Mechanistically, the reaction pathway was proposed to start from the photoexcitation of 4CzIPN photocatalyst, followed by reductive quenching with the saccharide-derived DHP 35 (Scheme 4-B). This results in the formation of a radical cation 36 , giving rise to a saccharyl radical 38 and an aromatized pyridine derivative from a rapid radical fragmentation. The saccharyl radical 38 then adds to the Ni(0) catalyst 43 , forming a saccharyl-Ni(I) complex 39 . Subsequently, oxidative addition of this complex with an aryl bromide takes place, leading to the Ni(III) species41 . This species then undergoes a reductive elimination, yielding a non-anomeric aryl C-glycoside product 34 and a Ni(I) species 42 that is in turn reduced to Ni(0) with the reduced 4CzIPN, thus regenerating the active catalysts. It is worth noting that the diastereomeric ratios (d.r.) of the product can be influenced by both the saccharide backbone and the aromatic partner. Previous mechanistic studies indicated high valence Ni(III) 41ultimately dictates the observed diastereoselectivity after the irreversible reductive elimination. [14] Thus, to improve the d.r. values, the authors tested the use of bidentate and tridentate ligands with both Ni(0) and Ni(II) species. Modifying the bipyridine backbone by replacing electron-donating methoxy groups with bulkier, less electron-rich tert-butyl substituents proved to be successful in achieving excellent diastereoselectivity (Scheme 4-C). Likewise, phenanthroline yielded >20:1 d.r. for34l , whereas dtbbpy (4,4‘-di-tert-butyl-2,2‘-bipyridine) did not show any improvement. A general approach for the coupling of saccharyl radicals with aryl and heteroaryl bromides has not yet been established.
Scheme 5 Synthesis of aryl/heteroaryl-C-glycosides via the nickel-catalyzed cross-coupling of glycosyl ester with aryl bromide