Domino meta-C-H Ethyl Glycosylation by Ruthenium(II/III) Catalysis: Modular Assembly of meta-C-Alkyl Glycosides.

Glycosyl anomeric radical addition reactions have been well-explored and proved efficient for the C-alkyl glycosides synthesis, but multicomponent Domino transformations for the rapid and controllable construction of structurally diversified C-alkyl glycosides in a single step are still rare. In contrast, we, herein, report a ruthenium(II)-catalyzed Domino meta-C-H ethyl glycosylation, enabling the construction of challenging meta-C-alkyl glycosides. Our ruthenium(II) catalysis was reflected by the mild reaction condition, exclusive meta-site selectivity and high levels of anomeric selectivity. In addition, the ruthenium(II)-catalyzed Domino meta-C-H glycosylation allowed for the synthesis of versatile 1,2-trans-C-alkyl glycosides with commercially available vinyl arenes, acrylates and easily accessible glycosyl bromides.

Late-stage C-H Functionalization of Tryptophan-Containing Peptides with Thianthrenium Salts: Conjugation and Ligation.

Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging, among other applications. Herein, we report on a palladium-catalyzed C-H arylation of tryptophan-containing peptides with readily accessible and modular arylthianthrenium salts. Under exceedingly mild reaction conditions, the late-stage diversification of structurally complex peptides was accomplished. The tunability and ease of preparation of arylthianthrenium salts allowed the expedient stitching of tryptophan-containing peptides with drug, natural product, and peptidic scaffolds by forging sterically congested biaryl linkages. The robustness of the palladium catalysis regime was reflected by the full tolerance of a plethora of sensitive and coordinating functional groups. Hence, our manifold enabled efficient access to highly decorated, labelled, conjugated, and ligated linear and cyclic peptides.

Remote C-H Glycosylation by Ruthenium(II) Catalysis: Modular Assembly of meta-C-Aryl Glycosides.

The prevalence of C-aryl glycosides in biologically active natural products and approved drugs has long motivated the development of efficient strategies for their selective synthesis. Cross-couplings have been frequently used, but largely relied on palladium catalyst with prefunctionalized substrates, while ruthenium-catalyzed C-aryl glycoside preparation has thus far proven elusive. Herein, we disclose a versatile ruthenium(II)-catalyzed meta-C-H glycosylation to access meta-C-aryl glycosides from readily available glycosyl halide donors. The robustness of the ruthenium catalysis was reflected by mild reaction conditions, outstanding levels of anomeric selectivity and exclusive meta-site-selectivity.