piperidines and propionaldehyde

A highly enantioselective approach for preparing optically active bicyclic piperidines is described. The key step for introducing chiral centers was a L-proline catalyzed direct enantioselective aldol reaction of 3-phthalimidopropanal with aliphatic ketones. In the reactions with alicyclic ketones, a highly enantioselective formation of anti-2-(3-phthalimido-1-hydroxypropyl)cycloketones 1a-1b (>99% ee) was observed. The aldol products 1 could be subsequently converted into bicyclic piperidines 2 via a consecutive reductive deprotection, acylation, ring closure, and hydrolysis.

Topics: Aldehydes; Bridged Bicyclo Compounds; Catalysis; Chemistry, Organic; Magnetic Resonance Spectroscopy; Molecular Structure; Phthalimides; Piperidines; Proline; Stereoisomerism