Aza-Darzens Type Reaction of Azirines: Access to Highly Substituted 1-Azabicyclo[1.1.0]butanes and Azetidines

A streamlined approach was developed for accessing 2,3,4-substituted 1-azabicyclo[1.1.0]butanes from azirines under aza-Darzens-type reaction conditions. The pronounced ring strain in these bicyclic systems enabled distinctive electrophilic transformations via activation of the N-C(3) bond, leading to the formation of substituted azetidines. The relative configurations of the 1-azabicyclo[1.1.0]butanes were established by 2D NMR, while single-crystal X-ray analysis of the azetidines confirmed their structures and, by analogy, supported the configurational assignments of both these synthesized classes.