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