In 2022, the Koh group described a practical strategy that merges glycosyl halide with redox-active derivatives of ubiquitous carboxylic acids and amines to synthesize alkyl C-glycosides viaphotoinduced nickel-catalyzed C–C coupling (Scheme 30).[40] In the report, two approaches, decarboxylative and deaminative glycosylation, were developed. Alkyl-substituted carboxylic acids and primary amines were activated to obtain stable redox-active electrophiles [N-(acyloxy)phthalimides (NHPI esters)] and pyridium salts, which then served as alkylating agents in cross-coupling reactions. The reactions feature a wide scope of alkylating agents (NHPI esters and pyridinium salts) and glycosyl halides, delivering desired products in moderate-to-good efficiencies. Notably, the glycosylation of complicated bioactive molecules, such as biotin (218g ), dehydrocholic acid (218h ), Lipitorintermediate (218q ), and (S)-amlodipine (218r ) preceded smoothly under the developed methods. The late-stage glycosylation of amino acids and oligopeptides further underscored the robustness of the developed strategies. These methods provided efficient access to the glycosylation of a freely exposed carboxylic acid or amine motif on peptides’ C-terminus, N-terminus, or side chain, affording corresponding glycopeptide conjugates in moderate-to-good yields (218s–218aa ). In contrast to furanosyl coupling partners, pyranosyl donors gave products in generally lower yields due to the competitive β-alkoxy elimination (218ah–218al ). Notably, in most cases, moderate-to-excellent control of selectivities were achieved.
Scheme 30 Photoinduced, nickel-catalyzed method for the stereoselective assembly of C-linked glycosides and glycopeptides