Role of Sterically Demanding Chiral Dirhodium Catalysts in Site-Selective C-H Functionalization of Activated Primary C-H Bonds

The influence of sterically demanding dirhodium tetracarboxylate catalysts on the site selectivity of C-H functionalization by means of rhodium carbene-induced C-H insertion is described. The established dirhodium tetraprolinate-catalyzed reactions of aryldiazoacetates cause preferential C-H functionalization of secondary C-H bonds as a result of competing steric and electronic effects. The sterically more demanding dirhodium tetrakis(triarylcyclopropanecarboxylate) catalysts, exemplified by dirhodium tetrakis[(R)-(1-(biphenyl)-2,2-diphenylcyclopropanecarboxylate)] [Rh-2(R-BPCP)(4)], favor C-H functionalization of activated primary C-H bonds. Highly site-selective and enantioselective C-H functionalization of a variety of simple substrates containing primary benzylic, allylic, and methoxy C-H bonds was achieved with this catalyst. The utility of this approach has been demonstrated by the late-stage primary C-H functionalization of (-)-alpha-cedrene and a steroid.