Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer

Abstract

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol intelligently bypasses the conventional metric of reduction reaction, i.e., the reductive potential, but instead, relies on chemical moieties’ triplet energies and kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups which were incompatible with previous (hetero)arene reductions, are retained in this work. We anticipate this protocol to trigger further advancement of chemoselective arene reductions and enable the current arene‐rich drug space escaping from flatland.