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