There are also two peaks ( 8 199.1 and 199.5) due to the carbonyl
group in the 13C-NMR spectrum. The conjugated carbonyl group was confirmed
by IR (1682 cm-‘) and UV (346 nm) spectra . Both high- and low- resolution Mass
spectra gave the identical molecular ion for starting ketone and product mixture.

Separation of the diastereomers was unsuccessful.

45

Because the diastereomeric ratios of 1-acetyl-7-isopropyl-8-oxatricyclo—
[7.2.0.05-91undeca-2,10-diene and 4-acetyI-10-isopropyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene are nearly identical, the major product of 4-
acetyl-10-isopropyl-11-oxabicyclo[6.3.0]undeca-1,3,5—trienes are assigned with
the bridgehead proton H3 and i-Pr1o trans to each other. The minor product has

the bridgehead proton H3 and i-Prm cis to each other.

9. p-M1M3K

 

 

 

A 0.024 M argon-degassed CD3OD solution of p-M1M3K and internal
standard (methyl benzoate) was photolyzed in a NMR tube through a Pyrex filter.
The reaction was monitored by 1H-NMR spectra to 100% conversion. The
products were characterized as two diastereomers of 1-acetyl-5,7-dimethyl-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene. Integration of the two 10-Me signals
determined a diastereomeric excess of 80 % and chemical yield 78%. Due to the
higher selectivity, the minor product was difficult to observe by 1H-NMR
spectroscopy. The major cyclobutene had an AB quartet (6 6.35 and 6.45, J =
2.9 Hz, H13 and H11) and two oiefinic protons (6 5.75 ,dd, J = 10.0, 2.9 H2, H2
and 6 5.77, ddd, J = 10.0, 6.1, 1.7 Hz, H3) and a bridgehead methyl group (6

46
1.08, 5-Me), instead of a proton. This simplified the interpretation of the 1H-NMR
spectrum. When the reaction was carried out in either C5D3 or CD3CN, identical
selectivity was observed.

NOe measurements showed that the major product had a bridgehead

methyl group, 5-Me, cis to the cyclobutene group but trans to the 7-Me.

Me
MeOH 0““‘tM

A degassed methanol solution of p-M1M3K (0.01 M) was irradiated at >

 

Me

 

 

290 nm. After completion, the solution was heated at 30°C in warm water for 24 h
until the solution color turned to yellow. After silica gel column chromatography,
the products were identified as an equilibrium of 4-acetyl-8,10-dimethyl-11-
oxabicyclo[6.3.0]undeca-1 ,3,5-triene and 4-acetyl-8,10-dimethyl-1 1-oxatricyclo-
[6.3.0.01s6]undeca-2,4-diene in a 3 : 1 ratio at room temperature. The major
product had oiefinic proton signals typical of cyclooctatriene; 6 5.17 (d, J = 6.6
H2, H2), 6.19 (ddd, J = 10.8, 9.1, 7.1 H2, H5), 6.36 (d, J = 10.8 H2, H5) and 7.17
(d, J: 6.6 H2, H3), but the minor isomer had oiefinic signals characteric of a
cyclohexadiene; 6 5.59 (d, J = 10.2 H2, H2), 6.68 (dd, J = 10.2, 1.6 H2, H3) and
7.01 (dd, J = 6.5, 1.6 H2, H5). in particular, the spectrum indicated an allylic
proton at 6 3.14 (dt, J = 10.4, 6.5, Hz) which was assigned to H5 of
cyclohexadiene. The 3 : 1 ratio was measured by integration of the acetyl methyl

group in cyclooctatriene (6 2.32) and cyclohexadiene( 6 2.30). A small amount of

47
the other cyclohexadiene diastereomer was detected by its characteristic vinyl
proton signals.

Since only one major stereoisomer of the cyclooctatriene was detected in
1H-NMR spectrum, the stereochemistry was assigned as in the 1-acetyl-5,7-
dimethyl-8-oxatricyclo—[7.2.0.05~9]undeca-2,1Oodiene example. This fact
determined that the major product has the bridgehead methyl group, 5-Me, trans
to the 7-Me group.

1. p-I1M3K

 

 

 

An oxygen-free CD3OD solution of p-I1M3K (0.016 M) containing methyl
benzoate was irradiated through a Pyrex filter for 1 h. The product detected by
1H-NMR spectroscopy was identified as 1-acetyl-7-isopropyl-5-methyl-8-
oxatricyclo[7.2.0.05i9]undeca-2,10-diene in 75% chemical yield and >95%
diastereomeric excess. The 1H-NMR spectrum is similar to 1-acetyl-5,7-dimethyl-
8-oxatricycio-[7.2.0.05v9]undeca-2,10-diene except for two new doublets at 6 0.71
(J = 6.6 Hz) and 6 0.88 (J = 6.6 Hz) attributed to the 7-iPr group. The bridgehead
methyl (5-Me) facilitated interpretation of the 1H-NMR spectrum. The 1(iC-NMR

spectrum was obtained at 20°C to prevent thermal rearrangement. The chemical

43

shift at 6 214.9 was assigned to the cyclobutene carbonyl substituent, which is
nonconjugated.
An nOe experiment indicated that the product has a bridgehead methyl

group , 5-Me, cis to the cyclobutene group but trans to the 7-iPr group.

 

 

 

Ketone p-I1M3K (0.008 M) was photolyzed in methanol in a manner similar
to p-M1M3K. After heating at 50°C overnight, the products were purified by silica
gel column chromatography and identified as an equilibrium mixture of 4-acetyl-
10-isopropyl-8-methyI-1 1-oxabicyclo[6.3.0]undeca-1 ,3,5-triene and 4-acetyl-10-
isopropyl-8-methyl-11-oxatricyclo[6.3.0.0‘I6]undeca-2,4-diene in a ratio of 3 : 1 at
room temperature This is similar to the previous example (p-M1M3K). No other
diastereomer could be detected.

1H-NMR showed different sets of peaks for each isomer; 61.14 (8-Me), 6
5.23 (d, J = 6.6 H2, H2), 6.18 (ddd, J = 10.6, 9.4, 7.2 H2, H5), 6.41 (d, J = 10.6
Hz, H5) and 7.08 (d, J: 6.6 Hz, H 3) for the cyclooctatriene and 6 1.13 (8-Me), 6
5.61 (d, J = 10.3 Hz, H2), 6.74 (dd, J = 10.3, 1.6 H2, H3) and 6.80 (dd, J = 6.2, 1.6
H2, H5) for the cyclohexadiene. The IR spectrum indicated two carbonyl group
absorptions (1676 cm '1 and 1647 cm '1 ), confirmed by 13C-NMR spectroscopy (6
198.6 vs. 6196.7). 2D-COSY spectroscopy also showed the equilibrium of

cyclooctatriene and cyclohexadiene. UV-visible spectra had an absorption at 344

(add) u

49

 

 

l
l—-
i.-
p

f

l...
i

 

 

 

| I 1 I I T lfi 1T1 Tl fl
‘7 6 5 4 3 2 lppn
A”
:8”
.‘l‘ m U" .‘7 ii, "i .7..5.1
q—l '
- $4
7 *3 I
as—
01'
m—
a— $ '-
4 .
.I
w...
_ ,|
- Qt
- '31
"‘ ' iii l
. . 4,
I :‘i
I-l— g “
at - ’

 

 

 

Figure 5. 2D COSY spectrum of the equilibrium of 4-acetyl-10-isopropyl-8-
methyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-triene (p-I1M3COT) and 4-
acetyl-I 0-isopropyl-8-methyl-1 1 -oxatricyclo[6.3.0.01v5]undeca-2,4-
diene (p-I1M3CH) in CDCI3

50

.22 wow x on. C 6:559: 5 5:9qu

5: m5 5 C8559 65355. P-eooeeao.m.e_o_o>o_oexo

- F 7356834365870Ebmomé Co 966% m_n_m_>->: pm>_om2-mEP .o 2:9“.

 

 

 

 

 

SKI

.mwmo.e .zzo.omn.4. gm. moxe. mm.

mpoom A.e~o\:zooron 6.66”
mt m ..l. -4 . dae.s+

A. Io .. i

...M

... 4
. s .A.:Hox
hem.

. s e
« Ii 6 a u .,.. p... O D o. N +

 

 

 

 

 

w

2\>

uzummwmomm ¢h¢c

51
nm due to the cyclooctatriene chromophore (Figure 5,6), and the mass spectrum
indicated a parent ion isomeric with the starting ketone p-I1M3K. Reirradiation of
the equilibrium mixture yielded the same 1-acetyl-7-isopropyl-5-methyl-8-
oxatricyclo[7.2.0.05-9]undeca-2,1O-diene obtained in the initial cycloaddition.
Furthermore, an nOe experiment showed that the bridgehead 8-Me is

trans to the 10-iPr group just as it is in the cyclobutene.

9. P'M2M3K

 

 

 

A solution of p-M2M3K and methyl benzoate in CD3OD was irradiated at >
290 nm for 12 h. The photoproducts were determined to be a pair of
diastereomers of 1-acetyl-5,6-dimethyl-8-oxatricyclo[7.2.0.05.9]undeca-2, 1 0-diene
in 82 % diastereomeric excess and 76 % chemical yield. The singlet at 6 0.92
and doublet at 6 0.97 (J = 6.9 Hz) could be assigned to 5-Me and 6-Me of the
major diastereomer, respectively. An AB quartet at 6 6.21, 6.33 (J = 3.0 Hz) is
characteristic of a cyclobutene ring (Figure 7).

An nOe experiment on this cyclobutene couldn't be carried out due to the
close proximity of the two methyls. However, the stereochemistry of the major
product could be determined as having the 5-Me and 6-Me trans to each other

from nOe experiments involving the thermally rearranged cyclohexadiene isomer.

52

. coszELBmu

29> .moEmzo m: use Qnéusdv 95532633297223
-m-_§oe_e-m.uv-.e .6 2.83 2.22-2. c2562.. 6:5 25 226m A 9:9“.

 

 

 

 

 

 

 

 

 

 

 

 

5.3. «.3
.} ...
2%.“ m m v m m N. m
.._-._p_.»—._p_.__.pbp__.._.L..._p._..5.~..r~...m...—......"F.P—~.L._5.L.Fll
i 41:. i7 ll.-llll. it
a
C
m.mm m.mm
..J 3
IIl<l==tlelLl yi..liIIl:\IjI—II filial
.3215
x. meme
M0] 7.51%....9
swan t
9 .9 I.
at a
\ 8
0? ....
”.1 1m
o .-.m m...
2.4... mm.

 

 

 

 

 

A large scale photolysis of p-M2M 3K (100 mL) was undertaken.
Photoproducts were allowed to stand in solution at room temperature for two
days Purification by silica gel column chromatography gave a diastereomeric
mixture of 4wacetyl-8,9-dimethyl-11-oxatricyc|o[6.3.0.01-6]undeca-2,4-dienes in 85
% diastereomeric excess. The peaks at 5 5.46 (dd, J = 10.2, 1.0 H2, Hz), 6.59
(dd, J = 10.2, 1.6 H2, H3) and 6.74 (dd, J = 5.5, 1.0 H2, H5) and at 5 5.20 (dd, J =
8.2, 1.1 Hz, H2), 6.60 (dd, J = 8.2, 1.5 H2, H3) and 6.75 (dd, J = 4.5, 1.1 H2, H5)
represented the major and minor cyclohexadiene, respectively. Only a very small
amount of the minor cyclooctatriene could be detected by 1H-NMFl spectroscopy,
9g. 8 5.20 (dd, J = 6.5, 1.1 Hz, 1H) 5.95-6.10 (m) 7.02 (d, J = 6.5 Hz, 1H).

An nOe experiment showed that B-Me and 9-Me of the major product are
trans to each other and that cyclobutane ring has a cis-fused to the

cyclohexadiene.

h- P-MalhK

 

 

 

54

An NMR tube containing 3.0 mg p-M3M4K (95 % trans and 5 % cis) and
4.4 mg methyl benzoate dissolved in 00300 was irradiated at > 290 nm for 1.5
h. 1-AcetyI-4,5-dimethyl-8-oxatricyclo[7.20.05.9]undeca-2,10-diene was the only
photoproduct (> 95 % diastereomeric excess and 45 % chemical yield)
determined by 1H-NMR spectroscopy.

Since this cyclobutene is stable in contrast to the previous examples,
isolation could be undertaken by silica gel column chromatography. Mass
spectroscopy indicated an identical molecular ion for the starting ketone p-
M3M4K (M.W. = 218) and this compound. The peak at 8 209.8 in 13C--NMR
spectrum and the stretching frequency at 1703 cm-1 in IR spectrum corresponds
to a nonconjugated carbonyl group. Two methyl groups at 5 0.93 (s) and 1.04 (d,
J = 7.4 Hz) represented 5-Me and 4-Me, respectively. The cyclobutene ring was
evident from an AB quartet at 5 6.33 ,6.44 (J = 2.9 Hz, H10, H11). UV-visible
spectrum showed a 11 11* absorption at 280 nm which had a much smaller
extinction coefficient (a = 875) compared with starting ketone (e = 16500).

The bridgehead 5-Me was cis to the cyclobutene ring but trans to 4-Me

determined by nOe experiments.

 

 

 

 

The cyclobutene product from the previous experiment was heated in

methanol at 40°C for 24 h, until conversion to 4-acetyI-7,8-dimethyl-11-

55
oxatricycloj6.3.0.01'61undeca-2,4-diene was completed. This compound was
purified by silica gel chromatography then recrystallized from hexane-ethyl
acetate mixture in the refrigerator.

Identical molecular ions for the starting ketone p—M3M4K and its CB (MW.
= 218) were obtained by Mass spectroscopy. The signal at 6 196.3 in 13C-NMFl
spectrum was interpreted as that of a conjugated carbonyl carbon. Two methyl
groups at 6 0.95 (d, J = 7.5 Hz) and 1.03 (s) represented 7-Me and 8-Me,
respectively. Olefinic peaks at 5 5.45 (d, J = 9.7 Hz, H 2), 6.59 (d, J = 9.7 Hz, H 3)
and 6.61 (d, J = 5.8 H2, H5) were characteric of the cyclohexadiene unit. UV-
visible spectrum showed a 1r 11* band at 295 nm which had a medium extinction
coefficient (a = 2200).

The methyls at C-7 and C-8 were determined by nOe to be trans to each

other.

i- P'M1M3M4K

 

 

 

The NMR scale photolysis of a cis + trans mixture of p-M1M3M4K with
methyl benzoate in CD300 (0.022 M) at > 290 nm provided a diastereomeric
mixture of 1-acetyl-4,5,7-trimethyl-8-oxatricyclo[7.2.0.05»9]undeca-2,10-dienes in

80 % diastereomeric excess and 49 % chemical yield. Three signals at 8 0.98 (s),

56
1.05 (d, J = 7.4 Hz) and 1.11 (d, J = 6.1 Hz) were characterized as 5-Me, 4-Me
and 7-Me, respectively. An AB quartet at 6 6.47, 6.50 (AB q, J = 3.0 Hz, H10, H11)
was assigned to olefinic protons of the cyclobutene ring.
NOe experiments verified that the major diastereomer had bridgehead 5-
Me cis to the cyclobutene ring but trans to both 4-Me and 7-Me. The minor had

R1 and R3 cis to each other and R3 and R4 trans .

 

 

 

A solution of p-M1M3M4K (cis and trans mixture, 0.014 M) in methanol was
irradiated at > 290 nm and then heated at 40°C for 24h. After purification by silica
gel column chromatography, photoproducts were identified as a pair of
diastereomers of 4-acetyl-7,8,10-trimethyl-1 1-oxatricyclo[6.3.0.01.6]undeca-2,4-
diene with 80 % diastereomeric excess. Three methyl groups at 6.0.89 (d, J = 7.5
Hz), 1.04 (s) and 1.32 (d, J = 5.9 Hz) were assigned to 7-Me, 8-Me and 10-Me,
respectively. The peaks at 6 3.42 (dd, J = 10.0, 6.3 H2, H6), 5.62 (d, J = 10.2 H2,
H2), 6.61 (dd, J = 10.2, 1.5 H2, H3) and 6.83 (dd, J = 6.3, 1.5 H2, H5) constituted
the cyclohexadiene skeleton.

The stereochemistry of this compound has a bridgehead 8-Me group trans
to both 7-Me and 10-Me. Isolated 4-acetyI-7,8,10-trimethyl-11-

oxatricyclo[6.3.0.01.6]undeca-2,4-diene could regenerate starting material p-

57
M1M3M4K at low conversion, however, after longer irradiation the 1-acetyl-4,5,7-

trimethyl-8-oxatricyclo[7.2.0.05-9]undeca-2,10-diene was again found.

j. p-M4K

 

 

 

A 0.02 M solution of pure trans p-M4K (purified from a trans and cis
mixture by silica gel column chromatography or HPLC) and 2.2 mg methyl
benzoate in C0300 was irradiated. At low conversion (7 % in 50 min), a signal
due to cis p-M4K was detected by 1H-NMFi spectrum and HPLC. After high
conversion (> 95 °/o in 18 h), a diastereomeric mixture (11 : 1) of 1-acetyl-4-
methyl-8-oxatricyclo[7.2.0.05.9]undeca-2,10-dienes was isolated in 41 % chemical
yield. A doublet in the 1H-NMR spectrum at 6 1.13 (J = 7.2 Hz) was assigned to
the 4-Me. There were also two sets of AB quartet olefinic peaks characteristic of

cyclobutenes.

 

 

 

58
Ketone p-M4K (0.2 g) was irradiated in methanol at > 290 nm for 16 h.
After a few days in the refrigerator, the colorless solution had turned yellow. The
mixture was purified by silica gel column chromatography. Products were
identified as a diastereomeric mixture (5 : 1) of two 4-acetyI-7-methyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-trienes and small amount (< 15 %) of 4-acetyI-7-
methyl-11-oxatricyclo[6.3.0.01-6]undeca-2,4-diene. The overall isolated yield was

34 %. This mixture was decomposed gradually even in the refrigerator.

 

k. p-M3M4M5K
O
/ hv, Pyrex l.‘ Me I...‘ Me
C0300 9‘ "'Me + 9 Me
O 1- o s
P'M3M4M5K 1 3 1

 

 

Irradiation of a methanol solution of a cis/trans mixture of p-M3M4M5K at >
290 nm provided a diastereomeric mixture of 1-acetyl-3,4,5-trimethyl-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene. The reaction is highly regioselective;
addition occurs toward the methyl group on the phenyl ring with a lower
diastereomeric excess (13 % in RdRs) than previously observed.

Two similar sets of patterns were observed in the 1H-NMFl spectrum,
except for H2, The major isomer has a quartet (J = 1.4 Hz) at 6 5.37 which
coupled only to 3-Me. However, the minor product has a quintet (J = 1.4 Hz) at 6

5.45 which is coupled to both 3-Me and H40, The major photoproduct was

59
assigned with 4-Me and 5-Me trans to each other, while the minor had 4-Me and

5-Me cis.

 

 

 

A mixture of 1-acetyI-3,4,5-trimethyl-8-oxatricyclo[7.2.0.05-9]undeca-2,10—
diene diastereomers obtained from above experiment was heated in methanol to
give two 4-acetyl-6,7,8-trimethyl-11-oxatricyclo[6.3.0.01-6]undeca-2,4-dienes with
the same diastereomeric excess (13 °/o)_ The singlets at 6 6.70 and 6 6.76 were

assigned to the methyls at C-5 for each diastereomer.

 

LP-M1M3M4M5K

0 O

O h Py e \f Me 1 M9
v, r x '

Q o / —»C,, I-G ..

\/ y

P‘M1M3M4M5K M: Me

1

 

 

A 0.021 M methanol solution of a cisxtrans mixture of p-M1M3M4M5K was

photolyzed at > 290 nm for 8 h. Photoproducts were characterized as two

60
diastereomers of 1-acetyl-3,4,5,7-tetramethyl-8-oxatricyclo[7.2.0.05:9]undeca-
2,10—diene with diastereomeric excess (16 %) and chemical yield (55 °/o).

The 1H-NMR spectrum was similar to 1-acetyl-3,4,5-trimethyl-8-
oxatricyclo[7.2.0.05v9]undeca-2,10-diene except for one more methyl group at C-
10. Regioselectivity occurred only toward the methyl group during cycloaddition
with low diastereomeric excess (10 % in R4/R5). The major product was assigned
by nOe experiments with 4-Me and 7-Me trans to 5-Me. The minor product was
4-Me cis to 5-Me but 7-Me trans to 5-Me. There were other minor signals in 1H-

NMR spectrum which were not identified.

 

 

 

A mixture of the above 1-acety|-3,4,5,7-tetramethyl-8-
oxatricyclo[7.2.0.05'9]-undeca-2,10-diene diastereomers was heated in methanol
at 40°C for 36 h. Identical diastereoselectivity was obtained for the new 4-acetyl-
6,7,8,10-tetramethyl-11-oxatricyclo[6.3.0.01'6]undeca-2,4-dienes. Again, the 1H-
NMR spectrum was comparable with 4-acetyl-6,7,8-trimethyl-11-
oxatricyclo[6.3.0.01'5]undeca-2,4-dienes excluding the 10-Ha which is replaced
with 10-Mea. The nOe results indicated that the major product has its 6-Me, 7-Me
and 10-Me groups trans to its 8-Me. The minor product has its 7-Me cis to 8-Me,

but 6-Me and 10-Me trans to 8-Me.

61
m. p-M4M5K

 

 

 

The same photolysis procedures used for p-M3M4M5K were followed. Two
diastereomers of 1-acetyl-3,4-dimethyl-8-oxatricyclo[7.2.0.05'9]undeca-2, 1 0-diene
in 61 % chemical yield and 10% diastereomeric excess were obtained. This is
similar to the two previous examples. All three 1H-NMR spectra were similar
except the bridgehead substituent, which was hydrogen (H5) in this case. The

major product was assigned to the structure with H5 trans to 4-Me.

 

 

 

Two diastereomers of 1-acetyI-3,4-dimethyl-8-oxatricyclo[7.20.05.9]—
undeca-2,10-diene were heated in methanol to give diastereomers of 4-acetyl-
6,7-dimethyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene in the same ratio. It is
noteworthy that cycloéctatrienes ( 71m = 337 nm) were obtained instead of

cyclohexadienes in this case.

62

 

 

 

An NMR-scale solution of o-l1K (1.8 mg) and 1.6 mg methyl benzoate in
C0300 (0.013 M) was irradiated at > 290 nm (Pyrex) for 1 h. The photoproducts
were two diastereomers of 9-acetyl-5-isopropyl-4-oxatricyclo[7.2.0.03.7]undeca-
2,10—diene obtained in 71 % chemical yield. The 1H-NMR results were, therefore,
similar to the angular 1-acetyl-7-isopropyl-8-oxatricyclo-[7.2.0.05.9]undeca-2,10-
dienes obtained from p-I3K, except the partial protons; H1 6 3.42 (dd, J = 6.6, 1.7
Hz), H2 6 4.72 (dd, J = 6.6, 2.5 Hz). The structure was assigned as a linear 4-6-5
ring system. The diastereomeric excess of 60 % is close to that observed in p-l3K
case (67 %). Stereochemistry about the ring junction was assigned to be similar
to the angular case: that is, bridgehead H7 is trans to 5-iPr but cis to cyclobutene

ring for the major product.

 

 

 

A methanol solution of o-I1K (0.015 M) was irradiated at > 290 nm for 5 h.
The yellow product was purified by silica gel column chromatography to give
diastereomers of 6-acetyl-10-isopropyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene in
52% chemical yield and 60% diastereomeric excess. The splitting patterns of
these compounds were similar to those of the 4-acetyl-10-isopropyI-11-
oxabicyclo[6.3.0]undeca-1,3,5-trienes. The most significant difference between
them was the olefinic protons of cycloéctatrienes. These protons were coupled to
each other, for example, 6 5.33 (dd, J = 9.4, 2.5 Hz, H2), 5.73 (dd, J = 13.2, 6.1
H2, H4), 6.01 (dd, J = 13.2, 9.4 H2, H3) and 7.05 (d, J = 6.1 Hz, H 5) for the major
isomer. The extra double bond between oxygen and carbonyl shifted the UV-
visible absorption km to longer wavelength (377 nm).

Stereochemistry of the cyclodctatrienes was determined from the
cyclobutene, since both showed the same diastereoselectivity. The bridgehead

H3 was trans to 10-iPr in the major product but H3 was cis to 10-iPr in the minor.

0. O-I1M3K

 

 

 

Irradiation of 041M3K in C0300 provided one major product which was
characterized as 9-acetyl-5-isopropyI—7-methyl-4-oxatricyclo[7.2.0.03v7]undeca-

2,10—diene with a small amount of a second diastereomer in a 9 : 1 ratio with

54

chemical yield 67%. The product mixture contained a linear cyclobutene skeleton

with 1H-NMR signals at 6 6.24 (d, J = 2.8 Hz, H10) and 6.36 (dd, J = 2.8, 0.9 Hz,

H11) and a bridgehead methyl group at 6 1.28 (s, 7-Me) instead of a proton.
Stereochemistry of the major product was shown by an n06 experiment at

-20°C. Results indicated that the major product had a bridgehead methyl group,

7-Me, cis to the cyclobutene group but trans to the 5-iPr.
0
'4.
'— :Mfi 25°C “Me Me
Me0H
”‘4,

Large scale photolysis (0.2 g of o-I1M3K) followed by silica gel column

 

 

 

chromatography gave a diastereomeric mixture of 6-acetyl-10-isopropyl-8-
methyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene in 60 % isolated yield and 80 %
diastereomeric excess. UV absorption of the yellow mixture had Amax 388 nm.
Bridgehead methyl group at 6 1.03 (s, 8-Me) made interpretation of the 1H-NMR
spectrum easier. There were 4 sets of olefinic protons 6 5.13 (d, J = 8.2 Hz, H2),
5.88 (dd, J = 12.9, 5.9 H2, H4), 6.15 (dd, J = 12.9, 8.2 Hz, H3) and 7.29 (d, J = 5.9
H2, H5) corresponding to the cycloéctatriene structure.

Diastereomeric excess of cyclodctatrienes was identical to that for the
cyclobutenes. This indicated the major cycloéctatriene had 10-iPr group trans to

8-Me. Results from n0e studies support the above observation.

p. p-C4K

 

 

O \ hv, Pyrex
Me0H or

benzene

 

p-C4K

 

 

 

A methanol (or benzene) solution of p-C4K (0.017 M) as a cis/trans

(=1/1.7) mixture was irradiated at wavelengths >290 nm (or 313 nm). 1H-NMR
analysis showed no trace of residual cyclopropyl resonances and indicated the
formation of three isomers. They were assigned the followed structures: the 1,4-
adduct (major), the polycyclic ketone (secondary) and the 1,2-adduct (minor).
They were produced in the proportion of 5 : 3 : 1, respectively, as determined by
NMR, although the ratio differed in different experiments. The isolated secondary

and minor products have the same molecular weight (230), determined by MS

spectroscopy.

66

A typical trans vinyl proton coupling constant (16.0 Hz, see Table 33),60 a
pair of cis vinyl proton coupling constants (11.1 and 10.2 Hz) typical of 6-
membered rings, and a pair of W-proton coupling constants (2.4 and 2.1 Hz)
identify the major product as a tricyclic ketone with a cyclohexa-1,4-diene
skeleton and a ring containing a trans double bond. Unfortunately, the isolation
of this compound was unsuccessful because it decomposed during
chromatography and generated a non-identifiable rearranged isomer with only
one vinyl proton ; so the structure determination of the major product was based
on the NMR spectrum of the mixture of products (Figure 8).

The secondary product, after purification by column chromatography and
recrystallization, was identified by its simple AB quartet at 6 5.52 (dd, J = 9.9, 1.6
Hz, 1H), 5.86 (dd, J = 9.9, 0.9 Hz, 1H) due to its two vinyl protons. It was further
confirmed by its distinct 13C-NMR DEPT spectrum, with 6 128.2 and 134.0 for
olefinic carbons and 6 210.2 of the non-conjugated carbonyl group (Figure 9).
The non-conjugated carbonyl group was also confirmed by its IR spectrum, with
an absorption at 1693 cm-1 .

The minor product was assigned as the seven-six-five-fused tricyclic triene
from its five vinyl resonances, especially J values (10.5 Hz and 10.3 Hz)
characteristic only of cis double bonds.61 No product with a cyclopropyl group
was detected or isolated.

A C303 solution of p-C4K and methyl benzoate (ratio = 1.5:1 in
comparison with the acetyl and methoxy groups, measured by 1H-NMR) was
irradiated at 313 nm and room temperature. 1H-NMR showed that 1.5:1 ratio by
comparing the integrations of four acetyl groups of p-C4K and three
photoproducts to methoxy group of methyl benzoate is remained at 40%
conversion . This indicated that the material balance of this photoreaction was

maintained at low conversion.

o 2% a

.0030 5 9.6.3 305326336-72.236-33.865

-67». 6:913 B 98on $22-1. B cos—26m; .23 van 92mm .m 2:9".

m

m

w

_—_brbb_[p._.FL._._rlp_.._c_._.._

m

....—

m

._.__...p_..L.

N m

..th~...~_p.._—

 

_.P...r...-_..L.._..»

'1‘1

Ildllfi. l... l.-

r k
16
955 385206

 

..l11

 

)-

 

 

4.

 

|I||J..1 133 .- l

 

'“ISI J-

7016”"-
88 [091*
6 t.

m

'EBSi

f

-
C
U

S?

\‘llll'lillt

2. a

\\

l

(.8' 9!.“

L

.\.\._

SP ' IOU
BS'EOIJ
39'8“
"'32“
EL'VBU
1

5L ' 87!.)
SB'QBU N
EE'GBLI ’-

70' Bill
BS’OSL
70' 69L!
‘3' TEL
32' 61.13

68

1°C

2°C

3°C

 

 

 

 

 

 

 

 

 

 

 

 

mm
T0
.1.
“
W&
:93). n
- «2.8! .
i 32.3.5 .1
29.-2K “10
“'9... r IQ
$3.3.V/||I|.| h
£c.~v r
33:5 .1
38%| H
23.3.1 . 6
T
.10
. 3
.
2~......\. m
1l0
. w
fi
w
“10
.m
8. .8. l .1
we. 2. l n
11.0
. u.
a
..m
C r
o .1
3 1
+ H
C ..m
o r 1
2 fl
1
+ m
0 yo
0 mm
1 I
:~ 27 1 .1

Figure 9. DEPT spectra of polycyclic ketone in CDCI3.

9- HM

 

 

 

 

A 0.02 M C0300 solution of p44K (1/1.7 = cis/trans mixture) in an NMR
tube was photolyzed at >290 nm. The photoreaction was inefficient and could not
be carried to completion. The product was identified as 1-acetyl-4-isopropyl-8-
oxatricyclo[7.2.0.0519]undeca-2,10-diene but decomposed gradually during the
irradiation. It could, however, be characterized after 10 h irradiation at 50%
conversion. There was exclusively one diastereomer in 38 % chemical yield

which was assigned with the bridgehead proton trans to 4-iPr.

 

 

 

 

The above photoproduct was heated and 4-acetyl-7-isopropyl-11-
oxatricyclo[6.3.0.0‘vajundeca-2,4-diene was characterized. Only certain peaks,
such as, 6 3.17 (ddd, J = 7.7, 55,22 H2, H3), 6.26 (d, J = 10.1 H2, H2), 6.45 (d, J
= 10.1 H2, H3) and 6.70 (d, J = 7.7 H2, H5), could be found in 1H-NMR spectrum.

These were assigned to the typical cyclohexadiene structure.

70
Ill. Diastereoselectivity and Chemical Yields of Photoproducts
Table 3 Diastereomeric Excess (de) and Chemical Yields of Various 1-Acetyl-8-

oxatricyclo—[7.2.0.0519]undeca-2,1 0-dienes

 

R2
0
1
Reactants Ratio de Chemical yield a
p-M1K 2.5/ 1 41 % (R1 / R3) 85 %
p-I1K 5/1 67%(R1/R3) 90%
p-M1M3K 9/ 1 80 % (R1 / R3) 78 %
p41M3K b >95%(R1/R3) 75%
p-M3M3K 10/ 1 82 % (R2/ R3) 76 %
p-M3M4K b > 95 % (R3/R4) 45 %
p-M1M3M4K 9/ 1 so % (R1 ms), 49 %
> 95 % (Ra / R4)
p-MqK 11/1 83%(R3/R4) 43%
p-M3M4M5K 1.3/ 1 13 % (R3 / R4) 45 %
p-M1M3M4M5K 1.4/ 1 80 % (R1 / R3), 55 %
16 % (Pb / R4)
p-M4M5K 1.2/1 10% (R3/R4) 61%
p-hK b > 95 "/1: (R3 / R4) 38 %°

a: Z+E yields, determined by internal standard (methyl benzoate) on 1H-NMR
spectra to > 95% conversion except c.
b: Single diastereomer obtained from 1H-NMR spectrum.

c: 50% conversion.

71

Table 4 Diastereomeric Excess of Various 9-AcetyI-4-oxatricyclo-

[7.2.0.03-71undeca-2,1 0-dienes

 

Reactants Ratio de Chemical yield a
o-I1K 4/1 60 %(R1/R3) 71 %
041M3K 9/ 1 80 % (R1 /R3) 67 "/0

a: Z+E yields, determined by internal standard (methyl benzoate) on 1H-NMR

spectra to > 95% conversion.

Table 5 Diastereomeric Excess of Various 4- or 6-AcetyI-11-
oxabicyclo[6.3.0]undeca-1 ,3,5-triene

Reactants

P'M1K
P'HK
P'M1M3K
P'HMaK
p-M4K
P'M4M5K
041K

O-I 1M3K

a: Z+E yields

 

Ratio

3.2/1
4.7/1
9/1

9/1
1.2/1
4/1
9/1

72

de

56 % (R1 / R3)
65 % (R1 / R3)
so % (R1 / R3)
> 95 % (R1 / R3)
80 % (R3 / R4)
10 % (R3 / R4)
60 % (R1 / R3)
80 % (R1 / R3)

b: Single diastereomer obtained from 1H-NMR spectrum.

Isolated yield a

63 %
68 °/o
48 °/o
46 %
41 °/o
44 %
52 %
60 °/o

73
Table 6 Diastereomeric Excess of Various 4-Acetyl-11-oxatricyclo[6.3.0.01-6]

undeca-2,4-diene

 

Reactants Ratio de Isolated yield a
p-M2M3K 10 / 1 85 % (R2 / R3) 58 %
p-M3M4K b > 95 % (R3 / R4) 45 %
p-M1M3M4K 9 / 1 80 % (R1 ms), 50 %

> 95 % (Fla / R4)
p-M3M4M5K 1.3/1 13%(R3/R4) 47%
p-M1M3M4M5K 1.4 / 1 80 % (R1 /R3), 48 %

16 % (Ra / R4)

p4.K b > 95 °/. (R3/R4) 38 % c
a: Z+E yields.

b: Single diastereomer obtained from 1H-NMR spectrum.

6: Chemical Yield.

V.l

RAI

1:0

74

V. Quantum Yields and Kinetic Results

Quantum yields of [2+2] cycloadduct formation were measured at low
conversion (5-15 %) by means of GO or HPLC. The COT and CH were isolated
from silica gel chromatography after large scale irradiation. The response factors
of ketones, COT and CH were measured by either GO or HPLC. About 0.01 M
solution of starting ketones in methanol was degassed by the freeze-and-thaw
method and irradiated at 313 nm with valerophenone actinometer (0A1: = 0.33)62
in a merry-go-round apparatus at room temperature (see experimental section).

The concentrations of COT and CH were measured.

Table 7 Quantum Yields of Various Cycloéctatrienes or Cyclohexadienes

Reactants Quantum yield cb
p-MoK 5‘ 0.20 b
p-M1K 0.10 b
p41K 0.12 b
p41M3K 0.19 *3
o-I1K 0.25 b
041M3K 0.15 b
p-M3M4K 0.07 0
p44K 0.08 b

a: 4'-(3-Buten-1-oxy)acetophenone
b: COT determined by GC
6. CH determined by HPLC

75

Quantum yields of photocyclization of COTS were measured at moderate
conversion (30-60 %) by means of UV. About 104-110'5 M solution of
cyclobctatrienes (optical density < 2.5), which could be detected by UV in
methanol was degassed by the freeze-and-thaw method and irradiated at 313 nm
with valerophenone actinometer (<bAp = 0.33) or at 366 nm of light with
benzophenone and benzhydrol actinometer (<1) = 0.78)63 in a merry-go-round
apparatus at room temperature (see experimental section). The disappearance of
COT was measured. The sensitized reaction by adding 0.05 M 4-methoxy-
acetophenone in above COT solution was performed in parallel with the original
photocyclization of COT. The concentration of COT in sensitized reaction had no

change after irradiation since the 4-methoxy-acetophenone absorbed all the light.

Table 8 Quantum Yields of Various Cyclobutenes

Reactants Quantum yield tb
p-MoCOT ‘1 0.14 b
p-M1COT 0.05 '0
p-I1C0T 0.08 b
P'HCOT 0.10 M
p-I1M3COT 0.11 b
p-I1MaCOT 0.11 d
o-l1COT 0.10 b
041M3COT 0.21 b

a: 4-Acetyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-triene

b: At 313 nm

0: No significant change on COT concentration after irradiation by adding 4-
methoxy-acetophenone

(I: At 366 nm

76
Quantum yields of reversed [2+2] cycloaddition for recovery of starting
ketone were measured at low conversion (15 %) by means of HPLC. About 0.005
M solution of cyclohexadienes in methanol with different amount of quencher was
degassed by the freeze-and-thaw method and irradiated at 313 nm with
valerophenone actinometer (<I>Ap = 0.33) in a merry-go-round apparatus at room

temperature. The concentrations of starting ketones were measured.

Table 9 Quantum Yields and Kinetic Data of Starting Ketones

Reactants Quantum yield <I> kq‘i.’
p-M3M4CH 0.78 5.0 a
p-M3M4CH 0.70 4.1 b

a: Quencher = 2,5-dimethyl-2,4-hexadiene

b: Quencher = sorbic acid

 

I 00/0

00/0

 

 

 

 

[Q]. M

Figure 10. Stern-Volmer plots of 4'-(3-methyl-3-penten-1-oxy)acetophenone (p-
M3M4K) with 2,5-dimethyl-2,4-hexadiene in methanol, kq'c = 5.0.

 

I 00/0

00/0

 

 

 

 

[0]. M

Figure 11. Stern-Volmer plots of 4'-(3-methyl-3-penten-1-oxy)acetophenone (p-
M3M4K) with sorbic acid in methanol, qu = 4.1.

