Photocatalyzed, β-Selective Hydrocarboxylation of α,β-Unsaturated Esters with CO2 under Flow for β-Lactone Synthesis

A photocatalyzed, beta-selective hydrocarboxylation of alpha,beta-unsaturated esters employing CO2 radical anion generated under flow conditions was developed. A range of substrates bearing a variety of functional groups were tolerated, demonstrating chemoselectivity. A series of quaternary carboxylic acids were obtained from sterically demanding beta,beta-disubstituted alkenes including those derived from natural products. Mechanistic studies support a Giese-type CO2 radical anion conjugate addition followed by hydrogen atom transfer from (TMS)(3)SiH as the principal reaction pathway. Finally, a telescoped process involving the described beta-carboxylation followed by a alpha-bromination/beta-lactonization sequence provides a strategy for beta-lactone synthesis.

Automated summary

A photochemical, beta-selective hydrogenation of alpha, beta-unsaturated esters using CO2 radical anion under flow conditions was developed. The reaction tolerated various substrates with different functional groups and resulted in a series of quaternary carboxylic acids. Mechanistic studies suggest a Giese-type CO2 radical anion conjugate addition followed by hydrogen atom transfer as the main reaction pathway, and a telescoped process for beta-lactone synthesis.