Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters

The enantioconvergent radical C(sp3)-C(sp2)cross-coupling of alkyl halides with alkenylboronate esters is anappealing tool in the assemblyof synthetically valuableenantioenriched alkenes owing to the ready availability, lowtoxicity, and air/moisture stability of alkenylboronate esters.Here, we report a copper/chiral N,N,N-ligand catalytic systemfor the enantioconvergent cross-coupling of benzyl/propargylhalides with alkenylboronate esters (>80 examples) with goodfunctional group tolerance. The key to the success is the rationaldesign of hemilabile N,N,N-ligands by mounting steric hindrance atthe ortho position of one coordinating quinoline ring. Thus, thenewly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliverenantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utilityin the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.

Automated summary

In this study, a copper/chiral N,N,N-ligand catalytic system was developed for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters, providing enantiocontrol over highly reactive alkyl radicals.