Visible light-induced synthesis of 1,3-disubstituted bicyclo[1.1.1]pentane ketones via cooperative photoredox and N-heterocyclic carbene catalysis

Abstract

While 1,3-disubstituted bicyclo[1.1.1]pentanes (BCPs) represent an important class of bioisosteres with para-substituted aromatic rings, synthetic methods to access 1,3-disubstituted BCP ketones are still scarce throughout the literature. Herein, we report a cooperative N-heterocyclic carbene (NHC) and iridium dual-catalyzed three-component reaction involving radicals derived from diazo esters to perform an addition reaction onto [1.1.1]propellane to afford BCP radicals. Cross-coupling with a corresponding Breslow intermediate radical then forms a disubstituted BCP ketone. Mild conditions, operational simplicity, and high atom economy render this method a powerful strategy to construct 1,3-disubstituted-BCP ketones from readily available starting materials and with suitable functional group tolerance.