Diastereoselective synthesis of substituted prolines via 5-endo-trig cyclisations of aza-[2,3]-Wittig sigmatropic rearrangement products

The major diastereoisomers of aza-[2,3]-Wittig sigmatropic rearrangement products from alpha-amino acid derivatives are susceptible to a rare nucleophilic 5-endo-trig cyclisations of an amine onto a non-conjugated vinylsilane in high yield and complete diastereocontrol. Five examples are presented, with cyclisation yields between 35 and 87%. A rationale for the stereoselectivity of the cyclisation is forwarded based upon the steric control factors that have been documented for the aza-[2,3]-Wittig sigmatropic rearrangement. A discussion of the mechanism in the context of the reaction conditions is also presented. Oxidation of the silyl group to a hydroxyl group and complete removal were demonstrated for synthetic utility. (C) 2010 Elsevier Ltd. All rights reserved.