ABSTRACTDEVELOPMENT OF PORPHYRIN TWEEZER SYETEM FOR DETERMINING ABSOLUTE CONFIGURATION OF CHIRAL MOLECULES VIA ECCDByXiaoyong Li This dissertation focuses on three parts. The first portion introduces the concept of exciton coupled circular dichroism (Chapter I) and the rationale about how we design and prepare electronically tuned porphyrin tweezers with enhanced sensitivity for chirality sensing (Chapter II). A number of porphyrin tweezers with electron deficient or electron rich phenyl rings at the meso positions were synthesized and evaluated for chirality sensing of chiral diamines and derivatized chiral carboxylic acids via ECCD protocol. This screening afforded TPFP tweezer which contains three pentafluorophenyl groups at 10,15,20 positions as the best candidate for chirality sensing of chiral molecules. Chapter III-VI constitute the second portion of this dissertation describing the successful application of TPFP tweezer as a chirality reporter for a wide range of chiral molecules which are difficult subjects for conventional methods. Chirality assignment of acylic bisfunctionalized molecules has been a tough task due to their flexible skeleton. Erythro substrates are the most difficult ones among those bisfunctionalized molecules. Chapter III describes how we solved this issue using the newly developed TPFP tweezer devoid of chemical derivatiation. Upon complexation of the substrates with TPFP tweezer in solution, intense ECCD signals arose and consistent trend was obtained. The proposed binding modes provide unambiguous assignment of substrate chirality in a non-empirical fashion. Chiral epoxy alcohols are extremely useful building blocks for organic synthesis, however there is no direct method for their absolute stereochemical assignment. In Chapter IV, the TPFP tweezer demonstrated its power again by rendering fairly strong and consistent ECCD signals uponr complexation with 20 epoxy alcohols (2,3-disubstituted, 2,2-disubstituted, 2,2,3-trisubstituted and 2,3,3-trisubstituted). The elicited binding mechanism led to a rapid and reliable way for stereochemical determination of epoxy alcohols. In addition, while extending this study to long chain (3,4-, 4,5- 5,6-, 6,7-, 7,8- substituted) epoxy alcohols, a striking odd-even effect was discovered. Chapter V centers on the chirality assignment of chiral 1,n-glycols with long alkyl chains which are also very tough molecules for chirality analysis using conventional methods. Chapter VI illustrates the natural extension of this project to the ECCD study of chiral aziridinols which also lack an efficient method for chirality determination. Free aziridinols proved to behave the same as epoxy alcohols and to our surprise some N-protected aziridinols are also ECCD active. The last chapter is devoted to further demonstrate the great potential of TPFP tweezer in stereochemical determinations by challenging it with more complex molecules like steroids which contain multiple oxygenated functionalities (hydroxyl, ketone, epoxide, etc.). A number of steroids yielded strong ECCD signals. So did several substrates containing complicated bisTHF ring system. This work will attract not only organic chemists in academic labs but also pharmaceutical companies that are interested in elucidating absolute configurations of functionalities in complex molecules.
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