Koh and co-workers disclosed a nickel-catalyzed three-component synthesis of acyl C-glycoside, wherein they realized the consecutive cross-electrophile couplings of three different organohalide substrates, namely, glycosyl halides (195 ), organoiodides (197 ), and isobutyl chloroformate (196 ) (Scheme 27).[35] The reaction features a wide scope of various functionalized organoiodides and glycosyl halides, producing desired products in good yields (Scheme 27-B). Notably, high 1,2-trans selectivity was observed in coupling partners derived from furanose (198a–198n ), D-mannopyranose (198o–198q ), and L-rhamnopyranose (198v–198x ). Glycosyl halide coupling partners derived from D-glucopyranose (198r ), D-galactopyranose (198s, 198t ) and L-fucopyranose (198u ) produced good 1,2-cis selectivities. The synthetic applicability of the developed methods was further underlined by the glycosylation of oligopeptides (198y–198ae , Scheme 27-C) and the preparation of (1→2)-linked C-disaccharides (198ag–198aj , Scheme 27-D).
Preliminary mechanistic studies provide evidence supporting that the oxidation of the active ligated Ni(0) species by isobutyl chloroformate occurs preferentially, and cross-electrophile coupling between isobutyl chloroformate with organoiodides likely precedes the subsequent coupling with glycosyl chloride. Based on
Scheme 27 Nickel-catalyzed multicomponent synthesis of acyl C-glycosides