Synthesis of heteroatom-containing pyrrolidine derivatives based on Ti(O-iPr)4 and EtMgBr-catalyzed carbocyclization of allylpropargyl amines with Et2Zn

Abstract

The Ti(O-iPr)₄ and EtMgBr-catalyzed regio and stereoselective carbocyclization of N-allyl-substituted 2-alkynylamines with Et₂Zn, followed by deuterolysis or hydrolysis, affords the corresponding methylenepyrrolidine derivatives in high yields. It was found that Ti–Mg-catalyzed carbocyclization of N-allyl-substituted 2-alkynylamines with Et₂Zn is equally selective in dichloromethane, hexane, toluene, and diethyl ether. The reaction was tolerant to the presence of aryl, alkyl, trimethylsilyl, methoxymethyl and aminomethyl substituents on the alkyne. A selective method was proposed for the preparation of bis-pyrrolidine derivatives using Ti–Mg-catalyzed carbocyclization of bis-allylpropargyl amines with Et₂Zn.