Terminal Trifluoromethylation of Ketones via Selective C-C Cleavage of Cycloalkanols Enabled by Hypervalent Iodine Reagents.

We report the first terminal trifluoromethylation at aryl and alkyl ketones' γ, δ, ε, or more remote sites via the selective C-C bond cleavage of cycloalkanols. The noncovalent interactions between alcohols and hypervalent iodines(III) reagents were disclosed to activate both alcohols and the Togni I reagent in the dual photoredox/copper catalysis for the transformation. This reaction was scalable to the gram-scale synthesis, applicable to the structurally complex steroid trifluoromethylation, and extendable to the pentafluoroethylation.

Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis.

The alkynylbenziodoxole derivatives are recently developed alkynylation reagents in organic synthesis, which demonstrate excellent radical alkynylation reactivity in photoredox catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted to study the radical acceptor and oxidative quencher reactivity of alkynylbenziodoxoles, in which unsubstituted alkynylbenziodoxoles played balancing roles in both processes, while electron-rich benziodoxole derivatives demonstrate synthetic advantages in some cases.

Visible-light-induced alkoxyl radical generation for inert chemical bond cleavage/functionalization.

Inert chemical bond cleavage and functionalization reactions provide expedient synthetic routes and are fundamental in organic synthesis. Alkoxyl radicals enable inert chemical bond cleavages by hydrogen atom transfer and ß-fragmentation reactivity; however their further synthetic transformations and functional group compatibility are limited by traditional alkoxyl radical generation methods. Recently, visible-light-induced alkoxyl radical generation methods have emerged and led to new advancements in inert chemical bond cleavage reactions and subsequent functionalization, with excellent chemoselectivity and functional group compatibility. In this Feature Article, the generation of alkoxyl radicals by different visible-light-induced methods and their common or distinct reactivity are discussed, which are categorized by C(sp3)-H, C(sp3)-C(sp3), and C(sp3)-X bond cleavages and subsequent transformations.

Selective P-C(sp3 ) Bond Cleavage and Radical Alkynylation of α-Phosphorus Alcohols by Photoredox Catalysis.

Herein the first P-C(sp3 ) bond cleavage and radical alkynylation of α-phosphorus alcohols to construct phosphonoalkynes is reported. The phosphorus radical is generated upon P-C bond cleavage reaction via the alkoxyl radical through photoredox catalysis with cyclic iodine(III) reagents. Various arylphosphinoyl-, alkylphosphinoyl-, phosphonate-, and phosphonic amide alcohols serve as radical phosphorus precursors to construct phosphonoalkynes for the first time.

Selective Carbonyl-C(sp3 ) Bond Cleavage To Construct Ynamides, Ynoates, and Ynones by Photoredox Catalysis.

Carbon-carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl-C(sp3 ) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl-radical-enabled carbonyl-C(sp3 ) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for ß-carbonyl alkoxyl radical generation from ß-carbonyl alcohols, including alcohols with high redox potential (Epox >2.2 V vs. SCE in MeCN). ß-Amide, ß-ester, and ß-ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio- and chemoselectivity under mild reaction conditions.

Visible-Light-Induced Alkoxyl Radical Generation Enables Selective C(sp(3))-C(sp(3)) Bond Cleavage and Functionalizations.

The alkoxyl radical is an important reactive intermediate in mechanistic studies and organic synthesis; however, its current generation from alcohol oxidation heavily relies on transition metal activation under strong oxidative conditions. Here we report the first visible-light-induced alcohol oxidation to generate alkoxyl radicals by cyclic iodine(III) reagent catalysis under mild reaction conditions. The ß-fragmentation of alkoxyl radicals enables selective C(sp(3))-C(sp(3)) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols, and for the first time with linear alcohols.

Hypervalent iodine reagents enable chemoselective deboronative/decarboxylative alkenylation by photoredox catalysis.

Chemoselective C(sp(3))-C(sp(2)) coupling reactions under mild reaction conditions are useful for synthesizing alkyl-substituted alkenes having sensitive functional groups. Reported here is a visible-light-induced chemoselective alkenylation through a deboronation/decarboxylation sequence under neutral aqueous reaction conditions at room temperature. This reaction represents the first hypervalent-iodine-enabled radical decarboxylative alkenylation reaction, and a novel benziodoxole-vinyl carboxylic acid reaction intermediate was isolated. This C(sp(3))-C(sp(2)) coupling reaction leads to aryl-and acyl-substituted alkenes containing various sensitive functional groups. The excellent chemoselectivity, stable reactants, and neutral aqueous reaction conditions of the reaction suggest future biomolecule applications.