2.2. Acyl C-glycoside synthesis
The first report detailing the nickel-catalyzed synthesis of acyl C-glycosides via reductive coupling of aliphatic carboxylic acids and glycosyl halides featuring α-selectivities emerged from the Gong group (Scheme 21). [30] The initial mechanistic investigation ruled out the double oxidation reaction pathway (Scheme 21-B, left) and suggest instead a radical chain mechanism (Scheme 21-B, right). The critical role of MgCl2 in reducing Ni(II) species was also disclosed. The proposed mechanism for this transformation is shown in Scheme 21-B. The oxidative addition of acid anhydride 153b formed in situ to Ni(0) 155 affords Ni(II) species 156 . The combination of intermediate156 with an alkyl radical 159 furnishes intermediate157 , which undergoes reductive elimination affording the product 154 . It is suggested that the initial generation of intermediate 158 may arise from the halide abstraction of an alkyl halide 152 with complex 156 to afford R1C(O)-Ni(III)[OC(O)R]-X, followed by reductive elimination of acyl-X. This catalytic strategy provides access to several acyl C-glycosides derived from D-glucose (154a–154d ), D-mannose (154c-154g ), and D-galactose (154h-154l ), wherein α-anomers are the favored products across all reactions.
In 2015, the Gong group reported an improved nickel-catalyzed method for synthesizing alkyl-aryl ketones via directly coupling unactivated alkyl bromides with an excess of acids (Scheme 22). [31]This method applies to the synthesis of aroyl C-glycosides. The reductive coupling of 1-glucosyl/galactosyl bromides with benzoic acid derivatives delivered desired products in moderate-to-excellent yields with moderate diastereoselectivities (167a–167k ). Notably, α-aroyl C-mannoside was exclusively obtained in the coupling of mannosyl bromide (167l ), albeit with moderate yield. The authors suggested that the low yield obtained was presumably owing to E-2 elimination during silica column chromatography.
Scheme 21 Nickel-catalyzed synthesis of acyl C-glycosides via reductive coupling of aliphatic carboxylic acids and glycosyl halides