Facile synthetic route to enantiopure unsymmetric cis-2,5-disubstituted pyrrolidines.
The (+/-)-cis-5-arylcarbamoyl-2-ethoxycarbonylpyrrolidines 6a-g were firstly synthesized in 53-64% yields by using meso-diethyl-2,5-dibromoadipate 3 and (S)-(-)-1-phenylethylamine in three steps. The diastereomeric mixture (S;2S,5R)-(-)-7 and (S;2R,5S)-(+)-8 were prepared by the Grignard reaction and separated by a flash column chromatography in 29 and 52% yields. The absolute configurations of (+)-8 was confirmed by X-ray crystallographic analysis and the enantiopure pyrrolidines (2S,5R)-(-)-9/(2R,5S)-(+)-9 and (2S,5R)-(-)-10/(2R,5S)-(+)-10 were obtained in good yields.
Wang
Ping-An
PA
Department of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Xu
Zheng-Shuang
ZS
Chen
Chun-Feng
CF
Gao
Xu-Guang
XG
Sun
Xiao-Li
XL
Zhang
Sheng-Yong
SY
D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D011759:Pyrrolidines