Development of an Efficient "Chiral Technology" Based on the Chiral Coordinating Agent Protocol

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1. Enantioselective S_E2 Reaction of alpha-Methoxy Benzyllithium Generatedvia t-BuLi/Chiral Bisoxazoline System In recent years the extemal chiral ligand (ECL) -based asymmetric lithiation/S_E2 reaction has emerged as an efficient strategy for enantioselective C-C bond formations. While most of the successes so far have been made using (-) -sparteine as ECL,the development of other ECL's effective for different reactions is a significant challenge. We have developed the highly enantioselective S_E2 reactions of alpha-methoxy benzyllithium generated via the lithiation (deprotonation) with t-BuLi complexed with the chiral bisoxazoline, (S,S) -Box-i-Pr, as ECL (Lc^*). Of special interest is the reaction with the acetylenic aldehyde which affords the 1,2-diolmonomethyl ether with an extremely high % ee along with a relatively high anti diastereoselectivity.2. Carbanion Cyclization : Absolute Stereochemistry and Enantiocontrol The carbanion cyclization of 5-alkenyllithiums and their hetero … More analogues has emerged as an efficient method for stereoselective carbocyclization. We have investigated the absolute stereochemistry of the carbanion cyclization and the developed the its enantioselective version.Absolute Stereochemistry of Carbanion Cyclization : Treatment of enatiomerically defined (R) -alpha-alkenyloxystannanes with n-BuLi at -78ﾟC was found to afford the cyclization product (S) in high stereoselectivity. Tus the rearrangement is proved to proceeds with completely retention of configuration at the Li-bearing chiral center.Enantioselective Version of Carbanion Cyclization : Upon treatment with (-) -sparteine / s-BuLi, alkenylcarbamate gave cyclopentane in a high enatioselectivity, along with 6-phenylbicyclo [3.1.0] hexane. More significantly, a similar cyclization of the 4-silyloxy substrate (racemic) was found to afford the silyoxy cyclopentane and the 2-silyloxy bicyclohexane of which the absolute configurations are opposite each other.3. Enantioselective [2,3] -Wittig Rearrangement Induced by Asymmetric Lithiation with t-Butyllithium/Chiral Bisoxazoline System The [2,3] -Wittig rearrangement, particularly its asymmetric version using enantio-enriched substrates, enjoys wide spread application in many facets of organic synthesis. However, only a few examples have been reported of the enantioselective version that permit direct access to an enantio-enriched product from an achiral substrate. In view of the recent progress in the asymmetric lithiation protocol, we became intriguted by the exploration of enantioselective [2,3] -Wittig variants induced by the ECL-based asymmetric lithiation protocol. Now we have developed the highly enantioselective [2,3] Wittig rearrangement using the chiral bisoxazoline ((S,S) -Box-i-Pr) / t-BuLi system. This is the first example of the utilization of a chiral bisoxazoline as ECL for the enantioselective [2,3] -Wittig rearrangement. Less