Zhang, Wang, and co-workers presented a photoredox/nickel dual-catalyzed cross-coupling approach for the stereoselective synthesis of aryl/heteroaryl-C-nucleosides (Scheme 11). [21]This method allowed for the cross-coupling of various anomeric ribosyl/deoxyribosyl carboxylic acids with a wide range of aryl/heteroaryl bromides, resulting in nucleoside products in moderate-to-good yields. Both O-benzyl protected α- and β-ribosyl acids served as competent coupling partners (83a ), whereas O-benzoyl-protected ribosyl acids (83b ) suppressed the reaction presumably due to the extra coordination interaction induced by the Bz group at the C2 position with nickel catalysis. Low diastereoselectivity was noted in the reaction of O-benzyl protected β-deoxyribosyl acid (83g ), indicating that C2-substituents could be essential for controlling the anomeric configuration. Moreover, the position of bromo groups on pyridine coupling partners was observed to dramatically affect diastereoselectivity, with the variation of Br from C3 or C4 to C2 producing utterly opposite diastereoselectivity (83h, 83i, 83j ), although the exact mechanism underlying this phenomenon remains unclear. Non-anomeric furanosyl acids were also found to be effective coupling partners (83m ), whereas the pyranosyl ones failed to produce the desired products.
Mechanistically, the authors proposed that initial photoexcitation of 4CzIPN generates a potent excited state (E*red = +1.35 V vs. SCE, CH3CN) that induces an oxidative fragmentation of ribosyl/deoxyribosyl acids (EOX = +1.15 V vs. SCE, CH3CN), delivering anomeric radical84 (Scheme 11-B). Concurrently, the active Ni(0) species85 undergo oxidative addition with aryl bromides 82a , producing the electrophilic aryl-Ni(II) intermediate 85 . Subsequently, Ni(II) species 85 intercept the anomeric ribosyl radical intermediates 84 , forming an aryl-Ni(III)-ribosyl complex 86 , which subsequently undergoes reductive elimination to give the desired glycoside product 83n . Furthermore, the versatility of this method was further highlighted by synthesizing various vinyl-C-nucleosides. Notably, the coupling of a mixture oftrans - and cis -styryl bromides with ribosyl acids furnished exclusive trans -products.
Scheme 12 Nickel/photoredox catalytic synthesis of 2-deoxy-α-C-glycosylation using β-glycosyl trifluoroborates