Desymmetrization of 2-(1,5-Dialkoxypent-3-yl)phenyl Grignard Reagents by Rhodium-Catalyzed Asymmetric 1,4-Shift/β-Alkoxy Elimination

Abstract

The Grignard reagents generated from 2-(1,5-dialkoxypent-3-yl)aryl bromides were treated with a chiral rhodium catalyst with either a segphos or binap ligand to give high yields of 3-aryl-5-alkoxy-1-pentenes with high enantioselectivity (up to 99% ee). Based on deuterium labeling studies, it is proposed that the catalytic cycle consists of (1) transmetalation of the Grignard reagent to a RO-Rh catalyst generating an aryl-Rh intermediate, (2) a 1,4-shift of Rh from aromatic carbon to one of the two homobenzylic carbons, which is not an enantioselectivity-determining step, (3) migration of Rh to a β-alkoxyalkyl position ready for selective β-alkoxy elimination through a sequence of β-hydrogen elimination/hydrorhodations, and (4) β-alkoxy elimination resulting in the formation of an enantioenriched elimination product.