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