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. 2023 Jan 16;62(3):e202213055.
doi: 10.1002/anie.202213055. Epub 2022 Dec 8.

Chemoselective Decarboxylative Protonation Enabled by Cooperative Earth-Abundant Element Catalysis

Yen-Chu Lu  1 , Julian G West  1
Affiliations

Chemoselective Decarboxylative Protonation Enabled by Cooperative Earth-Abundant Element Catalysis

Yen-Chu Lu et al. Angew Chem Int Ed Engl. .

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.

Keywords: Decarboxylation; Earth-Abundant Metal; Hydrogen Atom Transfer; Radicals; Synthetic Methods.

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Figures

Figure 1.
Figure 1.
Current state of decarboxylative protonation. (a) decarboxylative protonation of activated redox ester. (b) direct decarboxylative protonation using acridinium photoredox catalyst. (c) this work: iron catalyzed chemoselective decarboxylative protonation.
Figure 2.
Figure 2.
Proposed mechanism for the iron/thiol cocatalyzed decarboxylative protonation
Figure 3.
Figure 3.
Decarboxylative protonation of arenes with different electronic properties: acridinium photoredox shows low reactivity in the presence of electron-rich arenes whereas iron-catalyzed decarboxylative protonation has broad arene scope.
Figure 4.
Figure 4.
Decarboxylation in the presence of electron-rich olefins: acridinium photoredox selectively oxidizes alkene over carboxylic acid whereas iron catalysis enables decarboxylation in the presence of electron-rich olefins.
Figure 5.
Figure 5.
(a) Isotope labeling of iron-catalyzed decarboxylative protonation provided high deuterium incorporation. (b) 50% TEMPO drastically hampered the formation of 2. (c) Radical clock experiment produced high yield of linear olefin as an isomeric mixture.
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