Highly Enantioselective Catalytic [6+3] Cycloadditions of Azomethine Ylides

摘要

Stereocontrolled cycloaddition reactions give efficient access to bioactive cyclic molecules through concerted formation of two bonds and several stereocenters in one step. In particular, the reaction of activated alkenes with azomethine ylides derived from amino acids and aldehydes is a powerful method for the highly stereoselective synthesis of substituted pyrrolidines [Eq. (1)] bearing up to four stereogenic centers. In contrast, catalytic enantioselective higher-order cycloadditions have been explored in only a few cases. Recently, a related approach to racemic pentasubstituted piperidines that employed azomethine ylides in a [6+3] cycloaddition was reported by Hong et al. [Eq. (2)] Herein, we report the first catalytic enantioselective [6+3] cycloaddition of azomethine ylides with fulvenes to provide piperidine derivatives having four stereocenters with high regio- and enantioselectivity. We demonstrate that the enantioselective [6+3] cycloaddition can be combined with a [4+2] cycloaddition in one pot to yield complex annulated piperidines with eight stereocenters.