Base-Mediated (3 + 3) Annulation of Bicyclo[1.1.0]butanes with Diarylmethyl Isothiocyanates for Access to 3-Azabicyclo[3.1.1]heptanes

A transition-metal-free, base-mediated (3 + 3) annulation of bicyclo[1.1.0]butanes with diarylmethyl isothiocyanates has been reported for the synthesis of 3-azabicyclo[3.1.1]heptanes. The transformation operates under mild conditions and proceeds via strain-enabled activation of the central C-C bond of the BCB framework and displays broad substrate compatibility and high yields of products. Base-mediated generation of nucleophiles and subsequent interception with the BCB framework in a (3 + 3) pathway resulted in the product formation. Scalability and post-synthetic diversification demonstrate the synthetic value of this methodology for accessing medicinally relevant azabicyclic scaffolds.