78

Quantum yields of the formation of polycyclic ketone and 1,2-adduct from
4'-(4-cyclopropyI-3-buten-1-oxy)acetophenone were measured at 313 nm three
times at low conversion by the means of GC. Procedures as for the previous
starting ketones were followed. The quantum yields were 0.21, 0.15 and 0.16,
respectively. Since the major product wasn't stable on GC column and the ratio
between the major product and overall product mixture is 4/9 from the
determination of NMR spectroscopy, the above values only represented about

4/9 of the overall quantum yield.

79
V. Conformation Analysis

The Karplus equations are some of the most powerful theoretical rules for
solving the structural and conformational problems in organic chemistry. They
predict an approximate relation between the dihedral angle 0 and the vicinal
coupling constant J 11-33”, Vicinal coupling is defined as the interaction between
nuclei bound to contiguous atoms, i.e. a coupling across three bonds. The
Karplus rule is usually expressed by the following equations. In general, trans

vicinal coupling constants are larger than cis.64

J H-C-C—H' = 8.5 0082 0 - 0.3 0° < (j) < 90°
JH-C-C-H' = 9.5 cos2 0 - 0.3 90° < (I) < 180°

The photoproduct structure was firstly minimized by molecular mechanics
(MM2),‘35'66 then further optimized at the semi-empirical level (AM1).‘57168 All
calculations were performed using unrestricted Hartree-Fock (UHF) treatment.
The structure of the secondary polycyclic photoproduct from p-C4 was calculated
to give the best geometry (Figure 12) and dihedral angles (Table 10). From
dihedral angles, vicinal coupling constants J H-C-C-H' were calculated by the
Karplus equations. Theoretical vicinal coupling constants correlate well with the
experimental vicinal coupling constants obtained experimentally.

The best geometry and dihedral angles of other CB, CH and COT were

also obtained and shown in the following pages.

80

Figure 12. Best geometry of polycyclic ketone

 

Table 10 Coupling Constants of Polycyclic Ketone

Atoms ¢ dihedral angle J calc (HZ) J 9pr (Hz) a
H(18)-C(5)-C(6)-H(19) 49.076 3.4 6.5
H(18)-C(5)-C(7)-H(28) 82.079 0.0 0.0
H(18)-C(5)-C(7)-H(29) -44.255 4.1 7.1
H(19)-C(6)-C(9)-H(26) -62.414 1.4 1.0
H(20)-C(2)-C(3)-H(21) -0.633 b 9.9
H(24)-C(12)-C(13)-H(22) -27.406 6.4 6.5

H(25)-C(12)-C(13)-H(22) -1 54.780 6.7 6.7

H(24)-C(1 2)-C(1 3)-H(23)
H(25)-C(12)-C(1 3)-H(23)
H(32)-C(1 1)-C(12)-H(24)
H(32)-C(1 1)-C(12)-H(25)
H(26)-C(9)-C(1 0)-H(27)
H(31 )-C(8)-C(9)-H(26)
H(30)-C(8)-C(9)-H(26)
H(27)-C(10)-C(1 1 )-H(32)
H(28)-C(7)-C(8)-H(30)
H(28)-C(7)-C(8)-H(31 )
H(29)-C(7)-C(8)-H(30)
H(29)-C(7)-C(8)-H(31 )

a. 500 MHz 1H-NMR

b. Olefinic protons

81

102.147
-25.224
-120.335
7.040
85.582
37.497
-89.028
65.621
-121 .841
4.684
4.500
131 .031

Figure 13. Best geometry of p-I4CB

/\
(32

0.1
6.7
1.8
8.0
0.0
5.1
0.0
1.1
2.0
8.1
8.1
3.8

 

0.0
6.7
1.9
9.1
0.0
6.2
0.0
1.6
3.0
9.1
9.2
7.1

82
Table 11 Coupling Constants of p-I4CB

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)a
H(19)-C(10)-C(11)-H(18) -2.742 b 2.9
H(20)-C(2)-C(3)-H(21) -0.316 b 10.3
H(21)-C(3)-C(4)-H(22) -33.703 5.5 4.4
H(22)-C(4)-C(5)-H(23) -38.941 4.8 7.3
H(22)—C(4)-C(15)-H(31) -129.253 3.5 6.3
H(23)-C(5)-C(6)-H(24) -1 1.164 7.9 10.5
H(23)-C(5)-C(6)-H(25) 108.570 1 .6 5.0
H(24)-C(6)-C (7)-H(26) 131 .035 3.8 3.6
H(24)-C(6)-C(7)-H(27) 6.326 8.1 7.5
H(25)-C(6)-C(7)-H(26) 11.979 7.9 7.5
H(25)-C(6)-C(7)-H(27) -112.731 1.2 1.6
H(31)-C(15)-C(16)-H(32) 67.135 0 6.7
H(31)-C(15)-C(16)—H(33) -172.849 c 6.7
H(31)-C(15)-C(16)-H(34) -53.162 C 6.7
H(31)-C(15)-C(17)-H(35) -58.334 0 6.7
H(31)-C(15)-C(17)-H(36) -179.368 C 6.7
H(31)-C(15)-C(17)-H(37) 61.184 c 6.7

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 14. Best geometry of p-M1CB

H(1?

      
        

we

0

  

30

Table 12 Coupling Constants of p-M1CB

Atoms

H(16)-C(2)-C(3)-H(17)
H(17)-C(3)-C(4)-H(19)
H(17)-C(3)-C(4)-H(18)
H(18)-C(4)-C(5)-H(20)
H(19)-C(4)-C(5)-H(20)
H(20)-C(5)-C(6)-H(21)
H(20)-C(5)-C(6)-H(22)
H(21)-C(6)-C(7)-H(23)
H(22)-C(6)-C(7)-H(23)
H(23)-C(7)-C(15)-H(29)

4’ dihedral angle

2.969
-82.340
33.254
-88.309
27.426

1 54.009
32.825
—1 48.090
-27.223
63.1 85

H72?)

4

J calc (HZ)

W
.130
; 7’. 14)

.111 0
\ .\
H31.

0.0
5.6
0.0
6.4
7.4
5.5
6.8
6.5

J expl (HZ) a

10.1
2.3
6.6
2.1
8.0

12.8
6.0

1 1.3
5.1
6.0

84

H(23)-C(7)-C(15)-H(30) -176.337 c 6.0
H(23)-C(7)-C(15)-H(31) -56.659 c 6.0
H(24)-C(10)-C(1 1)-H(25) -3.917 b 2.8

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 15. Best geometry of p-M1M3CB

 

Table 13 Coupling Constants of p-M1M3CB

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ) a
H(17)-C(2)-C(3)-H(18) 1.675 b 10.0
H(18)-C(3)-C(4)-H(19) -82.420 0.0 1.7

H(18)-C(3)-C(4)-H(20) 33.017 5.7 6.1

85

H(21)-C(6)-C(7)-H(23) -24.951 6.7 10.4
H(22)-C(6)-C(7)-H(23) -145.252 6.1 5.7
H(23)-C(7)-C(16)-H(32) -52.006 0 6.2
H(23)-C(7)-C(16)-H(33) 68.046 0 6.2
H(23)-C(7)-C(16)-H(34) -171.440 0 6.2
H(24)-C(10)-C(1 1)-H(25) -3.876 b 2.9

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 16. Best geometry of p-I1M3CB
H127)

‘g@ (30)

819% 2°98 $29)
H(22
@-
(2 :90:

H e30: H37)
(23 \ (25
c 115-Le 17)
H - £3} )
“1,59 )
H‘um
Table 14 Coupling Constants of p-I1M3CB
Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)°

H(19)-C(2)-C(3)-H(20) 0.949 b 10.2

86

H(20)-C(3)-C(4)-H(21) -83.541 0.0 1.6
H(20)-C(3)-C(4)-H(22) 32.692 5.8 5.8
H(23)-C(6)-C(7)-H(25) -23.567 6.8 10.4
H(24)-C(6)-C(7)-H(25) -144.367 6.0 5.7
H(25)-C(7)-C(16)-H(34) -174.130 9.0 5.7
H(34)-C(16)-C(17)-H(35) -178.210 0 6.6
H(34)-C(16)-C(17)-H(36) -58.016 0 6.6
H(34)-C(16)-C(17)-H(37) 61.952 0 6.6
H(34)-C(16)-C(18)-H(38) 61.202 c 6.6
H(34)-C(16)-C(18)-H(39) -58.663 0 6.6
H(34)-C(16)-C(18)-H(40) -179.163 0 6.6
H(26)-C(10)-C(1 1)-H(27) 3.759 b 2.9

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

87

Figure 17. Best geometry of p-M2M303
H(25)

 

Table 15 Coupling Constants of p-M2M3CB

Atoms

H(17)-C(2)-C(3)-H(18)
H(1 8)-C(3)-C(4)-H(19)
H(18)—C(3)-C(4)-H(20)
H(21 )-C(6)-C(7)-H(22)
H(21 )-C(6)-C(7)-H(23)
H(21)-C(6)-C(16)-H(32)
H(21)-C(6)-C(16)-H(33)
H(21 )-C(6)-C(16)-H(34)
H(24)-C(10)-C(1 1 )-H(25)
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

¢ dihedral angle

-0.316
-84.417
31 .292
-12.220
1 12.857
-59.502
60.314
-179.368
-2.866

J calc (HZ)

0.0
5.9
7.8
1 .2

J expl (HZ) a

9.8
2.6
6.8
8.1
4.0
6.9
6.9
6.9
3.0

88

Figure 18. Best geometry of p-M3M 4C8

 

Table 16 Coupling Constants of p-M3M4CB

Atoms

H(17)-C(2)-C(3)-H(18)
H(18)-C(3)-C(4)-H(19)
H(19)-C(4)-C(15)-H(29)
H(19)-C(4)-C(15)-H(30)
H(19)-C(4)-C(15)-H(31)
H(20)-C(6)-C(7)-H(22)
H(20)—C(6)-C(7)-H(23)
H(21)-C(6)-C(7)-H(22)
H(21 )-C(6)-C(7)-H(23)
H(24)-C(10)-C(1 1 )-H(25)
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

¢ dihedral angle

-0.346
-88.876
-63.508
175.935

56.019
-17.157
108.181

-138.261
-12.923
-3.350

J calc (HZ)

0.0

7.5
0.6
4.9
7.7

J expl (HZ) a

10.0
4.1
7.4
7.4
7.4
7.7
5.9
6.9
8.3
2.9

89

Figure 19. Best geometry of p-M1M3M4CB
+1125)

    
  

£61...

"I 1 mm» H 23)
1i 1
1319.12?ch

tail?-

   
 

)

Table 17 Coupling Constants of p-M1M3M4CB

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)a
H(18)-C(2)-C(3)-H(19) 1.343 b 10.0
H(19)-C(3)-C(4)-H(20) -91.422 0.0 4.3
H(20)-C(4)-C(14)-H(29) -68.300 0 7.4
H(20)-C(4)-C(14)-H(30) 174.934 0 7.4
H(20)-C(4)-C(14)-H(31) 55.245 0 7.4
H(21)-C(6)-C(7)-H(23) -36.833 5.1 7.3
H(22)-C(6)-C(7)-H(23) -1 57.735 7.9 7.3
H(23)-C(7)-C(1 6)-H(35) -58.380 C 6.1
H(23)-C(7)-C(16)-H(36) 61 .550 C 6.1
H(23)-C(7)-C(16)-H(37) -178.551 0 6.1
H(24)-C(10)-C(1 1)-H(25) -3.324 b 3.0

a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

Figure 20. Best geometry of p-M4CB

 

Table 18 Coupling Constants of p-M4CB

Atoms

H(16)-C(2)-C(3)-H(17)
H(17)-C(3)-C(4)-H(18)
H(18)-C(4)-C(5)-H(19)
H(18)-C(4)-C(15)-H(29)
H(18)-C(4)-C(15)-H(30)
H(18)-C(4)-C(15)-H(31)
H(19)-C(5)-C(6)-H(20)
H(19)-C(5)-C(6)-H(21)

¢ dihedral angle

1 .360
-92.681
41.146
-64.545
175.337
55.316
153.592
32.630

J calc (HZ) J expl (HZ)a
b 10.1
0.0 3.7
4.5 7.2
C 7.2
c 7.2
C 7.2
7.3 9.3
5.7 5.2

91

H(20)-C(6)-C(7)-H(22) -15.459 7.6 7.5
H(20)-C(6)-C(7)-H(23) -140.000 5.3 6.7
H(21)-C(6)-C(7)-H(22) 105.261 0.3 3.4
H(21)-C(6)-C(7)-H(23) -19.276 7.3 7.5
H(24)-C(10)-C(1 1)-H(25) -4.443 b 2.9

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 21. Best geometry of p-M3M4M5CB
2123')

     
  
    

011 WWW

117191?
gm 12111162.?)

' 2@ @
1. r I

Table 19 Coupling Constants of p-M3M4M5CB

Atoms ‘1) dihedral angle J calc (HZ) J expl (HZ) a
H(19)-C(4)-C(16)-H(32) -68.158 C 7.2
H(19)-C(4)-C(16)-H(33) 171 .483 C 7.2
H(19)-C(4)-C(16)-H(34) 51 .150 C 7.2

H(20)-C(6)-C(7)-H(22) -15.681 7.6 7.4

92

H(20)-C(6)-C(7)-H(23) 109.636 0.6 3.9
H(21)-C(6)-C(7)-H(22) -137.066 4.6 6.5
H(21)-C(6)-C(7)-H(23) -1 1.566 7.6 7.6
H(24)-C(10)-C(11)-H(25) -3.196 b 3.0

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 22. Best geometry of p-M1M3M4M50B

 

143)

Table 20 Coupling Constants of p-M1M3M4M5CB

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ) a
H(20)-C(4)-C(1 6)-H(32) -69.326 C 7.4
H(20)-C(4)-C(1 6)-H(33) 170.212 C 7.4

H(20)-C(4)-C(16)-H(34) 49.946 c 7.4

H(21 )-C(6)-C(7)-H(23)
H(22)-C(6)-C(7)-H(23)
H(23)-C(7)-C(18)-H(38)
H(23)-C(7)-C(18)-H(39)
H(23)-C(7)-C(1 8)-H(40)
H(24)-C(10)-C(1 1 )-H(25)
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

93

-24.707 6.7
-145.1 12 6.0
-171 .226 c

-51 .634 c

68.339 c
-3.637 b

10.2
5.8
6.2
6.2
6.2
2.9

94
Figure 23. Best geometry of HIM sea

 

 

 

 

 

Table 21 Coupling Constants of p-M4M5CB

Atoms ¢ dihedral angle J calc (HZ) J expl (H2)a
H(18)-C(4)-C(5)-H(19) 44.236 4.1 2.6
H(16)-C(4)-C(16)-H(32) -66.746 0 6.4
H(18)—C(4)-C(16)-H(33) 173.426 0 6.4
H(18)-C(4)-C(16)—H(34) 52.935 0 6.4
H(19)-C(5)-C(6)-H(20) 31.323 5.9 7.7
H(19)-C(5)-C(6)-H(21) ‘ 152.076 7.1 10.2
H(20)-C(6)-C(7)-H(22) 43.035 7.7 7.2
H(20)-C(6)-C(7)-H(23) 1 12.322 1.0 4.1
H(21)-C(6)-C(7)-H(22) -133.624 4.2 6.0
H(21)-C(6)-C(7)-H(23) -6.267 8.0 6.9

H(24)-C(10)-C(1 1)-H(25) -3.467 b 2.8

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 24. Best geometry of o-I1CB
H127)

11) H19)

423) r ' >01 +1136)
1 r 21 C1
Hg V) VLS) H1212: )H ’ ) @4)
HQ ) H33)
Table 22 Coupling Constants of o-I1CB
Atoms ii) dihedral angle J calc (HZ)
H(18)—C(1)-C(2)-H(19) 33.121 5.7
H(20)-C(5)-C(6)-H(21) -14.167 7.7
H(20)-C(5)-C(6)-H(22) -134.175 4.3
H(20)-C(5)-C(15)-H(31) -176.621 9.2
H(21)-C(6)-C(7)-H(23) 19.510 7.3
H(22)-C(6)-C(7)-H(23) 140.092 5.3
H(23)-C(7)-C(8)-H(24) -55.675 2.5
H(23)-C(7)-C(8)-H(25) -173.326 9.0
H(31)-C(15)-C(16)-H(32) -59.453 c
H(31 )-C(1 5)-C(16)-H(33) 60.534 c
H(31)-C(15)-C(16)-H(34) -180.000 0

.‘ $111 2
H(26' .
9 . - (2
E)
9

(35)

J expl (Hz)a

6.6
12.4
4.9
6.7
9.8
3.8
5.2
8.7
6.7
6.7
6.7

H(31)-C(15)-C(17)-H(35) 61.178 0 6.7
H(31)-C(15)-C(17)-H(36) -179.051 0 6.7
H(31)-C(15)-C(17)-H(37) -58.962 0 6.7
H(26)-C(10)-C(1 1 )-H(27) -3.259 b 2.8
a. 300 MHz 1H-NMR
b. Olefinic protons
c. Free rotation protons
Figure 25. Best geometry of 041M368
H 2
A His?» (31
H(21) H8 CE) V
n ' fl “£3 0 C 1(a)
H “#1“ (91911 H 39)
A 9' .2 ‘ ' la: 3%1 :
H 28) . H(24 1 (3
12) H(23) -- 1
E) V H 34) (3
(30 V ( )
(29) V v
Table 23 Coupling Constants of o-I1M30B
Atoms ¢ dihedral angle J calc (HZ) J expl (Hz)a
H(19)-C(1)-C(2)-H(20) 31 .858 5.8 6.6
H(21)-C(5)-C(6)-H(22) -9.1 17 8.0 1 1 .0
H(21)-C(5)-C(6)-H(23) -130.568 3.7 5.0
H(21)-C(5)-C(16)-H(34) 176.636 9.1 6.9
H(34)-C(16)-C(17)-H(35) -59.684 0 6.8
H(34)-C(16)-C(17)-H(36) 60.314 0 6.8
H(34)-C(16)-C(17)-H(37) -180.000 0 6.8

96

97

H(34)-C(16)-C(18)-H(38) 61.741
H(34)-C(16)-C(18)-H(39) -176.296
H(34)-C(16)-C(18)-H(40) -56.259
H(26)-C(10)-C(11)-H(27) -3.162

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 26. Best geometry of p-MzM 3CH

61‘;
L ) H 19)
CE 3
H127) -. {1% 0‘
(23) H(18

Table 24 Coupling Constants of p-M2M3Cl-I

Atoms ¢ dihedral angle
H(17)-C(2)-C(3)-H(18) 0.633
H(19)-C(5)-C(6)-H(20) -54.526
H(20)-C(6)-C(7)-H(21) -131.334
H(20)-C(6)-C(7)-H(22) 5.289
H(23)-C(9)-C(10)-H(24) -136.91O
H(23)-C(9)-C(10)-H(25) -13.567

H(23)-C(9)-C(1 6)-H(32) -71 .754

 

J calc (HZ)

3.0
3.8
8.1
4.8
7.7

6.8
6.8
6.8
2.8

J expl (Hz)a

10.2
5.5
6.9

10.9
7.0

10.9
6.8

98

H(23)-C(9)-C(16)-H(33) 47.626 0 6.6
H(23)-C(9)-C(16)-H(34) 167.572 0 6.8
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

Figure 27. Best geometry of p-MgM 4CH

 

A
H3
0 4) H( 9)
c1
F1156 ,9
HQ 13) ”33) £9}
H536)

Table 25 Coupling Constants of p-M3M4CH

Atoms li> dihedral angle J calc (HZ) J expl (HZ) a
H(17)-C(2)-C(3)-H(18) 0.448 b 9.7
H(19)-C(5)-C(6)-H(20) -53.638 3.2 5.8
H(20)-C(6)-C(7)-H(21) 136.126 4.6 10.7
H(21)-C(7)—C(15)-H(29) 66.827 0 7.5
H(21)-C(7)-C(15)-H(30) -172.424 0 7.5
H(21)-C(7)-C(15)-H(31) -52.549 C 7.5
H(22)-C(9)-C(10)-H(24) 7.919 6.0 9.2

H(22)-C(9)-C(10)-H(25) 1 31 .627 3.9 6.2

99

H(23)-C(9)-C(10)-H(24) -1 10.920 0.9 3.6
H(23)-C(9)—C(10)-H(25) 12.785 7.7 7.5
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

Figure 28. Best geometry of p-M1M3M46H

 

Table 26 Coupling Constants of p-M1M3M4CH

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)a
H(18)-C(2)-C(3)-H(19) 0.316 b 10.2
H(20)-C(5)-C(6)-H(21) 51.447 3.2 6.3
H(21)-C(6)-C(7)-H(22) 139.936 5.3 10.0
H(22)-C(7)-C(15)-H(29) 66.665 0 7.5
H(22)-C(7)-C(15)-H(30) -169.181 C 7.5
H(22)-C(7)-C(15)-H(31) 50.130 c 7.5
H(23)-C(9)-C(10)-H(25) 163.008 8.3 10.8
H(24)-C(9)-C(10)-H(25) 43.654 4.1 4.8

H(25)-C(1 0)-C(1 7)-H(35) -63.834 0 5.9

100

H(25)-C(10)-C(17)-H(36) 175.923 0 5.9
H(25)-C(10)-C(17)-H(37) 55.920 c 5.9
a. 300 MHz 1H-NMR

b. Olefinic protons

c. Free rotation protons

Figure 29. Best geometry of p-MgCOT

n H(19)
(2 ) V iii/27> H@

O
V

 

“412

Table 27 Coupling Constants of p-MoCOT

Atoms ¢ dihedral angle J calc (HZ) J expl(1"1z)a
H(15)-C(2)-C(3)-H(16) 50.074 b 8.1
H(17)-C(5)-C(6)-H(18) -3.330 b 1 1.3
H(18)-C(6)-C(7)-H(19) 30.673 5.9 4.0
H(18)—C(6)-C(7)-H(20) 147.650 6.4 7.9
H(19)-C(7)-C(8)-H(21) 75.292 0.3 3.5
H(20)-C(7)-C(8)-H(21) -40.683 4.5 6.2
H(21)-C(8)-C(9)-H(22) -26.845 6.5 7.7
H(21)-C(8)-C(9)-H(23) -147.137 6.4 6.0

H(22)-C(9)-C(10)-H(24) -106.937 3.6 5.4

101

H(22)-C(9)-C(10)-H(25) 16.420 7.5 8.8
H(23)-C(9)-C(10)-H(24) 1 1.663 7.6 9.2
H(23)-C(9)-C(10)-H(25) 137.016 4.6 4.9

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 30. Best geometry of p-M1COT

1472‘s)
427)
0‘5 V
1323; 1) ((51 (‘0)
4 .
”may
36‘.
H(16)
V

 

(2)
Table 28 Coupling Constants of p-M1COT
Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)a
H(16)-C(2)-C(3)-H(17) 50.207 b 6.0
H(18)-C(5)-C(6)-H(19) -2.900 b 1 1.3
H(19)-C(6)-C(7)-H(20) 29.699 6.1 7.9
H(19)-C(6)-C(7)-H(21) 147.654 6.4 7.9

H(20)-C(7)-C(8)-H(22) 75.360 0.3 3.0

102

H(21)-C(7)-C(8)-H(22) -40.991 4.4 10.5
H(22)-C(8)-C(9)—H(23) 26.625 6.3 5.4
H(22)-C(8)-C(9)-H(24) -148.969 6.5 1 1.9
H(23)-C(9)-C(10)-H(25) 20.739 7.1 9.9
H(24)-C(9)-C(10)-H(25) 141.200 5.4 6.0
H(25)-C(10)-C(15)-H(29) 57.233 0 6.2
H(25)-C(10)-C(15)-H(30) 62.707 0 6.2
H(25)-C(10)-C(15)-H(31) 177.031 0 6.2

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 31. Best geometry of p-M1M3COT

A Hi?!)
H(28) 14727) H"
(3 ._
(26). ) 3111113026 22) mm”)
. 24
“11“” :10 39: v)
A a .' 5 3 2
H(18 .. 1 ,, ~ g
o' .1 m
{1) H\(3/)
Table 29 Coupling Constants of p-M1MchT
Atoms (1’ dihedral angle J calc (HZ) J expl (Hz)a
H(17)-C(2)-C(3)-H(18) 52.277 b 6.6
H(19)-C(5)-C(6)-H(20) -2.215 b 10.8

H(20)-C(6)-C(7)-H(21 ) -41 .375 4.5 9.1

103

H(20)-C(6)-C(7)-H(22) 72.791 1.4 7.1
H(23)-C(9)-C(10)-H(25) 2.451 6.2 10.2
H(24)-C(9)-C(10)-H(25) 116.700 1.6 4.9
H(25)-C(10)-C(16)-H(32) -180.000 c 6.1
H(25)-C(10)-C(16)-H(33) 60.625 0 6.1
H(25)—C(10)-C(16)-H(34) 59.291 c 6.1

a. 300 MHz 1H-NMFi
b. Olefinic protons

c. Free rotation protons

Figure 32. Best geometry of p-I1MchT

H723)
A
H(29)
V A
w i H 31)
‘28 (B @14- (32,
£21 (20) H 2 ) M2}
H(grr ‘ ‘. , e)
H(- 39: C210? 3) ..
H(19) 1 (2 ) H39)
V ‘..1..1 V
V HC 6)": "1168)
' H 40)
«3‘7 13’)
Table 30 Coupling Constants of p-I1MchT
Atoms ‘1) dihedral angle J calc (HZ) J expl (Hz)a
H(1 9)-C(2)-C(3)-H(20) 58.366 b 6.6

H(21)-C(5)-C(6)-H(22) -0.448 b 10.6

104

H(22)-C(6)-C(7)-H(23) 59.393 4.8 9.4
H(22)-C(6)-C(7)-H(24) 73.457 1.2 7.2
H(25)-C(9)-C(10)-H(27) 114.500 1.3 5.2
H(26)-C(9)-C(10)-H(27) -3.182 6.2 11.4
H(27)-C(10)-C(16)-H(34) -172.123 8.9 7.6
H(34)-C(16)-C(17)-H(35) -179.051 0 6.7
H(34)-C(16)-C(17)-H(36) 60.920 0 6.7
H(34)-C(16)-C(17)-H(37) 56.403 0 6.7
H(34)-C(16)-C(18)-H(38) 160.000 0 6.7
H(34)-C(16)-C(18)-H(39) 59.216 0 6.7
H(34)-C(16)-C(18)-H(40) 50.333 0 6.7

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

Figure 33. Best geometry of o-I1COT

42%)
if) 5)
(f) :19 H133)

H127) (19 H ' (3 @méfiz)
:60: ': ’6‘ , 1 .)
61‘. 216‘” - is) ‘

‘ H611
H( v C&;U4) H(18 1@)

(2
1 ) (3) 36)
H29)

105
Table 31 Coupling Constants of o-l1COT

Atoms ¢ dihedral angle J calc (HZ) J expl (HZ)a
H(18)-C(2)-C(3)-H(19) 53.675 b 9.4
H(19)-C(3)-C(4)-H(20) 2.645 b 13.2
H(20)-C(4)-C(5)-H(21 ) -43.729 b 6.1
H(22)-C(7)-C(8)-H(24) 61.793 1.6 1.8
H(23)-C(7)-C(8)-H(24) 177.390 9.1 7.4
H(24)-C(8)-C(9)-H(25) -92.258 0.0 5.4
H(24)-C(8)-C(9)-H(26) 25.868 6.5 8.8
H(25)-C(9)-C(10)-H(27) 1 10.348 0.8 4.7
H(26)—C(9)-C(10)-H(27) -9.232 6.0 10.9
H(27)-C(10)-C(15)-H(31) -178.483 9.2 7.5
H(31)-C(15)-C(16)-H(32) 179.294 0 6.8
H(31)-C(15)-C(16)-H(33) 58.530 C 6.8
H(31)-C(15)-C(16)-H(34) -60.868 C 6.8
H(31)-C(15)-C(17)-H(35) -179.453 C 6.8
H(31)-C(15)-C(17)-H(36) 60.786 0 6.8
H(31)-C(15)-C(17)-H(37) 56.619 c 6.8

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

106

Figure 34. Best geometry of o-I1M3COT
3730) —- HES) H/(3\8

H(40
u-

   
  
 

 
 
  

 
 

{2‘2
H(39) L

Table 32 Coupling Constants oi o-I1M3COT

Atoms ii) dihedral angle J calc (HZ) J expl (HZ)a
H(19)-C(2)-C(3)-H(20) 54.928 b 8.2
H(20)-C(3)-C(4)-H(21) -4.509 b 12.9
H(21)-C(4)-C(5)-H(22) -40.491 b 5.9
H(25)-C(9)-C(10)-H(27) 116.195 1.5 5.2
H(26)-C(9)-C(10)-H(27) -1 .002 8.2 1 1.0
H(27)-C(10)-C(15)-H(31) -177.878 9.1 7.3
H(31)-C(15)-C(16)-H(32) 179.051 c 6.7
H(31)-C(15)-C(16)-H(33) 56.427 0 6.7
H(31)-C(15)-o(16)-H(34) -61.076 c 6.7
H(31)-C(15)-C(17)-H(35) -178.775 C 6.7
H(31)-C(15)-C(17)-H(36) 61.198 C 6.7
H(31)-C(15)-C(17)-H(37) 56.166 0 6.7

a. 300 MHz 1H-NMR
b. Olefinic protons

c. Free rotation protons

i

107
The following table 12 is given to demonstrate the cis olefinic coupling
constants69 in comparison with the cyclobutenes, cycloheptenes, cyclohexenes

and cyclononenes obtained in this dissertation.

Table 33 Cis Olefinic Coupling Constants in Cyclic Systems

Ring size J H - C=C- H (Hz)
3 0.5 - 1.5
4 2.5 - 3.7
5 5.1 - 7.0
6 8.8 - 11.0
7 9.0 - 12.5 a
8 10.0 - 13.0
cis -Cyclononene 10.7 b

cis -Cyclodecene 10.8

a: J trans = 15.0 - 17.2 Hz
b: J “as: 15.5 - 16.5 Hz

DISCUSSION

I. Diastereoselectivity

Diastereoselectivity in organic reactions relates to the control of relative
stereochemistry. Stereoselective reactions are those which involve preferential
formation of one stereoisomer when more than one is possible.

The diastereoselectivity with which 0- and p-butenoxy acetophenones
undergo intramolecular [2+2] photocycloadditions were measured in this work.
Twelve para - and two ortho- substituted acetophenones with alkyl substitution on
the tether or phenyl ring were examined in terms of the diastereomeric excess of
their photocycloaddition products.70 The basic reaction creates six new
stereocenters, two of which (the 6/4 bridge) are lost when the initial
cyclohexadiene (CH) photoproduct opens to cyclooctatriene (COT). However,
two more stereocenters are created at the new 6/4 bridge when this
cyclooctatriene photocyclizes to cyclobutene (CB). Substituents on C-1, C-2 and
C-4 of tether produce stereocenters that persist throughout the reaction. Each
can exist in two geometrical relationships relative to stereocenter created by
photolysis.

The diastereoselectivity in intramolecular [2+2] ortho cycloaddition of
double bonds to triplet benzenes is extremely high. This photocycloaddition is
able to produce a cycloadduct with two new rings and up to six new
stereocenters in one steps. These six new stereocenters include four reactive
centers and two inducible centers (on the tether). Theoretically, there are at most
thirty two possible diastereoisomers of cycloadducts. However, there is
exclusively one major diastereomer obtained in most cases and the

diastereoselectivity is impressive.

108

109

The stereochemistry of substituents on the tether is established when the
first bond is formed, to produce an intermediate 1,4-biradical. Alkyl groups on the
tether or the double bond show high trans stereoselectivity with regard to
configuration of the bridgehead stereocenters. Within the error limits of 1H-NMFi
integration, identical diastereoselectivities were obtained in both photostable CB
and thermally stable CH or COT. This is understandable since no bonds are
broken adjacent to the stereocenters during interconversion.

Since the first bond formation in these intramolecular [2+2]
photocycloadditions generates a five-membered ring, the observed
diastereoselectivity is related to the energies of transition state conformations
leading to the five-membered ring. There are two possible low-energy
conformations for a simple five-membered ring model, cyclopentane, and both of
which have analogous in the cyclohexane series. One is chair-like (half chair)
and the other is boat-like (envelope).71 Both of them are flexible forms which are
easily interconvertible by pseudorotations. There is no energy maxima or minima
on the cyclopentane profile. It seems that conformational analysis is more difficult
for cyclopentane than cyclohexane.

This degeneracy can, however, be changed by suitable substitution. In our
system, replacement of a methylene group by an oxygen atom would induce a
preference for chair-like conformation because two pairs of H-H eclipsing
interaction (torsional strain) have been removed. The severe non-bonded
interaction between R1 and phenyl hydrogen (or R5)ortho to the tether also favors
the chair-like conformation (if R1 is in a favored pseudoequatorial position in Sch.
19). Therefore, the chair-like conformation is more favored and will be employed
as the transition state model.

The most stable chair-like conformation requires the substituents to

occupy pseudoequatorial position. Since the degree of diastereoselectivity is

110
representative of the conformational preference of the substituent, it should be

most pronounced with bulky groups.

Scheme 19

   

Chair-like Boat-"k6
In all cases the major product has R1 or R2 trans to R3. Biradical formation
sets the R1 /R3 or R2/ R3 relationship shown in Scheme 20. When R1 = methyl
and R3 = H in p-M1K, diastereoselectivity is only modest ( de = 41% for CB and
de = 56% for COT). Diastereoselectivity is improved ( 67% for CB and 61% for
COT ) for R1 = isopropyl and R3 = H in p—I1K due to increased steric bulk of an

isopropyl compared to a methyl substituent.

Scheme 20
R5 R2
my '0
\ R
I \ H
0 / R3 H
Chair-like

 

"A' values ( conformational free energy difference ) for equatorial
preference in cyclohexane systems indicate that Arsopmpy. (2.28) is larger than
A,,,.,my.(1.74).72 This means that the isopropyl group is more sterically
demanding than a methyl group. Isopropyl group still favors a pseudo-equatorial
position in TS-1 , although 'A' values are considered to be smaller in

cylcopentane than in cyclohexane.73

1 1 1

When R1 = methyl and R3 = methyl in p-M1M3K, diastereoselectivity
increases to 80% in both CB and COT. Diastereoselectivity become total (> 95%)
when R1 = isopropyl and R3 = methyl in p-I1M3K. Scheme 21 depicts Newman
projections viewing down the tether C—O bond. The two approaches of the
double bond to the benzene ring that produce diastereomeric products with
different degrees of pseudo-1,3-diaxial nonbonded interaction are shown by TS-1
, TS-2 and TS-3. In Ts-1, R1 group favors to occupy at pseudo-equatorial
position, which is also away from the phenyl ring. In both TS-2 and TS-3, R1
group occupies an unfavored pseudo-axial position and also suffers from a
severe pseudo-1,3-diaxial nonbonded interaction either from R3 or from R4.

Scheme 21

 

 

 

 

1 12

The difference between TS-1 and TS-4 is in vinyl bond orientation which is
achieved by a bond rotation. Regardless of bulk of R3, the double bond prefers to
occupy a pseudo-equatorial position. TS-1 seems to suffer from a pseudo-1,3-
diaxial nonbonded interaction between R3 and hydrogen at C-1 when R3 is methyl
group. However, the secondary orbital electronic effect plays an important role in
this model and leads the double bond to remain at pseudo-equatorial
position.”75 When the double bond approaches the phenyl group for bond
formation, the 1r* orbital of double bond is stabilized by the phenyl 1: orbital to
produce a secondary attractive interaction in chair-like transition state. There is
no such an effect in TS-4. The double bond occupies at pseudo-axial position in
T84 and the 1r* orbital of double bond is away from the phenyl ring, especially
after the first bond formation.

Pre-existing torsional effects between R2 = Me and R3 = Me favor R3
being trans to R2 in p-MzM 3K. The transition-state model ( TS-4 ) emphasizes
the importance of minimization of eclipsing interaction76 of R2 and R3 instead of
1,3-allylic strain.7"-78 Interaction between the methyl group and vinyl group is
small when R4 is hydrogen.

For ortho-ketones, diastereoselectivity of R1 and R3 is similar to the para.
case. Diastereoselectivity of CB and COT is 60% in MK and 80% in o-I1M3K.
Selectivity decreases slightly for CB formation in o-l1M3K compared to p-I1M3K
(> 95%). This is probably due to the increased steric strain found in the angular
ring system compared to the linear.

The above diastereoselectivity reveals that there is a delicate balance
among nonbonded interaction, torsional strain, allylic strain and secondary orbital
electronic effect. The minor products may be generated from either TS-2, TS-3,

TS-4 or boat-like transition state mentioned previously.

113

Beckwith has proposed general guidelines to predict the stereochemical
outcome of intramolecular free-radical cyclization reactions of simple substituted
hex-5-enyl radicals.”81 Cyclization of 1- and 3-substituted hex-5-enyl radicals
leads mostly to cis-disubstituted cyclopentyl products, whereas 2- and 4-
substituted hex-5-enyl radicals give predominantly trans products. Observed
stereochemical results were rationalized by invoking a theoretically derived
'chair-like' transition state (Scheme 22) which has a long incipient bond (ca. 2.3

A), in accordance with an early transition state predicted for these reactions.82

Scheme 22

R3

R4
R5 H

The major product is formed via a conformation where the substituents
occupy a pseudo-equatorial position. The diastereomeric excess formed in 3-
methyl-hex-5-enyl radical cyclization was 46% of cis-methyl- cyclopentyl product.
This is similar to the results of p-M1K (41%). The only difference is a
replacement of the methylene group in position 2 by an oxygen atom in our
system.

Diastereoselectivity of ring closure for each radical is due primarily to
differences in activation energy between conformations leading to the two
diastereomers. For modest diastereoselectivity (46%) obtained above, 0.63

kcal/mol of difference in activation energy is required.80 This difference was

1 14
calculated to be 0.36 kcal/mol by Houk with the inclusion of a boat-like exo
transition structure in addition to Beckwith's chair-like transition structure.83 The
difference in activation energy of two diastereomers in our system should also be
relatively small and close to 0.6 kcal/mol.

In 4-methyl hex-5-enyl radical cyclization, the trans-dimethyl cyclopentyl
product was obtained with 64% diastereomeric excess.80 In our system using p-
M2M3K the opposite selectivity was observed. The reaction appeared to proceed
via formation of the cis-dimethyl-oxy-cyclopentyl radical with R2 being trans to R3.
This is attributed to the torsional interaction between R2 and R3 as mentioned
previously.

Biradical closure sets the R3/ R4 relationship. This intermediate itself
shows strong conformational preferences during its cyclization, which results
from steric effects of substituents on the tether. In p-M3M 4K, only one
diastereomer is observed (> 95%) for R3 = R4 = methyl. As shown in Scheme 23,
the best conformation of the biradical BR-1 has R4 pointed away from the six-
membered ring and placed it anti to R3.

