Directed Nickel-Catalyzed pseudo-Anomeric C-H Alkynylation of Glycals as an Approach towards C-Glycoconjugate Synthesis

The synthesis of complex C-glycoconjugates is presented here using a key directed nickel-catalyzed C-H alkynylation step. Thanks to a bidentate amidoquinoline-type directing group, the insertion of diverse alkynyl moieties onto the pseudo-anomeric position of glycal substrates was performed on ten examples in moderate to good yields. These platforms were used as starting substrates in a click reaction with complex azides to form original C-glycoconjugates. By this route, a C-glycosylated amino acid, a C-linked disaccharide and a C-glycosylated biotin derivative were synthesized. Preliminary conditions to remove the directing group are also proposed.