In 2021, Hirai and co-workers presented a method to synthesize
2-deoxy-α-C-glycosylation using β-glycosyl trifluoroborates as glycosyl
radical precursors (Scheme 12). [22] This approach
allowed for the successful coupling of three different
glycosyltrifluoroborates, such as potassium glucosyltrifluoroborate,
2-deoxy-D-galactosyltrifluoroborate, and
2,6-dideoxy-D-arabinosyltrifluoroborate, with a wide range of aryl
bromides, delivering desired products in good efficiencies. Aryl
bromides were found to be more reactive than their corresponding aryl
chlorides and aryl iodides. Although the free amino group disturbed the
formation of the coupling product, the acetamide derivative was obtained
in an acceptable yield (89l ). Moreover, the coupling with
heteroaromatic halides, such as 2-bromofuran (89m ) or
3-bromothiophene (89n ), also proceeded smoothly. While
unprotected 5-indole derivative 89o was produced in only 18%
yield, the reaction with Boc-protected 5-bromoindole afforded the
desired product 89p in 53%. The authors suggested that
D-Olivose-type C-glycoside products exhibited a flipped conformation
from the standard 4C1 conformation to
a 1C4 conformation with an α-aryl
group (89t ). This is likely due to glycosyl radical reactivity
and a steric repulsion between the C1-aryl group and C3 and C5 hydrogen
atoms. Additionally, the reaction conditions were also examined withE -vinyl halides, resulting in a good efficiency of the desired
aliphatic C-glycoside (89w–89y ). Furthermore, the utility of
this method was further demonstrated through the successful synthesis of
CH2- and CHF-linked 2-deoxydisacharides (91, 92 ). A plausible
reaction mechanism was proposed, as shown in Scheme 13. The desired
products 89 are generated by the reductive elimination of
glycosyl-Ni(II)-aryl species 96 .
Scheme 13 Plausible mechanism