The diastereomeric excess of 80% observed in p-M1M3M4K example is
similar to that measured from irradiation of p-M1M3K and p-M3M4K; R1 and R3
have 80% diastereomeric preference to be trans to each other and R3 and R4
have > 95% diastereomeric excess trans to each other.

Diastereoselectivity (80%) observed when R3 = H and R4 = methyl in p-
M4K progresses to > 95% when an isopropyl group (R4) is placed in p-l4K. The
trans preference between R3 and R4 exists regardless if R3 is H or a methyl

group in above cases.

1 15
Scheme 23

R
”\d4

R, R4: Me oriPro R1
‘— ’IO\\‘
F13

BR-2 BR-1

Becker and coworkers investigated the diastereoselectivity induced by

 

 

substituents at the end of olefins in [2+2] intramolecular photocycloaddition of
cycloenones. In contrast to our phenyl ketone systems, lower selectivity was
obtained“).41 Their explanation for the selectivity by the relative stability using
molecular mechanics (MM2) was inconclusive since the calculations gave similar
steric energies for both stereoisomers. An alternative explanation can be based
on a model proposed for oxetanes by Griesbeck.84 This assumed that for
effective triplet to singlet spin inversion the p orbitals of a 1,4-biradical
intermediate have to be perpendicular to each other. It seems reasonable that
the methyl or bulky isopropyl group will orient itself to the least crowded

environment, which is away from the ring skeleton. (Scheme 24)

Scheme 24

 

 

BR-2

1 16

The ring methyl in p-M4M5K, p—M3M4M5K and p-M1M3M4M5K promotes
complete regioselectivity.‘3 This means that the double bond approach toward the
methyl group on the benzene ring is not hindered by R4, however the
diastereoselectivity of R3 and R4 is reduced. Scheme 25 portrays the high
selectivity of R3/ R, which decreases when there is a methyl group on the
benzene ring. Steric interactions between R4 and R5 ( = Me ) cause the 1,4-
biradical to have no rotational preference as shown in BR-3 and BR-4.

1H-NMR analysis of cyclobutene geometry indicated that there is only one
proton H43 having allylic coupling with vinyl proton H2. The other, H43, doesn't
show allylic coupling in most cases. From AM1 calculations, the dihedral angle of
C2-C3-C4-H4a is normally about 145° and the dihedral angle of CZ-CS-C4—H4g
about 90°. However, H45 has allylic coupling with vinyl proton H 2 in p-M4CB (1.9
Hz) and p-I4CB (1.7 Hz) and their dihedral angle of C2-C3-C4-H4p are 131° and
147°, respectively. This means that the substituents change the geometry of
cyclobutene remarkably and the allylic coupling constants are sensitive to

geometry variation as observed in vicinal coupling constants (see Results).

Scheme 25

 

 

R3 and the cyclobutene ring are always cis to each other in all bicycloocta-

2,10-diene (CB) compounds as Scheme 26 indicates. The initial cycloaddition to

1 17

the benzene ring must be cis, disrotatory thermal opening furnishes a boat-
shaped all-cis cyclooctatriene. The regiospecific photoclosure of a diene is also
disrotatory and forms a cis 4/6 ring fusion, but proceeds only in the direction that
also produces a cis 5/6 ring fusion, such that the five-membered ring is trans to
the cyclobutene ring. Presumably the more conjugated diene unit with the strong
oxygen-to-carbonyl donor-acceptor property2-4v7o flattens out when excited and
the fused five-membered ring then allows the eight-membered ring to pucker only
in one direction.

In compounds formed from p-tethered ketones, this selectivity probably
represents a simple steric effect. There is no obvious steric hindrance; yet
stereoselectivity is complete. Compounds generated from o-tethered ketones
also show high stereoselectivity. The minimum energies of both cis and trans
conformers of linear cyclobutenes were calculated using PC MODEL (MMX) after

optimization. The minimum energies of cis isomers were much lower than

trans.85
Scheme 26
O
6‘" 6
0 e“ /
O
O

 

Valence tautomerism between bicyclo[4,2,0]octa-2,4-diene and cycloocta-
1,3,5-triene is affected by the additional bulky groups on the methylene carbons.

Without bulky groups, equilibrium of basic skeleton favors cyclobctatriene. The

118
equilibrium is reversed to cyclohexadiene with 95% preference when both
methylene carbons are methyl-substituted.86 It is particularly noteworthy that
most of the examples in our system favor the cyclooctatriene in the equilibrium
mixture (Scheme 27). However, equilibrium is reversed when R, is changed from
H to an alkyl group. This indicates that the alkyl substituents have a remarkable
effect on the equilibrium between cyclooctatriene and cyclohexadiene. The
variations in the equilibrium constant for this reaction is estimated to be at least

two orders of magnitude at room temperature.

Scheme 27

 

Thermal conversion of the cyclobutenes (CB) back to cyclooctatriene is
much more facile than originally thought. Thermal opening of CB has been found
to be greatly accelerated in methanol. Since this cyclobutene ring opening is
disrotatory rather than the orbital symmetry allowed conrotatory, it is thought to
involve an zwitterionic intermediate with donor-acceptor property (Scheme 28).4
Catalysis by a trace of acid in methanol provides further support for a charge
separated intermediate in this thermal transformation. The enhancement of ring
opening rate catalyzed by a trace of acid in benzene is also observed by other

co-workers in the similar photoreaction.5v6

119

Scheme 28
0
CI]
0
O O O"
/
0 0
o 0 ‘0+

 

 

Ab initio quantum mechanical calculations on model of the transition state
structures of disrotatory electrocyclizations of butadienes indicated the
substituent effects. The electron-withdrawing groups at the bridgehead have
larger effects than electron-donating groups on reducing the activation energy for
this orbital symmetry forbidden process. Electron-donating groups have smaller
effects. 97 This can explain why an acetyl group at the bridgehead in our reaction
enhances ring opening.

Steric effect plays an important role in diastereoselectivity of
photocycloaddition. The nonbonded interactions and torsional strain are
supposed to be minimized in the biradical closure. Steric interaction results in a
conformational preference during biradical coupling. In summary, the bridgehead
methyl group (R3) induces homoallylic (R1), allylic (R2) and terminal (R4) centers
trans to itself during cycloaddition.

A promising discovery was made by Wender group in total synthesis of

natural products by using photocycloaddition. Meta-photocycloaddition was used

120

as a key step in synthesis of several angular (e.g., Cedrene,35 Isocomene,88
Subergorgic Acid“) and linear triquinane compounds, (e.g., Hirsutene,89
Coriolin.9°) The mechanism is proposed via singlet excited state and concerted
pathway different from that proposed for our triplet cycloaddition. High
stereoselectivity in meta-photocycloaddition was also observed.

In synthesis of Isocomene, the cycloadduct has two methyl groups (on C-3
and C-4) on the double bond trans to each other. This is similar to our results
except ithat it involves concerted singlet reaction. The methyl group (on C-4) also

induces benzylic methyl (on C-7) to becis to itself. (Scheme 29)

Scheme 29

 

The synthesis of Subergorgic Acid reflects on the developing relative
stereochemistry between hydrogen (on C-7) of the double bond and allylic methyl
group (on C-11) trans to each other. (Scheme 30)

Scheme 30

121
The examination of stereoinduction by a homo-allylic stereogenic center
was performed in synthesis of Grayanotoxin II. The bridgehead hydrogen on C-9
of cycloadduct is trans to the large protecting TBSO group on homo-allylic
stereogenic center C-11. (Scheme 31) Stereoselectivities shown below are

attributed to the steric effect involved in transition states.

Scheme 31

 

From a synthetic viewpoint, our ortho-photocycloaddition offers access to
4-5-6-membered rings and eight-membered rings instead of poly-five-membered
rings obtained in meta-photocycloaddition. High stereo- as well as regio-
selectivity was observed in both cases. Therefore, our triplet ortho-
photocycloaddition shows a remarkable potential to become the key step in a

total synthesis.

122

ll. Biradical Intermediacy

Efficient cis -> trans isomerization of the double bond of p-(cis-3-
hexenoxy)-phenyl ketone occurs during photolysis with a quantum yield <I> =
0.27.1 This reveals that the cycloaddition mechanism does not proceed via a
concerted process. It has been thought to represent the cleavage of 1,4-biradical
intermediates that are characteristic of other triplet [2+2] photocycloadditions"1 .92
and of Norrish type II reactions.93 The previous chapter about diastereoselectivity
was concentrated on conformational preferences during biradical formation and
closure. Incorporation of a cyclopropylcarbinyl radical clock in this reaction, the
intermediacy of a 1,4-biradical was confirmed. Results show that cyclization is
very slow.94

Rapid opening of cyclopropylcarbinyl radicals to allylcarbinyl radicals is
well known in free radical chemistry and has been widely used both as a kinetic
clock57'95 and as a mechanistic probe96 for radical and biradical intermediates.
Such isomerization has been observed in the [2+2] photocycloadditions of
enones92'97v98 and ketones99 to double bonds, as well as in a host of other
photogenerated biradicals.1°°

Becker and co-workers generated a biradical from the dienone with a
cyclopropyl substituent on the double bond in the side chain.42 The isolated
rearrangement product as well as normal [2+2] cycloadduct showed in a ratio of
1:2. This indicated that the ring-opening of biradical occurred on roughly same

order of rate as ring closure. (Scheme 32)

123

Scheme 32

 

 

 

Irradiation of p-C4K resulted in formation of three products. NMR analysis
showed no trace of residual cyclopropyl resonances. These products were
assigned the following structures: 1,4-adduct, polycyclic ketone and a 1,2-
adduct (Scheme 33). They are produced in the proportion of 5 : 3 : 1,
respectively, as determined by NMR integration. The polycyclic ketone; and
the 1,2-adduct were the only isolated products. The 1,4-adduct was unstable

thermally and could not be isolated by chromatography.

Scheme 33

 

O \ hv O
—-—>
>00 MeOH

I3434K 5:321

124
Existence of a 1,4-adduct and a 1,2-adduct in product mixtures was also
observed in the photochemical reactions of benzene with furans.1°1v102 The major
1,4-adduct, minor 1,2-adduct and other minor products were obtained. Product
ratios were affected by changes in relative concentration of reactants or
irradiation condition. In most cases, the major 1,4-adduct product was too

thermally labile at room temperature, which is similar to our results. (Scheme 34)

Scheme34
O
O hv / 0
© +\/———> %+m+lsomers
5: 1

The mechanism presented in Scheme 35 shows three products might be
formed by ring-opening of the suspected initial 1,4-biradical BR-S to a cis/trans
mixture of the 1,7(9)-biradical BR-6 and BR-7. The major product is formed by
para closure of BR-6 as a 1,9- biradical. Such a para addition is similar to the
photoaddition of a diene to benzene.”103

Minor product 1,2-adduct is formed by ortho coupling of BR-7 as a 1,7-
biradical. While it seems reasonable that BR-6 can cyclize only to a 9-membered
ring, due to steric strain in a trans-1,4-adduct; it is not so evident why BR-7
cyclizes to the 7-membered ring. The instability of 1,4-adduct suggests that
para-coupling introduces sufficient ring strain that BR-6 so couples only instead
of doing nothing. As a bicyclo[4.5.0]undecadiene, 1,2-adduct is less strained
than the bicyclo[4.2.0]octadienes normally formed by cyclization of biradicals like

BR-5; so it does not undergo the further electrocyclic rearrangements observed

125

for the initial [2+2] photoadduct of most 0- and p-alkenoxyacetophenones.1 It is
considered to be unlikely that any of the observed products arise by secondary
rearrangements of p-C4CH, since the cyclopropyl group is not on a double bond
in any such rearrangement products.

The formation of polycyclic ketone can be explained by a tandem
biradical cyclization process obeying the “rule of five”, comparable to a tandem
radical cyclization,1°‘1'106 as shown in Scheme 36. The first step is a normally
disfavored endo-cyclization, here facilitated by the two frozen bonds of the spiro
structure. If we assume that polycyclic ketone is formed equally from trans and
cis allylcarbinyl biradicals, the ratios of BR-6 and BR-7 can be estimated as
2.4/1, the same as the 2.3/1 trans/cis 2-penten-5-yl radical ratio measured for the
opening of 1-cyclopr0pylethyl radical.107

The total quantum yield for formation of isolated compounds was
measured, ch = 0.21-0.15, by irradiating samples of p-C4K in parallel with a
valerophenone actinometer. The total quantum yield for reaction thus is 0.47-
0.34. It agrees with our earlier measurement that almost half of the 1,4- biradicals
BR-S undergo rearrangement and the rest revert to starting ketone.1 Since the
rate constant for opening of the model 1-cyclopropylethyl radical to the
allylcarbinyl radical is known to be 7 x 107 S'1 ,108 the rate constant of cleavage of
biradical BR-5 can be concluded to be 8 x 107 3'1, whereas coupling is relatively

slow,k53x106s4.

1 26
Scheme 35

 
    

\ hV / MeOH

W0

1,4-adduct polycyclic 1,2-adduct

127

Scheme36

 

Low cyclization / cleavage ratio for BR-S is similar to that deduced for
several of the 1,4-biradicals that intervene in enone cycloadditions,1°9 given that
both processes require the same biradical conformation. However, the reasons
remain unknown. This 1,4-biradical intermediate with one highly conjugated
radical site is shorter-lived than most other 1,4-biradicals, which have lifetimes
from 24 to 2200 ns as determined by laser flash photolysis11°v111 or
photoacoustic calorimetry.112

In contrast, the 1,7(9)-biradicals BR-6 and BR-7 are much longer lived,
since one third of the time they undergo a relatively slow 5-hexenyl radical
cyclization.113 The slow coupling is normal for 1,4-biradicals;114 the cleavage is
unusually fast and may be aided by rearomatization.

The main issues that this work addresses are the presence of a biradical
intermediate involved in the triplet ortho-photocycloaddition reaction and the

estimation of the triplet 1,4-biradical BR-5 closure rate using a appropriate

128

cyclopropylcarbinyl radical clock. From above results, the 1,4-biradical BR-5
seems to behave like a monoradical in undergoing rearrangement and tandem
cyclization. 1051115

In fact, a similar estimation of 1,4-biradicals lifetime was first presented in
Norrish type II photoreactions by Wagner.96 The photochemistry of )-
cyclopropylbutyrophenone shows that the 1,4-biradical generated by triplet-state
hydrogen y-abstraction undergo typical radical rearrangement in competition with
its normal type II reaction. (Scheme 37) The rearrangement percentages and
biradical lifetime could be properly predicted if the biradicals rearrange with the

same rate constants characteristic of monoradicals.

Scheme 37
0

Ph OH
hV O 0
Ph -—-> + /u\/\/\/ +
Ph/lL MC Ph /

Recently, there is another example using cyclopropylcarbinyl clock to
study the perpendicular alkene triplets. Caldwell and Zhou reported that the triplet
states of B-cyclopropylstyrene can be described as 1,2-biradicals.116 The
reactivities of the triplets in reactions for which the termini act independently are
similar to corresponding reactivities for cyclopropylcarbinyl free radical opening.
(Scheme 38)

Scheme 38

A hv i
\ >

‘
cis / trans isomerization

 

 

129

In terms of possible synthetic potential, the tandem radical cyclization
illustrates an efficient approach to construct multiple five-membered rings. Curran
and co-workers have reported several studies of total syntheses by employing a
tandem radical cyclization strategy.1°5 Tandem cyclization initiated by the tin
hydride has appeared to be a powerful key step in synthesizing the complicated
compounds, such as triquinane Hirsutene117 and tetraquinane Crinipellin A113.
(Scheme 39)
Scheme 39

 

The basic component of tandem radical cyclization is to allow intermediate
radicals to live long enough to cyclize. This means that all cyclization must be
faster than radical-radical or radical-solvent reactions. The tandem cyclization
has both the advantage and disadvantage of biradical vs. free radical
cyclizations. The intramolecular biradical cyclization, which is very clean,
competes better with the various internal cyclizations than does the bimolecular
trapping employed in traditional tin,1°4 oxidative manganese-based119 or
reductive Smlg120 methods. The control of initiator concentration is the main
problem of the above intermolecular-initiated radical cyclizations. However, there
is no such problem associated with intramolecular biradical cyclization. The
biradical cyclization is easily conducted (only by light) and is compatible with a
wide variety of functional groups. The only issue which needs to be addressed is

how to delay the biradical coupling to achieve tandem cyclization.

130
Since there is only one stereoisomer of polycyclic ketone obtained after
photolysis, our tandem biradical cyclization has proven to have high
stereoselectivity and chemical yield. Formation of four bonds and four rings in
one step has an important synthetic potential. The bowl-shaped polycyclic

ketone also seems to be a good host candidate in host-guest chemistry.

131

Ill. Overall Mechanism

From the photocycloaddition of alkoxyacetophenone p-MoK, the
cyclobutene and a small amount of cyclooctatriene were observed in the time-
resolved 1H-NMR spectrum. After extended irradiation only cyclobutene is
obtained. Cyclooctatrienes were claimed never to be detected during irradiation
in 1H-NMR spectrum before.59 Similar results were obtained for other
compounds. Cyclobutene with its thermodynamically preferred cyclooctatriene in
p-M1K and cyclobutene with its thermodynamically favored cyclohexadiene in p-
M3M4K were identified at low conversion by 1H-NMR spectroscopy. This follows
the proposal of first formation of cyclohexadiene, which is in thermal equilibrium
with cyclooctatriene, followed by photoelectrocyclization to cyclobutene.

The mechanism of [2+2] ortho photocycloaddition for formation of
cyclohexadiene was verified to be stepwise and revertible. Initial kinetic studies
showed p-alkoxyphenyl ketone, an acceptor, undergoes intramolecular charge
transfer with the remote donor double bond to generate an exciplex followed by
1,4-biradical formation‘ The ortho addition mode and a charge transfer process
might be predicted by the Bryce-Smith ionization potential difference rule;17 A LP.
is larger than 0.5 eV between p-alkoxyphenyl ketone (8.7 eV) and multi-
substituted alkenes (ca. 9.3 eV).121

Exciplex formation is supported by the regioselectivity from electronic
inductive substituents on the benzene observed in the triplet decay kinetics.5i6
However, both electron-withdrawing (CONH2) and electron-donating (CH3)
groups showed similar regioselectivity. This indicated that there is another
controlling steric factor of regioselectivity.

1,4-Biradical intermediacy was confirmed by the diastereoselectivity and

utility of 'radical clock“ in p-C4K mentioned previously in this thesis. The former

132
was explained by the conformational preferences in both biradical formation and
closure processes. The latter showed an efficient biradical rearrangement.

A wide range of quantum yields <1) = 0.07 to 0.25 (r able 7) for formation of
either cyclohexadienes or cyclooctatrienes were measured. All of the quantum
yields were measured at low conversion (< 15%) to prevent secondary
photoreactions. Ortho compounds have higher quantum yields than para which is
similar to early reports,2 and non-substituted compounds have higher quantum
efficiencies than substituted ones. It is believed that these retarding effects of the
alkyl substitution on the tether would result if the rate-determining step is radical
formation, with cyclization of the 5-hexenyl radical as the model.122 The alkyl-
substituted 5-hexenyl radicals have lower rate constants for cyclization than the

unsubstituted ones. (Table 34)

Table 34 Rate Constants for Cyclizations of Substituted
5-Hexenyl Radicals at 25°C

 

 

Radical k1,5exo
' / 2.3x105
(\f 2.2x105
kr 1.4x104
, /

2.5x104
' /
0r 3.5x104
- /
k/( 7.5x104

 

133

The efficient photoreversion of the thermally stable cyclohexadiene p-
M3M4CH to phenyl ketone p-M3M4K (ch = 0.70 - 0.78) explains the lowest
quantum yield (<b = 0.07) for conversion of p-M3M4K to p-M3M4CH. No p-
M3M4CB could be detected at low conversion during irradiation of p-M3M4CH.
Extended irradiation may generate some p-M3M 4COT, which could photo-convert
to p-M3M4CB (Scheme 40). Similar behavior has been observed for meta-
methoxy p- butenoxyacetophenone and its analog in which the anchoring oxygen
is replaced with a methylene group. 6’7

It is well-known that the photoreversions of biradicals in cycloaddition of
triplet enones to double bonds are efficient. ‘23 From analysis of kinetic data for
the addition of cyclohexene to cyclopentenone, de Mayo concluded that over half
of the biradicals formed reverted to alkene and ground-state ketone.114 In
general, reversion of the biradical is a major source of inefficiency in the
cycloaddition reaction. Agosta and coworkers determined that the quantum yields
for reversion are much higher than for product formation in intramolecular [2+2]
photocycloadditions of dienones.124 The similar situation has been observed in
our reaction with the increasing cleavage of the cyclobutane ring to form 1,4-

biradical and thus, the enhancement of reversion to phenyl ketone.

Scheme 40

 

134

Quantum yields of formation of cyclobutenes in secondary photochemical
electrocyclizations are 0.05-0.21 (Table 8). Alkyl substitutions seem to have no
significant influence on the quantum yields. The possibility of involving a triplet
sensitized reaction by the original phenyl ketones in photochemical
electrocyclization has been ruled out. There was no enhancement of quantum
yields for cyclobutenes formation from parallel experiments using 4-methoxy-
acetophenone. The moderate quantum yields may be attributed to cis/trans
photoisomerization of cyclooctatrienes since an intensely efficient
photoisomerization between cis,cis and cis,trans cycloocta-1,3-diene was
observed (Scheme 41 ). ‘25

Scheme 41

hv, <1) = 0.28

 

’

 

hv, (b = 0.80

AM1 calculations showed that the heat formation is -34.5 Kcanole for
cis,cis-acetyl-11-oxabicyclo[6.3.0]undeca-1,3-5-triene and -14.5 KcaI/mole for
cis,trans-acetyl-11-oxabicyc|o[6.3.0]undeca-1,3-5-triene.68 The cis,cis isomer is
20 Kcal/lmole more stable than cis, trans one in ground state. However, both of

them can undergo cisxfrans isomerization photochemically.

135

V. Conclusion

High diastereoselectivities of cyclohexadienes, cyclooctatrienes and
photostable cyclobutenes are observed in the intramolecular ortho cycloaddition
of double bonds to triplet benzenes. The observed diastereoselectivities are
explained by the chair-like transition states involved in biradical-generated and
biradical-coupled processes. The steric effects containing non-bonded
interaction, eclipsing and allylic strains, and secondary orbital effect are the
factors that determine high diastereoselectivity.

A free radical clock (cyclopropylcarbinyl radical-allylcarbinyl radical
rearrangement) provided evidence to confirm presence of a biradical
intermediate in this reaction. The lifetime of biradical could also be estimated by
this radical clock.

A rare tandem biradical cyclization process is observed. Generation of four
five-membered rings with high yield and stereoselectivity in one step may offer a

particularly attractive route to synthesize some congested natural products.

136
V. Suggestions of Further Research

Previous work has demonstrated the directing effect of a carbonyl
substituent ortho to a butenoxy tether; ortho [2+2] photoaddition of the double
bond to the benzene ring is regiospecific. The high diastereoselectivity of this
reaction was studied in this work. This has prompted an investigation into the
feasibility of promoting enantioselectivity.

Recently, high enantioselectivity was induced using either trans-(-)-
(2R,5R)-2,5-dimethylpyrrolidine or (7R)-(+)-camphorsultam chiral auxiliary
reagents located ortho to a tether. ‘26 A second approach might be to include the

chiral auxiliary groups directly on the tether itself.

0

R
)\'<:\>— 0M0
— /
R1 R3 43‘3“"

Both methods may help to reach the goal of establishing a feasible route
to the asymmetric photochemical synthesis of a series of natural products, e. g.

the sesquiterpene class.127

 

137
The isolated cyclooctatrienes consist of a skeleton of bicyclic eight-five-
membered rings. This means that our [2+2] ortho photocycloaddition may provide
considerable impetus for the development of new synthetic methodology of

medium ring compounds, such as Ceroplastol L123

 

Preliminary studies using tethers containing triple bonds were
unsuccessful. However, the reaction may become successful by the assistance
of the electronic substituents on either benzene or the alkyne. This may prove to

be another method to provide the derivatives of cyclooctatetraene.

EXPERIMENTAL

I. General Procedures

All 1H NMR and 13C NMR spectra were obtained on a 300 MHz Varian
Gemini, 3 300 MHz Varian VXR-300 or a 500 MHz Varian-500 instrument. All
the IR spectra were recorded by using a solution in CCI4 or a solid in KBr on a
Nicolet 2R/42 Fourier Transform IR spectrometer with a Hewlett Packard color
pro recorder and 0.025 mm Z12308-0 Aldrich IR cell. UV spectra were recorded
on a Shimadzu UV-160 spectrometer. Low resolution Mass spectra were
obtained on a Hewlett Packard 5890 GC/MS trio-1 and high resolution Mass
spectra were obtained on a Joel JMS-HX110 Mass spectrometer in the MSU
Mass spectrosc0pic facility. The electron impact (El) and direct probe method
were used. The range of molecular weight detected was between 45 and 750.

Gas chromatographic analyses were performed on Varian 1400 or 3400
machines with flame ionization detectors. The GC was connected to either a
Hewlett-Packard 3395A, 3393A, or 3392A integrating recorder. Three types of
columns were used for GC analysis; Magabore DB-1, Magabore D3210 and
Magabore DBWAX. HPLC analyses were performed on a Beckman 332 gradient
system equipped with a Perkin Elmer LC-75 UV detector, on a silica column.
The HPLC system was connected to a Hewlett-Packard 6080 integrating
recorder. Preparative collections were done on a Rainin Dynamax HPLC
system. For the preparative TLC, Analtech Uniplate silica gel plates of 20 x 20

cm, 1000 microm were used.

138

139
ll. Purification of Chemicals

A. Solvents

Benzene- The mixture of 0.5 L conc. sulfuric acid and 3.5 L of reagent grade
benzene were stirred for a couple of days at room temperature. The benzene
layer was separated and extracted with 200 mL portions of cone. sulfuric acid
several times until the sulfuric acid layer didn't turn yellow. The benzene was
washed with distilled water and then extracted with saturated aqueous sodium
bicarbonate solution till pH = 7. The benzene was separated, dried over
magnesium sulfate and filtered into a 5 L round bottomed flask. Phosphorous
pentoxide ( 100 g ) was added and the solution was refluxed overnight. The
benzene was distilled through a one meter column packed with stainless steel

helices. The first and last 10 % portions were discarded.

Methanol- 500 mL reagent grade absolute methanol was refluxed over 5 9
magnesium turnings with several pieces of iodine for 6 hours then distilled
through a half meter column packed with glass helices. The first and last 10 %

portions were discarded. ‘29

B. Internal Standards

Methyl benzoate- Methyl benzoate was purified by fractional distillation by Boli
Zhou.

n-Penty benzoate- n-Pentyl benzoate was purified by fractional distillation by Boli
Zhou.

n-Heptyl benzoate- n-Heptyl benzoate was purified by fractional distillation by
Boll Zhou.

140
n-Octyl benzoate- n-Octyl benzoate was purified by fractional distillation by Boli
Zhou.
meta-Dibutyl phthalate- meta-Dibutyl phthalate was purified by fractional
distillation.
Ethyl phenyl acetate- Ethyl phenyl acetate was purified by fractional distillation by
Kung-Lung Cheng.
Dodecane(012)- Dodecane was washed with sulfuric acid and distilled by Dr.
Peter J. Wagner.
Pentadecane(C15)- Pentadecane was washed with sulfuric acid and distilled by
Dr. Peter J. Wagner.
Hexadecane(C16)- Hexadecane was washed with sulfuric acid and distilled by
Dr. Peter J. Wagner.
Valerophenone- Valerophenone was prepared from the acylation of benzene with

valeryl chloride by Bong Ser Park.

C. Column Chromatography

All columns were run flash style with 200-425 mesh silica gel or 60-325
mesh neutral alumina. The column diameter was selected according to the
amount of material to be loaded: for up to one gram the diameter was 0.5", for
one to three grams the diameter was 1", and for three to ten grams the diameter
was 2'. The column was packed using cotton balls at the stopcock. Silica gel,
after being stirred with solvent completely, was poured to fill about 60% of the
total column length. The solvent was poured onto the column carefully so as not
to disturb the silica gel and about one volume was allowed to elute by gravity. A
layer of sand was placed on the top of the column to insure that the silica gel
would not be disturbed during loading. The material was loaded carefully by

pipet. Amount of solvent were added behind the loaded material as it eluted into

141
the silica gel. Once the material was completely eluted onto the silica gel, a full
volume of solvent was added and an eluting pressure to produce two

drops/second was applied.130

III. Equipment and Procedures

A. Photochemical Glassware

All photolysis glassware including pipets, volumetric flasks, syringes and
Pyrex test tubes for irradiations were rinsed with acetone, then with distilled
water, and boiled in a solution of Alconox laboratory detergent in distilled water
for 24 h. The glassware was rinsed with distilled water, and boiled in distilled
water for a couple of days, with the water being changed every 24 h. After final
rinse with distilled water, the glassware was dried in an oven at 140 °C overnight
and then cooled to room temperature.

Ampoules used for irradiation were made by heating 13 X 100 mm Pyrex
culture tubes ( previously cleaned by the procedure mentioned above )
approximately 2 cm from the top with an oxygen-natural gas torch and drawing

them out to an uniform 15 cm length.

B. Sample Preparations
All solutions were prepared either by directly weighing the starting material
into volumetric flasks or by dilution of a stock solution. Equal volume (2.8 mL) of

sample were placed via syringes into each ampoule.

C. Degassing Procedures
Filled irradiation tubes were attached to a vacuum line with a diffusion

pump. These tubes were arranged on a circular manifold equipped with twelve

142
vacuum stopcocks which fitted with size 00 one hole rubber stoppers. The
sample tubes were frozen to liquid nitrogen temperature and evacuated for 5- 10
min. The vacuum was removed and the tubes were allowed to thaw to the room
temperature in distilled water. This freeze-pump-thaw cycle was repeated three
times. The tubes were then sealed with an oxygen-natural gas torch while still

under vacuum.

D. Irradiation Procedures

All samples for quantum yield measurements were irradiated in parallel
with actinometer solutions in a merry-go-round apparatus immersed in a water
bath at approximately 25 °C. A water cooled Hanovia medium pressure mercury
lamp was used as the irradiation source. An alkaline potassium chromate
solution ( 0.002 M K2Cl04 in 1 % aqueous potassium carbonate ) was used to
isolate the 313 nm emission band. A Coming CS 737 Filter was used for 366
nm emission band.

For chemical yield and diastereoselectivity measurement using NMR, the
NMR tubes containing samples with internal standard ( Methyl Benzoate ) were
fixed into 13 X 100 mm Pyrex culture tubes with rubber septum and bubbled with
argon through a nine inches needle and then irradiated. Both the yield and
selectivity were determined by the integration of well-separated and high-
resolution 1H NMR spectra.

Preparative scale irradiation was done in two different method. A large
test tube (100 mL) with sample solution was fitted with a 24/40 rubber septum
and the sample was degassed by bubbling argon through for 20 min. or
throughout the irradiation. The test tube was attached to an immersion well by
wire and irradiated. For the larger scale reaction, photolysis was done in an

immersion well equipped with a quartz cooling jacket, a water cooling condenser.

143
Hanovia 450 W medium pressure lamp with a Pyrex filter tube was used as the

light source and argon was bubbled during the irradiation.

E. Calculation of Quantum Yields

Quantum yields were calculated with the following equation,

<I>=[p]/l (5)

where [ p ] is the concentration of photoproducts and l is the intensity of light
absorbed by samples.

The intensity of light, I, was determined by either valerophenone
actinometer for 313 nm or benzophenone actinometer for 366 nm depending
upon the efficiency of the photoreaction. A degassed 0.10 M valerophenone or
0.01 M benzophenone and 0.10 M benzhydrol solution in benzene was irradiated
in parallel with the samples to be analyzed. After irradiation was stopped at the
period of conversion ( less than 10 % of GC determination, 10-15 % of HPLC
determination and 30-60 % of UV determination ), the valerophenone sample

was analyzed by SC for acetophenone using the following equation.

[AP]=RrX[Std]XAAP/Asrd (6)

where [AP ] is the concentration of acetophenone, Rf is the instrument response
factor of acetophenone, [ Std ] is the concentration of the added internal
standard, AM) is the integrated area of acetophenone, and A331 is the integrated

area of the internal standard.

144
The intensity of light can be calculated using the acetophenone
concentration based on <bAp = 0.3362 or d) = 0.78 for disappearance of

benzophenone by UV spectrometer.63
l=[AP]/0.33 or l=A[BP]/0.78 (7)

The concentration of the photoproduct, [ P ], can be calculated using the

following equation.
[P]=Ri(P)X[Std]XAp/A61d (8)

where Rflp) is the response factor of photoproduct and Ap is the integrated area
for the photoproduct.
The instrumental response factors for photoproducts were obtained from

the following relationship.
Rr(P)=([Pl/[Stdl)X(AStd/Ap) (9)

If photoproducts are difficult to isolate or too unstable to analyze
accurately, the following equation was used to calculate the response factors.

This method is known to give pretty reasonable value for GC response factor.

{# of Carbons + 1 / 2 (# of C — 0 bonds)},,,,

R. F =
{# of Carbons+1l2 (# of c-o honds)},.,,,,, (10)

 

145
IV. Preparation of Starting Ketones

All ketones were assured to be > 99% pure on gas chromatography or no

extra peak to interfere the interpretation in 1H-NMR spectra before irradiation.

4'-(1-Methyl-3-buten-1-oxy)acetophenone (p-M1K):

A solution of 4-penten-2-ol (4.98 g, 0.057 mol) and pyridine (24.5 g, 0.31
mol, purified by distillation from barium oxide) was placed in a 100 mL three
necked round bottom flask with condenser and drying tube and treated with
recrystallized p-toluenesulfonyl chloride (1 19, 0.057 mol) by portions at 0 °C for 3
h.131 The reaction mixture was poured into 20 % sulfuric acid aqueous solution
(60 mL) and then extracted with ether (3 x 100 mL). The organic layer was
washed with 2N NaOH (150 mL), saturated NaHCO3 (150 mL), brine (150 ml.)
and dried over M9804. After solvent was evaporated, the residue was purified by
chromatography ($102, hexane/ethyl acetate = 4/1, R1 = 0.38) and a slightly
yellowish oil (10.3 g, 75 %) was obtained.
1H-NMR (CDCI3) : 5 1.23 (d, J = 6.2 Hz, Me) 2.34 (m, 2H) 2.42 (s, Me) 4.62 (sext,
J = 6.2 Hz, 1H) 5.02 (m, 2H) 5.56 (m, 1H) 7.31 (d, J = 6.4 Hz, 2H) 7.77 (d, J = 8.4
Hz, 2H).
13O-NMR (CDCI3) : 520.0, 21.4, 40.6, 79.3, 118.8, 127.9, 129.9, 132.3, 134.6,
144.7.
lR(CCI4) : 3080, 2980, 1654, 1601, 1507, 1250, 1216, 1169, 920 cm'1.

p-M1K:
A solution of 2-tosyl-4-pentene (1.0 g, 4 mmol), 4-hydroxyacetophenone

(0.68 g, 5 mmol) and anhydrous potassium carbonate (0.69 g, 5 mmol) in

146
acetone (25 mL) was placed in a 100 mL three necked round bottom flask with
condenser and refluxed for 42 h under an argon atmosphere. The potassium salt
was removed by filtration and acetone was evaporated under vacuum. The
mixture was dissolved in ether (50 mL) and washed with 2N NaOH (2 x 50 mL),
saturated NaHCO3 (50 mL), brine (50 mL) and dried over MgSO4. After solvent
was evaporated, the residue was purified by column chromatography ($102,
hexane/ethyl acetate = 4/1, Rf = 0.32) and the product was colorless and

obtained as an oil (0.2 g, 25 %).

1H-NMR (CDCI3) : 6 1.31 (d, J = 6.1 Hz, Me) 2.35 (ddddd, J = 12.7, 7.0, 6.1, 1.6,
1.3 Hz, Hd) 2.48 (ddddd, J = 12.7, 7.0, 6.1, 1.6, 1.3 Hz, Hd) 2.52 (s, COMe) 4.50
(sext, J = 6.1 Hz, Hc) 5.07 (ddt, J = 10.2, 1.6. 1.3 Hz, Ht) 5.13 (dq, J = 17.1, 1.6
Hz, Hg) 5.82 (ddt, J = 17.1, 10.2, 7.0 Hz, He) 6.89 (d, J = 6.9 Hz, 2Hb) 7.89 (d, J =
6.9 Hz, 2H a).

13C-NMR (CDCI3) : 5 16.9, 25.9, 40.1, 73.1, 115.1, 117.6, 130.1, 130.6, 133.7,
162.1, 196.9 (C=O).

lR(CCl4) : 2961, 1633 (C=O). 1601, 1507, 1253, 1171 cm-1.

UV(MeOH) : Amen: = 271 nm (16210), 313 nm (1140).

MS (m/e) : 204 (M1) 189, 163, 136, 121, 69, 68 (base), 68, 65, 53, 43, 41.
Hi-Res Ms : C13H1302, Calculated : 204.1150, Found : 204.1141.

147
4'-(1-Isopropyl-3-buten-1-oxy)acetophenone (p-I1 K):

A solution of isobutyraldehyde (10 g, 0.13 mol) in 100 mL anhydrous
ether was added dropwise to stirred solution of allyl magnesium bromide
(prepared from 7.5 g of magnesium turnings and 35 g of allyl bromide in a 200
mL anhydrous ether) under an argon atmosphere at room temperature. The
resulting mixture was refluxed under argon for 6 h. The mixture was cooled down
to room temperature and was poured into saturated NH4CI aqueous solution (400
mL). After the precipitation was filtered, two layers were separated and the
aqueous layer was extracted with ether (3 x 100 mL). The combined organic
layers were washed with distilled water, saturated sodium bicarbonate solution
and saturated NaCl solution. After drying over MgSO4, the solvent was
evaporated to give a yellow oil. The oil was purified by vacuum distillation to give
a colorless liquid (9.1 g, 62 %) with boiling point = 75 °C (5.0 Torr).
1H-NIIIR (CDCI3) : 5 0.91 (d, J = 6.8 Hz, Me) 0.92 (d, J = 6.8 Hz, Me) 1.56 (s, O-
H) 1.67 (septd, J = 6.8, 5.6 Hz, 1H) 2.09 (dddt, J = 14.0, 9.0, 8.0, 1.0 Hz, 1H)
2.29 (dddt, J = 14.0, 6.3, 3.6, 1.4 Hz, 1H) 3.37 (ddd, J = 9.0, 5.6, 3.6 Hz, 1H)
5.12(m, 2H) 5.32 (dddd, J = 14.3, 10.0, 3.0, 6.3 Hz, 1H).
13C-NMR (CDCI3) : 5 17.2, 18.5, 32.8, 38.6, 117.3, 135.4.

