In 2018, Molander and co-workers described a route to synthesize non-anomeric acyl C-glycosides via a nickel/photoredox dual catalytic system, wherein a range of glycosyl-based radicals generated from 1,4-dihydropyridines efficiently coupled with functionalized carboxylic acids (Scheme 23). [32] Utilizing this protocol, a range of carboxylic acids as cross-coupling partners were coupled with pyranosyl- or furanose-based DHP, which tolerated various functionalities, for example, including free hydroxyl groups (170f–170i ), protected amino groups (170h, 170k ), and strained rings (170j, 170l, 170m, 170o, 170p ), furnishing ketone products in high efficiencies with acceptable diastereoselectivities. The utility of this transformation was highlighted by the modification of naturally occurring or medicinally relevant molecules (170t, 170v ) and difficult-to-synthesize disaccharide alkyl ketones (170u, 170x ).
Meanwhile, the Molander group reported a nickel-mediated synthesis of non-anomeric acyl C-glycosides from the coupling of two different activated carboxylic acid sources, which is driven by the synergistic interaction of electron donor-acceptor complex and nickel catalysis (Scheme 24). [33] The reaction exhibits a wide scope of various glycosyl acids and alkyl redox-active esters, producing desired products in good efficiencies. Both pyranose- and furanose carboxylic acid derivatives are competent coupling partners. Remarkably, carboxylic acid derived from uridine nucleoside afforded the desired products in good yield (173e ). Moreover, primary, secondary, and tertiary alkyl radicals were all efficiently inserted, which establishes the synthetic value of the reaction. A great functional group tolerance was also observed. For example, sulfur-containing moieties (173g, 173l, 173w, 173x ), bicyclic groups (173s–173v ), medicinally/biologically relevant motifs (173j–173m ), and strained small-size rings (173n, 173o ) were all compatible with the reaction. Notably, photoisomerization of internal alkene moiety in coupling partners was observed (173k ).
Scheme 23 Nickel/photoredox-catalyzed synthesis of non-anomeric acyl C-glycosides