Synthesis of Chiral Azetidines

Significance

The synthesis of chiral 2,3- and 2,4-di­substituted N-p-methoxyphenyl-azetidines from γ-aminoalcohols using 1,1-carbonyldiimidazole as the cyclization agent is reported. Although a reasonably broad range of substituted azetidines, many bearing oxygen functionality for further transformation, was prepared, the method was not amenable to extension to bicyclic systems. The relative stereochemistry was deduced from NOE experiments as well as an X-ray crystal structure analysis. Extension to pyrrolidines and piperidines was achieved but not generally explored.