IR(CCI4) : 3492 (O-H), 3079, 2963, 1640, 1496, 1367, 992, 917 cm‘1.

The same procedure used to make 2-tosyl-4-pentene was used. The 2-
methyl-5-hexen-3-ol (13 g, 0.13 mol) and p-toluenesulfonyl chloride (22 Q, 0.13
mol) in pyridine (45 mL) produced 2-methyl-3-tosyI-5-hexene (27.2 g, 78 %) with
boiling point = 105 °C (0.5 Torr).

148

1H-NMR (CDCI3) :5 0.32 (d, J = 6.9 Hz, Me) 0.34 (d, J = 6.9 Hz, Me) 1.90 (septd,
J = 6.9, 5.4 Hz, 1H) 2.33 (m, 2H) 2.41 (s, Me) 4.41 (dd, J = 7.1, 5.4 Hz, 1H) 4.97
(m, 2H) 5.59 (m, 1H) 7.30 (d, J = 3.1 Hz, 2H) 7.76 (d, J = 3.1 Hz, 2H).

[*1th

A solution of 2-methyl-3-tosyl-5-hexene (10 g, 0.037 mol), 4-
hydroxyacetophenone (6.4 g, 0.047 mol) and anhydrous potassium carbonate
(15 g, 0.11 mol) in DMF (100 mL) was placed in a 250 mL three necked round
bottom flask with condenser and refluxed for 10 h under an argon atmosphere.132
The mixture was poured into water (200 mL) and extracted with ether (3 x 150
mL). The ether layer was washed with 2N NaOH (2 x 200 mL), saturated
NaHCO3 (200 mL), brine (200 mL) and dried over MgSO4. After solvent was
evaporated, the residue was purified by column chromatography (SiOz,

hexane/ethyl acetate = 9/1, R1 = 0.60) to give a colorless oil (3.0 g, 35 %).

 

1H-NMR (c0300) :5 0.96 (d, J = 6.6 Hz, M61) 1.00 (d, J = 6.8 Hz, M61) 2.01
(septd, J = 6.8, 5.3 Hz, Hh) 2.41 (ddd, J = 6.0, 5.8, 1.2 Hz, 2Hd) 2.54 (s, COMe)
4.32 (td, J = 5.8, 5.3 Hz, Hc) 5.02 (ddt, J = 10.1, 2.1, 1.2 H2, H1) 5.08 (dt, J =
17.1, 2.1 Hz, Hg) 5.33 (ddt, J = 17.1, 10.1, 6.0 Hz, He) 6.93 (d, J = 9.0 Hz, 2H5)
7.94 (d, J = 9.0 Hz, 2Ha).

149

11’C-lllMR(CDCI3) : 5 13.2, 26.2, 30.9, 34.9, 32.1, 114.1, 115.2, 117.4, 130.6,
134.0, 162.9, 196.6 (C=O).

IR(CCI4) : 2965, 2876, 1682 (C=O). 1600, 1576, 1506, 1357, 1270, 1252, 1169,
986 cm1 .

UV(MeOH) : Arrax = 277 nm (18470), 313 nm (1540).

MS (m/e) : 232 (Wt), 191, 136, 121,96, 81 (base), 77,65, 43, 41.

Hi-Res MS : C15H2302, Calculated : 232.1463, Found : 232.1468.

4'-(1,3-Dimethyl-3-buten-1oxy)acetophenone (p-M1M3K):

A solution of acetaldehyde (0.88 g, 0.02 mol) and 3-chloro-2-
methylpropene (2.72 g, 0.03 mol) in 30 mL anhydrous ether was added dropwise
to a stirred ether solution (5 mL) of magnesium turnings (0.84 g, 0.035 mol)
under an argon atmosphere with heating provided by a heating gun.133 The
duration of adding process lasted more than 1h. Then the resulting mixture was
gently refluxed under argon for 6 h. The mixture was cooled down to room
temperature and poured into a saturated NH4CI aqueous solution (50 mL). After
the precipitate was filtered, two layers were separated and the aqueous layer
was extracted with ether (3 x 50 mL). The combined organic layers were washed
with distilled water, saturated sodium bicarbonate solution and saturated NaCl
solution. After it was dried over MgSO4, solvent was evaporated to give a
yellowish oil. The oil was purified by vacuum distillation to give a colorless liquid
(1.2 g, 60 %) with boiling point = 78 °C (5.5 Torr).
1H-NMR (CDCI3) : 8 1.19 (d, J = 6.1 Hz, Me) 1.73 (s, Me) 2.11 (d, J = 7.6 Hz, 2H)
2.13 (s, OH) 3.91 (tq, J = 7.6, 6.1 Hz, 1H) 4.77 (s, 1H) 4.36 (s, 1H).

150

4-Methyl-4-penten-2-ol (0.5 g, 5 mmol) and p-toluenesulfonyl chloride (1.6
g, 7.5 mmol) in pyridine (4 mL) produced 4-methyl-2-tosyl-4-pentene (1.07 g, 84
%, hexane/ethyl acetate = 4/1, R1 = 0.54), by the same procedure as used for 2-
tosyl-4-pentene.
1H-NMR (CDCI3) : 61.25 (d, J = 6.2 Hz, Me) 1.56 (3, Me) 2.15 (dd, J = 14.0, 6.6
Hz, 1H) 2.33 (dd, J = 14.0, 6.4 Hz, 1H) 2.42 (s, Me) 4.66 (s, 1H) 4.71 (ddq, J =
6.6, 6.4, 6.2 Hz, 1H) 4.73 (s, 1H) 7.30 (d, J = 8.4 Hz, 2H) 7.77 (d, J = 8.4 Hz, 2H).

p-M1M3K:

The same procedure was used as for 4'-(1-isopropyI-3-buten-1-
oxy)acetophenone . A solution of 4-methyl-2-tosyl-4-pentene (0.45 g, 1.8 mmol),
4-hydroxyacetophenone (0.27 g, 2 mmol) and anhydrous potassium carbonate
(0.9 g, 6 mmol) in DMF (50 mL) produced 4'-(1,3-dimethyl-3-buten-1-
oxy)acetophenone which was purified by silica gel column chromatography (0.13
g, 34 %, methylene chloride/hexane = 19/1, Rf = 0.70) and obtained a colorless

oil.
Ha Hb

0 Hd 1
He
0 / H
0
Me Hd

M61 Me2

1H-NMR (CDCI3) : 5 1.31 (d, J = 6.1 Hz, Me1) 1.75 (s, Me2) 2.25 (dd, J = 14.2,
6.4 Hz, Hd) 2.49 (dd, J = 14.2, 6.3 Hz, Hd) 2.52 (s, COMe) 4.61 (ddq, J = 6.4, 6.3,
6.1 Hz, Hc) 4.76 (d, J = 1.5 Hz, He) 4.31 (d, J = 1.5 H2, H1) 6.69 (d, J = 9.0 Hz,
2113) 7.90 (d, J = 9.0 Hz, 2Ha).

151

13C-NMR (CDCI3) : 5 19.4, 22.9, 26.3, 44.3, 72.3, 113.2, 114.9, 130.0, 130.6,
141.7, 162.0, 196.7 (C=O).

IR(CCI4) : 2977, 2936, 1682 (C=O), 1601, 1507, 1357, 1253, 1170 cm '1.
UV(MeOH) : Annex = 274 nm (16360), 313 nm (1080).

MS (m/e) : 218 (M) 163, 137, 121, 82, 67, 55 (base), 41.

Hi-Res MS : C14H1302, Calculated : 218.1307, Found : 218.1303.

4'—(1-lsopropyI-3-methyl-3-buten-1oxy)acetophenone (p-I1M3K):
.. .. . .. - I-

The same procedure employed for the synthesis of 4-methyl-4-penten-2-ol
was used. The isobutyraldehyde (1.44 g, 0.02 mol) and 3-chloro-2-
methylpropene (2.72 g, 0.03 mol) in a 35 mL anhydrous ether generated 2,5-
dimethyl-5-hexen-3-ol (2.05 g, 80 %, b.p. = 82°C at 4.5 Torr).
1H-NMR (CDCI3) : 5 0.92 (d, J = 6.8 Hz, Me) 0.94 (d, J = 6.8 Hz, Me) 1.70 (m,
1H) 1.75 (s, Me) 1.33 (s, O-H) 2.04 (dd, J = 12.0, 5.5 Hz, 1H) 2.20 (dd, J = 12.0,
9.7 Hz, 1H) 3.47 (m, 1H) 4.80 (s, 1H) 4.87 (s, 1H).

The same procedure as used to make 2-tosyl-4-pentene was employed.
2,5-Dlmethyl-5-hexen-3-ol (2.1 g, 0.016 mol) and p-toluenesulfonyl chloride (3.2
g, 0.017 mol) in pyridine (7.1 mL) produced 2,5-dimethyl-3-tosyl-5-hexene (3.7 g,
82 %, b.p. = 102°C at 0.5 Torr).
1H-NMR (CDCI3) : 8 0.84 (d, J = 6.9 Hz, Me) 0.86 (CI, J = 6.9 Hz, Me) 1.60 (s, Me)
1.94 (septd, J = 6.9, 3.3 Hz, 1H) 2.26 (d, J = 6.6 Hz, 2H) 2.41 (s, Me) 4.53 (td, J =
6.6, 3.8 Hz, 1H) 4.65 (d, J = 1.5 Hz, 1H) 4.68 (d, J = 1.5 Hz, 1H) 7.28 (d, J = 8.0
Hz, 2H) 7.75 (d, J = 8.0 Hz, 2H).

152
P41M3K=
The coupling procedure as for the synthesis of 4'-(1-isopropyl-3—buten-1 -
oxy)acetophenone was followed. A solution of 2.5-dimethyl-3-tosyI-5-hexene (21
g, 0.07 mol), 4-hydroxyacetophenone (12.8 g, 0.09 mol) and anhydrous
potassium carbonate (30 g, 0.22 mol) in DMF (250 mL) produced 4'-(1-isopropyl-
3-methyl-3-buten-1-oxy)acetophenone which was purified by silica gel column

chromatography (4.3 g, 25 %, hexane/ethyl acetate = 4/1, Rf = 0.53).

Ha I"1b
0 d Hi
0 C
M / H°
e Hd
”9 M62
M61 Me1

1H-NMR (CDCI3) : 8 0.95 (d, J = 6.9 Hz, Mei) 0.98 (d, J = 6.9 Hz, Me1) 1.74 (s,
Me2) 2.01 (septd, J = 6.9, 4.4 Hz, Hg) 2.29 (dd, J = 14.5, 5.2 Hz, Hd) 2.36 (dd, J =
14.5, 7.0 Hz, Hd) 2.53 (s, COMe) 4.34 (ddd, J = 7.0, 5.2, 4.4 Hz, Hc) 4.75 (d, J =
1.5 Hz, He) 4.78 (d, J = 1.5 Hz, Ht) 6.89 (d, J = 8.9 Hz, 2Hb) 7.88 (d, J = 8.9 Hz,
2Ha).

136-NMR (CDCI3): 5 17.4, 18.1, 23.0, 26.3, 30.8, 38.5, 81.0, 113.1, 115.1, 129.9,
130.6, 142.2, 162.9, 196.7 (C=O).

IR(CC|4) : 2966, 1682 (C=O). 1600, 1575, 1506,1357, 1252, 1169, 895 cm'1.
UV(MeOH) : Amen: = 279 nm (16040), 313 nm (1310).

MS (m/e) : 246 (M+), 191, 137, 121, 110, 95, 69 (base), 55,43.

Hi-Res MS : C(3H2202, Calculated : 246.1620, Found : 246.1617.

153

4'o(2,3-DimethyI-3-buten-1oxy)acetophenone (p-M2M3K):

A solution of 1-hydroxy-2-methyl-3-butan0ne (9.8 g, 0.09 mol) and DMSO
(280 mL) was added dropwise to a mixture of acetic anhydride (196 mL) and
acetic acid (35 mL) over 30 min under argon atmosphere-134 The resulting
solution was stirred for 24 hours at room temperature. The mixture was then
poured into water (500 mL) and extracted with ether (400 mL x 3). The ether
layer was washed with saturated NaHSO4 (500 mL x 2) and 2N NaOH (500 mL),
and then dried over MgSO4. Solvent and excess DMSO could be removed by
distillation and the product was further purified by silica gel column
chromatography (7.3 g, 75 %, hexane/ethyl acetate = 4/1, Rf = 0.51).
1H-NMR (CDCI3) : 6 1.06 (d, J = 8.0 Hz, Me) 2.07(s, Me) 2.14 (s, Me) 3.10 (qdd,
J = 3.0, 7.5, 5.2 Hz, 1H) 3.53 (dd, J = 9.3, 5.2 Hz, 1H) 3.63 (dd, J = 9.3, 7.5 Hz,
1H) 4.55 (s, 2H).

A solution of methyl triphenylphosphonium bromide (36 g, 0.1 mol) in dry
THF (250 mL) was cooled to -78°C using a dry ice-acetone bath. After 20 min, n-
BuLi (2M, 55 mL) was added by syringe to the solution; the color changed from
white to dark yellow.135 The solution was allowed to warm to room temperature
for 1 h. The solution was again cooled by dry ice-acetone bath, and a solution of
3-methyl-5-oxa-7-thia-2-octanone (8.1 g, 0.05 mol) in THF (70 mL) was added
dropwise. The solution was then stirred vigorously at room temperature for 3 h.
The mixture was quenched by water (500 mL) and extracted with ether (300 mL x
3). The ether layer was washed with 3 % H202 aqueous solution (500 mL),
saturated NaHSO4 (500 mL x 2) and saturated brine (500 mL), and then dried

over MgSO4. After the solvent was evaporated, the residue was purified by

154
column chromatography (SiO2, hexane/ethyl acetate = 4/1, Rf = 0.92) and a
slightly yellowish oil (4.4 g, 58 %) was obtained.
1H-NMR (CDCI3) : 8 1.03 (d, J = 7.0 Hz, Me) 1.71 (d, J = 1.2 Hz, Me) 2.12 (3, Me)
2.43 (dqdd, J = 7.1, 7.0, 6.6, 1.5 Hz, 1H) 3.39 (dd, J = 9.2, 6.6 Hz, 1H) 3.51 (dd, J
= 9.2, 7.1 Hz, 1H) 4.62 (s, 2H) 4.75 (dq, J = 1.7, 1.2 Hz, 1H) 4.76 (dd, J = 1.7, 1.5
Hz, 1H).

A solution of 2,3-dimethyl-5-oxa-7-thia-1-octene (3.0 g, 19 mmol) and
mercury chloride (8.0 g, 29 mmol) in a 80 % acetonitrile aqueous solution (200
mL) was stirred at 25°C for 24 h.133 The acetonitrile was carefully removed by
low temperature evaporation and the resulting solution was filtered through celite
and repeatedly eluted by ether (250 mL). The filtration was added with 1N
NH4OAc aqueous solution (250 mL) and extracted. The aqueous layer was
extracted by another portion of ether (250 mL) and the combined ether layers
were washed with saturated brine and dried over K2CO3. After the solvent was
evaporated, the product was purified by column chromatography (SiO2,
hexane/ethyl acetate = 4/1, Rf = 0.26) and a colorless oil (1.3 g, 65 %) was
obtained.
1H-NMR (CDCI3) : 6 1.01 (d, J = 7.0 Hz, Me) 1.69 (d, J = 1.0 Hz, Me) 2.19 (s, O-
H) 2.36 (qtd, J = 7.0, 6.7, 1.5 Hz, 1H) 3.49 (d, J = 6.7 Hz, 2H) 4.79 (dq, J = 1.9,
1.0 Hz) 4.86 (dd, J = 1.9, 1.5 Hz, 1H).

The same procedure as used to make 2-tosyl-4-pentene was employed.

2,3-Dimethyl-3-buten-1-ol (1.1 g, 0.011 mol) and p-toluenesulfonyl chloride (3.2

155
g, 0.017 mol) in pyridine (7.1 mL) produced 2,3-dimethyl-1-tosy|-3-butene (1.6 g,
57 %, b.p. = 111°C in 0.6 Torr).
1H-NMFI (CDCI3) :6 0.99 (d, J = 7.0 Hz, Me) 1.60 (6, Me) 2.42 (6, Me) 2.46 (dqd,
J = 7.2, 7.0, 6.6 Hz, 1H) 3.84 (dd, J = 9.5, 7.2 Hz, 1H) 3.97 (dd, J = 9.5, 6.6 Hz,
1H) 4.67 (d, J = 1.5 Hz, 1H) 4.76 (d, J = 1.5 Hz, 1H) 7.32 (d, J = 8.3 Hz, 2H) 7.76
(d, J = 8.3 Hz, 1H).

P'MzMsKi

The coupling procedures of the title compound was that used to make 4'-
(1-isopropyl-3-buten-1-oxy)acetophenone. A solution of 2,3—dimethyl-1-tosyl-3-
butene (1.2 g, 4.7 mmol), 4-hydroxyacetophenone (0.8 g, 6 mmol) and
anhydrous potassium carbonate (3 g, 0.022 mol) in DMF (50 mL) produced a
colorless oil of 4'-(2,3-dimethyl-3-buten-1-oxy)acetophenone after purified by
silica gel column chromatography (0.2 g, 25 %, hexane/ethyl acetate = 4/1, Rf =
0.55).

1H-NMR (CDCI3) : 6 1.15 (d, J = 6.9 Hz, Me1) 1.75 (s, Me2) 2.53 (s, COMe) 2.64
(dqd, J = 7.1, 6.9, 6.3 Hz, Hd) 3.84 (dd, J = 9.1, 7.1 Hz, Hc) 4.00 (dd, J = 9.1, 6.3
Hz, Hc) 4.80 (d, J = 1.5 Hz, He) 4.83 (d, J = 1.5 Hz, Hf) 6.90 (d, J = 8.9 Hz, 2Hb)
7.90 (d, J = 8.9 Hz, 2Ha).

13C-NMR(CDCI3): 616.3, 20.4, 26.2, 40.3, 71.7, 111.1, 114.2, 130.1, 130.5,
146.5, 162.9, 196.7 (C=O).

156
lR(CCl4) : 2970, 1683 (C=O). 1602, 1577, 1509, 1358, 1253, 1170 cm '1.
UV(MeOH) : xrnar = 270 nm (16070), 313 nm (340).
MS (m/e) : 218 (M+), 189, 161, 149, 136, 121 (base), 97, 85, 69, 55, 43.
Hi-Res MS: c14H1302, Calculated : 218.1307, Found: 218.1269.

4'—(3-Methyl-3-penten-1-oxy)acetophenone (p-M3M4K):
WWW

Magnesium turnings (6.0 g, 0.25 mol) in anhydrous THF (25 mL) with a
few pieces of iodine were added dropwise with 2-bromo-2-butene (28 mL, 0.27
mol, cis/trans mixture in a ratio of 1/5 obtained from Aldrich) in anhydrous THF
(75 mL) and then with gently reflux under argon atmosphere. The Grignard
solution was cooled down using dry ice lacetonitrile mixture (-40°C) for 20 min.
The dropping tunnel was removed and GUI (4.3 g, 0.023 mol) was added directly
into the Grignard solution, with strong stirring. A gas condensing dropping tunnel
was fitted to the flask. After 10 min, ethylene oxide (ca. 13 mL) was gently added
by gas condensed dropping funnel containing a mixture of dry ice/acetone. The
solution was allowed to warm to room temperature. After 2 h, acetic acid (20 mL)
in ice (100 g) was added. The green salt was filtered using celite and the
THF/water solution was extracted with other (150 mL x 2). The combined
THF/ether solution was washed with saturated NaHSO4 (200 mL x 2), saturated
brine (200 mL) and dried over MgSO4, The resulting alcohol in a cis/trans mixture
1/5.5 (determined by the integration of methyl groups at 6 1.67 and 1.69 in 1H-
NMR) was a colorless oil, purified by vacuum distillation (b.p. = 80-84°C at 4.5
Torr, 22 g, 88%). Since the starting material 2-bromo-2-butene was obtained in a
cis/trans mixture 1/5 from Aldrich, we assumed that the major product is trans.
1H-NMR (CDCI3) : (trans) 6 1.58 (d, J = 6.6 Hz, Me) 1.69 (s, Me) 1.72 (s, O-H)
2.31 (t, J = 6.7 Hz, 2H) 3.66 (t, J = 6.7 Hz, 2H) 5.39 (q, J = 6.6 Hz, 1H); (cis) 6

157
1.60 (d, J = 6.3 Hz, Me) 1.67 (s, Me) 1.75 (s, OH) 2.22 (t, J = 6.1 Hz, 2H) 3.64 (t,
J = 6.1 Hz, 2H) 5.29 (q. J = 6.3 Hz, 1H).

The same procedure to make 2-tosyl-4-pentene was used. 3-Methyl-3-
penten—1-ol (11 g, 0.11 mol) and p-toluenesulfonyl chloride (32 g, 0.17 mol) in
pyridine (70 mL) produced 3-methyl-1-tosyl-3-pentene (14 g, 53%, b.p. = 105-108
°C in 0.6 Torr) with cis/trans = 1/6.2, determined by the integration of vinyl
protons at 6 5.19 and 5.29 in 1H-NMR. (Fig. 35 )
1H-NMR (CDCI3) : (trans) 61.48 (d, J = 6.8 Hz, Me) 1.58 (6, Me) 2.35 (t, J = 7.3
Hz, 2H) 2.43 (5, Me) 4.02 (t, J = 7.3 Hz, 2H) 5.29 (q, J = 6.8 Hz, 1H) 7.32 (d, J =
8.3 Hz, 2H) 7.77 (d, J = 8.3 Hz, 2H); (cis) 6 1.53 (d, J = 6.6 Hz, Me) 1.59 (s, Me)
2.23 (t, J = 6.7 Hz, 2H) 2.47 (s, Me) 4.03 (t, J = 6.7 Hz, 2H) 5.19 (q, J = 6.6 Hz,
1H) 7.35 (d, J = 3.0 Hz, 2H) 7.75 (d, J = 3.0 Hz, 2H).

p-M3M4K:

The coupling procedure used to make 4'-(1-isopropyl-3-buten-1-
oxy)acetophenone was followed. A solution of 3-methyI-1-tosyl-3—pentene (3.0 g,
12 mmol), 4-hydroxyacetophenone (2.5 g, 18 mmol) and anhydrous potassium
carbonate (10 g, 72 mmol) in DMF (70 mL) produced the colorless 4'-(3—methyl-3-
penten—1-oxy)acetophenone, which was purified by silica gel column
chromatography (0.73 g, 28 %, hexane/ethyl acetate = 4/1, Rf = 0.55), in a
cis/trans .= 1/5.2 mixture determined by the integration of M61 at 6 = 1.64 and

1.74 in lH-NMR. (Fig. 36 )

158

6.000 :. 82599.38...7.2.65.0 6:93.26 6 52.8% $22.1. .mm 2.6.“.
mm;

2% m m w m a N

.L . _ . _ _ _ .1. __».Llr.l..-_._.........__._____._.__.__....__.:_._....117...2:71.121.....-r_i-_:-.--Fr

51:25 - a 3.. J. .

 

 

 

 

 

 

 

 

 

 

/ owe

3.363 3.08 E 24532-6 866.66 32.8% $22-1. .3 2:9”.

..P»__r.___._|L.__»_L___F_H...._..t__p_L____».__..3_________F

511 ... _

 

159

 

0 “cl M92
0 0
Me Hd

Hc M31

1H-NMR (CDCI3) : (trans) 6 1.59 (d, J = 6.8 Hz, Me2) 1.74 (s, Me1) 2.50 (s,
COMe) 2.52 (t, J = 7.2 Hz, 2Hd) 4.03 (t, J = 7.2 Hz, 2H0) 5.36 (q, J = 6.8 Hz, He)
6.89 (d, J = 8.9 Hz, 2Hb) 7.90 (d, J = 8.9 Hz, 2Ha); (cis) 6 1.57 (d, J = 6.4 Hz,
Me2) 1.66 (s, Me1) 2.45 (t, J = 7.0 Hz, 2Hd) 2.51 (s, COMe) 4.05 (t, J = 7.0 Hz,
2Hc) 5.34 (q, J = 6.4 Hz, He) 6.39 (d, J = 3.9 Hz, 2Hb) 7.90 (d, J = 3.9 Hz, 2Ha).
13C-NMR (CDCI3) : (trans) 513.1, 23.5, 25.9, 30.9, 66.1, 113.9, 121.7, 129.9,
130.1, 131.4, 162.6, 196.1; (cis) 6 13.2, 15.7, 26.0, 38.6, 66.9, 113.8, 120.9,
130.0, 130.3, 131.2, 162.7, 196.2 (C=O).

IR(CCI4) : (mixture) 2972, 1683 (C=O), 1603, 1506, 1469, 1455, 1357, 1255, 955
cm'l.

UV(MeOH) : (mixture) 216 nm (12500), kmax = 270 nm (16285), 290 nm (10465),
313 nm (1255).

MS (m/e) : 218 (M+), 176, 136, 121 (base), 91, 82, 67, 55, 43.

Hi-Res MS : C14H1302, Calculated : 218.1307, Found : 218.1319.

4'-(1,3-Dimethyl-3-penten-1-oxy)acetophenone (p-M1M3M4K):

A solution of vinyl magnesium bromide-prepared from magnesium turnings
(3.8 g, 0.16 mol) and 2-bromo-2—butene (18.3 mL, 0.18 mol, cis/trans mixture in a
ratio of 1/5, obtained from Aldrich), Cul (2.85 g, 0.015 mol) and propylene oxide
(5.8 g, 0.1 mol) in THF (150 mL) produced the colorless 4-methyl-4-hexen-2-ol

161
(11.0 g, 95 %) which was purified by vacuum distillation (b.p. = 83-86°C at 4.5
Torr).
1H-NMR (CDCI3): (trans) 6 1.19 (d, J = 6.3 Hz, Me) 1.59 (d, J = 6.6 Hz, Me) 1.69
(d, J = 1.5 Hz, Me) 1.71 (s, O-H) 2.02 (dd, J = 13.3, 4.4 Hz, 1H) 2.32 (dd, J =
13.3, 3.6 Hz, 1H) 3.92 (dqd, J = 8.6, 6.3, 4.4 Hz, 1H) 5.40 (qq, J = 6.6, 1.5 Hz,
1H); (cis) 51.15 (d, J = 6.2 Hz, Me) 2.13 (dd, J = 13.3, 3.3 Hz, 1H) 2.23 (dd, J =
13.3, 7.6 Hz, 1H) 3.35 (m, 1H) 5.30 (q, J = 5.9 Hz, 1H).
IR(CCI4) : (mixture) 3339 (OH), 2975, 1445, 1380, 1037 cm'1.

The tosylation procedure used to make 2-tosyl-4-pentene was followed.
The 4-methyl-4-hexen-2-ol (11.4 g, 0.1 mol) and p-toluenesulfonyl chloride (22.8
g, 0.12 mol) in pyridine (47 mL) produced 4-methyl-2-tosyl-4-hexene (16 g, 60%,
b.p. = 102-106°C at 0.5 Torr).
1H-NMR (CDCI3): (trans) 6 1.25 (d, J = 6.2 Hz, Me) 1.46 (d, J = 6.7 Hz, Me) 1.51
(d, J = 1.5 Hz, Me) 2.17 (dd, J = 13.7, 7.1 Hz, 1H) 2.35 (dd, J = 13.7, 6.6 Hz, 1H)
2.42 (s, Me) 4.66 (ddq, J = 7.1, 6.6, 6.2 Hz, 1H) 5.21 (qq, J = 6.7, 1.5 Hz, 1H)
7.30 (d, J = 3.3 Hz, 2H) 7.76 (cl, J = 3.3 Hz, 2H); (cis) 51.23 (d, J = 6.3 Hz, Me)
1.45 (d, J = 6.3 Hz, Me) 2.03 (dd, J = 14.0, 6.7 Hz, 1H) 2.27 (dd, J = 14.0, 6.9 Hz,
1H) 2.43 (s, Me) 4.67 (ddq, J = 6.9, 6.7, 6.3 Hz, 1H) 5.20 (m, 1H) 7.74 (d, J = 6.3
Hz, 2H).

P-M1M3M4K2

The previous coupling procedure to make 4'-(1-isopropyl-3-buten-1-
oxy)acetophenone was used. A solution of 4-methyl-2-tosyl-4-hexene (10 g, 37
mmol), 4-hydroxyacetophenone (5.5 g, 40 mmol) and anhydrous potassium

carbonate (16.5 g, 80 mmol) in DMF (70 mL) produced 4'-(1,3-dimethyl—3-penten-

162

1-oxy)acetophenone cis/trans in a ratio of 1/5.5 measured from M62 groups at 6
1.74 (cis) and 1.79 (trans) in 1H-NMR, which was purified by silica gel column
chromatography (3.3 g, 38 %, hexane/ethyl acetate = 4/1, Rf = 0.59) and

colorless.

M61 M92

1H-NMR (CDCI3) : (trans) 6 1.31 (d, J = 6.1 Hz, Me1) 1.61 (d, J = 6.9 Hz, M63)
1.74 (d, J = 1.5 Hz, M62) 2.35 (dd, J = 13.6, 6.1 Hz, Hd) 2.50 (dd, J = 13.6, 6.9
Hz, Hd) 2.53 (s, COMe) 4.72 (tq, J = 6.9, 6.1 Hz, Hc) 5.34 (qq, J = 6.9, 1.5 Hz,
He) 6.97 (d, J = 9.0 Hz, 2Hb) 7.92 (d, J = 9.0 Hz, 2Ha); (cis) 6 1.29 (d, J = 6.0 Hz,
Mei) 1.64 (d, J = 6.9 Hz, M63) 1.79 (d, J = 1.6 Hz, M62) 2.30 (dd, J = 13.4, 6.0
Hz, Hd) 2.50 (dd, J = 13.4, 6.9 Hz, Hd) 2.55 (s, COMe) 4.75 (tq, J = 6.9, 6.1 Hz,
Hc) 5.31 (qq, J = 6.9, 1.6 Hz, He) 6.97 (d, J = 9.0 Hz, 2H3) 7.92 (d, J = 9.0 Hz,
2Ha).

130-NMR (CDCI3) : (trans) 6 13.6, 19.5, 24.1, 26.2, 38.0, 72.9, 114.9, 122.2,
129.9, 130.5, 131.7, 162.1, 196.6 (0:0); (cis) 5 13.4, 19.3, 25.1, 27.2, 400,723,
114.7, 123.1, 128.9, 131.1, 131.9, 162.5, 196.2 (C=O).

lR(CCl4) : (mixture) 2966, 1632 (C=O), 1600, 1506, 1479, 1450, 1357, 1252,
1169, 955 cm'l.

UV(MeOH): (mixture) lrnax = 271 nm (16500) 313 nm (1350).

MS (m/e) : 232 (M+), 189, 163, 136, 121 (base), 113, 111, 95,43.

Hi-Res MS : C(5H2go2, Calculated : 232.1463, Found : 232.1441.

163
4'-( trans-3-Penten-1-oxy)acetophenone (p-M 4K):

A solution of 1-bromo-3—pentene (2.5 g, 17 mmol, > 95% trans- isomer,
purchased from K&K Chemical Company and checked by 1H-NMR), 4-
hydroxyacetophenone (2.5 g, 18 mmol) and anhydrous potassium carbonate (7.5
g, 50 mmol) in DMF (30 mL) produced colorless trans 4'-(3-penten-1-
oxy)acetophenone which was purified by silica gel column chromatography (1.1

g, 33 %, hexane/ethyl acetate = 19/1, Rf = 0.35).

1H-NMR (CDCI3) : 6 1.65 (dd, J = 6.3, 1.2 Hz, Me1) 2.45 (qd, J = 6.8, 1.2 Hz,
2Hd) 2.51 (s, COMe) 3.98 (t, J = 6.8 Hz, 2Hc) 5.46 (dtq, J = 15.3, 6.8, 1.2 Hz, He)
5.56 (dqt, J = 15.3, 6.3, 1.2 H2, H1) 6.88 (d, J = 9.0 Hz, 2Hb) 7.88 (d, J = 9.0 Hz,
2Ha). (see Table 33)

13C-NMR (CDCI3) : 6 17.9, 26.2, 32.2, 67.9, 114.0, 126.1, 127.9, 130.1, 130.5,
162.8, 196.6 (C=O).

IR(CCI4) : 1682 (C=O), 1602, 1577,1509, 1357, 1254, 1170 cm'1.

UV(MeOH) : 215 nm (12000), Nnax = 270 nm (16085), 290 nm (10265), 313 nm
(1210).

MS (m/e) : 204 (M+), 163, 136, 121, 91, 77, 69 (base), 43, 41.

Hi-Res MS : C13H1go2, Calculated : 204.1150, Found : 204.1149.

3'-Methyl-4'-(3-methyl-3-penten-1oxy)acetophenone (p-M3M4M5K):
3'-MethyI-4'-(1,3-dimethyl-3-penten-1-oxy)acetophenone (p-M1M3M4M5K):

164
3'-Methyl-4'-(trans-3-penten-1-oxy)acetophenone (p-M4M5K):
W

A solution of o-cresol (229, 0.2 mol) in benzene (100 mL) was added to
pyridine (32.3 g, 0.4 mol) in 0°C under argon atmosphere. After 30 min, acetyl
chloride (24 g, 0.3 mol) was added dropwise to the benzene solution. The ice
bath was removed and the solution was stirred vigorously at room temperature
for 24 h. Aqueous HCI (5%, 50 mL) was added and the mixture was extracted
with benzene (100 mL x 2). The combined benzene layer was washed with 2N
NaOH (100 mL x 2), saturated NaHSO4 (200 mL), saturated brine (200 mL) and
dried over Mgso4, Evaporation of benzene and the colorless o-acetoxytoluene
was isolated (31.8 g, 99 %, hexane/ethyl acetate = 4/1, Rf = 0.66).
1H-NMR (CDCI3) :6 2.17 (3, Me) 2.30 (s, Me) 6.97 (d, J = 7.7 Hz, 1H) 7.13 (dd, J
= 9.1, 7.3 Hz, 1H) 7.19 (dd, J = 7.7, 7.3 Hz, 1H) 7.23 (d, J = 9.1 Hz, 1H).

o-Acetoxytoluene (31.8 g, 0.21 mol) was added dropwise at 0°C to a
solution of alumina chloride (68 g, 0.5 mol) in nitrobenzene (500 mL). After
addition, the solution was stirred strongly at room temperature for 90 h. Aqueous
HCI solution (5%, 125 mL) and ether (400 mL) were added and the organic layer
was separated. The nitrobenzene and ether organic layer was extracted with 2N
NaOH (aq). The aqueous layer was acidified to pH 2 with HCI, and then extracted
with ether (2 x 500 mL). The combined ether layers were washed with saturated
NaHSO4 (500 mL), saturated brine (500 mL) and dried over MgSO4, The ether
was evaporated to give 4-hydroxy-3-methylacetophenone (15.7 g, 50 %,
hexane/ethyl acetate = 4/1, R. = 0.20).
1H-NMR (CDCI3) :6 2.29 (s, Me) 2.57 (s, COMe) 6.88 (d, J = 9.0 Hz, 1H) 7.31 (s,
O-H) 7.72 (dd, J = 9.0, 1.5 Hz, 1H) 7.79 (d, J = 1.5 Hz, 1H).

165

13C-NMR (CDCI3) : 5 15.9, 26.2, 114.8, 124.4, 128.7, 129.6, 132.0, 159.4, 198.5
(C=O).

P'M3M4M5K2

A solution of 3-methyl-1-tosyl-3-pentene (4 g, 16 mmol, cis/trans mixture in
a ratio of 1/6.2, see above), 4-hydroxy-3-methylacetophenone (2.4 g, 16 mmol)
and anhydrous potassium carbonate (10 g, 72 mmol) in DMF (50 mL) produced
the colorless 3'-methyl-4'-(3-methyI-3-penten-1-oxy)acetophenone (cisxfrans
mixture in a ratio of 1/5.6 measured by the integration of M62 groups in 1H-NMR)
after purification by silica gel column chromatography (32 %, hexane/ethyl

acetate = 4/1, R1 = 0.40).

Me Hd

Hf M63

1H-NMR (CDCI3) : (trans) 6 1.61 (d, J = 6.8 Hz, M62) 1.76 (s, M61) 2.22 (s, M63)
2.52 (s, COMe) 2.55 (t, J = 6.9 Hz, 2Hd) 4.05 (t, J = 6.9 Hz, 2Hc) 5.36 (q, J = 6.6
Hz, He) 6.81 (d, J = 8.3 Hz, Hb) 7.75 (s, Hr) 7.78 (d, J = 8.3 Hz, Ha); (cis) 61.59
(d, M62) 1.68 (s, M61) 1.75 (s, M63) 2.52 (s, COMe, overlap with trans) 2.47 (t, J
= 6.6 Hz, 2H) 4.07 (t, J = 6.6 Hz, 2H) 5.35 (m) 7.79 (d).

13C-NMR (CDCI3) : (trans) 5 13.3, 16.3, 23.7, 26.2, 31.2, 66.3, 109.7, 121.7,
126.7, 128.3, 129.6, 130.8, 131.7, 161.1, 196.9 (C=O); (cis) 5 12.4, 15.9, 22.7,
27.1, 33.2, 66.4, 109.9, 122.7, 124.3, 127.8, 128.6, 130.2, 133.5, 164.1, 196.4
(C=O).

166
IR(CCI4) : (mixture) 2924, 1681 (C=O),1603, 1502, 1357, 1261, 1252, 1143 cm-1.
UV(MeOH): (mixture) 221 nm (12950), Kmax = 273 nm (14170), 313 nm (1420).
MS (m/e) : 232 (M+), 190, 161, 151, 150, 136 (base), 83, 77,67, 55, 43.
Hi-Fles MS : C15H2002, Calculated : 232.1463, Found : 232.1461.

P'M1M3M4M5K=

A solution of 4-methyl-2-tosyl-4-hexene (2.7 g, 10 mmol, cis/trans mixture,
see above), 4-hydroxy-3-methylacetophenone (1.5 g, 10 mmol) and anhydrous
potassium carbonate (4.5 g, 30 mmol) in DMF (50 mL) produced 3'-methyl-4'-
(1,3-dlmethyl-3-penten-1-oxy)acetophenone, which was colorless after purified
by silica gel column chromatography (35 %, hexane/ethyl acetate = 4/1, Rf =
0.40, cis/trans mixture in a ratio of 1/4.8, determined by the integration of M63

groups in 1H-NMR).

