Synthesis of 3-alkylpyrrolidines by anionic cyclization

Abstract

α-Aminocarbanions, generated by transmetallation of aminomethylstannanes, cyclize onto an unactivated alkene to give 3-alkylpyrrolidines. The intermediate organolithium either reincorporates trimethyltin or, from the tributylstannanes, can be trapped with a variety of electrophiles. From the trimethylstannane, the cyclization can be promoted catalytically using 0.2 equivalents of methyllithium. The trimethyltin group in the product can be cleaved using ceric ammonium nitrate. Trapping the 3-lithiomethylpyrrolidine with ethylchloroformate, followed by hydrolysis provides a four step synthesis of the GABA uptake inhibitor 3-pyrrolidineacetic acid.