Strain-Release Asymmetric Multicomponent Reaction to Access Diverse N-α-Bisaryl-C3-quaternary Azetidines

Azetidines are valuable motifs in drug discovery, yet access to densely substituted N-α-bisaryl-C3-quaternary azetidines remains limited. We report a strain-release multicomponent Petasis borono-Mannich reaction that enables the modular synthesis of N-α-bisaryl-C3-quaternary azetidines from readily available azabicyclo[1.1.0]butane (ABB)-carbinols, arylboronic acids, and aldehydes. This mild, operationally simple process tolerates diverse bisaryl combinations and overcomes the multistep constraints of existing methods. Importantly, an asymmetric variant was achieved using a BINOL-derived catalyst, providing the first access to chiral N-α-bisaryl-C3-quaternary azetidines in high enantiomeric purity.