H3 He
0 Hd M93
0 C
M6 Hd
M61 M32
Hf M64

1H-NMR (CDCI3) : (trans) 6 1.31 (d, J = 6.1 Hz, M61) 1.61 (d, J = 6.8 Hz, M63)
1.72 (s, M62) 2.20 (s, M64) 2.32 (dd, J = 13.7, 6.1 Hz, Hd) 2.51 (s, COMe) 2.53
(dd, J = 13.7, 6.6 Hz, Hd) 4.61 (d quint, J = 6.6, 6.1 Hz, Hc) 5.32 (q, J = 6.8 Hz,
He) 6.82 (d, J = 9.0 Hz, Hb) 7.75 (s, Hf) 7.78 (d, J = 9.0 Hz, Ha); (cis) 6 1.30 (d,
Me) 1.55 (d, J = 6.7 Hz, M63) 2.19 (3, M64) 2.43 (m) 2.45 (m) 4.59 (m) 5.31 (m)
7.79 (d, 1H).

167

136-NMR (CDCI3) : (trans) 5 16.5, 19.6, 24.1, 26.2, 36.1, 46.3, 72.9, 110.7,
122.0, 127.4,128.2, 129.3, 131.1, 131.9, 160.3, 196.9 (C=O); ; (cis) 612.7, 17.8,
25.5, 26.8, 32.3, 45.2, 67.3, 109.6, 125.3, 126.5, 126.6, 128.1, 129.4, 130.5,
160.8, 196.6 (C=O).

lR(CCl4) : (mixture) 2978, 1680 (C=O), 1602, 1498, 1357, 1261, 1142 cm '1.
UV(MeOH): (mixture) 223 nm (13200), Max = 277 nm (13560), 313 nm (2000).
MS (m/e) : 246 (M1), 203, 190, 177 (base), 113, 97, 81, 69, 55, 43.

Hi-Res Ms : C13H22O2, Calculated : 246.1620, Found : 246.1622.

P'M4M5K=

A solution of trans 1-bromo—3-pentene (1.08 g, 7.5 mmol, obtained from
Aldrich), 4-hydroxy-3-methylacetophenone (1.34 g, 8.9 mmol) and anhydrous
potassium carbonate (4.5 g, 30 mmol) in DMF (25 mL) produced trans 3'-methyl-
4'-(3-penten-1-oxy)acetophenone after 6 h gentle refluxed. The ketone was
colorless after purified by silica gel column chromatography (39 %, hexane/ethyl

acetate = 4/1, Rf = 0.48).

Ha b

Me Hd
Hg M62

1H-NMR (CDCI3) : 5 1.67 (dd, J = 5.9, 1.0 Hz, M61) 2.22 (s, M62) 2.48 (q, J = 6.7
Hz, 2Hd) 2.53 (s, COMe) 4.00 (t, J = 6.7 Hz, 2Hc) 5.52 (dq, J = 15.9, 5.9 H2, H1)
5-57 (dtq, J = 15.9, 6.7, 1.0 Hz, He) 6.79 (d, J = 8.2 Hz, Hb) 7.76 (s, Hg) 7.77 (d, J
= 8.2 Hz, Ha).

168

13C-NMR (CDCI3) : 6 16.0, 17.8, 26.0, 32.2, 67.7, 109.7, 126.2, 126.5, 127.7,
128.2, 129.4, 130.6, 160.9, 196.7 (C=O).

IR(CCI4) : 2922, 1680 (C=O), 1603, 1581, 1503, 1260 cm'l.

UV(MeOH) : 221 nm (12850), Amax = 273 nm (13870), 313 nm (1420).

MS (m/e) : 218 (Mr), 150, 135, 121, 107, 77, 69 (base), 53,43.

Hi—Res MS : C14H1302, Calculated : 218.1307, Found : 218.1321.

2'-(1-IsopropyI-3-buten-1-oxy)acetophenone (o-I1 K):

A solution of 2-methyl-3-tosyl-5-hexene (15 g, 0.06 mol, see above), 2-
hydroxyacetophenone (9.6 g, 0.07 mol) and anhydrous potassium carbonate
(22.5 g, 0.16 mol) in DMF (100 mL) in 250 mL three-necked round bottom flask
was refluxed at 100°C for 7h. The solution was added by water (150 mL) and
extracted by diethyl ether (3 x 100 mL). After the ether was removed, the
colorless ketone was obtained after purified by silica gel column chromatography

(3.2 g, 23 %, hexane/ethyl acetate = 17/1, Rf = 0.70).

 

1H-NMR (CDCI3) : 6 0.97 (d, J = 6.9 Hz, M61) 1.01 (d, J = 6.9 Hz, M61) 2.08
(septd, J = 6.9, 4.9 Hz, Hh) 2.43 (ddt, J = 7.0, 4.9, 1.2 Hz, 2Hd) 2.61 (s, COMe)
4.30 (q, J = 4.9 Hz, Hc) 5.02 (ddt, J = 10.1, 2.1, 1.2 Hz, Hr) 5.03 (ddt, J = 17.1,
2.1, 1.2 Hz, Hg) 5.73 (ddt, J = 17.1, 10.1, 7.0 Hz, H6) 691 (d, J = 7.2 Hz, H r) 6.93

169
(dd, J = 8.2, 8.0 Hz, Hb) 7.39 (ddd, J = 8.2, 7.2, 1.9 Hz, Hi) 7.68 (dd, J = 8.0, 1.9
Hz, Ha).
13C-NMR (CDCI3) : 5 17.9, 18.2, 30.4, 32.2, 34.6, 81.9, 113.0, 117.6, 120.1,
129.1, 130.6, 133.3, 133.9, 157.6, 200.3 (C=O).
IR(CCI4) : 3077, 2965, 1681 (C=O), 1597, 1479, 1450, 1357, 1237, 985 cm-1.
UV(MeOH) : Arnex = 247 nm (7700), 306 nm (4050) 313 nm (3850).
MS (m/e) : 232 (W) 191, 136, 121 (base), 97, 81,77, 65, 55, 43.
Hi-Res MS : C15H2OO2, Calculated : 232.1463, Found: 232.1473.

2'-(1-Isopr0pyI-3-methyI-3-buten-1oxy)acetophenone (o-I1M3K):

A solution of 2,5-dimethyl-3—tosyl-5-hexene (5.0 g, 0.018 mol, see above),
4-hydroxyacetophenone (2.5 g, 0.019 mol) and anhydrous potassium carbonate
(7.5 g, 0.05 mol) in DMF (70 mL) was refluxed at 110°C for 6h. The solution was
added by water (100 mL) and extracted by diethyl ether (2 x 100 mL). The ether
layer was washed by NaHSO4 (100 mL) and NaCl (100 mL) aqueous solution.
After the ether was removed, the colorless 2'-(1-isopropyl-3-methyl-3—buten-1 -
oxy)acetophenone was obtained after purified by silica gel column

chromatography (0.9 g, 21 %, hexane/ethyl acetate = 4/1, Rf = 0.67).

0
Ha
Hd Hf
Hc
H); O / He
Hd
Hg M62

Hh Hi M61 M61

1H-NMR (CDCI3) : 6 1.01 (d, J = 6.9 Hz, M61) 1.04 (d, J = 6.9 Hz, M61) 1.73 (t, J
= 1.2 Hz, M62) 2.09 (septd, J = 6.9, 4.0 Hz, Hg) 2.37 (dd, J = 14.5, 5.1 Hz, Hd)

170
2.46 (dd, J = 14.5, 7.7 Hz, Hd) 2.60 (s, COMe) 4.46 (ddd, J = 7.7, 5.1, 4.0 Hz, Hc)
4.76 (dq, J = 1.6, 1.2 Hz, He) 4.88 (dq, J = 1.6, 1.2 Hz, Ht) 6.93 (ddd, J = 7.7, 6.6,
1.0 Hz, Hi) 7.11 (dd, J = 3.5, 1.0 Hz, Hb) 7.45 (ddd, J = 3.5, 6.6, 1.9 Hz, Hh) 7.59
(dd, J = 7.7, 1.9 Hz, Ha).
13C-NMR (CDCI3) : 5 17.5, 18.1, 22.7, 30.3, 32.2, 38.3, 80.4, 112.8, 113.1, 120.0,
129.2, 130.5, 133.3, 141.9, 157.7, 200.4 (C=O).
IR(CCI4) : 2965, 1680 (C=O), 1597, 1479, 1450, 1357, 1290, 1236, 986 cm'1.
UV(MeOH) : Amer = 245 nm (6360), 306 nm (3470) 313 nm (3280).
MS (m/e) : 246 (M+), 191, 149. 136, 121 (base), 95, 77, 69, 55, 43.
Hi-Res MS : C13H2202, Calculated : 246.1260, Found: 246.1260.

4'-(4-Cycl0propyl-3-buten-1-oxy)acetophenone (p-C4K):
E-III ll'l || |' II'I'

A solution of triphenylphosphine (75 g, 0.29 mol) and 3-chloropropanol (27
g, 0.29 mol) in benzene (250 mL) was refluxed for 4 days. A white solid was
filtered, dried and identified as 3-hydroxypropyltriphenylphosphonium chloride
salt (20 g, 20%, mp. = 222°C).
1H-NMR (co3oo) :5 1.35 (it, J = 3.3, 5.3 Hz, 2H) 3.46 (dt, J p-H = 16.5 Hz, J =
3.3 Hz, 2H) 3.70 (t, J = 5.3 Hz, 2H) 5.30 (s, O-H) 7.33 (m, 15 Ar-H).

A solution of 3-hydroxypropyltriphenylphosphonium chloride (1.44 g, 4
mmol) in dry THF (25 mL) was cooled to -78°C. After 30 min, n-BuLi (2N, 2.2 mL)
was added by syringe. The color changed from white to dark yellow. The solution
was allowed to warm to room temperature over 1 h. The solution was cooled
again to -78°C, and a solution of cycIopropane-carboxaldehyde (0.14 g, 2 mmol)

in THF (10 mL) was added dropwise. The resulting solution was stirred strongly

171

at room temperature for 3 h.139-14° The mixture was quenched by water (100 mL)
and extracted with ether (30 mL x 3). The organic layers were washed with 3 %
H202 aqueous solution (100 mL), saturated NaHSO4 (100 mL x 2) and saturated
brine (100 mL) and then dried over MgSO4. After solvent was evaporated, the
residue was purified by column chromatography (SiO2, hexane/ethyl acetate =
4/1, R, = 0.25) to give the product as a mixture of trans lcis (=1.6/1, determined
by the integration of vinyl protons at 6 = 5.39 for trans and 5.22 for cis in 1H-NMR,
Fig. 37 ) isomers(0.12 g, 48%).

1H-NMR (CDCI3) : (trans) 6 0.25 (dt, J = 6.6, 4.2 Hz, 2H) 0.58 (ddd, J = 8.2, 6.6,
4.2 Hz, 2H) 1.23 (dtt, J = 3.7, 3.2, 4.2 Hz, 1H) 2.17 (qd, J = 6.5, 1.2 Hz, 2H) 2.56
(s, O-H) 3.52 (t, J = 6.5 Hz, 2H) 4.97 (ddt, J = 15.2, 8.7, 1.2 Hz, 1H) 5.39 (dt, J =
15.2, 6.5 Hz, 1H); (cis) 6 0.25 (dt, J = 6.5, 4.3 Hz, 2H) 0.66 (ddd, J = 8.0, 6.5, 4.3
Hz, 2H) 1.49 (dtt, J = 9.4, 3.0, 4.3 Hz, 1H) 2.37 (qd, J = 6.6, 1.4 Hz, 2H) 2.56 (s,
O-H) 3.58 (t, J = 6.6 Hz, 2H) 4.81 (ddt, J = 10.7, 9.4, 1.4 Hz, 1H) 5.22 (dt, J =
10.7, 6.6 Hz, 1H)

13C-NMR (CDCI3) : (trans) 5 6.3, 13.5, 35.7, 61.9, 123.4, 136.8; (cis) 5 6.7, 9.50,
30.9, 62.1, 123.2, 137.0.

4- l r l-1- l-- n:

The standard tosylation procedure was used. 4-CyclopropyI-3-buten-1-ol
(trans/cis = 1.7/1 mixture, 0.11 g, 1 mmol) and p-toluenesulfonyl chloride (0.3 g,
1.5 mmol) in pyridine (0.6 mL) were stirred at 0°C for 12 h. After ether / dilute HCI
aqueous solution work-up, the residue was purified by column chromatography
(SiO2, hexane/ethyl acetate = 4/1, R, = 0.62, 78 %) and a slightly yellowish oil
with the trans/ cis = 1.7/1 ratio (determined by the integration of vinyl protons at 6

= 5.29 for trans and 5.12 for cis in 1H-NMR) was obtained.

172

6.000 E _o-T:m.:a-m-_>aoao_o>o-v 6:95.230 :55QO $22-1. Km 6.5mm

 

 

 

m

.».L_(_.FLL

 

mfmv Vow ”3.5—.3 5:52.? m 2 3 mm. 550% m:
,. A , . ..f. . . .. J .
.LJ 1173 ..-_ -«lrJ 1....-. :..._ 1-3m. a. .lrb Lair
3 2;; _ .J * v r w
“22£V__PTWNL 3”»p ._ ........ ..-tt:.l.1.--. r».rl» 3.11. l .-ertl..r F_. pt». 2

 

 

 

\\ , Q- Q

 

 

4

OI

173

1H-NMR (CDCI3) : (trans) 5 0.26 (dt, J = 6.1, 4.1 Hz, 2H) 0.63 (ddd, J = 3.1, 6.1,
4.1 Hz, 2H) 1.27 (dtt, J = 8.6, 3.1, 4.1 Hz, 1H) 2.29 (qd, J = 6.9, 1.3 Hz, 2H) 2.43
(s, Me) 3.93 (t, J = 6.9 Hz, 2H) 4.96 (ddt, J = 15.3, 8.6, 1.3 Hz, 1H) 5.29 (dt, J =
15.3, 6.9 Hz, 1H) 7.32 (d, J = 8.4 Hz, 2H) 7.76 (d, J = 3.4 Hz, 2H); (cis) 5 0.23 (dt,
J = 6.4, 4.4 Hz, 2H) 0.69 (ddd, J = 3.1, 6.4, 4.4 Hz, 2H) 1.40 (dtt, J = 8.6, 3.1, 4.1
Hz, 1H) 2.43 (s, Me) 2.50 (qd, J = 7.1, 1.4 Hz, 2H) 4.03 (t, J = 7.1 Hz, 2H) 4.31
(ddt, J = 10.5, 3.6, 1.4 Hz, 1H) 5.12 (dt, J = 10.5, 7.1 Hz, 1H) 7.32 (d, J = 3.4 Hz,
2H) 7.73 (d, J = 3.4 Hz, 2H).

PC4K=

A solution of 4-cyclopropyl-1-tosyl-3-butene (1.50 g, 5.6 mmol), 4-
hydroxyacetophenone (1.25 g, 8 mmol) and anhydrous potassium carbonate
(5.02 g, 32 mmol) in DMF (50 mL) produced 4'-(4-cyclopropyl-3-but6n-1-
oxy)acetophenone with the trans/ cis = 1.7/1 ratio, determined by the integration
of He protons at 6 = 5.55 for trans and 5.36 for cis in 1H-NMR. This compound
was purified by silica gel column chromatography (0.44 g, 34 %, hexane/ethyl

acetate = 4/1, R( = 0.43) and colorless.

Me

 

1H-NMR (CDCI3) : (trans) 5 0.32 (dt, J = 6.1, 4.0 Hz, 2H1) 0.67 (ddd, J = 3.1, 6.1,
4.0 Hz, 2Hh) 1.36 (dtt, J = 3.7, 3.1, 6.0 H2, H9) 2.47 (qd, J = 6.9, 1.3 Hz, 2Hd)
2.53 (s, COMe) 4.00 (t, J = 6.9 Hz, 2Hc) 5.09 (ddt, J = 15.3, 8.7, 1.3 Hz, Hr) 5.55

174
(dt, J = 15.3, 6.9 Hz, He) 6.89 (d, J = 8.9 Hz, 2Hb) 7.90 (d, J = 8.9 Hz, 2Ha); (cis)
6 0.34 (dt, J = 6.3, 4.4 Hz, 2H1) 0.74 (ddd, J = 8.0, 6.3, 4.4 Hz, 2Hh) 1.55 (dtt, J =
8.5, 8.0, 4.4 Hz, Hg) 2.53 (s, COMe) 2.67 (qd, J = 7.1, 1.4 Hz, 2Hd) 4.05 (t, J =
7.1 Hz, 2Hc) 4.89 (ddt, J = 10.4, 8.5, 1.4 H2, H1) 5.36 (dt, J = 10.4, 7.1 Hz, He)
6.92 (d, J = 8.9 Hz, 2Hb) 7.91 (d, J = 8.9 Hz, 2Ha).
13C-NMR (CDCI3) : (trans) 5 6.2, 13.4, 27.4, 31.9, 67.7, 114.3, 122.1, 130.0,
130.1, 136.8, 162.2, 196.3 (C=O); (cis) 5 6.7, 9.5, 25.9, 31.9, 67.5, 113.8, 122.4,
129.8, 130.3, 136.6, 162.2, 196.1 (C=O).
IR(CCI4) : (mixture) 3006, 1633 (C=O), 1602, 1509, 1357, 1254, 1171 cm -1.
UV(MeOH): (mixture) Amex = 270 nm (17530), 313 nm (975).
MS (m/e) : 230 (M+), 187, 121 (base), 95, 81, 77, 67, 53, 43.
Hi-Res MS : C(5H1go2, Calculated : 230.1307, Found : 230.1327.

4'-(4-lsopropyI-3-buten-1-oxy)acetophenone (p-I4K):

The same Wittig reaction procedures were followed as for 4-cyclopropyI-3-
buten-1-ol. A solution of 3-hydroxypropyltriphenylphosphonium chloride (1.44 g, 4
mmol) in dry THF (25 mL) was cooled to -78°C. After 30 min, n-BuLi (2N, 2.2 mL)
was added by syringe. The color changed from white to dark yellow. The solution
was allowed to warm to room temperature over 1 h. The solution was cooled
again to -78°C, and a solution of isobutyraldehyde (0.15 g, 2 mmol) in THF (10
mL) was added dropwise. The resulting solution was stirred strongly at room
temperature for 3 h. The mixture was quenched by water (100 mL) and extracted
with ether (30 mL x 3). The organic layers were washed with 3 % H202 aqueous
solution (100 mL), saturated NaHSO4 (100 mL x 2) and saturated brine (100 mL)
and then dried over MgSO4. After solvent was evaporated, the residue was

purified by column chromatography (SiO2, hexane/ethyl acetate = 4/1, Rf = 0.29)

175

to give the product as a mixture of trans Icis (=2.1/1 from vinyl proton integration
at 6 5.33 for trans and 5.21 for cis in 1H-NMR) isomers (0.10 g, 43%).

1H-NMR (CDCI3) : (trans) 6 0.96 (d, J = 6.9 Hz, 2Me) 1.50 (s, O-H) 2.23 (q, J =
6.3 Hz, 2H) 2.60 (septd, J = 6.9, 6.5 Hz, 1H) 3.60 (t, J = 6.3 Hz, 2H) 5.33 (dt, J =
15.4, 6.3 Hz, 1H) 5.52 (dd, J = 15.4, 6.5 Hz, 1H); (cis) 5 0.90 (d, J = 6.9 Hz, 2Me)
1.90 (s, OH) 2.31 (q, J = 6.5 Hz, 2H) 2.40 (septd, J = 6.9, 5.7 Hz, 1H) 3.62 (t, J =
6.5 Hz, 2H) 5.21 (dt, J = 10.9, 6.5 Hz, 1H) 5.52 (dd, J = 10.9, 5.7 Hz, 1H).

The same tosylation procedures were followed as for 4-cycl0pr0pyl-1-
tosyl-3-butene.
1Hr-NMR (CDCI3) : (trans) 5 0.90 (d, J = 6.8 Hz, 2Me) 2.17 (septdd, J = 6.8, 6.5,
1.2 Hz, 1H) 2.29 (qd, J = 6.7, 1.3 Hz, 2H) 2.42 (s, Me) 3.99 (t, J = 6.7 Hz, 2H)
5.17 (dtd, J = 15.5, 6.7, 1.2 Hz, 1H) 5.42 (ddt, J = 15.5, 6.5, 1.3 Hz, 1H) 7.32 (d, J
= 8.2 Hz, 2H) 7.76 (d, J = 8.2 Hz, 2H); (cis) 6.0.88 (d, J = 6.7 Hz, 2Me) 2.37 (qd,
J = 7.1, 1.4 Hz, 2H) 2.42 (s, Me) 2.47 (dseptd, J = 9.5, 6.7, 0.9 Hz, 1H) 3.97 (t, J
= 7.1 Hz, 2H) 5.06 (dtd, J = 10.8, 7.1, 0.9 Hz, 1H) 5.28 (ddt, J = 10.8, 9.5, 1.4 Hz,
1H) 7.32 (d, J = 3.2 Hz, 2H) 7.76 (d, J = 6.2 Hz, 2H).

P44K=

The standard coupling method was used. A solution of 5-m6thyI-1-tosyI-3-
hexene (3.10 g, 11 mmol), 4-hydroxyacetophenone (2,35 9, 15 mmol) and
anhydrous potassium carbonate (10.02 g, 64 mmol) in DMF (100 mL) was
refluxed at 90°C for 6h and produced cis/trans products in a ratio of 2.2/1,
measured by the integration of vinyl protons in 1H-NMR.(Fig. 38) Ketone was
colorless after purified by silica gel column chromatography (1,12 9, 44 %,

hexane/ethyl acetate = 4/ 1, Rf = 0.46).

176

 

 

 

 

309251—
lt'ZBSI --
71981:!-
095651
3
W

 

  

 

637291 ~ 1
r3 ' 629i f

E57891 -

 

£75791 "" x

tassel-r

    

0619911-

3E ‘ ZLSI

 

 

 

 

lift
IPPM

I

I

I

rrr

 

Figure 38. 1H-NMR spectrum oi of /trans p-I4K in CDCI3

177

 

1H-NMR (CDCI3) : (trans) 6 0.96 (d, J = 6.8 Hz, 2Me) 2.25 (septdd, J = 6.8, 6.4,
1.0 Hz, Hg) 2.46 (qd, J = 6.9, 1.1 Hz, 2Hd) 2.53 (s, COMe) 4.00 (t, J = 6.9 Hz,
2Hc) 5.40 (dtd, J = 15.5, 6.9, 1.0 Hz, He) 5.53 (ddt, J = 15.5, 6.4, 1.1 Hz, Hr) 6.90
(d, J = 8.9 Hz, 2Hb) 7.90 (d, J = 8.9 Hz, 2Ha); (cis) 6 .0.96 (d, J = 6.8 Hz, 2Me)
2.53 (s, COMe) 2.55 (qd, J = 6.9, 1.2 Hz, 2Hd) 2.62 (dseptd, J = 8.7, 6.8, 2.0 Hz,
Hg) 3.99 (t, J = 6.9 Hz, 2Hc) 5.30 (m, 2H) 6.89 (d, J = 8.8 Hz, 2Hb) 7.90 (d, J =
8.8 Hz, 2H a).

13C-NMR (CDCI3) : (trans) 5 22.3, 26.1, 26.5, 32.2, 67.9, 114.0, 121.6, 130.0,
130.4, 140.6, 162.8, 195.5 (C=O); (cis) 22.9, 26.4, 27.2, 30.9, 67.6, 113.9, 121.7,
130.1, 130.2, 140.3, 162.7, 196.4 (C=O).

moor.) : (mixture) 2993, 1679 (C=O), 1601, 1510, 1255 cm-1.

UV(MeOH): (mixture) Arnax = 273 nm (18630), 313 nm (1400).

MS (m/e) : 232 (M+), 192, 137, 121, 96, 81, 69, 55 (base), 43.

Hi-Res Ms : C(5H2go2, Calculated : 232.1463, Found : 232.1465.

3-Butyn-1-ol (0.1 mol, 7 g, Aldrich) was converted into its tosylate in the
presence of pyridine (50 mL) and p-toluenesulfonyl chloride (20 g, Aldrich) at
0°C.

178

1H-NMR (CDCI3) :5 1.96 (t, J = 2.7 Hz, 1H) 2.44 (s, Me) 2.53 (td, J = 7.0, 2.7 Hz,
2H) 4.19 (t, J = 7.0 Hz, 2H) 7.32 (d, J = 3.2 Hz, 2H) 7.73 (d, J = 3.2 Hz, 2H).

The tosylate was coupled with 4-hydroxyacetophenone by the standard
coupling method. Ketone was purified by silica gel column chromatography
(hexane/ethyl acetate = 4/1, R1 = 0.56).
1H-NMR (CDCI3) : 6 2.16 (t, J = 2.7 Hz, 1H) 2.56 (s, COMe) 2.71 (td, J = 7.0, 2.7
Hz, 2H) 4.27 (t, J = 7.0 Hz, 2H) 6.94 (d, J = 3.9 Hz, 2H) 7.92 (d, J = 3.9 Hz, 2H).
13C-NMR (CDCI3) : 5 25.9, 27.6, 62.2, 66.7, 76.6, 111.6, 126.7, 131.5, 163.4,
196.6 (C=O).

IR(CCI4) : 2254, 1663 (C=O), 1609, 1545, 1451, 1216 cm'1.
MS (m/e) : 188 (Mr), 173, 121 (base), 65, 53, 43.

The 4'-(3-butyn-1-oxy)acetophenone (8.4 g, 0.045 mol) and excess
ethylene glycol (6.2 g, 0.1 mol) were refluxed in a catalytic amount p-
toluenylsulfonic acid in benzene (100 mL) for 24 h. After the solvent was
removed, the acetal (10.2 g, 95%) was obtained.
1H-NMR (CDCI3) :6 1.64 (s, Me) 2.11 (t, J = 2.7 Hz, 1H) 2.68 (td, J = 7.0, 2.7 Hz,
2H) 3.76 (ddd, J = 7.4, 6.3, 3.6 Hz, 2H) 4.00 (ddd, J = 7.4, 6.3, 3.6 Hz, 2H) 4.09
(t, J = 7.0 Hz, 2H) 6.87 (d, J = 8.9 Hz, 2H) 7.39 (d, J = 8.9 Hz, 2H).

A solution containing acetal of 4'-(3-butyn-1-oxy)acetophenone (10.2 g,
0.09 mol) and THF (100 mL) was cooled to -78°C. n-BuLi (2M, 55 mL) was
added by syringe and the temperature was kept at -78°C over 1 h. Trimethylsilyl

179
chloride (10.5 g, 0.1 mol) in THF (30 mL) was added dropwise. After ether
extraction, the product was recrystallized from hexane.
1H-NMR (CDCI3) :6 0.14 (s, 3M6) 1.62 (3, Me) 2.70 (t, J = 7.4 Hz, 2H) 3.77 (ddd,
J = 7.4, 6.3, 3.6 Hz, 2H) 4.01 (ddd, J = 7.4, 6.3, 3.6 Hz, 2H) 4.07 (t, J = 7.4 Hz,
2H) 6.35 (d, J = 3.9 Hz, 2H) 7.36 (d, J = 3.9 Hz, 2H).

Wannabe:

The above acetal of 4'-(4-trimethylsilyl-3—butyn-1-oxy)acetophenone was
dissolved in THF (50 mL) and 10 % HCI aqueous solution (25 mL) was added
dropwise. After 3 h, the resulting solution was extracted with ether and then the
ether was removed. Ketone was failed to recrystallize from hexane at 0°C and
then purified by silica gel column chromatography (hexane/ethyl acetate = 4/1, Rf
= 0.65) to obtain a colorless oil.
1H-NMR (CDCI3) : 6 0.15 (s, 3M6) 2.52 (s, COMe) 2.72 (t, J = 7.2 Hz, 2Hd) 4.13
(t, J = 7.2 Hz, 2Hc) 6.92 (d, J = 8.9 Hz, 2Hb) 7.91 (d, J = 8.9 Hz, 2Ha).
13C-NMR (CDCI3) : 5 0.0, 20.9, 27.6, 63.7, 66.2, 77.0, 111.2, 126.5, 130.4, 162.4,
196.7 (C=O).

IR(CCI4) : 2254, 1683 (C=O), 1604, 1559, 1450, 1216, 983 cm‘1.
MS (m/e) : 260 (M) 245, 219, 173, 121, 73, 71(base), 43.

Hd
Me Hd k

1 80
V. Identification of Photoproducts:

Reactant : p-MgK

The ketone p-MgK (obtained from Nahm) was dissolved in 0.7 mL CD3OD
in an NMR tube (2.0 X 10'2 M). The solution was irradiated by mercury arc (Pyrex
filtered) for 1 h. The colorless photoproduct was identified as 1-acetyI-8-
oxatricyclo-[7.2.0.05-9]undeca-2,10-diene by the following spectroscopic
properties. The same CD3OD solution, left on the bench at room temperature for
two days, converted to yellowish 4-acetyl-10-methyI-11-oxabicyclo[6.3.0]undeca-
1,3,5-triene, identified by the 1H-NMR spectroscopy.

Low temperature (-30°C) nOe results (see appendix for details) indicated
that 1-acetyl-8-oxatricyclo-[7.2.0.05-9]undeca-2,10-diene had enhancements of
H13 (4.2 %). H43 (1.4 %). H33 (1.0 %) and H73 (2.0 %) when bridgehead proton H5
was irradiated.

4.2%
1.4°/ c H

o filth/£0 \J
H—CE‘1'1‘C,/C,o

lMeH 0
Hr‘ 05""I 2.0%

(1.10%

WWW

1H-NMR (c0300) : 51.73 (dddd, J = 12.6, 11.5, 10.4, 7.0 H2, H3,,) 1.35 (dddd, J
= 11.3, 10.4, 9.0, 5.1 Hz, H33) 2.13 (s, COMe) 2.20 (dddd, J = 17.0, 6.0, 3.0, 2.2
Hz, H43) 2.26 (ddd, J = 17.0, 7.6, 4.5 Hz, H43) 2.39 (dddd, J = 12.6, 9.0, 7.6, 6.0
Hz, H53) 3.73 (ddd, J = 13.5, 11.5, 5.1 Hz, H73) 3.32 (ddd, J = 13.5, 11.3, 7.0 Hz,
H73) 5.75 (dd, J = 10.2, 3.0 Hz, H2) 5.35 (ddd, J = 10.2, 4.5, 2.2 Hz, H3) 6.27,
6.37 (A8 q, J = 2.3 Hz, H13, H11 ).

131

1H-NMR (coaoo) : 5 1.96 (dddd, J = 11.7, 9.2, 7.7, 4.9 H2, H9“) 2.13 (dddd, J =
11.7, 3.3, 6.0, 5.4 Hz, H93) 2.31 (s, COMe) 2.35 (dddd, J = 13.2, 3.2, 7.9, 2.1 Hz,
H75) 2.50 (dddd, J = 13.2, 4.0, 3.5, 2.1 Hz, H73) 3.10 (dddd, J = 3.2, 7.7, 3.0, 3.5
Hz, H53) 4.20 (ddd, J = 12.2, 9.2, 5.4 Hz, H103) 4.23 (ddd, J = 12.2, 3.3, 4.9 Hz,
H1m)5.41 (d, J = 3.1 Hz, H2) 5.95 (ddd, J = 11.3, 7.9, 4.0 Hz, H5) 3.23 (dt, J =
11.3, 2.1 Hz, H5) 7.12 (d, J = 3.1 H2, H3).

Reactant : p-M1K

In an NMR tube, 4.8 mg p-M1K was dissolved in 0.7 mL CD3OD (3.4 x1012
M) with internal standard methyl benzoate 3.3 mg and bubbled with argon for 20
min. lrradiations were performed with a mercury arc filtered only by Pyrex or by
alkaline K20r04 filter solution (313 nm). Both of them provided identical results.
1H-NMR spectra were obtained (every 15 min) during the irradiation until 100 %
conversion. A pair of photoproducts was identified as the diastereomers of 1-
acetyl-7-methyl-8-oxatricyclo[7.2.0.05-9]undeca-2,1O-diene in a ratio of 70 :30, as
determined by integration of 1H-NMR spectra. The major photoproduct has
bridgehead proton H5 and Me7 trans to each other. The minor photoproduct has
bridgehead proton H5 and M37 cis to each other according to the following nOe
results.

In nOe experiments, which were performed at -20°C to prevent further
thermal rearrangement, the major product had enhancements of H 10 (6.6 %), H43
(3.3 %), H53 (3.9 %) and H73 (5.0 %) when bridgehead proton H5 was irradiated.
Similarly, there was an enhancement of H5 (4.3 %), H53 (4.5 %) and 7-Me (3.9 %)
when H7 was irradiated. The minor product had enhancements of H15 (0.7 %),
H53 (1.9 %), H33 (2.6 °/o) and H70, (9.4 %) when 7-Me was irradiated.

182

The notations of 01- and [3- used in this dissertation are defined as the
stereochemistry of substituents below the plane of the ring and above the plane

of the ring in the cyclic form, respectively.

H H H
= 4.3% - o -
' 6.3% 3 19k 3
3.3%} H Q, H c H H c H 0.7%
”- ‘ ”023410 H—C’C‘ Cal .0 “—0-‘07 C31 0
H/C\C/ / /C‘C/C ’C O‘c/ ’0‘
Me’ H / \
(L /OH L Me 0 ‘ Me/ OM
0° 6
HI" \9; 5.0/ Hr \C/’H H'C\c/’
C H 3. r311 m1
3.9% Me 4.5/o (‘Me 2.6% (‘ H

 

 

 

1H-NMIR (CD30D) : (major) 8 1.05 (d, J = 6.0 Hz, 7-Me) 1.48 (ddd, J = 12.8, 11.3,

10.5 Hz, Hag) 1.83 (ddd, J = 10.5, 6.0, 5.1 Hz, H53) 2.14 (dddd, J = 17.1, 8.0, 3.1,
2.3 H2, H4“) 2.185 (s, COMe) 2.26 (ddd, J = 17.1, 6.6, 2.1 Hz, H43) 2.51 (dddd, J
= 12.3.3.0, 3.0, 2.1 Hz, H53) 4.03 (dqd, J = 11.3, 3.0, 5.1 Hz, H73) 5.74 (dd, J =
10.1, 3.1 H2, H2) 5.81 (ddd, J = 10.1, 6.6, 2.3 H2, H3) 6.29, 6.42 (AB q, J = 2.8
HZ. H10. H11 )-

13C-NMR((:0300) : (major) 521.4, 25.0, 30.1, 33.3, 42.3, 73.3, 92.7, 103.3,
123.3, 123.9, 140.2, 140.3, 215.0 (C=O).

1l-l-NMlii (00300) : (minor) 5 1.14 (d, J = 6.3 Hz, 7-Me) 1.56 (ddd, J: 12.1, 7.9,
3.8 H2, H5“) 1.83 (m, H53) 2.07 (m, H4“) 2.183 (s, COMe) 2.22 (m, H43) 2.46 (m,

183
H5) 4.09 (m, H73) 5.71 (dd, J = 10.1, 2.1 H2, H2) 5.34 (ddd, J = 10.1, 3.0, 3.0 Hz,
H3) 6.28, 6.34 (AB q, J = 2.9 HZ, H10, H11).

Ketone p-M1K 0.12 g was dissolved in 75 mL dry MeOH (8 x 10'3 M) and
bubbled with argon for 20 min. During the irradiation (Pyrex filter), reaction was
monitored by TLC or GC (received the sample by the syringe) until 100 °/o
conversion. Solvent was evaporated and the residue was purified by column
chromatography (SiOz, Rf = 0.33 with hexane/ethyl acetate = 9/1) and a
yellowish oil was obtained (0.075 g, 63 %). The diastereomers of cyclooctatriene
were separated by neutral alumina chromatography with gradient hexane/ethyl
acetate ratio from 99/1 to 95/5 (volume/volume). The chemical shifts and
coupling constants obtained from the NMR spectra of isolated cyclooctatrienes
are identical to the NMR spectra of mixture.

The major cyclooctatriene has bridgehead proton H5 and M910 trans with
each other. In nOe experiments, the major product had enhancements of H3 (3.0
%), H73 (4.0 %), H93 (3.7 %) and H103 (1.9 °/o) when bridgehead proton Hg was
irradiated.

The 3.221 ratio of cycloéctatriene diastereomers (3.0 mg) was dissolved in
00300 (0.75 mL) in NMR tube, bubbled with argon for 10 minute, and then
irradiated (Pyrex filter) to obtained the same ratio of cyclobutene diastereomers.
However, the irradiation time of this experiment (0.5h) was shorter than the

previous one from p-M1K (1 .5h).

Me 4.0%
0§é 3.0%) fl
\ H H 3.7%
C§é H I [H

184

 

 

 

A o- 0.10:... -ri‘n"
1H-NMR (CDCI3) : (major) 5 1.33 (d, J = 6.2 Hz, 10-Me).1.51 (td, J = 11.9, 9.9 Hz,
Hga) 2.19 (ddd, J = 11.9, 6.0, 5.4 Hz, H93) 2.25 (ddd, J = 13.7, 10.5, 7.9 H2, H7“)
2.31 (s, COMe) 2.56 (ddd, J = 13.7, 7.9, 3.0 Hz, H73) 3.07 (dddd, J = 11.9, 10.5,
5.4, 3.0 Hz, H33) 4.41 (tq, J = 9.9, 6.0 Hz, H103) 5.36 (dd, J = 8.0, 2.2 H2, H2)
6.02 (01, J = 11.3, 7.9 Hz, H5) 6.36 (d, J = 11.3 H2, H5) 6.89 (d, J = 8.0 H2, H3).
13C-NMFI (CDCI3) : (major) 5 20.4, 26.2, 28.8, 39.5, 43.5, 77.3, 95.8, 127.2,
133.3, 133.7, 137.4, 170.7, 199.7 (C=O).

._-3: I -1.— :\--Ol:. - -o

.,-:: um; :(- O-ncl -1-.,._. .. o 3.3,.5- -'-n--
1H-NMR (CDCI3) : (minor) 8 1.34 (d, J = 6.1 Hz, 10-Me) 1.77 (dt, J = 12.2, 8.0
H2, H9“) 1.90 (ddd, J = 12.2, 3.0, 3.3 Hz, H93) 2.32 (m, 1H) 2.35 (s, COMe) 2.42
(m, 1H) 3.20 (m, 1H) 4.71 (tq, J = 3.0, 3.1 Hz, H10) 5.41 (d, J = 3.3 Hz, H 2) 5.39
(dt, J = 13.1, 5.0 Hz, H5) 3.25 (dt, J = 13.1, 1.3 Hz, H5) 7.04 (d, J = 3.3 Hz, H3).
13C-NMI71'l(t‘.2DCI3) : (minor) 3 21.0, 23.1, 29.3, 33.5, 40.7, 73.3, 93.3, 125.0,
132.3, 133.9, 138.4, 171.3, 199.2 (C=O).

IR(CC|4) : (mixture) 2929, 1682 (C=O), 1600, 1507, 1358, 1253, 1170 cm 4.
UV(MeOH) : 313 nm (6900), kmax = 344 nm (10800).
MS (m/e) : (mixture) 204 (M+), 161, 121, 105, 91, 69, 55, 43 (base).

