Chemoselective Catalytic α-Oxidation of Carboxylic Acids: Iron/Alkali Metal Cooperative Redox Active Catalysis

Abstract

We developed a chemoselective catalytic activation of carboxylic acid for a 1e − radical process. α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under radical conditions, proceeded efficiently under the optimized conditions. Chemoselective enolization of carboxylic acid was also achieved even in the presence of more acidic carbonyls. Extensive mechanistic studies revealed that the cooperative actions of iron species and alkali metal ions derived from 4 Å molecular sieves substantially facilitated the enolization. For the first time, catalytic enolization of unprotected carboxylic acid was achieved without external addition of stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently coupled with free radical TEMPO, providing synthetically useful α-hydroxy and keto acid derivatives.

On the Use of Iron in Organic Chemistry

“…The Brønsted acidity of the carboxylic acid is a further complication for the deprotonation of the α-proton, and therefore two equivalents of a strong base such as LDA are normally required for efficient enolization. In 2020, the group of Ohshima reported the α-functionalization of carboxylic acids through an iron-catalyzed 1e -radical process [74]. The use of molecular sieves was found to be crucial in suppressing undesired decarboxylation and the alkali metal salt component of the sieves (sodium or potassium carboxylate) was found to play a crucial role in promoting the reaction.…”

Pentafluorophenyl Group as Activating Group: Synthesis of α‐Deuterio Carboxylic Acid Derivatives via Et3N Catalyzed H/D Exchange

“…Therefore, methods for introducing deuterium into carboxylic acids or their derivatives will be crucial for developing new deuterated pesticides, drugs and materials. Generally, two strategies can be used for the synthesis of deuterated carboxylic acids [3a–f] . In the first strategy, aldehyde is used as the precursor (Figure 3a) [3a] .…”

“…The second strategy is direct H/D exchange of carboxylic acid (Figure 3b) [3b] . Although more convenient, this method is only applicable to specific carboxylic acids and requires harsh reaction conditions, which always requires the usage of NaH, [3c] n ‐BuLi, [3b] CH 3 ONa [3d] and/or high temperature. Recently, Yu and co‐worker have reported a palladium‐catalyzed H/D exchange reaction of benzilic carboxylic acids substituted with electron withdrawing groups (Figure 3c) [3g] .…”

Siloxy Esters as Traceless Activators of Carboxylic Acids: Boron‐Catalyzed Chemoselective Asymmetric Aldol Reaction**

“…Yazaki and Oshima achieved a-oxidation of various a-aryl-carboxylic acids with TEMPO,w hich proceeded via redox-active iron/ alkali metal heterobimetallic enediolates. [8] Sawamura and Shimizu recently reported boron-catalyzed a-allylation with allylsulfones under blue LED irradiation. In their work, CÀC bond formation proceeded through single-electron transfer from photoexcited boron enediolates to the allylsulfones.…”

“…Following these studies, chemoselective α‐functionalization of α‐aryl‐carboxylic acids via a radical mechanism were reported (Scheme 1 c). Yazaki and Oshima achieved α‐oxidation of various α‐aryl‐carboxylic acids with TEMPO, which proceeded via redox‐active iron/alkali metal heterobimetallic enediolates [8] . Sawamura and Shimizu recently reported boron‐catalyzed α‐allylation with allylsulfones under blue LED irradiation.…”