Metal-Catalyzed Ionic Decarboxylative Cross-Coupling Reactions of C(sp³) Acids: Reaction Development, Mechanisms, and Application

Abstract

The direct transition-metal-catalyzed conversion of carboxylic acid groups into other C−C or C−X bonds provides a complementary bond disconnection to traditional cross-coupling manifolds. Decarboxylative coupling strategies can be divided into two mechanistic frameworks: decarboxylative homolysis processes that generate radicals and decarboxylative heterolysis processes that generate carbanions. The challenge of both inducing decarboxylation with unmodified substrates and enabling efficient interception by a suitable transition-metal complex has made achieving general approaches to catalytic cross-couplings of carboxylic acids elusive. Thus, more wasteful indirect strategies involving preactivation of the acid unit are more common. This Perspective article highlights recent work in the area of metal-catalyzed ionic decarboxylative crosscoupling reactions of unmodified C(sp 3 ) carboxylic acids. In these processes, the carboxylic acid unit serves as a surrogate for nucleophiles normally generated by deprotonation or by the use of organometallic reagents. In many cases, this approach can allow for alkylation reactions under less-basic conditions, improving functional group compatibility, ease of access to starting materials, and inhibit undesirable overfunctionalization of products. Commentary on reaction development, mechanism, and application is provided along with comparisons to related transformations.

Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

“…Within the last two decades, a rapidly growing number of decarboxylative functionalization reactions have been disclosed based on these concepts. Most decarboxylative C−C couplings are covered by recent reviews, [7–29] but decarboxylative reactions with the formation of C‐heteroatom bonds are only considered on the sideline or limited to discussion on one specific C‐heteroatom bond [30–35] . Hence, this review aims at providing a comprehensive overview of decarboxylative heterofunctionalization, especially highlighting the progress made within the last decade until January 2021 (Scheme 2).…”

Utilization of C(sp3)‐Carboxylic Acids and Their Redox‐Active Esters in Decarboxylative Carbon−Carbon Bond Formation

“…Carboxylic acids are an inexpensive and abundant feedstock, existing in Nature in a wide range of diverse and stable structures that make them ideal starting materials for chemical synthesis. Decarboxylative coupling reactions can engage in two broad mechanistic pathways: i) decarboxylative heterolysis processes that generate carbanions and ii) decarboxylative homolysis processes that generate radicals [7] . An ionic decarboxylation involving a heterolytic cleavage of a C−CO 2 H bond generates synthetically useful carbanions.…”

Organometallic Gas‐phase Ion Chemistry and Catalysis: Insights Into the Use of Metal Catalysts to Promote Selectivity in the Reactions of Carboxylic Acids and Their Derivatives

“…Indeed, the use of cuprates (Krause, 2002;Rappoport & Marek, 2009; in cross-coupling reactions with alkylhalides is a textbook reaction (McMurry, 2008). There has been considerable interest in developing decarboxylative versions of these catalytic reactions in which carboxylic acids are used as substrates Goossen, Zimmermann, & Knauber, 2010;Rodriguez & Goossen, 2011;Shang & Liu, 2011;Dzik, Lange, & Goossen, 2012;Goossen & Goossen, 2013;Miao & Ge, 2014;Li et al, 2016;Satoh & Miura, 2015;Patra & Maiti, 2017;Perry & Larrosa, 2017;Sandfort et al, 2017;Campeau & Hazari, 2019;Daley & Topczewski, 2020;Moon & Lundgren, 2020). The solution-phase equivalent of the metal-mediated decarboxylative conversion of a carboxylate to a dithiocarboxylate discussed above (Equations 9,32,and 33), however, appears to be unprecedented in the literature.…”