185

Reactant : p-I1K

A mixture of 2.0 mg of p-I1K in 00300 (0.6 mL, 0.015 M) with 4.3 mg
internal standard methyl benzoate was irradiated by mercury arc with a Pyrex
filter. 1H-NMR showed photoproducts as a pair of diastereomers of 1-acetyl-7-
isopropyl-8-oxatricyclo[7.20.05:9]undeca-2,10-diene like the previous 1-acetyl-7-
methyl-8-oxatricyclol7.2.0.05.9]undeca-2,10-diene compound. Chemical yield (90
%) and diastereomeric excess (67 %) were measured by integration of two H13
groups in 1H-NMR spectra.

In nOe experiments, performed at -20°C, the major product had
enhancements of H10 (5.1 %), H43 (2.6 %), H53 (3.3 °/o) and H73 (4.3 °/o) when

bridgehead proton H53 was irradiated.

0:011:

’ 5.1%

\J

2.6% H

/C
H—A: 0150. c//
| Me’ /0/
H..‘c\ H 4.3%
c
(H , K/
3.637%“ /\Me

\r" 7f
O V. OX
)0”? %f; Q *

 

 

 

 

- -- -- ' 591110999323;

1H-NMH (coaoo) : (major) 3 0.74 (d, J = 3.3 Hz, Me) 0.33 (d, J = 3.3 Hz, Me)
1.27 (ddd, J = 12.0, 11.4, 10.3 Hz, H55) 1.43 (ddd, J = 12.0, 3.3, 5.2 Hz, H53)
1.35 (dsept, J = 9.3, 3.3 Hz, 1H) 2.09 (dddd, J = 13.3, 3.5, 3.2, 2.1 H2, H4,,) 2.20

133
(s, COMe) 2.22 (dddd, J = 11.4, 3.3, 3.5, 2.2 Hz, H53) 2.44 (ddd, J = 13.3, 3.7,
2.2 Hz, H43) 3.43 (ddd, J = 10.3, 9.3, 5.2 Hz, H73) 5.75 (dd, J = 10.1, 3.2 Hz, H2)
5.31 (ddd, J = 10.1, 3.7, 2.1 Hz, H3) 3.25 (d, J = 2.3 Hz, H11) 3.45 (dd, J = 2.3,
0.7 Hz, H10).

 

1H-NMR (coaoo) : (minor) 5 0.33 (d, J = 3.3 Hz, Me) 0.90 (d, J = 3.3 Hz, Me)
1.31 (ddd, J = 9.4, 5.7, 2.5 Hz, H53) 1.53 (ddd, J = 9.4, 7.9, 1.3 Hz, H53) 1.72 (m,
1H) 2.11 (m, 1H) 2.13 (m, 1H) 2.17 (s, COMe) 2.43 (m, 1H) 3.33 (ddd, J = 7.9,
7.0, 5.7 Hz, H73) 5.35 (m, 2H) 3.27, 3.35 (A8 q, J = 2.9 Hz, H10, H11).

A solution of 0.20 9 mm in a 60 mL dry MeOH, bubbled with argon for
20 min, was irradiated through Pyrex filter and monitored by TLC or GC until 100
% conversion. After solvent was evaporated, the residue was purified by silica gel
column chromatography (Rf = 0.43 with hexane/ethyl acetate = 4/1) to give a
mixture of diastereomers in 68% (0.136 g). Attempts to separate the
diastereomers by TLC, HPLC, silica gel or alumina column chromatography were
unsuccessful.

The major product had enhancements of H3 (1.2 %), H73 (3.3 %), H93 (2.7
%) and H103 (1.5 %) when bridgehead proton H53 was irradiated in nOe

experiments.
Me 3.3%

187

 

 

 

.. - 5: 1 -4-A-1l-10-i err-.- l-11-ox-i I .3 I nu. -1 -rin:
1H-NMlii (00300) : (major) 5 0.90 (d, J = 6.7 Hz, Me) 1.00 (d, J = 6.7 Hz, Me)
1.53 (ddd, J = 12.4, 11.5, 10.2 Hz, H93) 1.72 (dsept, J = 7.5, 3.7 Hz, 1H) 2.20
(ddd, J = 12.4, 7.5, 5.4 Hz, H93) 2.23 (ddd, J = 13.0, 10.5, 3.1 H2, H7“) 2.31 (s,
COMe) 2.59 (ddd, J = 13.0, 8.1, 3.1 Hz, H73) 3.09 (dddd, J = 11.5, 10.5, 5.4, 3.1
Hz, H53) 4.00 (ddd, J = 10.2, 7.5, 4.9 Hz, H153) 5.37 (dd, J = 8.4, 2.2 H2, H2) 6.05
(dt, J = 10.8, 8.1 H2, H5) 6.32 (d, J = 10.8 H2, H5) 7.09 (d, J = 8.4 H2, H3).
1:‘C-NMR (CDCI3) : (major) 5 17.7, 18.8, 26.4, 28.7, 32.9, 34.3, 39.2, 86.1, 95.6,
123.7, 130.2, 133.6, 138.5, 171.0, 199.5 (C=O).

r. - .0R1R-4-A -10I-1-i 09ru l-11-o.-xi lo ., . n3: -1 -rin:
1H-NMR (C0300) : (minor) 6 0.89 (d, J = 6.7 Hz, Me) 0.99 (d, J = 6.7 Hz, Me)

1.73 (m, 1H) 1.87 (ddd, J = 11.75, 8.8, 1.6 H2, H9) 2.08 (m, 1H) 2.27 (m, 1H)
2.34 (s, COMe) 2.43 (m, H73) 3.13 (m, H33) 4.30 (ddd, J = 3.3, 7.4, 3.3 Hz, H10)
5.40 (d, J = 6.3 H2, H2) 5.86 (dt, J = 13.2, 4.3 H2, H5) 6.20 (dt, J = 13.2, 2.2 Hz,
H5) 7.17 (d, J = 6.3 H2, H3).
1"C-NMFi (CDCI3) : (minor) 5 17.8, 18.9, 26.5, 32.8, 33.4, 35.4, 43.4, 86.8, 95.7,
127.0, 132.1, 132.9, 137.1, 170.5, 199.1 (C=O).

IR(CCI4) :(mixture) 2963, 2930, 1682 (C=O), 1600, 1507, 1357, 1253, 1171 cm 4.
UV(MeOH) : 313 nm (7350), Amax = 346 nm (11800).
MS (m/e) : (mixture) 232 (Mr), 189, 137, 133, 121, 105, 91, 81,69, 55, 43 (base).

l-li-Res MS : Calculated : 232.1464, Found : 232.1490.

188

Reactant : p-M1M3K

A mixture of 4.0 mg p-M1M3K and 2.8 mg methyl benzoate in a 0.75 mL
00300 (0.024 M) was placed in a NMR tube and irradiated through Pyrex filter
after bubbled with argon. The reaction was followed by 1H-NMFi and was finished
in 3 h. The products were characterized as two diastereomers of 1-acetyl-5,7-
dimethyI-8-oxatricyclo[7.2.0.05.9]undeca-2,10-diene which has 78 % chemical
yield and a 9:1 diastereomeric ratio, determined by the integration of two H7
protons.

The nOe experiments performed on the major product at -20°C indicated
an enhancement of H10 (6.1 %), H43 (2.6 %), H53 (1.8 %) and H73 (5.1 %) when
5-Me was irradiated and of 5-Me (2.9 %), H53 (4.4 %) and 7-Me (3.2 %) when H7

was irradiated.

L1 317 2.9% '5'
°o ' ' ° H C
2.3/ He fl chfiu H _ 1 /,C,H
'- M C Mec/
‘ Me’/o ‘ Me/O
. H 1.3% .4: 4H
H“ C\C‘ H‘l \
(5.1% Me 4.4% Me

 

 

 

. - : ': - -. :1 - an: I l-3-0.=_' 0 105-9111051991219;

1H-NMR (00300) : (major) 8 1.02 (d, J = 6.2 Hz, 7-Me) 1.08 (s, 5-Me) 1.52 (dd, J
= 12.0, 5.7 Hz, H53) 1.37 (dd, J = 12.0, 10.4 Hz, H33) 1.91 (ddd, J = 13.2, 3.1, 2.9

189

 

 

 

 

 

0038 5 3035.573 356-2.m-momu§_s.mo.o.m§ 3.96335
-m-.E.mE_E.m-_asom-TEQmmmmd:33 3 2:33:85 moz .3 25mm

. m m v m m m

_ — p p b p _ p p p p _ b - p p — — p p p — h _ _ p —

 

 

 

 

 

 

190

Hz, H43) 2.15 (dd, J = 13.2, 1.7 Hz, H43) 2.17 (s, COMe) 4.13 (dqd, J = 10.4, 3.2,
5.7 Hz, H73) 5.75 (dd, J = 10.0, 2.9 Hz, H2) 5.77 (ddd, J = 10.0, 3.1, 1.7 Hz, H3)
3.35, 3.45 (AB q, J = 2.9 Hz, H10, H11).

 

1H-NMR (00300) : (minor) 6 1.075 (s, 5-Me) 1.19 (d, J = 6.3 Hz, 7-Me) 4.02
(dqdv H70.)'

A methanol solution of p-M1M3K 0.01 M was irradiated at > 290 nm and
completed in 12 h. The solution was heated in 30°C warm water for 24 h until its
color changed to yellow. The solvent was removed. After silica gel column
chromatography (hexane / ethyl acetate = 19 / 1, R1 = 0.52), the product was
identified as the equilibrium mixture of 4-acetyl-8,10-dimethyl-11-
0xabicyclo[6.3.0]undeca-1,3,5-triene and 4-acetyl-8,10-dimethyI-11-
0xatricyclo[6.3.0.0]undeca-2,4-diene in a ratio of 3 : 1, determined by two acetyl
groups. A tiny amount of the other cyclohexadiene diastereomer could be

detected by\¢o1H-NMR. The overall isolated yield was 48 %.

 

 

 

I O I
.-3: O -1.- :1-3 .-0_I“:| - '0439, o. 0 lo:,._- - :1:

1H-NMR (CDCI3) : 5 1.20 (s, 8-Me) 1.30 (d, J = 3.1 Hz, 10-Me) 1.95 (dd, J = 12.7,
10.2 H2, H9) 2.09 (dd, J = 13.4, 7.1 Hz, H7) 2.17 (dd, J = 12.7, 4.9 Hz, H9) 2.32
(s, COMe) 2.33 (dd, J = 13.4, 9.1 Hz, H7) 4.53 (dqd, J = 10.2, 3.1, 4.9 Hz, H10)

191

5.17 (d, J = 6.6 H2, H2) 6.19 (ddd, J =10.8,9.1,7.1 H2, H3) 6.36 (d, J =10.8 H2,
H5) 7.17 (d, J: 6.6 H2, H3).
WWW
1H-NMR (CDCI3) : 8 1.16 (s, 8-Me) 1.32 (d, J = 6.0 Hz, 10-Me) 1.42 (dd, J = 11.8,
3.5 Hz, H7) 1.31 (dd, J = 11.3, 10.4 H2, H7) 1.93 (dd, J = 12.4, 9.3 Hz, H9) 2.25
(dd, J = 12.4, 4.3 Hz, H9) 2.30 (s, COMe) 3.14 (dt, J = 10.4, 3.5, Hz, H3) 4.29
(dqd, J = 9.6, 6.0, 4.8 Hz, H13) 5.59 (d, J = 10.2 H2, H2) 6.68 (dd, J = 10.2, 1.6
H2, H3) 7.01 (dd, J = 6.5, 1.6 H2, H5); (another minor diastereomer) 61.18 (s)
1.70 (m) 5.47 (d) 6.58 (dd) 6.98 (dd).

Reactant : p-I1M3K

A 00300 solution (0.6 mL) of p—l1M3K (2.4 mg) and methyl benzoate (3.1
mg) was irradiated through Pyrex filter for 1 h. It provided only one product which
was identified by 1H-NMR spectroscopy as trans-1-acetyl-7-isopropyl-5-methyl-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene. The chemical yield was 75 %. 130-NMR
spectroscopy was obtained at -20°C to prevent thermal rearrangement.

The nOe experiment, also carried out at -20°C, had an enhancement
shown below when the bridgehead methyl group 5-Me was irradiated; H13 (6.7
%), H43 (2.3 %), H33 (1.5 %) and H73 (4.0 %). This indicated that 5-Me is trans to

7-iPr but cis to the cyclobutene ring.

2.37}... Hafiz, H67%

H—A-C—IM‘B‘! '
H/cdcl/ijéo
LE Me 0

C1H .M5% e/\Me

192

 

 

 

._- : ':--‘ -1I- -'oo oo ”11:. ”I.” ' o7 ”5:9W:

1H-NMR (00300) : 8 0.71 (d, J = 6.6 Hz, iPr) 0.88 (d, J = 6.6 Hz, iPr) 1.08 (s, 5-
Me) 1.24 (septd, J = 6.6, 5.7 Hz, 1H) 1.53 (dd, J = 11.9, 5.7 Hz, H33) 1.68 (dd, J =
11.9, 10.4 Hz, H33) 1.90 (dd, J = 13.5, 1.3 Hz, H43) 2.12 (dd, J = 13.5, 5.3 Hz,
H43) 2.20 (s, COMe) 3.51 (dt, J = 10.4, 5.7 Hz, H73) 5.72 (ddd, J = 10.2, 5.3, 1.3
H2, H3) 5.78 (d, J = 10.2 H2, H2) 6.34, 6.47 (AB q, J = 2.9 Hz, H13, H11 ).
13C-NMR (CD3OD) : 6 19.6, 21.8, 24.2, 31.0, 34.6, 36.6, 40.8, 46.8, 70.7, 86.2,
95.7, 127.0, 127.5, 139.7, 140.9, 214.9 (C=O).

UV(MeOH) : Am = 275 nm (750).

The ph0t0product from p-I1M3K was heated at 50°C overnight and purified
by silica gel column chromatography (Rf = 0.50 with hexane / ethyl acetate = 85 /
15). 1H-NMR spectra showed an equilibrium between cyclooctatriene and
cyclohexadiene with a 3 : 1 ratio by the integration of two acetyl groups at room
temperature. The overall isolated yield was 46 %.

The nOe experiment on cyclooctatriene provided enhancements of H2 (0.6
%), H3 (0.3 %), H73 (1.9 %), H93 (1.3 °/o) and H133 (4.3 %) when the bridgehead

methyl group 8-Me was irradiated.

 

 

 

1H-NMR (CDCI3) : 5 0.88 (d, J = 6.7 Hz, iPr) 0.99 (d, J = 6.7 Hz, iPr) 1.14 (s, 8-
Me) 1.77 (dsept, J = 7.6, 6.7 Hz, 1H) 1.88 (dd, J = 11.4, 10.7 Hz, H93) 2.03 (dd, J
= 10.7, 5.2 Hz, H93) 2.03 (dd, J = 13.5, 7.2 Hz, H73) 2.34 (s, COMe) 2.40 (br. dd,
J = 13.5, 9.4 Hz, H73) 4.07 (ddd, J = 11.4, 7.6, 5.2 Hz, H13) 5.23 (d, J = 6.6 H2,
Hz) 3.13 (ddd, J = 10.3, 9.4, 7.2 Hz, H3) 3.41 (d, J = 10.3 Hz, H5) 7.03 (d, J: 3.3
H2, H3).

1i’C-NMR (CDCI3) : (major) 5 18.3, 19.4, 20.8, 28.2, 33.1, 36.8, 42.3, 47.2, 84.6,
94.2, 129.2, 131.4, 135.3, 1386,1722, 198.6 (C=O).

I
.-:. O -1- :1-|Ioooo ”311:1 - -o

' ' '61'61ufldm:

A'.

1H-NMR (c0013) : 5 0.92 (d, J = 3.7 Hz, iPr) 0.94 (d, J = 3.7 Hz, iPr) 1.13 (s, 3-
Me) 1.45 (dd, J = 11.3, 9.2 H2, H7) 1.74 (dd, J = 11.3, 4.4 Hz, H7) 1.73 (dsept, J =
3.9, 3.7 Hz, 1H) 2.00 (dd, J = 11.2, 4.2 Hz, H9) 2.17 (dd, J = 11.2, 9.7 H2, H9)

194
2.23 (s, COMe) 3.03 (ddd, J = 9.2, 3.2, 4.4 Hz, H3) 3.33 (ddd, J = 9.7, 3.9, 4.2
Hz, H13) 5.61 (d, J = 10.3 H2, H2) 6.74 (dd, J = 10.3, 1.6 H2, H3) 6.80 (dd, J =
6.2, 1.6 H2, H5).
13C-NMI‘I (CDCI3) : (minor) 6 17.6, 19.0, 25.1, 26.4, 33.2, 35.9, 39.1, 46.1, 56.2,
31.9, 33.0, 122.4, 125.5, 132.9, 133.3, 193.7 (C=O).
lR(00l4): (mixture) 2936, 2929, 1676 (C=O), 1647 (C=O), 1361, 1253, 1166,
1097, 1044 cm".
UV(MeOH) : (mixture) 313 nm (5300), m = 334 nm (7030).
MS (m/e) : (mixture) 246 (M+), 147, 137, 121, 110, 95, 91, 77, 69, 55, 43 (base).

Reactant : p-MZM 3K

An NMR scale irradiation of a 00300 solution of p—M2M3K with a 0.9 mg
methyl benzoate at > 290 nm for 12 h provided a pair of diastereomers of 1-
acetyl-5,6-dimethyl-B-oxatricyclo[7.20.05-9]undeca-2,10-diene in a 10:1 ratio

(measured by the integration of 5-Me groups) and 76 % chemical yield.

 

 

 

._ - : o 6: - -. :1 - o-o“: I ”30‘, ' o 7 O 15.9mm

1H-NMR (00300) : (major) 6 0.97 (s, 5-Me) 1.02 (cl, J = 6.9 Hz, 6-Me) 1.42 (dqd,
J = 10.3, 3.9, 4.0 Hz, H33) 1.39 (dd, J = 15.9, 3.3 Hz, H43) 2.03 (s, COMe) 2.15
(ddd, J = 15.9, 2.9, 2.6 Hz, H43) 3.54 (dd, J = 10.8, 8.1 Hz, H73) 3.95 (dd, J = 8.1,

195
4.0 Hz, H73) 5.70 (dd, J = 9.8, 2.9 H2, Hz) 6.01 (ddd, J = 9.8, 6.8, 2.6 H2, H3)
6.21, 6.33 (AB q, J = 3.0 HZ, H10, H11).

WWW" -2 1
31333311141113 (00300) : (minor) 8 1.11 (s) 1.07 (d) 2.20 (m) 3.79 (m).

Large scale photolysis (0.2 g) in a test tube of p-M2M3K was undertaken
similar to NMR scale experiments. Photoproducts were allowed to stay at room
temperature for a couple of days and then purified by silica gel column
chromatography in 58 % isolated yield (hexane/ethyl acetate = 4/1, R4 = 0.45).
The diastereomeric ratio was determined by the integration of 8-Me groups in 1H-
NMR.

The nOe experiment indicated there was an enhancement of Hz (3.3 %),
H73 (2.3 %), H33 (5.8 %) when bridgehead 8-Me was irradiated and H5 (13.2 %),
H73, (4.4 %), H133, (8.7 %) when 6-H was irradiated

2.3°o / 4.4%
Q 11 H ('6'

\

Q .‘
C\6.66 366° 13.27 OJ)“ 5666
H4 / 0‘3, 5.3% c~c,
o c / *LJ 0 H”" X0 / H
\ 90’ g \ I \\ QC ' \ I o
\ - C “H " C .\ 87/0
IC—C\C§C‘ \ /C;H C—C\C__H__Cl \ /C\E/
M6 4 ‘ 0 Me I \ O H
H (H H H
3.3%

 

 

 

1l-f-NMI=1(000I3) : (major) 8 0.84 (d, J = 6.8 Hz, 9-Me) 1.08 (s, 8-Me) 1.38 (dd, J
= 12.4.3.9 Hz, H73) 1.33 (ddq, J = 10.9, 7.0, 3.3 Hz, H33) 2.27 (s, COMe) 2.33

196
(dd, J = 12.4, 10.9 Hz, H-,,,) 2.94 (ddd, J = 10.9, 6.9, 5.5 Hz, H6) 3.68 (dd, J =
10.9, 9.2 Hz, Hm) 4.08 (dd, J = 9.2, 7.0 Hz, H1013) 5.46 (dd, J = 10.2, 1.0 Hz, H2)
6.59 (dd, J = 10.2, 1.6 Hz, H3) 6.74 (dd, J = 5.5, 1.0 Hz, H5).

. 1'6 lungggg-ZA-gieng:
1H-NMR (CDCI3) : (minor) 8 0.91 (d, J = 6.7 Hz, 9-Me) 0.95 (s, 8-Me) 1.54 (dd, J

 

= 11.7, 7.2 Hz, H7) 1.84 (tq, J = 8.1, 6.7 H2, H9) 2.28 (s, COMe) 2.29 (m, H7) 3.05
(ddd, J = 10.2, 7.2. 4.5 H2, H6) 3.95 (t, J = 8.1 Hz, H10a)4.22 (t, J = 8.1 Hz, H105)
5.20 (dd, J = 8.2, 1.1 Hz, H 2) 6.60 (dd, J = 8.2, 1.5 H2, H3) 6.75 (dd, J = 4.5, 1.1
H2, H5).

1H-NMR (CDCI3) : (small amount of cycloéctatriene) 8 5.20 (dd, J = 6.5, 1.1 Hz,
1H) 5.95-6.10 (m) 7.02 (d, J = 6.5 Hz, 1H).

Reactant : p-M3M 4K

An NMR tube containing 3.0 mg p-M3M4K and 4.4 mg methyl benzoate
was dissolved in CD3OD and irradiated at > 290 nm for 1.5 h. Only one
photoproduct was identified by 1H-NMR spectroscopy in 45 % chemical yield.

Since this cyclobutene was stable compared with others, large scale
isolation could be undertaken. A solution 0.2 g of p-M3M 4K in 70 mL methanol
was photolyzed at > 290 nm for 90 h. Solvent was removed at room temperature
and the residue was purified by silica gel column chromatography with 1 "/6
triethyl amine (hexane/ethyl acetate = 3/1, Rf = 0.43). The first fractions collected
from the column contained a cyclobutene which the remained fractions contained
mixtures of cyclobutene and cyclohexadiene.

There is an enhancement of H10 (2.4 %), H413 (1.0 %), H65 (1.5 %) and H75

(1.2 %) from nOe experiment when 5-Me was irradiated.

197

. H24%
1.021.. [1:11,
H—c sC—I‘C 694/:
Me /C\C/C/\CO
Me 0
H,..‘C\g/ H 1.2%

(11.45%

 

 

 

._ - .; : .._-- :(u -'.“;. --:.,., ' o 005.9W
diene;
‘H-NMR (CDCI3) : 5 0.93 (s, 5—Me) 1.04 (d, J = 7.4 Hz, 4-Me) 1.61 (ddd, J = 13.7,
7.7, 5.9 Hz, H513) 2.14 (s, COMe) 2.16 (ddd, J = 13.7, 8.3, 6.9 H2, H3“) 2.33 (qdd,
J = 7.4, 4.1, 1.6 Hz, H413) 3.75 (ddd, J = 14.2, 8.3, 5.9 H2, H7“) 3.82 (ddd, J =
14.2, 7.7, 6.9 Hz, H713) 5.64 (dd, J = 10.0, 1.6 H2, H2) 5.77 (dd, J = 10.0, 4.1 H2,
H3) 6.33 ,6.44 (AB q, J = 2.9 Hz, H10, H11).

1H-NMR (coaoo) : 8 0.96 (s, 5-Me) 1.04 (d, J = 7.4 Hz, 4-Me) 1.71 (ddd, J =
13.7, 7.7, 5.9 Hz, H65) 1.86 (ddd, J = 13.7, 8.3, 6.9 H2, H6“) 2.15 (s, COMe) 2.27
(qdd, J = 7.4, 4.1, 1.6 Hz, H413) 4.10 (ddd, J = 14.2, 8.3, 5.9 H2, H7“) 4.17 (ddd, J
= 14.2, 7.7, 6.9 Hz, H713) 5.64 (dd, J = 10.0, 1.6 H2, H2) 5.79 (dd, J = 10.0, 4.1 H2,
H3) 6.46 .650 (AB q, J = 2.9 Hz, H10, H11).

13C-NMR (CDCla) : 5 15.2, 18.7, 28.4, 35.6, 36.8, 45.2, 50.5, 64.7, 92.6, 124.9,
134.5, 139.5, 141.0, 209.8 (C=O).

|R(CCI4) : 2968, 1703 (C=O), 1300, 1250, 1022 cm-‘.

UV(MeOH) :lmax = 280 nm (875), 290 nm (550) .

MS (m/e) : 218 (M+), 203, 175, 147, 91, 86, 84 (base), 77, 55, 43.

198
All fractions containing a mixture of cyclobutene and cyclohexadiene from
the previous experiment were combined. The photoproducts then heated in
methanol at 40°C for 24 h to ensure the cyclobutene totally converted into
cyclohexadiene. The cyclohexadiene was then isolated by silica gel column
chromatography (hexane/ethyl acetate = 3/1, Rf = 0.30, 45 %). The
enhancements of H2 (3.2 %), H713 (1.0 %) and H93 (3.0 %) were recorded when 8-

Me group was irradiated. This confirmed two methyl groups trans to each other.

 

 

 

1H-NMR(CDCI3) : 8 0.95 (d, J = 7.5 Hz, 7-Me) 1.03 (s, 8-Me) 1.76 (ddd, J = 12.4,
9.2, 7.5 H2, H9) 1.85 (ddd, J = 12.4, 6.2, 3.6 H2, H9) 2.30 (s, COMe) 2.54 (do, J =
10.7, 7.5 Hz, H75) 3.35 (dd, J = 10.7, 5.8 Hz, H6“) 4.07 (ddd, J = 12.2, 7.5, 3.6
Hz, H10) 4.15 (ddd, J = 12.2, 9.2, 6.2 Hz, H10) 5.45 (d, J = 9.7 Hz, H2) 6.59 (d, J =
9.7 H2, H3) 6.61 (d, J = 5.8 H2, H5).

13C-NMFI (CDCI3) : 5 11.4, 15.9, 25.2, 39.5, 41.7, 42.6, 56.3, 67.0, 82.5, 122.1,
1257,1352, 137.5, 196.3 (C=O).

UV(MeOH) : 290 nm (2160), Am = 295 nm (2200), 313 nm (1635).

MS (m/e) : 218 (M+), 203, 176, 137, 121, 83, 55, 43 (base).

8.08 :_ 220.2824: 6864.066856.5.6.8.8.
6.32285; F-.EEEBé.H-_amom-v-Em.mb-oE 6 2:05:83 moz .3 2:2...

Ema m m w m

avioou

199

 

 

5L’1£SI

mu.“-

EL'VELZ

36'6685

LZ'SOEE

an
. b
v-

52'90

E
BE'BOEE

.
h
V

ET'LO

 

 

 

 

200

Reactant : p-M1M3M4K

An NMR scale photolysis of p-M1M3M4K (3.0 mg) and methyl benzoate
(3.7 mg) in CD300 (0.6 mL) was undertaken at > 290 nm for 18 h under oxygen-
free condition. Diastereomeric ratio was formed to be 9:1 from two acetyl groups
and chemical yield was 49 %, measured from 1H-NMR spectroscopy. The nOe
experiment verified that the major diastereomer has bridgehead 5-Me group cis
to cyclobutene ring but trans to 4-Me and 7-Me since there was an enhancement
of H10 (7.2 %), H413 (2.3 %), Hap (1.7 %) and H75 (4.3 %) when 5-Me was

irradiated.
t'
2.3% [10 ' 7 2 %

 

 

 

/H .
(1H7% Me
)_©_ hv, Pyrex
h. MM6+ ‘MB
Me
.- .; : ':---1.~.-4 -'11=1 --:-.=.' . ”5'91undeca;
2.1(tdiene;

1H-NMR (C0300) : (major) 8 0.98 (s, 5-Me) 1.05 (d, J = 7.4 Hz, 4-Me) 1.11 (d, J
= 6.1 Hz, 7-Me) 1.71, 1.74 (A8 q, J = 7.3 Hz, 2H6) 2.13 (s, COMe) 2.29 (qdd, J =
7.4, 4.3, 1.6 Hz, H43) 4.12 (ddq, J = 9.0, 7.3, 6.1 Hz, H713) 5.68 (dd, J = 10.0, 1.6
Hz, H2) 5.80 (dd, J = 10.0, 4.3 H2, H3) 6.47, 6.50 (AB q, J = 3.0 Hz, H10, H11).

.- -. -1-' -1'1:1:o.._' . 00591111351803;

_ 1. I I.
'. I I I

201
‘H-NMR (C030D) : (minor) 8 0.86 (s), 1.12 (d) 1.20 (d) 2.0-2.2 (m) 2.13 (s) 2.50
(m) 4.22 (m) 5.69 (dd) 5.80 (dd) 6.25, 6.36 (AB 0).

A 120 mL methanol solution of p-M1M3M4K (0.014 M) was irradiated
through Pyrex filter for 45 h. The solution was heated and the residue was
purified on silica gel column chromatography (hexane/ethyl acetate = 4/1, R1 =
0.47) in 50 % isolated yield and 80% de from the integration of H2 protons. The
stereochemistry of this compound, confirmed by nOe experiments, has
bridgehead 8-Me group trans to 7-Me and 10-Me. An enhancement was
observed for H2 (2.3 %), H75 (0.6 %), H95 (2.4 %) and H101; (1.9 °/o) when 8-Me
was irradiated or for H5 (8.9 %), 7-Me (1.0 %) and 10-Me (1.0 %) when 6-H was
irradiated.

1 .0%

 

 

 

1H-NMI-‘l(CD3()D) : (major) 8.0.89 (d, J = 7.5 Hz, 7—Me) 1.04 (s, 8-Me) 1.32 (d, J
= 5.9 Hz, 10-Me) 1.96 (dd, J = 12.3, 10.8 Hz, H9“) 2.19 (dd, J = 12.3, 4.8 Hz, H95)
2.31 (s, COMe) 2.52 (dq, J = 10.0, 7.5 Hz, H75) 3.42 (dd, J = 10.0, 6.3 Hz, Hm)

.0088
s Spins—2.5 828-2 .N-68E=_s.modmfisafismxo
-33653-3.1388-755.3%de:69 6 989:st moz .3 2:9“.
.55 m.“ 9m. m.m o.m m.m oé m6 0...... mun. ob

ur—-._-_-—-——-——————_—__—lb1.——.L———-_.—-___—————___l—__—_rh—

.. ; a1. 1 d j

 

L
f‘

 

 

 

 

202

A:

 

 

 

 

E
a
Z c. E
{.7 RT. are a.“ ma .9 m
3.2: 3.? .L V8 R w t . v w. mmfi
} } ..r. .1... n .L w w w ...u. .7. w ....
.1. a m m
6 a a
if u L fr if D it I.’ 1 P
11 1141111 111 11 J;
/ ./ / _ .
oI «I NI 0:...—

 

 

203
4.27 (dqd, J = 10.8, 5.9, 4.8 Hz, H1013) 5.62 (d, J = 10.2 H2, H2) 6.61 (dd, J = 10.2,
1.5 Hz, H3) 6.83 (dd, J = 6.3, 1.5 H2, H5).
136-NMR (CDCI3) : (major) 8 12.1, 15.2, 21.2, 25.3, 40.3, 44.9, 54.6, 56.9, 79.7,
83.0, 123.2, 127.9, 136.4, 139.0, 198.7 (C=O).

 

1H-NMR (c0300): (minor) 8 1.09 (d) 2.33 (s) 4.60 (m) 5.41 (d) 6.48 (d) 7.03 (d).

Reactant : p-M4K

A solution of 3.5 mg pure trans p-M4K and 2.2 mg methyl benzoate in 0.75
mL CD30D was irradiated through Pyrex filter under oxygen-free condition. The
100% pure trans p—M4K was purified from trans (> 95%) and cis mixtures by
silica gel column chromatography (hexane/ethyl acetate = 99/1) and detected by
HPLC to assure only trans isomer. At low conversion (7 "/6 in 50 min), the signal
of cis p-M4K could be detected by either 1H-NMR spectrum or HPLC. The
retention time of trans p-M4K is 13.0 min and cis p-M4K is 13.6 min in HPLC with
hexane/ethyl acetate = 95/5 elute solvent system. After high conversion (> 95 %
in 18 h), a diastereomeric mixture of CB's in a ratio of 11 : 1 by the integration of
acetyl groups was isolated in 41 °/o chemical yield.

The nOe experiment verified that the major diastereomer has bridgehead
group H55 cis to cyclobutene ring but trans to 4-Me since there was an
enhancement of H3 (1.9 %), H45 (3.6 %), and H60, (0.7 %) when 4-Me was
irradiated and H10 (4.2 %), H45 (1.3 %), H65 (1.7 %) and H75 (3.3 %) when 5-H

was irradiated.

o

___.___n

2% _

___.__L___.._.

0068 s 60.2-3 966-2.m-88cs_%odd-2-966586
-9359: 4 3.86.76.35.56:99 6 2:85:88 moz we 2:9”.
N _.. a

m m

 

204

 

 

 

__.___~.___...____~__._.rhph._%b..._..___....~_le___.___

-5133 13

 

 

 

33.4. - --

I
m...
56/ o...
O \05. _C Mofix
\/O
O“0\l\m..w\ A /\o o
I\U I 0.“ 01—1— \omé
40k .1 C
I o .xbm
vo.m1 m.

.IFJ

205

:1 H
3 6% 0, H 133% 6 4.2%
”2 / C‘ /’C‘H\J
1 9% H—c ‘0‘"— 6/4 0 H— gc‘fi‘Qé/scm
\ / / C
Me/ C M /\ Me/ \C/ X
/ A 1 e O n | Me /O
. c H . H 3.3%
0.7 AH.“ \%A 1.7 /°'_lp‘4C\ 9‘
H H

 

 

 

1l-l-NMR (CD300) : (major) 8 1.13 (d, J = 7.2 Hz, 4-Me) 1.87 (ddd, J = 13.4, 7.5,
5.2 Hz, H33) 1.89 (ddd, J = 13.4, 9.3, 7.5 H2, H3“) 2.02 (qddd, J = 7.2, 5.2, 3.7,
1.9 Hz, H43) 2.12 (s, COMe) 2.37 (ddd, J = 9.3, 7.2, 5.2 Hz, H53) 3.81, 3.83 (A8
q, J = 6.7 Hz, 2H7) 5.71 (dd, J = 10.1, 1.9 Hz, H2) 5.82 (dd, J = 10.1, 3.7 Hz, H3)
6.31, 6.43 (A8 q, J = 2.9 Hz, H10, H11).
WES'QW
1H-NMR (c0300) : (minor) 8 2.16 (s, COMe) 3.84 (AB q, 2H7) 5.60-5.70 (m)
6.22, 6.37 (AB q, J = 2.9 Hz, H10, H11).

Large scale (0.2 g) of p-M4K was irradiated at > 290 nm in dry MeOH for
16 h. After a few days in a refrigerator, the original colorless solution has turned
yellow. The mixture was purified by silica gel column chromatography. Products
were identified as a 5:1 diastereomeric mixture of 4-acetyI-7-methyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene and to a small amount (< 15 %) of 4-acetyl-
7-methyl-1 1-oxatricyclo[6.3.0.01 v5]-undeca-2,4-diene. The overall ratio is 15
(major COT) :2 (minor CDT) :2 (major CH) :1 (minor CH), determined by the
integration of H3 groups in NMR.

206

 

 

 

._- :;;-..‘._ :\--“3| - -'.,.. o. o ...: ._- -'-.--

1H-NMR (CDCI3) : (major) 8 1.08 (d, J = 6.8 Hz, 7-Me) 1.85 (ddd, J = 12.4, 12.0,
3.2 H2, H9“) 2.06 (ddd, J = 12.4, 6.8, 3.4 Hz, H93) 2.32 (s, COMe) 2.46 (dqd, J =
8.8, 6.8, 1.4 Hz, H73) 3.05 (ddd, J = 12.0, 3.4, 1.4 Hz, H33) 4.15, 4.17 (AB q,
2H1o) 5.45 (d, J = 7.4 H2, H2) 5.63 (dd, J = 12.3, 8.8 H2, H6) 6.17 (d, J = 12.3 H2,
H5) 6.98 (d, J = 7.4 H2, H3).

13C-NMI‘HCDCI3) : 8 20.1, 26.2, 32.8, 39.5, 41.5, 72.2, 91.8, 127.2, 134.3, 135.7,
137.2, 170.1, 199.2 (C=O).

._- ::-i; ;(--“:. - -.,._. o. o ...:5- -'-.--
1H-NMR (CDCI3) : (minor) 8 1.02 (d, J = 6.7 Hz, 7-Me) 1.95-2.20 (m) 2.31 (s,
COMe) 4.25 (m) 5.32 (d, J = 6.1 H2, H2) 5.65 (m, H3) 6.26 (d, J = 11.0 H2, H5)
7.00 (d, J = 6.1 H2, H3).
1H-NMR (CDCI3) : (major) 8 1.06 (d, J = 7.4 Hz, 7-Me) 2.29 (s, COMe) 2.80 (m,
H3) 3.92 (ddd, J = 14.5, 8.5, 6.0 Hz, H10) 4.05 (ddd, J = 14.5, 8.7, 6.0 Hz, H13)
5.91 (d, J = 10.5 H2, H3) 6.52 (d, J = 10.5 Hz, H2) 6.81 (d, J = 6.1 H2, H5).
1H-NMI‘I (CDCI3) : (minor) 8 5.90 (d) 6.62 (m).
UV(MeOH) : (mixture) 313 nm (8500), m = 337 nm (10400).

207
Reactant : p-M3M4M5K

A 0.015 M methanol solution of cisxfrans mixture of p-M3M4M5K in 3 NMR
tube was photolyzed at > 290 nm for 6 h. The diastereomeric excess (13 %,
measured by acetyl groups) and chemical yield (45 %) were directly obtained
from the 1H-NMR spectrum.

