1-Cl-2-deoxyglucose, which is known for facile β-H elimination of C2,
can afford aryl glycoside product (66y ) smoothly under the
developed conditions, though with 1:1 diastereoselectivity. Acceptable
1,2-trans-selectivities were also observed in glycosyl halides lacking
C5-substituents, such as arabinose (66aa ), xylose
(66ab ), and lyxose (66ac ). Heteroaryl bromides.
Thiophenes (66q ) and indoles (66r, 66s ) were also
competent coupling partners. Lastly, to demonstrate the synthetic
utility of this method, the successful synthesis of canagliflozin66ad was realized. A plausible mechanism was showcased in
Scheme 8-C. The initial step is the reductive quenching of the excited
photocatalyst [Ir(III)*] by a Hantzsch ester (HE), affording the HE
radical cation. Subsequent deprotonation of such radical cation produces
the HE radical (HE● ). This radical could
undergo either a SET process with a photocatalyst or the direct electron
transfer to glycosyl chloride to furnish the glycosyl radical67 . Concurrently, in the nickel catalytic cycle, the oxidative
addition of Ni(0) catalyst 69 into an aryl bromide 65generates aryl-Ni(II) intermediate 70 , which would be rapidly
intercepted by the glycosyl radical 67 , forming the
glycosyl-Ni(III) complex 71 . The subsequent reductive
elimination of this species would produce the desired aryl C-glycoside66 and Ni(I) species 68 . The resulting Ni(I) species
would be reduced by Ir(II) to afford active Ni(0) catalyst, while
simultaneously regenerating the ground-state photocatalyst
Ir(III).[19]
Scheme 9 Synthesis of unprotected aryl C-glycosides by
photoredox/nickel-catalyzed cross-coupling