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 ),
LipitorⓇintermediate (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