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

Abstract

A photocatalyzed, β-selective hydrocarboxylation of α,β-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 β,β-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)3SiH as the principal reaction pathway. Finally, a telescoped process involving the described β-carboxylation followed by a α-bromination/β-lactonization sequence provides a strategy for β-lactone synthesis.