Asymmetric induction using methyl (S)-lactate and application to the synthesis of Bao Gong Teng A

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Pham, Vinh C.
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An example of an stereoselective reaction is illustrated by the reduction of optically pure (3S)-3-tert-butylcyclohexanone, (S)-1 as shown in Scheme 1.* The reduction generates a new chiral center at C1, forming (3S,1R)-2 and (3S,1S)-2 in unequal amount, therefore, this reaction is an stereoselective reaction. The known efficiency of methyl (S)-lactate as a chiral auxiliary in some Diels-Alder reactions$\sp2$ encouraged further study of the use of this chiral auxiliary in other reactions. In these studies, the asymmetric induction imposed by the chiral auxiliary was examined. A final goal was to use reactions with high asymmetric induction for natural product synthesis. Photodeconjugation was one of the reactions chosen for a study of the effectiveness of the methyl (S)-lactate chiral auxiliary. In this study, the methyl (S)-lactate was incorporated into an $\alpha,\beta$-unsaturated ester, which was then subjected to irradiation in order to symmetrically form the corresponding $\beta,\gamma$-unsaturated ester with a new chiral center at the $\alpha$ position. Obtaining a high asymmetric induction, such that the reaction might be synthetically useful, and rationalizing the mechanism of the induction were the two main objectives of this study. Thus, the photodeconjugation reaction was performed under various conditions in order to search for the optimum induction, and also to examine trends in induction. The Diels-Alder reaction was the next reaction chosen for study of the asymmetric induction imposed by the lactate chiral auxiliary. The aim of this study was to incorporate methyl (S)-lactate or methyl (R)-mandelate, a similar chiral auxiliary, i to a new type of dienophile, a vinylsulfonate. The effectiveness of these new chiral dienophiles was examined in Diels-Alder reactions. These chiral vinylsulfonates should provide more choice for introducing specific functionality in chiral Diels-Alder cycloadducts. The chiral vinylsulfonates should also be highly reactive dienophiles due to the strong electron withdrawing ability of the sulfonate groups, and they should be useful for reactions with less reactive dienes such as furan and its derivatives. A 1,3-dipolar cycloaddition reaction was the last type of reaction chosen for the study of asymmetry induced by the methyl (S)-lactate chiral auxiliary. A study of N-benzyl 3-oxidopyridinium betaine undergoing a 1,3-dipolar cycloaddition with either a vinylsulfonate, or an acrylate, bearing the methyl (S)-lactate chiral auxiliary was undertaken. These reactions should form the azabicyclo (3.2.1) octane ring skeleton, a building block for a number of natural products, including the tropane alkaloids. The object of this study was to obtain high diastereoselectivities in the cycloadditions so that they could be used for the synthesis of Bao Gong Teng A, a tropane alkaloid. (Abstract shortened by UMI.) ftn*Please refer to the dissertation for diagram.