Asymmetric synthesis of bicyclic piperidines via L-proline catalyzed aldol reaction of 3-phthalimidopropanal.
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.
Zhang
Fanglin
F
Department of Chemistry, Huazhong University of Science and Technology, Hubei, China.
Peng
Yiyuan
Y
Gong
Yuefa
Y
D000447:Aldehydes / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010797:Phthalimides / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D001643:Bridged Bicyclo Compounds; D010797:Phthalimides; D010880:Piperidines; D011392:Proline; C005556:propionaldehyde