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.

Direct Decarboxylation of Trifluoroacetates Enabled by Iron Photocatalysis**

“…According to our research hypothesis, recent literature insights [40,41] and our experimental data, we propose the mechanistic pathway depicted in Scheme 4A. Initially, the catalytically active Fe(III) species ( 1 ) are formed via in situ coordination of L1 to Fe(OTf) 2 and subsequent oxidation with K 2 S 2 O 8 .…”

“…Inner‐sphere electron transfer arises from the population of a dissociative ligand‐to‐metal charge transfer (LMCT) excited state, an emerging concept in organic synthesis with Earth‐abundant metals, [30,31] rooted in fundamental studies in the past [32,33] . Complementary LMCT decarboxylation strategies of non‐fluorinated carboxylates with more accessible oxidation potentials have been recently reported with first‐row transition metals [34–43] and cerium salts, [44–46] which have displayed similar or competing reactivity patterns to traditional photoredox catalysts. Yet, the full potential of LMCT photocatalysis in organic synthesis, such as the activation of substrates beyond redox demands, is to be unveiled.…”

Vitamin B12 in Photocatalysis – An Underexplored Frontier in Cooperative Catalysis

“…This approach is particularly suited to the reaction of stable and available X‐type ligands such as (pseudo)halides, alkoxides, and carboxylates. Our group has recently leveraged this approach to enable powerful cooperative transformations such as decarboxylative protonation [4] and decarboxylative azidation [5] of carboxylates and diazidation of alkenes [6] using iron photocatalysis.…”

Radical Phosphorylation of Aliphatic C–H Bonds via Iron Photocatalysis

“…Based on the above results and literature reports, , a possible photoinduced radical phosphorylation mechanism is proposed in Scheme . First, the Fe(III)Cl 3 catalyst transforms into its excited state under 370 or 390 nm LEDs irradiation.…”