The nOe experiment at room temperature indicated the major
diastereomer has bridgehead group 5-Me cis to cyclobutene ring but trans to 4-
Me since there was an enhancement of H43 (2.2 %), H33 (1.6 %), H73 (4.1 %) and
H13 (3.5 %) when 5-Me was irradiated. The minor diastereomer has bridgehead
group 5-Me cis to cyclobutene ring and 4-Me due to an enhancement of 4-Me
(7.6 %), H33 (1.5 %), H73 (3H 4 °/o) and H13 (2. 2 %) when 5- Me was irradiated.

o O o
2.27}H §C [3% 35/. 7.6732 C}/C:

H 2.2%

U

Me—C. :C _M6.C O Me_c
M6 /C\c,/ C\’Cé :30,/\ch
Me’o

H\1-C\J‘H 4.1% H/H;C\C\/‘o"' 34%

1.6% 3 U 1.5% ? U

H J' H

 

 

 

1H-NMR (C0300) : (major) 81.06 (s, 5-Me) 1.08 (d, J = 7.2 Hz, 4-Me) 1.63 (ddd,
J =12.1,7.4,3.9 Hz, H33) 1.73 (ddd, J = 12.1, 7.6, 6.5 Hz, H33) 1.79 (d, J :14
Hz, 3-Me) 2.05 (0. J = 7.2 Hz, H43) 2.15 (s, COMe) 4.05 (ddd, J = 11.5, 7.6, 3.9

 

208
Hz, Hm) 4.15 (ddd, J = 11.5, 7.4, 6.5 Hz, H73) 5.37 (q. J = 1.4 Hz, H2) 6.39, 6.44
(AB q, J = 3.0 HZ, H10, H11).

 

1H-NMR (CD30D) : (minor) 6 1.03 (s, 5-Me) 1.13 (d, J = 7.3 Hz, 4-Me) 1.51(m,
2H3) 1.76 (d, J = 1.4 Hz, 3-Me) 2.15 (s, COMe) 2.25 (qd J = 7.3, 1.4 Hz, H4“)
3.78 (m, 2H-,) 5.45 (quintet, J = 1.4 H2, H2) 6.31, 6.33 (AB q, J = 2.9 Hz, H10,
H11)-

A MeOH solution of diastereomeric mixture of 1-acetyI-3,4,5-trimethyl-8-
oxatricyclo[7.2.0.05:9]undeca-2,1O-diene obtained from the above experiment
was heated at 40°C for 24 h and 1H-NMR was recorded.

The nOe experiments at room temperature showed that the major
diastereomer has bridgehead group 8-Me trans to 5—Me and 6-Me because there
was an enhancement of H5 (2.1%), H73 (2.2 %), H93 (1.3 %) and H103 (1.1 %)
when 8-Me was irradiated. The minor diastereomer has bridgehead group 8-Me
cis to 7-Me but trans to 6-Me since there was an enhancement of 7-Me (5.9 %),
H93 (0.8 %) and H103 (2.0 %) when 8-Me was irradiated.

2.2% Me/ 5%.; 1" N/
e H

2.1%} ‘C: Me H ‘0?
\ 1.: .:

o c/ /6.....C,H 1.3% ”4., / \6MC‘H 0.8%
\\ OC— \C o\\ 9-9\ / (I: U
C—C Me ...u‘ C—C M C ._mH

H’ ‘H (1.1% ’

H ‘H k 2.0%

 

209

 

 

 

1H-NMR (CD30D) : (major) 51.03 (s, 8-Me) 1.06 (d, J = 7.3 Hz, 7-Me) 1.09 (s, 6-
Me) 1.60 (m, 2H9) 2.20 (q, J = 7.3 Hz, H73) 2.32 (s, COMe) 4.15 (m, 2H13) 5.28
(d, J = 10.1 H2, H2) 6.41 (dd, J = 10.1, 1.6 H2, H3) 6.70 (5, H5).

- new

 

1H-NMH (coaoo) : (minor) 5 1.09 (s, 8-Me) 1.11 (d, J = 7.4 Hz, 7-Me) 1.13 (s, 6-
Me) 1.70 (m, 2H9) 2.21 (q. J = 7.4 Hz, H73) 2.30 (s, COMe) 4.10 (m, 2H13) 5.44
(d, J = 10.1 Hz, H 2) 6.55 (dd, J = 10.1, 1.7 Hz, H3) 6.76 (s, H3).

Reactant : p-M1M3M4M3K

A 0.021 M methanol solution of a cis/trans mixture of p-M1M3M4M3K in a
NMR tube was photolyzed at > 290 nm for 8 h. The diastereomeric excess (19
%) and chemical yield (55 %) were directly obtained from the 1H-NMR spectrum.

The nOe experiment showed that the major diastereomer has bridgehead
group 5-Me cis to cyclobutene ring but trans to 4-Me and 7-Me since there was
an enhancement of H43 (3.2 %), H33 (1.4 %), H73 (5.1 %) and H13 (3.9 %) when
5-Me was irradiated. The minor diastereomer has bridgehead group 5-Me cis to
cyclobutene ring and 4-Me but trans to 7-Me since there was an enhancement of
4-Me (11.6 %), H33 (1.1 %), H73 (4.0 %) and H13 (2.5 %) when 5-Me was
irradiated.

210

 

 

 

W5-9lunmzzmfl

1l-l-NIlIR (CD300) : (major) 5 1.00 (d, J = 6.2 Hz, 7-Me) 1.03 (d, J = 7.4 Hz, 4-
Me) 1.11 (s, 5-Me) 1.55 (dd, J = 12.1, 5.8 Hz, H33) 1.66 (dd, J = 12.1, 10.2 H2,
H3“) 1.78 (d, J = 1.5 Hz, 3-Me) 2.08 (q, J = 7.4 Hz, H43) 2.15 (s, COMe) 4.15
(dqd, J = 10.2, 6.2, 5.8 Hz, H73) 5.43 (q, J = 1.5 H2, H2) 6.43, 6.50 (AB o, J = 2.9
Hz, H13, H11).

W5-9lundmzmm

‘H-NMR (C0300) : (minor) 8 1.01 (d, J = 6.2 Hz, 7-Me) 1.07 (d, J = 7.4 Hz, 4-
Me) 1.12 (s, 5-Me) 1.42 (dd, J = 11.2, 10.5 Hz, H33) 1.54 (dd, J = 11.2, 5.6 Hz,
H33) 1.75 (d, J = 1.4 Hz, 3-Me) 2.16 (s, COMe) 2.22 (qd, J = 7.4, 1.4 Hz, H43)
4.11 (dqd, J = 10.5, 6.2, 5.6 Hz, H73) 5.47 (quintet, J = 1.4 Hz, H2) 6.31, 6.41 (AB
o, J = 2.9 Hz, H13, H11).

A mixture of 1-acetyl-3,4,5,7-tetramethyI-8-oxatricyclo[7.2.0.05.9]undeca-

2,10-diene diastereomers from the above experiment was heated in MeOH at

.9038 s Eon—24.2355
E 255-2H-852;5.5o.o.w.t-o_o>o_=mxo-m-_§d5.2.2

$655-38?7333256:55 .5 255:6on moz .8 2:9“.
58 mg 9m rim 9m mtm 0.5 m... c m Pm 05 m6

P__—_-__—_—b——__—p___p_—————l—Fb———b___—-_—

_—____r—__

__—~_L—_

 

 

 

 

 

2. _ O m: .m: . $5 . m1

211

 

 

 

 

212
40°C for 46 h. An identical diastereoselectivity was obtained for the
photoproducts.

The nOe results indicated that the major diastereomer has bridgehead
group 8-Me trans to 5-Me, 6-Me and 10-Me since there was an enhancement of
H3 (3.0%), H73 (1.8 %), H93 (2.3 %) and H193 (2.1 %) when 8-Me was irradiated.
The minor diastereomer has bridgehead group 8-Me cis to 7-Me but trans to 6-
Me and 10-Me since there was an enhancement of 7-Me (7.8 %), H93 (1.8 %)

and H133 (1.2 %) when 8-Me was irradiated.

 

 

 

1H-NMR (00900) : (major) 5 1.00 (s, 8-Me) 1.04 (d, J = 7.4 Hz, 10-Me) 1.11 (s,
6-Me) 1.17 (d, J = 6.0 Hz, 7-Me) 1.83 (m, 2H 9) 2.01 (q, J = 6.0 Hz, H73) 2.33 (s,
COMe) 4.50 (m, H133) 5.30 (d, J = 10.1 H2, H2) 6.41 (d, J = 10.1 H2, H3) 6.69 (8,
H5).

I
-1_- :1-. 3 O : :11:| - -o q o. 00 10.3.3.-

A

213

1H-NMH (00300) : (minor) 6 1.01 (s, 8-Me) 1.03 (d, J = 7.4 Hz, 10-Me) 1.13 (s,
6-Me) 1.21 (d, J = 5.5 Hz, 7-Me) 1.78 (m, 2H9) 2.10 (q, J = 5.5 Hz, H733) 2.31 (s,
COMe) 4.23 (m, H103) 5.56 (d, J = 10.1 H2, Hz) 6.58 (d, J = 10.1 H2, H3) 6.75 (s,
H5).

Reactant : p-M4M 5K
A 0.017 M methanol solution of p—M4M3K in an NMR tube was photolyzed
at > 290 nm for 6 h. The diastereomeric excess (10 %, measured by acetyl

groups) and chemical yield (61 %) were directly obtained from the 1H-NMR
spectrum.

 

 

 

1H-NMR (c0900) : (major) 5 1.12 (d, J = 6.4 Hz, 4-Me) 1.68 (dddd, J = 12.5,
10.2, 7.2, 4.1 Hz, H33) 1.74 (dddd, J = 12.5, 7.7, 6.9, 6.0 Hz, H33) 1.80 (d, J = 1.5
Hz, 3-Me) 2.13 (s, COMe) 2.23 (qd, J = 6.4, 2.6 Hz, H43) 2.42 (ddd, J = 10.2, 7.7,
2.6 H2, H5) 3.95 (ddd, J = 11.9, 6.9, 4.1 Hz, H73) 4.12 (ddd, J = 11.9, 7.2, 6.0 Hz,
H73) 5.42 (q, J = 1.5 Hz, Hz) 6.33, 6.35 (AB q, J = 2.8 Hz, H13, H11).

---- ‘1- ‘-'-u= - “svglundmidflz

diene;
1l-l-NMI=1(00900) : (minor) 8 1.16 (d, J = 7.2 Hz, 4-Me) 1.77 (d, J = 1.5 Hz, 3-
Me) 1.82-1.89 (m, 2H3) 2.14 (s, COMe) 2.30 (qdd, J = 7.2, 2.0, 1.5 Hz, H43) 2.39

 

214
(m, H3) 3.71-3.75 (m, 2H7) 5.40 (quint, J = 1.5 H2, H2) 6.29, 6.33 (A8 q, J -..- 2.9
HZ. H10. H11)-

A mixture of 1-acetyl-3,4-dimethyl-8-oxatricyclo[7.2.O.05-9]undeca-2,10-
diene diastereomers obtained from the above experiment was heated at 40°C in
MeOH for 40 h to give the same diastereoselectivity (10 %, measured by acetyl

groups) from NMR spectra.

 

O
\f 0 Me Me
i
Me A ...Me Me
-—-—> H + H
o . M" MeOH
\/’ H

 

 

._ - i 3: --.:1l---o_11: --o.-.,oo1 . . 0 1o: -1 - :'1:
1H-NMI=1(00300) : (major) 6 1.07 (d, J = 7.0 Hz, 7-Me) 1.93 (d, J = 1.5 Hz, 6-
Me) 2.20 (m, 2H9) 2.30 (s, COMe) 2.45 (qdd, J = 7.0, 6.5, 2.1 Hz, H73) 3.13 (ddd,
J = 7.8, 6.5, 4.4 Hz, H33) 3.98 (ddd, J = 13.7, 8.5, 6.4 Hz, H13) 4.12 (ddd, J =
13.7, 8.7, 6.0 Hz, H19) 5.34 (d, J = 6.9 H2, H2) 6.08 (q, J = 1.5 H2, H5) 7.10 (dd, J
= 6.9, 1.2 H2, H3).

.,- ::--‘; :(-. w...“ - -'.,._1 3.. o 3.: .,- -'-.--
1H-NMF1(00300) : (minor) 6 1.09 (d, J = 6.9 Hz, 7-Me) 1.82 (d, J = 1.5 Hz, 6-
Me) 2.00 (m, 2H9) 2.32 (s, COMe) 2.75 (qdd, H73) 3.12 (ddd, H33) 4.23 (m, 2H3))
5.44 (dd, J = 8.2, 2.0 H2, H2) 6.01 (q, J = 1.5 H2, H3) 7.08 (d, J = 8.2 H2, H3).
UV(MeOH) : (mixture) 313 nm (8500), Amen = 337 nm (10500).

Reactant : o-I1K
In an NMR tube, a solution of o-I1K (1.8 mg) and 1.6 mg methyl benzoate
was irradiated in 00300 (0.6 mL) at > 290 nm (Pyrex) for 1 h. The

 

215
photoproducts were identified as a pair of diastereomers of 9—acetyl-5-isopropyl-
4-oxatricyclo[7.2.0.03-7]undeca-2,10-diene in a ratio of 4 : 1 by the integration of
two H10 protons and in 71 % chemical yield in NMR spectra.
The nOe experiments performed at -20°C indicated that there was an
enhancement of major product of H10 (4.7 %), H11 (1.1 %), H2 (3.7 %), H55 (2.6
%), Hep (1.3 °/o) and H35 (1.2 %) when H7 was irradiated.

4.17:)

1.3% ;

 

CI? 003;” 311M EEK

"A :\ - -' on 00-1-0“ . 0 . .3'7W

 

 

diene;
1H-NMR (c0300) : (major) 5 0.89 (d, J = 6.7 Hz, iPr) 0.99 (d, J = 6.7 Hz, iPr)
1.40 (ddd, J = 13.5, 12.4, 9.8 Hz, Hm) 1.45 (ddd, J = 13.5, 4.9, 3.8 Hz, H65) 1.71
(octet, J = 6.7 Hz, 1H) 2.12 (dd, J = 12.9, 5.2 Hz, Hep) 2.17 (s, COMe) 2.24 (dd, J
= 12.9, 8.7 Hz, Hm) 2.56 (dddd, J = 9.8, 8.7, 5.2, 3.8 Hz, H73) 3.42 (dd, J = 6.6,
1.7 Hz, Hm) 8.87 (ddd, J = 12.4, 6.7, 4.9 Hz, H55) 4.72 (dd, J = 6.6, 2.5 H2, Hz)
6.11, 6.15 (AB q, J = 2.8 Hz, H10, H11).
WWW
diene;

1H-NMR (c0300) : (minor) 5 0.88 (d, J = 6.8 Hz, iPr) 0.98 (d, J = 6.8 Hz, iPr)
1.58 (m, 2H6) 1.80 (m, 1H) 2.07 (m, 1H) 2.16 (s, COMe) 2.27 (m, 1H) 2.67 (m,

 

216

1H) 8.41 (m, 1H) 3.85 (m, 1H) 5.61 (dd, J = 5.4, 0.8 Hz, Hz) 5.89, 5.91 (AB q, J =
2.5 HZ, H10, H11).

A solution of 0.2 g o-I1K in 60 mL dry methanol was irradiated at > 290 nm
for 5 h. The residue was purified by silica gel column chromatography (Rg = 0.53
with hexane/ethyl acetate = 4/1) with the isolated yield = 52 %. The
diastereoselectivity was 60 %, measured from the integration of two H5 in 1H-
NMR. Separation of diastereomers was unsuccessful.

In nOe experiments, the major product had enhancements of H3 (1.1 %),
H713 (3.5 %), H91; (2.5 °/o) and H101; (2.9 %) when bridgehead proton H313 was
irradiated.

 

 

 

._-3. O -o- :\--000 so - -o‘.hoq o. O _|0:A.A- -'-l'
1H-NMI‘! (CDCI3) : (major) 5 0.85 (d, J = 6.8 Hz, iPr) 0.93 (d, J = 6.8 Hz, iPr) 1.51
(ddd, J = 12.4, 10.9, 8.8 Hz, Hga) 1.51 (ddd, J = 12.4, 5.4, 4.7 Hz, H913) 1.70
(septd, J = 6.8, 7.5 Hz, 1H) 2.16 (dd, J = 12.7, 7.4 H2, H7,,) 2.33 (s, COMe) 2.70

 

217
(dddd, J = 8.8, 7.4, 5.4, 1.8 Hz, H33) 3.06 (dd, J = 12.7, 1.8 Hz, H75) 3.92 (ddd, J
= 10.9, 7.5, 4.7 Hz, H1013) 5.33 (dd, J = 9.4, 2.5 H2, H2) 5.73 (dd, J = 13.2, 6.1 H2,
H4) 6.01 (dd, J = 13.2, 9.4 H2, H3) 7.05 (d, J = 6.1 H2, H5).
13(2-NMR (CDCI3) : (major) 6 17.6, 25.4, 27.0, 31.3, 36.2, 44.4, 85.3, 95.7, 118.7,
130.5, 138.8, 141.5, 169.6, 198.0 (C=O).
r - R1R -o-A :1l-1-i uro- l- 1-o.x i I- ”.3. no: -1 - 'ne:
1H-NMFI (CDCI3) : (minor) 8 0.85 (d, J = 6.6 Hz, iPr) 0.91 (d, J = 6.6 Hz, iPr) 1.89
(m, 1H) 2.05 (ddd, J = 12.4, 5.8, 1.3 Hz, 1H) 2.25(m, 2H) 2.32 (s, COMe) 2.89
(m, 1H) 2.91 (dd, J = 13.5, 2.2 Hz, 1H) 4.07 (m, H10) 5.81 (m, H2) 5.75 (dd, J =
12.6, 7.1 H2, H4) 6.04 (dd, J = 12.6, 8.0 H2, H3) 7.03 (d, J = 7.1 H2, H5).
13c-NMR (coma) : (minor) 5 18.9, 25.0, 25.5, 32.5, 84.7, 40.2, 85.7, 95.3, 118.4,
131.9, 137.3, 140.3, 169.3, 199.2 (C=O).
UV(MeOH): (mixture) 313 nm (1525), Max = 377 nm (4500).

Reactant : o—MllaK

The same irradiation procedure for o-I1K was used. After half an hour
irradiation ( >290 nm), a solution of 3.0 mg o-I1M3K with internal standard in
00300 provided one major product which was characterized as trans-9-acetyI-5-
isopropyl-7-methyl-4-oxatricyclo[7.2.0.03:7]undeca-2,10-diene with a small
amount of the cis-isomer in a ratio of 9 : 1 by the H2 integration in NMR.
Chemical yield was 67 %.

The major product's stereochemistry was determined by nOe experiments
at -20°C, shown below. There was an enhancement when the bridgehead methyl
group 7-Me was irradiated; H2 (0.6 %), H10 (5.2 %), H11 (1.2 %), H35 (1.5 %), Hep
(1.3 °/o) and H51; (3.3 %). This indicated that the product has methyl group
bridgehead, 7-Me, cis to the cyclobutene group but trans to the 5-iPr.

 

 

 

 

A =\ ' -' H H - 11:: --‘o.-.' 0 ' 1371909998;

1H-NMR (c0300) : (major) 5 0.86 (d, J = 6.8 Hz, iPr) 0.98 (d, J = 6.8 Hz, iPr)
1.28 (s, 7-Me) 1.46 (br t, J = 11.5 H2, H6“) 1.65 (oct, J = 6.9 Hz, 1H) 1.82 (d, J =
18.8 Hz, Hm) 1.98 (dd, J =11.5,5.0 Hz, H613) 2.11 (d, J =18.8 Hz, Hap) 2.19 (s,
COMe) 8.49 (dd, J = 6.6, 0.9 Hz, Hm) 4.07 (ddd, J = 11.0, 7.5, 5.0 Hz, H513) 4.76
(d, J = 6.6 H2, H2) 6.24 (d, J = 2.8 Hz, H10) 6.86 (dd, J = 2.8, 0.9 Hz, H11).
“GM”! (00300) : (major) 8 18.8, 19.8, 25.0, 26.1, 84.8, 41.0, 41.9, 64.5, 79.7,
85.9, 90.8, 130.9, 140.6, 145.8, 165.0, 212.7 (C=O).

gamma-7111mm
1H-NMR(00300) : (minor) 5 4.83 (d) 6.23 (d) 6.31 (d).

Large scale (0.2 g) photolysis in a test tube was performed and the
residue was purified by silica gel chromatography (Rr = 0.53 with hexane/ethyl

acetate = 5/1). The product was dark yellow in 60 % isolated yield with a

219

diastereomeric excess 80 %, measured by the integration of acetyl groups in 1H-
NMR spectroscopy.

The nOe results indicated that the major cyclodctatriene has 10-iPr group
trans to 8-Me group. There was an enhancement of H75 (1.5 %), H913 (1.4 %) and

H105 (4.6 °/o) when the 8—Me was irradiated.

H 1.5V”I 1 1.4%
t'

\
94‘; i ,‘U
““6863 6’?‘C""‘H
/ gfic \ H4.6%
H A

 

 

 

r - R 1 --A :1I-1-i . .r. ,- I--mth l-11-o . -i I ., . no : -1 -
1H-NMR (C0300) : (major) 6 0.86 (d, J = 6.7 Hz, iPr) 0.96 (d, J = 6.7 Hz, iPr)
1.03 (s, 8-Me) 1.64 (dsept, J = 7.3, 6.7 Hz, 1H) 1.74 (dd, J = 12.2, 11.0 H2, H9“)
1.89 (dd, J = 12.2, 5.2 Hz, H913) 2.39 (s, COMe) 2.89, 2.93 (AB q, J = 12.2 Hz,
2H7) 4.04 (ddd, J = 11.0, 7.3, 5.2 Hz, H105) 5.18 (d, J = 8.2 Hz, Hz) 5.88 (dd, J =
12.9, 5.9 Hz, H4) 6.15 (dd, J = 12.9, 8.2 H2, H3) 7.29 (d, J = 5.9 Hz, H5).
13C-NMR (c0300) : (major) 8 18.0, 19.2, 25.5, 26.4, 84.8, 85.1, 44.4, 85.2, 95.5,
1089,1222, 182.6, 140.7, 143.8, 173.2, 201.7 (C=O).

 

220

.0030
E 308.2;9 686-2H-885.8o.o.m.s_-o_o>o_=oxo-v-_§oE
-n4305026-.>_oom-m-Em.mfiwm.m5-0m. .0 352.598 sz .3 0.59“.
m.« 9m m.m o.m .m.m oé mé o.m m.m ob

h—-—--——-_-—-—-—-—-p—n-nn—bP—u—L--——-—~—~»—-—__P-r—
él4l1 (jllll‘ 4? j

 

 

 

 

 

 

0: m1 mI NI OFT— :I
..
lNfiJql mv.m1 «NAM!
«N .5" on." . «n.01 Dfl.«l
} 1.. 1; .LJ } } }

 

221

 

8.000 E Coon—2.73 ocm_:-m.m. F-momuc:_o.m.m_o_o>o_nmxo
- F F-_>£oE-m-_>aoaom_-oEbooméAmoF£86m. .0 2:05:86 moz .3 0.59“.

 

 

 

can m m w m n

p _ p _ p — _ h — _ h p _ — p — _ p — p _ _ _ — _
g d fi 4 1“

mI NI o—I

mv.oo« mw.«r «m.:.
of?

} } 1.. Ir.
Lpl P) J L.) F ’1 lillj‘

/ z /

 

\

 

 

 

 

 

222
.A-:: o:--.; :100000--=11=1 - «no 0. o_ 1:. -
10.909;
1H—NMF1(003,00) : (minor) 6 2.40 (5, Me) 4.05 (m) 5.23 (d) 7.25 (d).
UV(MeOH) : (mixture) 313 nm (410), km = 388 nm (4400).

Reactant : p-04K

A NMR scale solution of p-C4K (1.7/1 = trans/cis mixture, 3.0 mg) and
methyl benzoate (1.7 mg) in 00300 was photolyzed at >290 nm for 1h. The
reactions were carried out repeatedly in different photolysis resource (313 nm) or
solvent (0605) but results were identical except the product ratio (5:321 or 5:2:1).
At complete conversion, there were three photoproducts: the 1,4-adduct (major);
the polycyclic ketone (secondary) and the 1,2-adduct (minor), detected directly
from 1H-NMFl spectra with 80 % overall chemical yield. The ratio is approximately
5 : 3 : 1 even though there is slightly change of ratio in the different runs .

A large scale photolysis (0.24 g ketone in 60 mL) was also carried out
through Pyrex filter during 20 h. The secondary polycyclic ketone (Rf = 0.38 with
hexane/ethyl acetate = 4/1) and 1,2-adduct (Rf = 0.35 with hexane/ethyl acetate
= 4/1) could be isolated by silica gel column chromatography. The secondary
polycyclic ketone could be further recrystallized from hexane/ethyl acetate
mixture in refrigerator. However, the major 1,4-adduct wasn't stable on silica gel
and generated a non-identified rearranged product after column chromatography

(Rr = 0.20 with hexane/ethyl acetate = 4/1).

 

223

 

 

 

0:; O 0 \I hv, Pyrex
lMeC»1or

benzene

 

 

 

 

1H NMR (c0300) : (major) 8 1.87 (m, 2H) 2.03 (s, COMe) 2.07 (m, 2H) 2.20 (m,
2H) 2.81 (m, 1H) 3.94 (ddd, J = 15.4, 10.8, 9.1 Hz, 1H) 4.03 (ddd, J = 15.4, 8.5,
6.8 Hz, 1H) 5.08 (dd, J = 16.0, 9.8 Hz, 1H) 5.51 (dddd, J = 16.0, 11.5, 9.8, 2.8
Hz, 1H) 5.69 (dd, J = 11.1, 2.1 Hz, 1H) 5.74 (dd, J = 11.1, 2.4 Hz, 1H) 5.85 (dd, J
= 10.2, 2.1 Hz, 1H) 5.94 (dd, J = 10.2, 2.4 Hz, 1H).

1H NMR (CDCI3) : (secondary) 5 1.49 (dddd, J = 12.6, 9.2, 6.2, 3.0 Hz, 1H) 1.59
(ddd, J = 12.3, 9.1, 3.0 Hz, 1H) 1.71 (ddd, J = 12.6, 9.1, 7.1 Hz, 1H) 2.02 (ddd, J
= 9.7, 6.5, 1.9 Hz, 1H) 2.04 (dd, J = 1.6, 0.9 Hz, 1H) 2.07 (ddd, J = 12.3, 9.2, 7.1
Hz, 1H) 2.10 (dd, J = 6.2, 1.0 Hz, 1H) 2.16 (s, COMe) 2.19 (dd, J = 7.1, 6.5 Hz,
1H) 2.44 (ddt, J = 9.7, 9.1, 6.7 Hz, 1H) 2.55 (dd, J = 6.5, 1.0 Hz, 1H) 2.77 (ddd, J
= 9.7, 1.9, 1.6 Hz, 1H) 3.95 (ddd, J = 11.7, 6.7, 6.5 Hz, 1H) 3.97 (dd, J = 11.7, 6.7
Hz, 1H) 5.52 (dd, J = 9.9, 1.6 Hz, 1H) 5.86 (dd, J = 9.9, 0.9 Hz, 1H).

224

13c NMR (CDCI3, DEPT) :8 24.5 (2°), 26.7 (2°), 27.8 (1°), 38.4 (2°), 44.4 (8°).
46.7 (3°), 47.0 (8°), 47.6 (8°), 54.9 (3°), 59.1 (4°), 60.8 (2°), 84.8 (4°), 128.2 (8°).
184.0 (3°), 210.2 (4°, (3:0).

lR(KBr) : 2958, 2920, 1693 (C=O), 1359, 1277, 1101, 757 cm -1,

MS (m/e) : 230 (W), 215, 202, 187, 107,81 (base), 43.

1H NMR (CDCI3) : (minor) 8 1.59 (m, 2H) 1.72 (dddd, J = 14.8, 7.2, 5.0, 3.6 Hz,
1H) 1.83 (dddd, J = 14.8, 8.6, 6.6, 2.2 Hz, 1H) 2.02 (m, 2H) 2.09 (s, COMe) 2.28
(ddd, J = 6.6, 6.4, 3.6 Hz, 1H) 2.87 (ddq, J = 8.0, 2.2, 1.5 Hz, 1H) 8.90 (ddd, J =
13.7, 8.6, 5.0 Hz, 1H) 4.11 (ddd, J = 13.7, 7.2, 2.2 Hz, 1H) 5.16 (dd, J = 10.5, 6.4
Hz, 1H) 5.52 (dd, J = 10.3, 1.5 Hz, 1H) 5.63 (ddd, J = 10.5, 6.1, 2.0 Hz, 1H) 5.70
(d, J = 8.0 Hz, 1H) 6.26 (dd, J = 10.3, 1.5 Hz, 1H).

130 NMR (CDCI3) : 8 25.4, 26.7, 30.9, 34.8, 46.7, 52.7, 68.0, 84.6, 124.7, 127.6,
133.4, 133.7, 133.9, 136.8, 199.0 (C=O).

lR(00l4) : 3155, 2984, 1709 (C=O), 1669, 1382, 1096 cm'i-

MS (m/e) : 230 (W) 187, 145, 107 (base), 81, 79, 43.

Reactant : p-I4K

A 0.020 M 00300 solution of p-I4K (1.7/1 = trans/cis mixture, determined
by NMR, see above) was photolyzed in a NMR tube at >290 nm. The
photoreaction was inefficient and couldn't be completed; product found
decomposed gradually during the irradiation. The best condition was 10 h
irradiation with barely 38 °/o chemical yield at 50 °/o conversion compared the
integration of acetyl groups of p—I4K and p-l408 to methoxy group of methyl
benzoate in 1H-NMR.

 

225

 

 

 

.. - .; : °: -1-. :1 .. .. -:--...' . -0 59mm

diam:
1H-NMFl (00300) : 6 0.87 (d, J = 6.7 Hz, iPr) 1.01 (d, J = 6.7 Hz, iPr) 1.87 (ddd,
J = 13.5, 10.5, 7.5 Hz, H53) 1.90 (ddd, J = 13.5, 7.5, 5.0 Hz, H63) 1.93 (septd, J =
6.7, 6.3 Hz, 1H) 1.98 (dddd, J = 7.3, 6.3, 4.4, 1.7 Hz, H413) 2.12 (s, COMe) 2.35
(ddd, J = 10.5, 7.3, 5.0 Hz, H53) 3.79, 3.81 (A8 q, J = 7.5 Hz, 2H7) 5.78 (dd, J =
10.3, 1.7 H2, H2) 5.94 (dd, J = 10.3, 4.4 H2, H3) 6.33, 6.43 (AB q, J = 2.9 Hz, H10,
i111).

The above product was heated at 40°C for 48 h. The baseline of NMR had

lots of noises and only portion of the peaks could be identified by 1H-NMR

spectroscopy.

 

 

 

1H-NMIR(00300) : 8 0.88 (d, J = 6.6 Hz, iPr) 0.99 (d, J = 6.6 Hz, iPr) 1.64 (m,
1H) 1.75 (m, 2H9) 2.00 (m, H73) 2.27 (m, H3) 2.83 (s, COMe) 3.17 (ddd, J = 7.7,
5.5, 2.2 Hz, H3) 4.12 (m, 2H10) 6.26 (d, J = 10.1 Hz, H2) 6.45 (d, J = 10.1 Hz, H3)
6.70 (d, J = 7.7 H2, H5).

 

226
2111.11.111 ”1.1.:

Photolyses in NMR tube scale of 4'-(4-trimethylsilyl-3-butyn-1-
oxy)acetophenone and 4'-(3-butyn-1-oxy)acetophenone were undertaken at >
290 nm in d-methanol, d-acetonitrile, d-hexane or d-benzene (concentration
0.015 M), but only starting materials were recovered after more than 48 h
irradiation. Irradiation of 4'-(3-butyn-1-oxy)acetophenone in 100 mL test tube
(concentration 0.005 M in methanol) for 36 h was failed to react but decompose
some ketone by checking with GC. Even sensitized photolysis of acetyl derivative
of 4'-(4-trimethylsilyI-3-butyn-1-oxy)acetophenone in acetone (0.001 M) through

quartz showed no cycloaddition.

 

227
Table 35 Nuclear Overhauser Effect (nOe) on the Major Product of Various 1-
Acetyl-B-oxatricyclo-[720.05:9]undeca-2,10-dienes (CB)

1.. (I)

 

Cyclobutene(CB) Irradiated H10 H41; H65 H75

Mo-caa 5-HB 4.2 % 1.4 % 1.0 °/o 2.0 %
M7-CB 5-H13 6.6 °/o 3.3 °/o 3.9 °/o 5.0 "/6
I7-CB 5H,, 5.1 % 2.6 °/o 8.3 % 4.3 %
M5M7-ce 5—Mep 6.1 % 2.6 % 1.8 % 5.0 %
M517-CB 5-Meg 6.7 % 2.3 °/o 1.5 % 4.0 °/o
M4M5-CB S-Mep 2.4 % 1.0 % 1.5 % 1.2 %
M4M5M7-CB 5-Me13 7.2 % 2.3 °/o 1.7 % 4.3 %
M3M4M5M7-CB S-Mep 3.9 % 3.2 °/o 1.4 °/o 5.1 °/o

a: non-substituted 1 -acetyI-8-oxatricyclo-[7.20.05.9]undeca-2, 1 0-dienes

228

Table 36 Nuclear Overhauser Effect (nOe) on the Major Product of Various 4- or

6-Acetyl-1 1-oxabicyclo[6.3.0]undeca-1,3,5-trienes (COT)

Cyclodctatriene
(GOT)

original 4-00T
4-M 1oCOT

4-l 1 000T
4-Mal1000T

G-I 1 oCOT
6-M3I1000T

Irradiated

8-H13
8-HB
8-H13
8-Meg
8-H5
8-MeB

4.1 °/o
3.0 °/o
1.2 °/o
0.3 %

7-H3

4.8 °/o
4.0 °/o
3.3 °/o
1.9 %
1.0 %
1.5 °/o

9-H13

5.4 %
3.7 %
2.7 %
1.3 %
0.9 "/11
1.4 %

1O'HB 2-H

1.8 °/o
1.9 %
1.5 °/o
4.3 %
3.5 °/o
4.6 %

0.6 °/o

 

229

Table 37 Nuclear Overhauser Effect (nOe) on the Major Product of Various 4-
Acetyl-11-oxatricyclo[6.3.0.01r6] undeca-2,4-dienes (0H)

Cyclohexadiene (0H)

MaMg-CH

M7M3-CH
M7M3M10CH

Cyclohexadiene (0H)

Malls-CH
M7M3M1o-CH

 

Irradiated
8-Meg

8-MeB
8-Meg

Irradiated

6-Ha
6‘Ha

2-H

3.3 °/o
3.2 %
2.3 °/o

5-H

13.2 °/o
8.9 %

7-H13 9-H13 10-HB

2.3 °/o 5.8 %
1.0 °/o 3.0 %
0.6 °/o 2.4 % 1.9 °/o

4.4 °/o (7-Ha) 8.7 °/o (10-Hu)
1.0 % (7-Me) 1.0 °/o (10-Me)

 

Table 38 010 Response Factors of Various Acetophenones (K) and

Cyclodctatrienes (001')

Isolated product / lntemal standard

Acetophenone (Ap) / C12

Ap /C15

AP / C16

Ap / Ethyl phenyl acetate

p-MoK / 0130H

p-MoCOT /C130H

p-MjK / n-Heptyl benzoate
p-M100T / n-Heptyl benzoate
p-I1K / n-Octyl benzoate
p-l100T / n-Octyl benzoate
p41M3K / m-Dibutyl pathalate
p-I1M300T / m-Dibutyl pathalate
o-I1K / n-Pentyl benzoate

o-l 100T / n-Pentyl benzoate
o-I1M3K / n-Pentyl benzoate
041M300T / n-Pentyl benzoate
p-04K / m-Dibutyl phthalate
polycyclic-K / m-Dibutyl phthalate
p-C4K / n-Octyl benzoate
polycyclic-K / n-Octyl benzoate
p-l4CH / n-Heptyl benzoate

1 .92
2.18
2.24
1 .10
1 .44
1 .83
1 .18
1 .33
0.96
1.12
1.17
0.86
0.62
0.71
0.89
0.88
0.93
0.90
0.95
0.99
0,89

CaIc'd

1 .72
2.15
2.28
1.28
1 .64
1 .64
1 .09
1 .09
1 .00
1.00
0.93
0.93
0.78
0.78
0.73
0.73
1.00
1 .00
1 .00
1 .00
0.93

 

231
Table 39 HPLC Response Factors of Acetophenones (K) and Cyclohexadienes

(CH)
Isolated product / lntemal standard Rf value
p-M3M4K 0.01 7

p-M3M40H 0.01 4

 

232
Nuclear Overhauser Enhancement (NOE)

The following parameters have been used for all NOE experiments

d1 = 15-18, the length of first delay and approximately five times of T1
bs = 2 or 4, the block size in order to store the data periodically
ii = 'y', in order to run the arrayed experiments

gain = 25, receiver gain

temp = 25, to set the temperature of sample in the probe

dpwr = 6-10, the decoupler power

nt = 64, 96, 128 or 160, the number of transients to be acquired
time, how much time does the experiment take

dof, to set the frequencies of the protons which are irradiated
sd, to obtain the frequencies of the protons which are irradiated
da, to assure the corrected frequencies of the irradiated protons
dssa, to display the overall spectra consecutively

clradd, to delete the original spectrum in experiment 5

spadd, to generate the new space in experiment 5

addi, to display both original and irradiated spectra

sub, to substrate the original and irradiated spectra

.-

233

The procedure of calculation was shown below. A structure was drawn in
a new file in CAChe program by the help of three dimension stereotype glasses.
This structure was minimized by molecular mechanics (MM2) to obtain the rough
geometry and stabilization energy.

Reopen the CAChe file to confirm the structure followed the valence bond
rule. The rough geometry was then optimized at the semi-empirical level (AM1)
by using unrestricted Hartree-Fock (UHF) treatment to obtain the better
geometry. This procedure was repeated a few times by little variation of bond
length and angle to acquire the best geometry and heat of formation. The best
geometry was translated to Chem30 file. The structure in cylindrical bond type
and dihedral angle were obtained and saved in ChemDraw file for conformational
analysis. The structure in ball and stick type was saved for the display of nOe

experimental data.

 

APPENDIX

235
Table 40 Quantum Yield Determination of Formation of 1-AcetyI-8-oxatricyclo-

[7.2.0.Mflundeca-2,10-diene at 313 nm in Methanol (COT -> CB)

1. Before irradiation

Sample: [COT] = 2.50 x 10-4 M in methanol, A = 343 nm

Actinometers: [VP] = 1.05 x 10-2 M, [Ethyl phenyl acetate] = 1.20 x 103 M in
benzene

2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration <1)
2.25 1.50 0.75 7.39 x 10'5 0.14
2.25 1.45 0.80 7.95 x 10'5 0.15
2.25 1.49 0.76 7.48 x 10’5 0.14

A(AP)/A(std.) = 0.137

Actinometers: [AP] = 1.81 x 104 M, IO = 5.43 x 10'4 M

3. Irradiation time: 20 min

4. G0 conditions

Actinometers: 15 meter 03210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 90°C, injector = 200°C, detector = 220°C.

