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