StereospecificStrain-Release-Driven Ring Openingof Azabicyclo[1.1.0]butanes to Access N-β-SubstitutedChiral Azetidines

Abstract Chiral azetidines bearing stereocenters remote from the azetidine ring represent highly valuable and structurally diverse motifs that are frequently encountered in a variety of bioactive compounds. Over the past few years, several catalytic ring-opening strategies involving azabicyclo[1.1.0]butanes (ABBs) have been developed for the synthesis of functionalized azetidines. However, the efficient synthesis of azetidines containing well-defined chiral centers remains a significant challenge. Herein, we report a dual strain-release ring-opening reaction of ABB carbinols with aziridines, merging two strained rings, enabling the synthesis of enantiopure N-β-amino-C3-quaternary chiral azetidines.