Chemoselective Decarboxylative Protonation Enabled by Cooperative Earth‐Abundant Element Catalysis

Abstract

Decarboxylative protonation is a general deletion tactic to replace polar carboxylic acid groups with hydrogen or its isotope. Current methods rely on the pre-activation of acids, non-sustainable hydrogen sources, and/or expensive/highly oxidizing photocatalysts, presenting challenges to their wide adoption. Here we show that a cooperative iron/thiol catalyst system can readily achieve this transformation, hydrodecarboxylating a wide range of activated and unactivated carboxylic acids and overcoming scope limitations in previous direct methods. The reaction is readily scaled in batch configuration and can be directly performed in deuterated solvent to afford high yields of d-incorporated products with excellent isotope incorporation efficiency; characteristics not attainable in previous photocatalyzed approaches. Preliminary mechanistic studies indicate a radical mechanism and kinetic results of unactivated acids (KIE = 1) are consistent with a light-limited reaction.

Iron Photocatalysis via Brønsted Acid Unlocking Ligand-to-Metal Charge Transfer

“…Iron as one of the most cheap and abundant metals 28,29 , whose LMCT catalytic abilities to generate radical are the ideal alternative for the excellent single electron transfer (SET) capacities of the excited noble-metal ruthenium and iridium polypyridyl complexes, have displayed impressive photochemical activities in photochemistry [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] . With the urgent demand of sustainable chemistry, we anticipate to develop a robust iron LMCT catalytic platform which can be adopted for inert bulk chemical activation and value-added molecular skeletons construction.…”