Concise synthesis of the retinoic acid receptor (RAR) agonist AGN-193836 utilizing a photochemical benzylic oxidation

Abstract A new, concise synthesis of retinoic acid receptor (RAR)-α agonist AGN-193836 (1) is described which employs a photochemical benzylic methyl oxidation with molecular oxygen as the key step (3 → 2). Further this route explores the application of green photochemistry in the synthesis of drug candidates and avoids a number of toxic or highly pyrophoric reagents that had been described in previous syntheses of 1. In addition, the oxidation proved to be higher yielding when compared to potassium permanganate, a metal oxidant typically used for this –CH3 to –CO2H functional group conversion.