Generation and [2,3]-Sigmatropic Rearrangement of Ammonium Ylides from Cyclopropyl Ketones for Chiral Indolizidines with Bridgehead Quaternary Stereocenters.

Abstract

A sequence of nucleophilic ring opening of cyclopropyl ketones, N-quaternization, deprotonation, and [2,3]-sigmatropic rearrangement of ammonium ylides has been developed. This method enables efficient synthesis of bicyclic indolizidines bearing bridgehead aza-quaternary stereocenters from easily available chiral cyclopropyl ketones. The reactions proceeded with an excellent level of chirality transfer and tolerated various functional groups, providing a diverse array of allenyl- or allyl-substituted indolizidines with high enantiomeric purities (up to >99% ee).