Free-Radical Triggered Ordered Domino Reaction: An Approach to C–C Bond Formation via Selective Functionalization of α-Hydroxyl-(sp³)C–H in Fluorinated Alcohols

Abstract

A free-radical mediated highly ordered radical addition/cyclization/(sp(3))C-C(sp(3)) formation domino reaction is developed. Three new C-C bonds are formed one by one in a mixed system. Furthermore, it represents the first example of cascade C-C bond formation via selective functionalization of α-hydroxyl-C(sp(3))-H in fluorinated alcohols.

A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

“…To our knowledge, methyl radical guided HAT has not been previously explored for photocatalytic C(sp 3 )–H functionalization 65 , 66 . As such, we set out to understand the reactivity and selectivity effects inherent to the system.…”

Free-Radical-Promoted Dehydrogenative Coupling of Polyfluorinated Alcohol with Quinone, Chromone, and Coumarin

“…One elegant resolution is hydrogen-atom-transfer (HAT) via a free-radical process since the bond dissociation energy (BDE) of the (α-OH)­C–H in fluorinated alcohol is comparable to that in general alcohol (BDE TFE = 92.5 kcal/mol; BDE ethanol = 91.5 kcal/mol) . Recently, Liu et al reported the first practical dehydrogenative hydroxyfluoroalkylation of heteroarene with polyfluorinated alcohol via a two-step HAT process (Scheme b) . Nevertheless, electron-deficient molecules are not compatible with this system since the active intermediate could not remain as the (α-OH)­C-centered radical under those conditions.…”

The Ag-promoted α-C–H arylation of alcohols

“…In 2014, Liu reported the reaction of alcohol molecules and isocyanide, and various alkyl-substituted phenanthridines were achieved. 9 …”