Ruthenium-Catalyzed Stereo- and Site-Selective ortho- and meta-C-H Glycosylation and Mechanistic Studies

C-aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium-catalyzed highly stereo- and site-selective ortho- and meta-C-Ar-H glycosylation is described. A series of C-aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N-heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho-C-Ar-H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta-C-H glycosylation was mediated by sigma-activation. Density functional theory calculations also showed that the high stereoselectivity of meta-C-Ar-H glycosylation was due to steric hindrance.

Automated summary

This paper describes a new ruthenium-catalyzed method for the ortho- and meta-C-Ar-H glycosylation, resulting in the synthesis of various C-aryl pyranosides and furanosides. The method shows broad substrate scope and compatibility with different N-heterocyclic directing groups. Mechanistic studies suggest different pathways for ortho- and meta-C-Ar-H glycosylation, and density functional theory calculations provide an explanation for the high stereoselectivity observed in the meta-C-Ar-H glycosylation.