In 2022, the Li group presented a chemoselective and diastereoselective method that enables the synthesis of aryl C-nucleotides by nickel-catalyzed cross-coupling of furanosyl acetates with aryl iodides (Scheme 19). [28] The method enabled chemoselective coupling of multihalogenated aryl iodide with furanosyl acetate (139a ), presumably owing to the higher oxidative addition rate of low-valent nickel to aryl iodide than other aryl halides in the examined solvent. The authors found that electron-rich (139b ), electron-neutral (139c ), and electron-poor aryl iodides (139d ) all coupled with equal levels of efficiency. Moreover, medicinally relevant heterocycles were also effective coupling partners in the reaction, affording the corresponding products in synthetically useful yields (139e–139g ). Limitations in scope were observed in reactions using para-dimethylaminophenyl iodide and aryl iodides bearing ketone moieties. Notably, exclusive 1,2-trans selectivity was observed when D-ribofuranosides were used as coupling partners, which could be attributed to the steric hindrance at the α-face of D-ribofuranose produced by substituents in C2 and C3. Moreover, other glycosyl acetates, such as mannofuranosyl acetate and three pyranosyl acetates, were also examined and furnished the desired aryl C-glycosides in moderate yields and with good 1,2-trans selectivities (139h–139j ), with one exception that benzyl-protected D-glucosyl acetate affords product with modest β-selectivity (139k ). To showcase the synthetic utility of this strategy, a series of late-stage functionalizations with the resulting aryl bromide was successfully realized (139la–139le , Scheme 19-A, bottom). Furthermore, a concise synthetic route of the IMPDH (inosine 5‘-monophosphate dehydrogenase) inhibitor was developed using the developed method. Remarkably, the reaction was successfully incorporated in the synthesis of BRDP-Hep (142 , Scheme 19-B), designed analogs of ADP-Hep (ADP-β-D-manno-heptose). BRDP-Hep showed better effects than the naturally occurring ADP-Hep on both the activation of NF-κB signaling and the phosphorylation induction of TIFA (TRAF-interacting protein with the forkhead-associated domain).
Scheme 19 Aryl C-nucleoside analog synthesis enabled by nickel-catalyzed cross-coupling of furanosyl acetates with aryl iodides