Catalytic Multicomponent Synthesis ofC‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

Abstract

C-Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross-coupling strategies to secure these molecules often relied on two-component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre-synthesized or generated in situ) under transition metal or dual catalysis to forge a CÀ C bond. Here, we disclose a three-component Ni-catalyzed reductive regime that facilitates the chemoselective union of glycosyl halides, organoiodides and commercially available isobutyl chloroformate as a CO surrogate. The method tolerates multiple functionalities and the resulting products are obtained in high diastereoselectivities. Theoretical calculations provide a mechanistic rationale for the unexpectedly high chemoselectivity of sequential crosselectrophile couplings. This approach enables the expeditious assembly of difficult-to-synthesize C-acyl glycosides, as well as late-stage keto-glycosylation of oligopeptides.

Diversification of Glycosyl Compounds via Glycosyl Radicals

“…In 2022, Koh and co‐workers developed a nickel‐catalyzed consecutive XEC approach to access stereodefined acyl C ‐glycosyl compounds from glycosyl chlorides, organoiodides and commercially available isobutyl chloroformate (Scheme 17). [19b] The reaction demonstrated extraordinary chemoselectivity, which was supported by control experiments and competition studies. Various alkyl and aryl iodides were competent coupling partners for pyranosyl and furanosyl chlorides, affording the desired acyl C ‐glycosyl compounds ( 65 and 66 ) in good yields and excellent anomeric selectivity, with the exception of glucose‐derived 65 c .…”

C‐Glycoside Synthesis Enabled by Nickel Catalysis

“…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). [ 38 ] 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 ).…”

C-Glycoside Synthesis Enabled by Nickle Catalysis

“…Scheme 25 Synthesis of acyl C-glycoside via nickel/photoredox catalyzed coupling of DHP esters with carboxylic acids image27.emf available at https://authorea.com/users/596681/articles/630065-c-glycosidesynthesis-enabled-by-nickle-catalysis Based on literature precedents and a previous radical trapping experiment, [15] 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 ).…”