Expeditious synthesis of functionalized piperidines by regioselective ring opening of aziridines by enals catalyzed by an N-heterocyclic carbene

Abstract

A novel, expeditious, and diastereoselective synthesis of 2,6-disubstituted piperidin-4-ones is reported. Regioselective ring opening catalyzed by an N-heterocyclic carbene (NHC) of terminal aziridines by enals affords β′-amino α,β-unsaturated ketones, which on intramolecular aza-Michael addition in the presence of potassium carbonate furnish 2,6-disubstituted piperidin-4-ones cis-selectively, in excellent yields (83-95%). The protocol involves carbonyl umpolung reactivity of enals, in which the carbonyl carbon nucleophilically attacks the electrophilic terminal aziridines. The absence of byproduct formation, operational simplicity, the use of ambient temperature, high yields, and regio- and diastereoselectivity are the salient features of this procedure. © 2010 Georg Thieme Verlag Stuttgart New York.