Enantioselective Pyrrolidine Synthesis
J. Y. L. Chung*, R. Cvetovich, J. Amato, J. C. McWilliams, R. Reamer, L. DiMichele
Merck Research Laboratories, New Jersey, USA
21 September 2005 (online)
The five-step, chromatography-free asymmetric synthesis of 3 from 1 in 71% overall yield is reported. Starting from one stereogenic center, which was induced by CBS reduction in >98% ee, the pyrrolidine ring was formed with complete inversion at the C-4 center. Following trans/cis epimerization-saponification afforded the pure trans-pyrrolidine carboxylic acid 3 in >99.6% chemical and optical purity. This synthesis was also shown to be applicable to aryl substrates with electronically neutral and rich substituents.