Carboxylic Acid Salts as Dual-Function Reagents for Carboxylation and Carbon Isotope Labeling

The potassium salts of carboxylic acids are developed as efficient carboxylating agents through CO2 exchange. We describe these carboxylates as dual-function reagents because they function as a combined source of CO2 and base/metalating agent. By using the salt of a commercially available carboxylic acid, this protocol overcomes difficulties when using CO2 gas or organometallic reagents, such as pressurized containers or strictly inert conditions. The reaction proceeds under mild conditions, does not require transition metals or other additives, and shows broad substrate scope. Through the preparation of several biologically important molecules, we show how this strategy provides an opportunity for isotope labeling with low equivalents of labeled CO2.

Automated summary

The potassium salts of carboxylic acids are developed as efficient carboxylating agents through CO2 exchange. These carboxylates function as a combined source of CO2 and base/metalating agent, making them dual-function reagents. By using the salt of a commercially available carboxylic acid, this protocol provides a convenient and practical alternative to using CO2 gas or organometallic reagents, without the need for pressurized containers or strictly inert conditions. The reaction is mild, transition metal-free, and exhibits a wide range of substrate compatibility. The strategy showcased the ability to isotopically label biologically important molecules using low amounts of labeled CO2.