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

An amine-catalyzed asymmetric formal aza [3 +3] cycloaddition of alpha,beta-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 allcylation of indole in the presence of BF3 center dot Et2O. (C) 2017 Elsevier Ltd. All rights reserved.