Many classical and emerging methodologies in organic chemistry rely on CO2 extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates, have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic acids and malonate half-esters, undergo uncatalyzed reversible decarboxylation in dimethylformamide solution. Decarboxylation/carboxylation occurs with substrates resistant to protodecarboxylation by Brønsted acids under otherwise identical conditions. Isotopically labeled carboxylic acids can be prepared in high chemical and isotopic yield by simply supplying an atmosphere of 13CO2 to carboxylate salts in polar aprotic solvents. An understanding of carboxylate reactivity in solution enables conditions for the trapping of aldehydes, ketones, and α,β-unsaturated esters.

Complex cyclic azomethine imines possessing a β-aminocarbonyl motif can be accessed readily from simple alkenes and hydrazones. This alkene aminocarbonylation approach allows formation of ketone-derived azomethine imines of unprecedented complexity. Since unsymmetrical hydrazones are used, two stereoisomers are formed: the reactivity of chiral derivatives is explored in both intra- and intermolecular systems.

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.

A borinic acid derived catalyst enables regioselective and β-selective reactions of 2-deoxy- and 2,6-dideoxyglycosyl chloride donors with pyranoside-derived acceptors having unprotected cis-1,2- and 1,3-diol groups. The use of catalysis to promote a β-selective pathway by enhancement of acceptor nucleophilicity constitutes a distinct approach from previous work, which has been aimed at modulating donor reactivity by variation of protective and/or leaving groups.

We demonstrate that metal-catalyzed enantioselective benzylation reactions of allylic electrophiles can occur directly from aryl acetic acids. The reaction proceeds via a pathway in which decarboxylation is the terminal event, occurring after stereoselective carbon−carbon bond formation. This mechanistic feature enables enantioselective benzylation without the generation of a highly basic nucleophile. Thus, the process has broad functional group compatibility that would not be possible employing established protocols.