Integrating Umpolung and CO 2 Shuttling Strategies for the Synthesis of 1 2 C- and 13 C-α-Ketoacids from Aldehydes

The direct carboxylation of aldehydes with CO is rare due to the polarity mismatch between these two electrophilic substrates. To address this challenge, we propose a sequential approach for synthesizing α-ketoacids from commercially available aldehydes by integrating umpolung and CO shuttling strategies. This transition metal-free shuttle carboxylation method enables the transfer of CO from triphenylacetic acid potassium salt to thioacetal, eliminating the need for handling pressurized CO gas or using specialized equipment, while also enhancing the reaction's functional group tolerance. Furthermore, the use of stoichiometric or slightly excess amounts of triphenylacetic acid potassium salt as a formal CO donor makes it suitable for complete C labeling of α-ketoacids.