Concise asymmetric synthesis of (+)-CP-99,994 and (+)-L-733,060 via efficient construction of homochiral syn-1,2-diamines and syn-1,2-amino alcohols.
An efficient asymmetric synthesis of human NK-1 SP receptor antagonists (+)-CP-99,994 and (+)-L-733,060 was achieved starting from a common chiral intermediate (5). Our route featured the SmI2-induced reductive coupling of N-tert-butanesulfinyl imine (7) with aldehyde (6) as the key step as well as pivotal transformations of the anti-1,2-amino alcohol thus obtained to homochiral syn-1,2-amino alcohol and syn-1,2-diamine for the asymmetric synthesis of 2,3-disubstituted piperidines.
Liu
Run-Hua
RH
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433.
Fang
Kai
K
Wang
Bing
B
Xu
Ming-Hua
MH
Lin
Guo-Qiang
GQ
D000605:Amino Alcohols / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry*; D006900:Hydroxylation; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000605:Amino Alcohols; D003959:Diamines; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine