Secondary amine-catalyzed asymmetric formal aza [3 + 3] cycloaddition to construct enantioenriched piperidines derivatives

Abstract

An amine-catalyzed asymmetric formal aza [3 + 3] cycloaddition of α,β-unsaturated aldehydes with N-Ts ketimines derived from both acyclic and cyclic ketones was developed, which was followed by an oxidation to afford chiral piperidine derivatives in good yields and excellent enantioselectivities (up to 99% ee). In addition, the corresponding cycloadduct piperidin-2-ols can be easily transformed to indolyl substituted chiral piperidine derivatives in good yields and excellent diastereoselectivities (>20:1) via Friedel-Crafts alkylation of indole in the presence of BF3·Et2O.