A unified strategy for α-alkoxyalkyl radical generation via pinacol boronic ester precursors

Abstract

A general method to generate α-alkoxyalkyl radicals from pinacol boronic ester precursors (R–Bpin) has been developed. These radical precursors are stable in air, easy to prepare, and readily accessible via Matteson homologation followed by a 1,2-metallate shift with a broad range of metal alkoxides. The key step is a transesterification with catechol methyl borate (MeOBcat), converting the inert Bpin species into a radical-active Bcat intermediate, which then undergoes nucleohomolytic substitution at boron to release the desired radical. This approach is practical, scalable (demonstrated at 4 mmol scale), and broadly applicable. It avoids toxic reagents and expensive photocatalysts, offering a straightforward route to ether-containing molecules relevant to the synthesis of natural product and bioactive compounds.