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

Article abstract of DOI:10.1021/jacs.9b08238

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.