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