Glycosyl Radical-Based, 1,2-trans-Selective Synthesis of C-Aryl Glycosides from Glycals Enabled by Photoredox PCET/Nickel-Dual Catalysis.

Abstract

We report a glycosyl radical-based, 1,2-trans-selective synthesis of C-aryl glycosides of 2-deoxy-2-amino-sugars from glycals via photoredox PCET/Ni dual catalysis. Mechanistic studies indicate that glycosyl radical formation involves the generation of an N-radical through a proton-coupled electron transfer (PCET) process, followed by its addition to the glycal. This protocol features: a) the use of an inexpensive organic photosensitizer and readily available glycals and aryl bromides; b) good functional group tolerance for both aryl bromides and glycal substrates; c) excellent diastereoselectivity, with exclusive formation of the 1,2-trans C-glycosides in all cases. Furthermore, the reaction could be conducted on gram-scale and is suitable for the late-stage modification of complex molecule. Deprotection experiments demonstrated complementary stability profiles between the oxazolidinone protecting group employed here and the dihydrooxazole group in our previous work.