Oxalates as Activating Groups for Tertiary Alcohols in Photoredox-Catalyzed gem-Difluoroallylation To Construct All-Carbon Quaternary Centers

Abstract

Construction of challenging and important allcarbon quaternary centers has received growing attention. Herein, with oxalates as activating groups for tertiary alcohols, we report photoredox-catalyzed gem-difluoroallylation to construct all-carbon quaternary centers enabled by efficient tertiary radical addition to α-trifluoromethyl alkenes. This transformation shows good functional group tolerance for both α-trifluoromethyl alkenes and oxalates. Moreover, this strategy is also successfully applied to the synthesis of monofluoralkenes from the corresponding electronrich gem-difluoroalkenes and cesium tertiary alkyl oxalates under modified conditions.

Deaminative defluoroalkylation of α-trifluoromethylalkenes enabled by photoredox catalysis

“…Based on the above mechanistic investigations and previous reports, 5,12,13 a proposed mechanism of this process is depicted in Scheme 4. First, the excited state of the 4CzIPN photocatalyst oxidized imine to an imidoyl radical intermediate A , which subsequently underwent β-scission to release an alkyl radical B .…”

“…Radical addition pathways are particularly advantageous in sharp comparison due to their mild reaction conditions (Scheme 1b). The radicals are readily initiated under photocatalysis, 5 electrocatalysis, 6 or transition metal catalysis, 7 along with the cleavage of C–halogen, C–B, C–C, C–O and C–other bonds.…”

Alkyl Radical Generation via C–C Bond Cleavage in 2-Substituted Oxazolidines

“…As for the above, finding new methods for the formation of tertiary radicals and their application is of utmost importance . The photogeneration of these radicals has been only sparsely reported using Barton esters, N -(acyloxy)­phthalimides, alkyl N -phthalimidoyl oxalates, and alkyl carboxylates . Thermal generation of these intermediates involved electrophiles such as alkyl halides or alkylsulfones, despite that in some cases, the desired C­(sp 3 )–C­(sp 3 ) bond formation failed to occur …”

Asymmetric synthesis of unnatural α-amino acids through photoredox-mediated C–O bond activation of aliphatic alcohols

“…20 Under these conditions, the oxalate salts are activated through one-electron oxidation by the photocatalyst to furnish a carboxylate radical, which eliminates two molecules of CO 2 and delivers the key Cradical intermediate. Alkyl oxalate salts were successfully employed as radical precursors in numerous transformations, such as Giese-type addition reactions, [21][22][23][24] alkynylation, [25][26][27] arylation, 28,29 halogenation, [30][31][32][33] and Minisci-type manifolds, 34 as well as in total synthesis. [30][31][32][33] Additionally, these radical precursors were incorporated into several metallaphotoredox manifolds.…”