Cobalt-Catalyzed Enantioselective Desymmetrization and Chemodivergent Parallel Kinetic Resolution of Unsaturated Substrates via C(sp<sup>3</sup>)–H Bond Activation
Keiji Yamada, Ryo Hashiyama, Takeshi Yasui, Yoshihiko Yamamoto
Abstract
In transition-metal-mediated chemical transformations, chemoselective or chemodivergent activation of inert C–H bonds in the presence of more reactive alkene or alkyne π-bonds is a fundamental challenge. Herein, we report the Co-catalyzed cycloisomerization of unsaturated substrates bearing a 1,6-diyne moiety via enantioselective desymmetrization and parallel kinetic resolution involving the chemoselective and chemodivergent activation of a C(sp 3 )–H bond. The enantioselective desymmetrization of symmetrical dienediynes was demonstrated using a 1,1′-binaphthyl-based chiral phosphine ligand to afford the corresponding enantioenriched 1,3-diene products. The parallel kinetic resolution of unsymmetrical substrates such as enetriynes, dienediynes, and diynenitriles was also demonstrated, where the chemodivergent activation of a C(sp 3 )–H bond and an alkene, alkyne, or nitrile π-bond was achieved. The 1,3-diene products were successfully derivatized to 5–8–5 tricyclic compounds via a central-to-helical-to-central chirality transfer involving memory of chirality.