Efficient synthesis of sterically hindered arenes bearing acyclic secondary alkyl groups by Suzuki-Miyaura cross-couplings

Abstract

Bulky P,P=O ligands were designed to inhibit isomerization and reduction side reactions during the cross coupling between sterically hindered aryl halides and alkylboronic acids. Suzuki-Miyaura cross-couplings between di-ortho-substituted aryl bromides and acyclic secondary alkylboronic acids have been achieved with high yields. The method has also enabled the preparation of ortho-alkoxy di-ortho-substituted arenes bearing isopropyl groups in excellent yields. The utility of the synthetic method has been demonstrated in a late-stage modification of estrone and in the application to a new synthetic route toward gossypol.

Keywords: aryl-alkyl cross-coupling; boronic acids; isopropyl arenes; ligand design; reductive elimination.