5. Quantum yield d) = 0.14

236

Table 41 Quantum Yield Determination of Formation of 4-AcetyI-11-

oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K -> COT)

1. Before irradiation

Sample: [K] = 1.05 x 10'2 M, [0130H]= 1.00 x 103 M in methanol

Actinometers: [VP] = 1.05 x 10'2 M, [Ethyl phenyl acetate] = 1.20 x103 M in

benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration
0.230 0.421 4.22 x 10‘4
0.235 0.430 4.31 x 10‘4
0.226 0.414 4.09 x 10‘4

A(AP)/A(std.) = 0.534
Actinometers: [AP] = 7.05 x 104 M, I0 = 2.10 x 10'3 M
3. Irradiation time: 45 min

4. 60 conditions

 

0.20
0.21
0.1 9

Sample: 15 meter 0B210 Megabore Column, Varian 3400, He = 25 mL/min,

column = 150°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,

column = 89°C, injector = 200°C, detector = 220°C.
5. Quantum yield O = 0.20

237
Table 42 Quantum Yield Determination of Formation of 1-Acetyl-7-methyI-8-
oxatricycIo-[7.2.0.05.9]undeca-2,10—diene at 313 nm in Methanol (COT -> 08)

1. Before irradiation

Sample: [COT] = 2.04 x 10'4 M in methanol, 1. = 344 nm
Actinometers: [VP] = 1.99 x 10'1 M, [012] = 4.40 x 101" M in benzene
2. After irradiation at 25°C

 

Before 00 After 00 A[Absorption] AConcentration (b
2.20 1.20 1.00 9.98 x 10'5 0.05
2.20 1.16 1.04 1.03 x 10'4 0.05
2.20 1.31 0.89 8.87 x 10'5 0.04

A(AP)/A(std.) = 0.076

Actinometers: [AP] = 6.39 x 10-4 M, IO = 1.94 x 101'3 M

3. Irradiation time: 25 min

4. 00 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100—185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield (b = 0.05

238
Table 43 Quantum Yield Determination of Formation of 4-Acetyl-10-methyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K -> COT)

1. Before irradiation

Sample: [K] = 1.00 x 10'2 M, [n-Heptyl benzoate] = 2.10 x 103 M in methanol
Actinometers: [VP] = 1.99 x 10-1 M, [012] = 4.40 x 104 M in benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration d>
0.231 0.307 5.72 x 10‘4 0.10
0.254 0.338 6.29 x 10‘4 0.11
0.231 0.307 5.72 x 10'4 0.10

A(AP)/A(std.) = 0.234

Actinometers: [AP] = 1.98 x 103 M, I0 = 5.99 x 10*3 M

3. Irradiation time: 1.5 h

4. 00 conditions

Sample: 15 meter 0B210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 145°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 0B210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield 0 = 0.10

 

239
Table 44 Quantum Yield Determination of Formation of 1-AcetyI-7-isopropyI-8-
oxatricyclo[7.2.0.05-9]undeca-2,10-diene at 313 nm in Methanol (1, COT -> CB)

1. Before irradiation
Sample: [COT] = 2.07 x 104 M in methanol, A = 346 nm

Actinometers: [VP] = 9.96 x 10'2 M, [015] = 1.90 x 10'3 M in benzene
2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration <I>
2.44 1.43 1.01 8.41 x 10‘5 0.08
2.44 1.42 1.02 8.50 x 10’5 0.09
2.44 1.44 1.00 8.33 x 10'5 0.08

A(AP)/A(std.) = 0.092

Actinometers: [AP] = 3.80 x 10*1 M, IO = 1.15 x 10-3 M

3. Irradiation time: 25 min

4. 60 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield (b = 0.08

240
Table 45 Quantum Yield Determination of Formation of 1-AcetyI-7-isopropyI-8-
oxatricyclo[7.2.0.05-9]undeca-2,10—diene at 313 nm in Methanol (2, COT -> 08)

1. Before irradiation

Sample: [COT] = 2.00 x 10'4 M in methanol, 1. = 346 nm
Actinometers: [VP] = 9.96 x 10"2 M, [012] = 2.20 x 10*3 M in benzene
2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration (I)
2.36 1.32 1.04 8.82 x 10'5 0.11
2.36 1.22 1.14 9.60x10‘5 0.12
2.36 1.60 0.76 6.41 x 10'5 0.08

A(AP)/A(std.) = 0.065

Actinometers: [AP] = 2.67 x 10'4 M, I0 = 8.28 x 104 M

3. Irradiation time: 30 min

4. G0 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield <I> = 0.10

6. No significant change on COT concentration by adding 4-methoxy-

acetophenone

241
Table 46 Quantum Yield Determination of Formation of 4-Acetyl-10-isopropyl-11-
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K -> COT)

1. Before irradiation

Sample: [K] = 1.01 x 10'2 M, [n-Octyl benzoate] = 2.00 x 103 M in methanol
Actinometers: [VP] = 9.96 x 10'2 M, [015] = 1.90 x 10<3 M in benzene

2. After irradiation at 25°C

 

j

A(product)/A(std.) A(product)/A(std.) Concentration (b !
0.256 0.287 5.72 x 10‘4 0.10
0.298 0.334 6.68 x 10‘4 0.12
0.410 0.459 9.19x10'4 0.17
0.343 0.384 7.66x 10'4 0.14

A(AP)/A(std.) = 0.430

Actinometers: [AP] = 1.78 x 10-3 M, IO = 5.41 x 103 M

3. Irradiation time: 2 h

4. CC conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 160°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield (1) = 0.12

242
Table 47 Quantum Yield Determination of Formation of 1-Acetyl-7-isopropyl-5-
methyl-8-oxatricyclo[7.2.0.05.9]undeca-2,10-diene at 313 nm in Methanol (COT ->
08)

1. Before irradiation

Sample: [001] = 3.31 x 10‘4 M in methanol, 71 = 334 nm

Actinometers: [VP] = 1.05 x 10'2 M, [Ethyl phenyl acetate] = 1.20 x 103 M in
benzene

2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration (b
2.33 1.78 0.55 7.79 x 10‘5 0.24
2.33 2.08 0.25 3.56 x 10'5 0.11
2.33 2.10 0.23 3.25 x 10'5 0.10

A(AP)/A(std.) = 0.079

Actinometers: [AP] = 1.04 x 10*1 M, IO = 3.13 x 104 M

3. Irradiation time: 15 min

4. 60 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 90°C, injector = 200°C, detector = 220°C.

5. Quantum yield (D = 0.11

243
Table 48 Quantum Yield Determination of Formation of 1-AcetyI-7-isopropyI-5-
methyl-8-oxatricyclo[7.2.0.05:9]undeca-2,10-diene at 366 nm in Methanol (COT ->
08)

1. Before irradiation

Sample: [COT] = 2.81 x 10“1 M, it = 334 nm

Actinometers: [Benzophenone] = 1.00 x10'2 M, [Benzhydrol] = 1.00 x10:1 M in
benzene r”

2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration (b
1.98 0.80 1.18 1.70x10'4 0.11
1.98 0.80 1.18 1.70x104 0.11
1.98 1.22 0.76 1.11 x 10'4 0.07

Actinometers: A [B.P.] = 1.27 x 103 14*, I0 = 1.59 x 10-3 M
3. Irradiation time: 13 min

4. UV conditions

Actinometers: average of 6 tubes

5. Quantum yield <I> = 0.11

* : Average of two tubes.

 

 

244
Table 49 Quantum Yield Determination of Formation of 4wAcetyI-10-isopropyl-8-
methyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K ->
COT)

1. Before irradiation

Sample: [K] = 1.07 x 10'2 M, [meta Dibutyl phthalate] = 8.99 x 10'4 M in methanol
Actinometers: [VP]: 1.05 x 10'2 M, [Ethyl phenyl acetate] = 1.20 x 10'3 M in
benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/A(s) Concentration <I>
0.549 0.472 5.70 x 10'4 0.36
0.289 0.248 3.01 x 10'4 0.19
0.290 0.249 3.09 x 10'4 0.19

A(AP)/A(std.) = 0.409

Actinometers: [AP] = 5.40 x 10'4 M, IO = 1.62 x 10-3 M

3. Irradiation time: 50 min

4. GC conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 160°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 90°C, injector = 200°C, detector = 220°C.

5. Quantum yield (D = 0.19

 

245

Table 50 Quantum Yield Determination of Formation of 9-Acetyl-5-isopropyl-4-
oxatricyclo[7.2.0.03-7]undeca-2,10-diene at 313 nm in Methanol (COT -> 08)

1. Before irradiation

Sample: [001] = 2.37 x 104 M in methanol, A = 377 nm
Actinometers: [VP] = 1.05 x 10'1 M, [012] = 5.10 x 10'3 M in benzene
2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration (I)
1.07 0.48 0.59 1.40 x10'4 0.10
1.07 0.47 0.60 1.47 x 10‘4 0.10
1.07 0.47 0.60 1.47 x10'4 0.10

A(AP)/A(std.) = 0.022

Actinometers: [AP] = 5.06 x 10'4 M, I0 = 1.53 x 10-3 M

3. Irradiation time: 15 min

4. 60 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield <1) = 0.10

246
Table 51 Quantum Yield Determination of Formation of 6-AcetyI-10-isopropyl-11 -
oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K -> CDT)

1. Before irradiation

Sample: [K] = 1.06 x 10'2 M, [n-Pentyl benzoate] = 1.30 x 10'3 M in methanol
Actinometers: [VP] = 1.02 x 10'1 M, [012] = 2.40 x 10'3 M in benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration (I)
0.877 0.623 8.10 x 10‘4 0.25
0.758 0.538 7.01 x 10‘4 0.23
0.974 0.692 9.00 x 10‘4 0.27

A(AP)/A(std.) = 0.237

Actinometers: [AP] = 1.09 x 10'3 M, I0 = 3.29 x 10'3 M

3. Irradiation time: 80 min

4. 60 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 145°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, foo-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield d) = 0.25

 

247
Table 52 Quantum Yield Determination of Formation of 9-Acetyl-5-isopropyI-7-
methyl-4-oxatricycIo-[7.20.03.7]undeca-2,10-diene at 313 nm in Methanol (COT
-> CB)

1. Before irradiation

Sample: [COT] = 5.75 x 10*1 M in methanol, 1. = 388 nm
Actinometers: [VP] = 9.84 x 10'2 M, [012] = 3.60 x 10-3 M in benzene
2. After irradiation at 25°C

Before 00 After 00 A[Absorption] AConcentration (I)
2.50 1.55 0.95 2.10 x10'4 0.21
2.50 1.60 0.90 1.99 x 10'4 0.20
2.50 1.60 0.96 2.13 x 10‘4 0.21

A(AP)/A(std.) = 0.044

Actinometers: [AP] = 3.04 x 104 M, I0 = 9.22 x 10-4 M

3. Irradiation time: 10 min

4. 60 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield d) = 0.21

 

248

Table 53 Quantum Yield <I> Determination of Formation of 6-Acetyl-10-isopropyl-
8-methyI-11-oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol (K ->
COT)

1. Before irradiation

Sample: [K] = 9.3 x 101'3 M, [n-Pentyl benzoate] = 3.00 x 10{3 M in methanol
Actinometers: [VP] = 9.84 x 10'2 M, [012] = 3.60 x 10'3 M in benzene

2. After irradiation at 25°C

 

A(product)/A(std.) Mol(p)/Mo|(s) Concentration (I)
0.177 0.156 4.67 x10'4 0.15
0.189 0.167 4.93 x10'4 0.16
0.180 0.158 4.75 x10’4 0.15

A(AP)/A(std.) = 0.152

Actinometers: [AP] = 1.05 x 10'3 M, IO = 3.18 x 10‘3 M

3. Irradiation time: 45 min

4. G0 conditions

Sample: 15 meter DB1 Megabore Column, Varian 1400, He = 25 mUmin, column
= 130°C, injector = 240°C, detector = 230°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield (b = 0.15

249
Table 54 Quantum Yield Determination of Formation of Polycyclic Ketone and
1,2-Adduct from 4'-(4-CyclopropyI-3-buten-1-oxy)acetophenone at 313 nm in
Methanol ( 1)

1. Before irradiation

Sample: [K] = 1.02 x 10'2 M, [meta Dibutyl phthalate] = 1.00 x 10-3 M in methanol
Actinometers: [VP] = 1.05 x 10'2 M, [Ethyl phenyl acetate] = 1.20 x 10'3 M in
benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration 0
0.370 0.333 3.33 x 10‘4 0.20
0.351 0.316 3.16 x104 0.19
0.443 0.399 3.99 x 10‘4 0.24

A(AP)/A(std.) = 0.421

Actinometers: [AP] = 5.56 x 10-4 M, IO = 1.67 x 10'3 M

3. Irradiation time: 1 h

4. 60 conditions

Sample: 30 meter DBWAX Megabore Column, Varian Aerograph 1400, He = 30
mL/min, column = 180°C, injector = 150°C, detector = 230°C.

Actinometers: 30 meter DBWAX Megabore Column, Varian Aerograph 1400, He
= 30 mUmin, column = 90°C, injector = 150°C, detector = 230°C.

5. Quantum yield <1) = 0.21

 

250
Table 55 Quantum Yield Determination of Formation of Polycyclic Ketone and
1,2-Adduct from 4'-(4-Cyclopropyl-3-buten-1-oxy)acetophenone at 313 nm in
Methanol (2)

1. Before irradiation

Sample: [K] = 1.05 x 10'2 M, [n-Octyl benzoate] = 2.00 x 103 M in methanol
Actinometers: [VP] = 9.92 x 10'2 M, [016] = 4.10 x 1013 M in benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration (b
0.227 0.225 4.50 x 10‘4 0.15
0.229 0.227 4.55 x 10'4 0.15
0.243 0.241 4.82 x 10“1 0.16

A(AP)/A(std.) = 0.109

Actinometers: [AP] = 9.99 x 104 M, I0 = 3.03 x 10-3 M

3. Irradiation time: 1 h

4. 60 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 165°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 900, injector = 200°C, detector = 220°C.

5. Quantum yield (1) = 0.15

251
Table 56 Quantum Yield Determination of Formation of Polycyclic Ketone and
1,2-Adduct from 4'-(4-0yclopropyI-3-buten-1-oxy)acetophenone at 313 nm in
Methanol (3)

1. Before irradiation

Sample: [K] = 1.05 x 10-2 M, [n-Octyl benzoate] = 2.00 x 10'3 M in methanol
Actinometers: [VP] = 1.05 x 10’1 M, [012] = 5.10 x 10'3 M in benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration (I)
0.376 0.372 7.46 x 104 0.15
0.427 0.423 8.45 x 104 0.17

A(AP)/A(std.) = 0.169

Actinometers: [AP] = 1.66 x 10~3 M, I0 = 4.98 x 10'3 M

3. Irradiation time: 1.5 h

4. 60 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 165°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield (D = 0.16

 

 

 

252
Table 57 Quantum Yield Determination of Formation of 4-AcetyI-7,8-dimethyl-11-
oxatricyclo[6.3.0.01-6]undeca-2,4-diene at 313 nm in Methanol (K -> CH)

1. Before irradiation

Sample: [K] = 1.22 x 10-2 M, [Methyl benzoate] = 3.96 x 10:2 M in methanol
Actinometers: [VP] = 1.03 x 10'1 M, [012] = 3.60 x 10'3 M in benzene

2. After irradiation at 25°C

A(product)/A(std.) Mol(p)/Mol(s) Concentration <1)
1.659 0.023 9.20 x 104 0.07
2.133 0.030 1.18 x10'3 0.09
1.180 0.017 6.57 x 10‘4 0.05

A(AP)/A(std.) = 0.620

Actinometers: [AP] = 4.29 x 10'3 M, I0 = 1.29 x 10'2 M

3. Irradiation time: 5 h

4. GC conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. HPLC condition

Sample: 4.6 x 250 mm, Dyn Microsorb Silica Column, Flow Rate 1.0 mL/ min, 80
°/o Hexane / 20 % Ethyl acetate, 290 nm.

6. Quantum yield <1) = 0.07

 

a“)-
r

 

253
Table 58 Quantum Yield Determination of Formation of 4'-(3,4-Dimethyl-3-buten-
1-oxy)acetophenone at 313 nm in Methanol (CH -> K) and Quenching Study by
2,5-Dimethyl-2.4-hexadiene

1. Before irradiation

Sample: [CH] = 5.01 x103 M, [Methyl benzoate] = 8.09 x 102 M in methanol
Actinometers: [VP] = 1.01 x 10'1 M, [C12] = 3.70 x101“3 M in benzene

2. After irradiation at 25°C

[01*1 M A(photo) / A(std) ¢o/ <1>
0.000 0.650 1 .00
0.089 0.448 1 .45
0.871 0.119 5.39

Actinometers: [AP] = 3.77 x 10*1 M, I0 = 1.14 x 1043 M
3. Irradiation time: 1 h

4. 60 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. HPLC conditions

Sample: 4.6 x 250 mm, Dyn Microsorb Silica Column, Flow Rate 1.0 mUmin, 80
% Hexane / 20 "/0 Ethyl acetate, 290 nm.

6. Quantum yield <1) = 0.78, qu = 5.0

* : Quencher = 2,5-dimethyI-2.4-hexadiene

 

 

 

 

254
Table 59 Quantum Yield Determination of Formation of 4'-(3,4-DimethyI-3-buten-
1-oxy)acetophenone at 313 nm in Methanol (CH -> K) and Quenching Study by
Sorbic Acid

1. Before irradiation
Sample: [CH] = 4.98 x 103 M, [Methyl benzoate] = 8.36 x 10-2 M in methanol
Actinometers: [VP] = 1.01 x 10'1 M, [012] = 3.70 x10-3 M in benzene

 

2. After irradiation at 25°C E 84
I
[Q]*. M A(ph0101/ A(std) (Do / (I) "I '
0.000 0.591 1.00
0.121 0.400 1.49
1.379 0.090 6.58

Actinometers: [AP] = 3.98 x 104 M, IO = 1.21 x 10'3 M

3. Irradiation time: 1 h

4. G0 conditions

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50-100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. HPLC conditions

Sample: 4.6 x 250 mm, Dyn Microsorb Silica Column, Flow Rate 1.0 mL/min, 80
°/o Hexane / 20 % Ethyl acetate, 290 nm.

6. Quantum yield <1) = 0.70, kq’t = 4.1

 

* : Quencher = sorbic acid

 

255
Table 60 Quantum Yield Determination of Formation of 4-Acetyl-7-isopropyI-11-
oxabicyclo[6.3.0.01r6]undeca-2,4-diene at 313 nm in Methanol (K -> CH)

1. Before irradiation

Sample: [K] = 1.23 x 10'2 M, [n-Heptyl benzoate] = 1.55 x 103 M in methanol
Actinometers: [VP] = 1.02 x 10-1 M, [012] = 2.40 x 10-3 M in benzene

2. After irradiation at 25°C

 

A(product)/A(std.) Mol(p)/Mol(s) Concentration <1)
0.515 0.458 7.1 1 x 10'4 0.08
0.773 0.688 1.08 x 10‘3 0.12
0.515 0.458 7.11 x 10‘4 0.08

A(AP)/A(std.) = 0.642

Actinometers: [AP] = 2.96 x 10-3 M, I0 = 8.88 x 10-3 M

3. Irradiation time: 5 h

4. G0 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 150°C, injector = 200°C, detector = 220°C.

Actinometers: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 50°C for 5 min, 50—100°C 10°C/min, 100°C for 1.5 min, 100-185°C
15°C/min, 185°C for 10 min, injector = 200°C, detector = 220°C.

5. Quantum yield <1) = 0.08

256
Table 61 Chemical Yield Determination of 4-Acetyl-10-isopropyI-11-

oxabicyclo[6.3.0]undeca-1,3,5-triene at 313 nm in Methanol

1. Before irradiation

Sample: [K] = 1.01 x 10'2 M, [n-Octyl benzoate] = 2.00 x 10‘3 M in methanol
2. 00 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mL/min,
column = 160°C, injector = 200°C, detector = 220°C.

3. Chemical yield = 95.0% (120 min.)

Irradiation Time A(Ketone)/A(std.) Concentration of A(P)/A(s)
(min.) Reacted Ketone
0 5.260 0 ----
30 5.168 1.77 x10‘4 0.078
60 5.074 3.57 x 10‘4 0.159

120 4.893 7.06 x 10'4 0.298

257
Table 62 Chemical Yield Determination of Polycyclic Ketone and 1,2-Adduct from

4'-(4-CyclopropyI-3-buten-1-oxy)acetophenone at 313 nm in Methanol

1. Before irradiation

Sample: [K] = 1.05 x 10'2 M, [n-Octyl benzoate] = 2.00 x 10'3 M in methanol
2. 60 conditions

Sample: 15 meter 08210 Megabore Column, Varian 3400, He = 25 mUmin,
column = 160°C, injector = 200°C, detector = 220°C.

3. Chemical yield = 45.0% (60 min.)

Irradiation Time A(Ketone)/A(std.) Concentration of A(P/A(s)
(min.) Reacted Ketone
0 5.526 0 ~-----
20 5.347 3.40 x 10‘4 0.099
40 5.149 7.17x10‘4 0.180

60 4.995 1.01 x 10‘3 0.228

(1 )
(2)
(3)

(4)

(5)
(6)

(7)
(8)

(9)
(1 0)

(11)

(12)
(13)
(14)
(15)

(16)
(17)

BIBLIOGRAPHY

Wagner, P. J.; Nahm, K. J. Am. Chem. Soc. 1987, 109, 4404.

Wagner, P. J.; Nahm, K. J. Am. Chem. Soc. 1987, 109, 6528.

Woodward, R. 8.; Hoffmann, R. The Conservation of Orbital Symmetry,
Verlag Chemie GmbH Academic Press Inc.: 1970, p. 73.

de Mayo, P.; Takeshita, H.; Sattar, A. B. M. A. Proc. Chem. Soc. 1962,

1 19.

Wagner, P. J.; Sakamoto, M. J. Am. Chem. Soc. 1989, 111, 8723.
Wagner, P. J.; Sakamoto, M.; Madkour, A. E. J. Am. Chem. Soc. 1992,
114, 7298.

Wagner, P. J.; Alehashem, H. Tetrahedron Lett. 1993, 34, 911.

Barltrop, J. A.; Coyle, J. 0. Principles of Photochemistry; London, 1978, p.
1.

Bryce-Smith, 0.; Blair, J. M. Proc. Chem. Soc. 1957, 287.

Wender, P. A.; Siggel, L.; Nuss, J. M. 3+2 and 5+2 Arena-Alkene
Photocycioadditions; Pergamon Press: Oxford, 1991; Vol. 2, p. 645.
Wender, P. A.; Siggel, L.; Nuss, J. M. Organic Photochemistry 1989, 10,
357.

ComeIisse, J. Chem. Rev. 1993, 93, 615.

Keukeleire, D. 0.; He, S.-L. Chem. Rev. 1993, 93, 359.

Angus, H. J. F.; Bryce-Smith, 0. Proc. Chem. Soc. 1959, 326.

Gilbert, A.; Taylor, 01. N.; Samsudin, B. J. Chem. Soc. Perkin Trans I 1980,
869.

Bryce-Smith, 0. Pure Appl. Chem. 1973, 34, 193.

Bryce-Smith, 0.; Gilbert, A.; Orger, B. H.; TyrreIl, H. J. Chem. Soc. Chem.
Commun. 1974, 334.

258

 

(18)
(19)

(20)
(21 )
(22)
(23)

(24)

(25)
(26)
(27)
(28)

(29)

(30)

(31)
(32)

(33)
(34)
(35)
(36)
(37)

259
Gilbert, A.; Yianni, P. Tetrahedron Lett. 1982,23, 255.
Atkinson, J. G.; Ayer, D. E.; Buchi, G.; Robb, E. W. J. Am. Chem. Soc.
1963, 85,2257.
Akhtar, I. A.; McCullough, J. J. J. Org. Chem. 1981, 46, 1447.
Sket, 8.; Zupan, M. J. Am. Chem. Soc. 1977, 99, 3504.
Wagner, P. J.; Sakamoto, M. J. Am. Chem. Soc. 1989, 111, 9254.
McCullough, J. J.; Maclnnis, W. K.; Lock, 0. J. L.; Faggiani, R. J. Am.
Chem. Soc. 1982, 104, 4644.
Aoyama, H.; Arata, Y.; Omote, Y. J. Chem. 800., Chem. Commun. 1990,
736.
Lippke, W.; Ferree, J. W.; Morrison, H. J. Am. Chem. Soc. 1974, 96,2134.
Pirrung, M. J. Org. Chem. 1987, 52, 1635.
Wilzbach, K. E.; Kaplan, L. J. Am. Chem. Soc. 1966, 88, 2066.
Bryce-Smith, 0.; Gilbert, A.; Orger, B. H. J. Chem. Soc. Chem. Commun.
1966, 512.
Osselton, E. M.; Eyken, C. P.; Jans, A. W. H.; Cornelisse, J. Tetrahedron
Lett. 1985, 26, 1577.
Ferree, J. W.; Grutzner, J. 8.; Morrison, H. J. Am. Chem. Soc. 1971, 93,
5502.
Gilbert, A.; Taylor, G. N. J. Chem. 800., Chem. Commun. 1979, 229.
Ellis-Davies, G. C. R.; Gilbert, A.; Heath, P.; Lane, J. 0.; Warrington, J. V.;
Westover, D. L. J. Chem. Soc. Perkin Trans. II1984, 1833.
Wender, P. A.; Ternansky, R. J. Tetrahedron Lett. 1985, 26,2625.
Wender, P. A.; Dreyer, G. B. Tetrahedron 1981 , 37, 4445.
Wender, P. A.; Howbert, J. J. J. Am. Chem. Soc. 1981, 103, 688.
Wender, P. A.; deLong, M. A. Tetrahedron Lett. 1990, 38, 5429.
Wender, P. A.; Singh, S. K. Tetrahedron Lett. 1990, 31, 2517.

 

260

(38) Bryce-Smith, 0.; Foulger, B. E.; Gilbert, A. J. Chem. Soc. Chem.
Commun. 1972, 664.

(39) Yang, N. C.; Chen, M. J.; Chen, P.; Mak, K. T. J. Am. Chem. Soc. 1982,
104, 853.

(40) Becker, 0.; Nagler, M.; Shahali, Y.; Haddad, N. J. Org. Chem. 1991, 56,
4537.

(41) Becker, 0.; Klimovish, N. Tetrahedron Lett. 1994, 35, 261.

(42) Becker, 0.; Haddad, N.; Sahali, Y. Tetrahedron Lett. 1989, 30, 2661.

(43) Somekawa, K.; Okuhira, H.; Sendayama, M.; Suishu, T.; Shimo, T. J. Org.
Chem. 1992, 57, 5708.

(44) Sieburth, S. M.; Chen, J.-L. J. Am. Chem. Soc. 1991, 113, 8163.

(45) Sieburth, S. M.; Joshi, P. V. J. Org. Chem. 1993, 58, 1661.

(46) Sieburth, S. M.; Hiel, G.; Lin, C.-H.; Kuan, D. P. J. Org. Chem. 1994, 59,
80.

(47) Cope, A. C.; Haven, J., A. C.; Ramp, F. L.; Trumbull, E. R. J. Am. Chem.
Soc. 1952, 74, 4867.

(48) Woodward, R. 8.; Hoffmann, R. The Conservation of Orbital Symmetry,
Verlag Chemie GmbH Academic Press Inc.: 1970, p. 63.

(49) Greathead, J. M.; Orchard, S. W. Int. J. Chem. Kinet.1987, 19,229.

(50) Warrener, R. N.; Pitt, I. G.; Nunn, E. E.; Kennard, C. H. L. Tetrahedron
Lett. 1994, 35, 621.

(51) deVaaI, P.; Lodder, G.; ComeIisse, J. Tetrahedron Lett. 1985, 4395.

(52) Leismann, H.; Mattay, J. Tetrahedron Lett. 1978,4265.

(53) Bryce-Smith, 0.; Longuet-Higgins, H. 0. J. Chem. Soc., Chem. Commun.
1966, 593.

(54) Houk, K. N. Pure & Appl. Chem. 1982, 54, 1633.

(55)

(56)

(57)

(58)

(59)

(60)

(61)

(62)

(63)

(64)

(55)

(66)

(67)

(68)

(59)

(70)

261
Fleming, I. Frontier Orbitals and Organic Chemical Reactions; John Wiley
8 Sons: New York, 1976, p. 51.
Wagner, P. J. In Creation and Detection of the Excited State; Marcel
Dekkeer: New York, 1971, pp. 174-212.
Griller, 0.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.
Seebach, D. Angew .Chem., Int. Ed. Engl. 1979, 18, 239.
Nahm, K. Thesis, Michigan State University, 1987.
Stierrnan, T. J.; Shakespeare, W. 0.; Johnson, R. P. J. Org. Chem. 1990,
55, 1043.
Squillacote, M.; Bergman, A.; Felippis, J. D. Tetrahedron Lett. 1989, 30,
6805.
Wagner, P. J.; Kochevar, I. E.; Kemppainen, A. E. J. Am. Chem. Soc.
1972, 94, 7489.
Wagner, P. J. Mol. Photochem. 1969, 1, 71-87.
Karplus, M. J. Chem. Phys. 1959, 30, 11.
Burkert, U.; Allinger, N. L. Molecular Mechanics; American Chemical
Society: Washington, DC, 1982.
Clark, T. A Handbook of Computational Chemistry, Wiley: New York,
1985.
Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. J. Am.
Chem. Soc. 1985, 107, 3902.
Stewart, J. J. P. MOPAC version 94.0; CAChe Scientific, Inc.: Beaverton,
OR 97006.
Jackman, L. M.; StemhelI, S. Applications of Nuclear Magnetic Resonance
Spectroscopy in Organic Chemistry; 2nd ed.; Pergamon Press: New York,
1969, p. 303.
Wagner, P. J.; Cheng, K.-L. Tetrahedron Lett. 1993, 34, 907.

(71)

(72)
(73)
(74)
(75)
(76)
(77)
(78)

(79)
(80)

(81 )
(82)
(83)
(84)
(85)
(86)

(87)

(88)
(39)
(90)
(91 )
(92)

262
Bassindale, A. The Third Dimension in Organic Chemistry; John Wiley and
Sons: New York, 1984, p. 92.
Winstein, S.; Lewin, A. H. J. Am. Chem. Soc. 1962, 84, 2464.
Pitzer, K. S.; Donath, W. E. J. Am. Chem. Soc. 1959, 81,3213.
Hoffmann, R. Acc. Chem. Soc. 1971, 4, 1.
Beckwith, A. L. J.; Phillipou, I. B. G. J. Amer. Chem. Soc. 1974, 96, 1613.
Hart, 0. J.; Krishnamurthy, R. J. Org. Chem. 1992, 57, 4457.
Hoffmann, R. W. Chem. Rev. 1989, 89, 1841.
Broeker, J. L.; Hoffmann, R. W.; Houk, K. N. J. Am. Chem. Soc. 1991,
113, 5006.
Beckwith, A. L. Tetrahedron 1981, 37, 3073.
Beckwith, A. L.; Easton, 0. J.; Lawrence, T.; Serelis, A. K. Aust. J. Chem.
1983, 36, 545.
Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925.
RajanBabu, T. V. Acc. Chem. Res. 1991,24, 139.
Spellmeyer, 0.0.; Houk, K. N. J. Org. Chem. 1987, 52, 959.
Griesbeck, A. G.; Stadtmuller, S. J. Am. Chem. Soc. 1991, 113, 6923.
Alehashem, H. Thesis, Michigan State University, 1992.
Vogel, E.; Kiefer, H.; Roth, W. R. Angew Chem, Int. Ed. Engl. 1964, 3,
442.
Spellmeyer, 0. 0.; Houk, K. N.; Rondan, N. G.; Miller, R. 0.; Franz, L.;
Fickes, G. N. J. Am. Chem. Soc. 1989, 111, 5356.
Wender, P. A.; Dreyer, G. B. Tetrahedron 1981, 37, 4445.
Wender, P. A.; Howbert, J. J. Tetrahedron Lett. 1982, 23, 3983.
Wender, P. A.; Howbert, J. J. Tetrahedron Lett. 1983, 24, 5325.
Schuster, D. I.; G., L.; Kaprinidis, N. A. Chem. Rev. 1993, 93, 1.
Rudolph, A.; Weedon, A. 0. Can. J. Chem. 1990, 68, 1590.

(93)

(94)
(95)

(95)
(97)

(98)
(99)

(100)

(101)
(102)

(103)
(104)
(105)

(106)

(107)
(108)

(109)
(110)

263
Wagner, P. J.; Kelso, P. A.; Kemppainen, A. E.; McGrath, J. M.; Schott, H.
N.; Zepp, R. G. J. Am. Chem. Soc. 1972, 94, 7506.
Cheng, K.-L.; Wagner, P. J. J. Am. Chem. Soc. 1994, 116, 0000.
Newcomb, M.; Manek, M. 8.; Glenn, A. G. J. Am. Chem. Soc. 1991, 113,
949.
Wagner, P. J.; Liu, K.-C.; Noguchi, Y. J. Am. Chem. Soc. 1981, 103, 3837.
Andrew, 0.; Hastings, 0.; OIdroyd, D. L.; Rudolph, A.; Weedon, A. 0.;
Wong, 0. F.; Zhang, 8. Pure Appl. Chem. 1992, 64, 1327.
Becker, 0.; Haddad, N.; Sahali, Y. Tetrahedron Lett. 1989, 30, 4429.
Shimizu, N.; Ishawa, M.; lshikura, K.; Nishida, S. J. Am. Chem. Soc. 1974,
96,6456.
Wagner, P. J. Rearrangements in Ground and Excited States; Academic
Press: New York, 1980; Vol. 3, p. 381.
Cantrell, T. S. J. Org. Chem. 1981, 46,2674.
Berridge, J. 0.; Gilbert, A.; Taylor, G. N. J. Chem. Soc. Perkin Trans. I
1980,2174.
Yang, N. 0.; Horner, M. G. Tetrahedron Lett. 1986, 27, 543.
Curran, D. P.; Kuo, S. C. J. Am. Chem. Soc. 1986, 108, 1106.
Curran, D. P. Comprehensive Organic Synthesis; Pergamon Press: New
York, 1991; Vol. 4, p. 779.
Beckwith, A. L. J.; Roberts, 0. H.; Schiesser, C. H.; Alex, W. Tetrahedron
Lett. 1985, 26, 3349.
Beckwith, A. L.; Moad, G. J. Chem. Soc. Perkin Trans. II1980, 1473.
Browry, V. W.; Lusztyk, J.; Ingold, K. U. J. Am. Chem. Soc. 1991, 113,
5687.
Hastings, 0. J.; Weedon, A. C. J. Am. Chem. Soc. 1991, 113, 8525.
Caldwell, R. A.; Majima, T.; Pac, C. J. Am. Chem. Soc. 1982, 104,629.

(111)
(112)

(113)

(114)
(115)

(116)
(117)
(118)
(119)
(120)

(121)

(122)

(123)
(124)

(125)
(126)
(127)

264
Scaiano, J. C. Acc. Chem. Res. 1982, 15, 252.
Kaprinidis, N. A.; Lem, G.; Courtney, S. H.; Schuster, D. I. J. Am. Chem.
Soc. 1993, 115, 3324.
Lusztyk, J.; Maillard, 8.; Deycard, S.; Lindsay, D. A.; Ingold, K. U. J. Org.
Chem. 1987, 52, 3509.
Loutfy, R. 0.; de Mayo, P. J. Am. Chem. Soc. 1977, 99,3559.
Motherwell, W. 8. Free Radical Chain Reactions in Organic Synthesis;
San Diego; Acedemic Press: London, 1992, p.213.
Caldwell, R. A.; Zhou, L. J. Am. Chem. Soc. 1994, 116, 2271.
Curran, D. P.; Rakiewicz, D. M. J. Am. Chem .Soc. 1985, 107, 1448.
Curran, D. P.; Schwartz, 0. E. J. Am. Chem .Soc. 1990, 112, 9272.
Boger, D. L.; Mathvink, R. J. J. Am. Chem. Soc. 1990, 112, 4003.
Curran, D. P.; Fevig, T. L.; Elliott, R. L. J. Am. Chem. Soc. 1988, 110,
5064.
Franklin, J. L.; Dillard, J. G.; Rosenstock, H. M.; Herron, J. T.; Draxl, K.;
Field, F. H. Ionization Potentials, Appearance Potential, and Heats of
Formation of Gaseous Positive Ions; U. S. Department of Commerce:
Washington, D. 0., 1969, p. 138.
Beckwith, A. L. J.; Ingold, K. U. Rearrangements in Ground and Excited
States, Academic Press: New York, 1980; Vol. 1, p. 161.
Baldwin, S. W. Org. Photochem. 1981, 5, 123.
Schroder, 0.; Wolff, S.; Agosta, W. C. J. Am. Chem. Soc. 1987, 109,
5491.
Liu, R. S. H. J. Am. Chem. Soc. 1967, 89, 112.
Wagner, P. J.; McMahon, K. J. Am. Chem. Soc. 1994, 116, 0000.
Cimino, G.; De Giulio, A.; De Rosa, 8.; De Stefano, S. Tetrahedron 1989,
45, 6479.

(128)

(129)

(130)
(131)
(132)

(133)
(134)
(135)
(136)
(187)
(138)

(139)
(140)

265
Paquette, L. A.; Wang, T.-Z.; Vo, N. H. J. Am. Chem. Soc. 1993, 115,
1676.
Perrin, 0. 0.; Annarego, W. L. F.; Perrin, D. R. Purification of Laboratory
Chemicals; 2nd ed.; Pergamon Press: New York, 1980.
Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,2923.
Wentworth, S. E.; Sciaraffa, P. L. Org. Prep. Proc. 1969, 1, 225.
Nagamatsu, T.; Tsurubayashi, 8.; Sasaki, K.; Hirota, T. Synthesis 1991,
303.
Dreyfuss, M. P. J. Org. Chem. 1963, 28, 3269.
Pojer, P. M.; Angyal, S. J. Aust. J. Chem. 1978, 31, 1031.
Koreeda, M.; Patel, P. 0.; Brown, L. J. Org. Chem. 1985, 50, 5910.
Corey, E. J.; Bock, M. G. Tetrahedron Lett. 1975, 38, 3269.
Derguini-Boumechal, F.; Linstrumelle, G. Tetrahedron Lett. 1976, 3225.
Huynh, 0.; Derguini-Boumechal, F.; Linstrumelle, G. Tetrahedron Lett.
1979, 1503.
Hands, A. R.; Mercer, A. J. H. J. Chem. Soc. (C) 1967, 1099.
Hands, A. R.; Mercer, A. J. H. J. Chem. Soc. (C) 1968, 2448.

 

"111111)1111111