Integrating Umpolung and CO2 Shuttling Strategies for the Synthesis of 12C- and 13C-α-Ketoacids from Aldehydes.

Abstract

The direct carboxylation of aldehydes with CO2 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 CO2 shuttling strategies. This transition metal-free shuttle carboxylation method enables the transfer of CO2 from triphenylacetic acid potassium salt to thioacetal, eliminating the need for handling pressurized CO2 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 CO2 donor makes it suitable for complete 13C labeling of α-ketoacids.