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

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.