Pyridine-boryl radical-catalyzed [3π + 2σ] cycloaddition for the synthesis of pyridine isosteres

Abstract

The pursuit of C(sp3)-enriched three-dimensional (3D) scaffolds as isosteric analogs for planar aromatic compounds is an area of increasing interest. In this report, we report a pyridine-boryl radical-catalyzed [3π + 2σ] cycloaddition reaction between vinyl azides and bicyclo[1.1.0]butanes (BCBs). The reaction leads to the synthesis of semisaturated bridged 2-azabicyclo[3.1.1]heptenes, a structural framework previously inaccessible. The semisaturation characteristic of these scaffolds results in an effective reproduction of the geometry of 1,3,5-substituted pyridine, with the imine group exhibiting comparable basicity to pyridine rings. Synthetic manipulation of these products reveals valuable synthetic handles, enabling a modular approach to the synthesis of potential pyridine isosteres.