In 2018, the Molander group reported a protocol for accessing
non-anomeric aryl C-glycosides via nickel/photoredox dual
catalysis (Scheme 4). [13] This method involved
the use of mono-saccharide DHPs (1,4-dihydropyridine derivatives) as
radical precursors, which gave the best results when used in conjunction
with 4-CzIPN photocatalyst, NiBr2●dme, and dMeOby as the ligand. The
reaction proved to be tolerant of a range of pentose-derived DHPs and
(hetero)aryl bromide partners, resulting in moderate-to-high yields of
products (34a–34f, 34l–34n, 34q ). Diastereoselectivity was
found to be excellent with certain furanosyl units, likely due to the
steric interactions with the adjacent substituent; this was evidenced by
comparing the effect of the vicinal substituent, where small
substituents, such as MeO (34b ) and F (34c ), gave low
diastereoselectivity, whereas sterically encumbered, TBS-protected
moieties gave high diastereoselectivity (34d ). Additionally,
good-to-excellent diastereoselectivities were observed in
D-ribofuranose-derived DHPs. The more flexible radicals generated from
hexosyl DHPs yielded lower diastereoselectivities (34g ).
Notably, a pinacol boronic ester was well accommodated in the reaction,
allowing for late-stage diversification (34j ). Furthermore,
electron-neutral aryl bromides gave diminished yields, likely due to a
challenging oxidative addition (34l ). To showcase the potential
of this method, the successful C-glycosylation of functionally dense
aryl bromides at a late stage was achieved (34o-34q ).
Scheme 4 Synthesis of non-anomeric aryl C-Glycosides via
nickel/photoredox dual catalysis