One-step Synthesis of Chiral 9,10-Dihydrophenanthrenes via Ligand-enabled Enantioselective Cascade ß,γ-Diarylation of Acids.

ABSTRACT

Pd(II)-catalyzed enantioselective C-H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd-catalyzed enantioselective cascade ß,γ-methylene C(sp3)-H diarylation of free carboxylic acids using bidentate chiral mono-protected amino thioether ligands (MPAThio), enabling one-step synthesis of a complex chiral 9,10-dihydrophenanthrenes scaffolds with high enantioselectivity. In this process, two methylene C(sp3)-H bonds and three C(sp2)-H bonds were activated, leading to the formation of four C-C bonds and two chiral centers in one pot. A plausible catalytic pathway starts with enantioselective ß,γ-dehydrogenation to form chiral ß,γ-cyclohexene. Intriguingly, this olefin serves as a norbornene-type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C-H alkylation reaction to furnish chiral 9,10-dihydrophenanthrenes along with meta-selective homocoupling products of iodoarene.