Late-Stage Photoredox-Catalyzed Aryl C-H Bond Diazomethylation with Atomic Carbon Reagents

Abstract

Herein, we present a novel class of diazo compounds as atomic carbon reagents substituted with two orthogonal redox-active leaving groups that were exploited in the late-stage construction of chiral centers with aryl C-H bonds from aromatic feedstocks and drug molecules. Key to the strategy was the use of photoredox catalysis to enable an initial C-H diazomethylation reaction able to generate diazomethyl-substituted redox-active esters. Subsequent construction of chiral centers with readily available starting materials proceeded using a broad range of well-known diazo and redox-active ester functionalizations. Moreover, the applicability of our novel atomic carbon reagent was tested in the automated parallel synthesis of a library of Fenofibrate derivatives.