configured products predominantly, the α-D-mannose-derived bromides (3r , 3x ) favored α-products. Unfortunately, 2-deoxyglucose failed to yield products due to the decomposition of glycosyl bromide and chloride. When furanose derivatives were investigated, D -ribofuranose-derived chloride produced the desired product in low yield with high β-selectivity (3u ), although D -arabinofuranose-derived bromide resulted in significant hydrolysis products. The authors found that ligand could play a significant role in the stereochemical outcome of the reaction. Take the synthesis of phenyl C-mannoside as an example. They found that by using tBuTerpy, a 2.9:1 ratio of α/β isomers was produced (3q ). However, good-to-excellent α-selectivities were achieved using Terpy and PyBox in good efficiency (3q ). These results suggested that different ligand catalysts may function by different mechanisms, with the observed selectivity indicative of a stereochemical mismatch between the ligated nickel catalysis and carbohydrate substrates. Catalyst such as PyBox/Ni(COD)2, which is smaller, provided good α-arylation selectivities likely viasubstrate control. Mechanistically, the authors proposed two variants of the nickel-catalyzed Negishi cross-coupling pathway. As shown in Scheme 1-C, the reaction could occur either by halogen abstraction (inner sphere, top) or by a single electron transfer (outer sphere, bottom) mechanism.[9] Lastly, the authors demonstrated the utility of this protocol with the successful total synthesis of Salmochelin SX (8 , Scheme 1-B).
Scheme 2 α-Vinyl/Aryl C-glycosides via nickel-catalyzed reductive couplings