Hemilabile Benzyl Ether Enables γ-C(sp3)–H Carbonylation and Olefination of Alcohols

Pd-catalyzed C(sp3)–H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C–H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct γ- or δ-C–H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C–H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.