Glycosyl-Radical-Based Synthesis of C-Alkyl Glycosides via Photomediated Defluorinative gem-Difluoroallylation

Abstract

We have developed a stereoselective, glycosyl radical-based method for the synthesis of C-alkyl glycosides via a photomediated defluorinative gem-difluoroallylation reaction. We demonstrate for the first time that glycosyl radicals, generated from glycosyl bromides, can readily participate in a photomediated radical polar crossover process, affording a diverse array of gem-difluoroalkene containing C-glycosides. Notable features of this method include scalability, mild conditions, broad substrate scope, and suitability for the late-stage modification of complex molecules.

Catalytic Multicomponent Synthesis ofC‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

“…Additional radical trapping studies in the presence of an exogenous acrylate 14 delivered the expected cross-coupling products (5 or 6) as well as the Giese reaction [32][33][34][35][36][37][38][39][40] adduct of 1 (15), supporting the possible generation of glycosyl radical [41][42][43][44][45][46][47][48][49][50][51][52][53][54] intermediates during the course of the reaction (Scheme 3C). Radical clock study using alkyl iodide 16 containing a pendant terminal olefin also led to a mixture of 17 and 18.…”

Copper‐Catalyzed Stereoselective Borylation and Palladium‐Catalyzed Stereospecific Cross‐Coupling to Give Aryl C‐Glycosides

“…The stereoselectivity for 1 a – c , 1 g , 1 i , 1 j is explained by direct borylation of the radical A by a borylcopper(II) complex (radical pathway in Scheme 1). On the other hand, the high β‐selectivity of 1 d – f , 1 h with an equatorial OBn group at C‐2 is not explained by the direct borylation of the radical A , since glycosyl radicals with an equatorial OBn group at C‐2 were also reported to show α‐selectivity [19d,f,g] . As glycosylcopper intermediates were proposed for Cu‐mediated α‐selective O ‐glycosidation [20] and β‐selective S ‐glycosidation [21] of glycosides with an alkoxyl group at C‐2, selective formation of the β‐glycosylcopper complex B from the glycosyl radical A followed by reductive elimination affording β‐glycosyl boronates is a plausible mechanism (organocopper pathway in Scheme 1).…”

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

“…The good functional group tolerance renders significant strategies for the chemoselective biomolecule modification. In recent years, a series of C ‐glycosylation strategies have been reported [13a–f] . Notably, in the reactions, the stereoselectivity of the C ‐glycosylation was dominantly determined by the conformation of the glycosyl radical intermediate [13h–k] .…”