Iron-catalyzed cross-coupling of sterically encumbered aryl Grignard reagents with allylic bromides: application to the synthesis of cannabigerol.

Abstract

This study presents an iron-catalyzed cross-coupling platform that addresses the persistent challenge of coupling sterically hindered ortho,ortho-disubstituted aryl Grignard reagents with allyl bromides. Using TMU as a high performance, low loading ligand, the system achieves excellent yields on bulky substrates. The methodology demonstrates good functional group compatibility and preserves ester moieties for downstream derivatization. Scalability is confirmed by multigram-scale synthesis. Successful conversion to cannabigerol validates practical utility in natural product synthesis.