Trifluoromethylation Of Alkenes Research Articles

Synthesis of gem-Difluoroalkenes by Merging Ni-Catalyzed C-F and C-C Bond Activation in Cross-Electrophile Coupling.

By merging C-F and C-C bond activation in the cross-electrophile coupling, we developed an efficient cyanide-free synthesis of diverse functional-group-rich cyano-substituted gem-difluoroalkenes using cyclobutanone oxime esters and trifluoromethyl alkenes as precursors. Notably, this Ni-catalyzed reaction is bestowed with broad substrate scope, low catalyst loading, complete regioselectivities, and high tolerance of a wide range of sensitive functional groups. Preliminary mechanistic studies indicate that an iminyl radical-initiated C-C bond cleavage is involved in the reaction pathway.

Enantioselective Arylative Trifluoromethylation of Alkenes

Enantioselective Arylative Trifluoromethylation of Alkenes

Metal-free defluorinative arylation of trifluoromethyl alkenes via photoredox catalysis.

Literature methods to access gem-difluoroalkenes are largely limited to harsh, organometallic-based methods, and known photoredox-mediated processes are not amenable to aryl radical addition to trifluoromethyl alkenes. A metal-free, functional group-tolerant method for the preparation of benzylic gem-difluoroalkenes is described. Halogen atom abstraction from (hetero)aryl halides generates aryl radicals that undergo a defluorinative arylation of α-trifluoromethyl alkenes, tolerating electronically disparate aryl radicals and α-trifluoromethyl alkenes.

Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters.

Herein, we report a nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes through reductive decarboxylation of redox-active esters. The present reaction enables the preparation of functionalized gem-difluoroalkenes with the formation of sterically hindered C(sp3)-C(sp3) bonds under very mild reaction conditions, while tolerating many sensitive functional groups and requiring minimal substrate protection. Therefore, this method provides an efficient and convenient approach for late-stage modification of biologically interesting molecules.

Photocatalytic hydroacylation of trifluoromethyl alkenes.

Hydrofunctionalization of trifluoromethyl alkenes is highly challenging, because the nucleophilic addition is oftentimes followed by β-F elimination in this case. By the use of tetrabutylammonium decatungstate (TBADT) as a hydrogen-atom-transfer (HAT) photocatalyst for acyl C-H activation, we successfully avoid the β-F elimination in the hydroacylation of trifluoromethyl alkenes with aldehydes. This light (390 nm) promoted reaction provides a facile and efficient access to various β-CF3 ketones in complete regiocontrol with high functionality tolerance and 100% atom economy.

Visible-Light-Promoted Cascade Alkene Trifluoromethylation and Dearomatization of Indole Derivatives via Intermolecular Charge Transfer.

An intramolecular dearomatization of indole derivatives has been developed via an electron donor-acceptor complex formed between indole derivatives and Umemoto's reagent. Without the requirement of any catalyst and additive, diverse trifluoromethyl-substituted spiroindolenines bearing a quaternary stereogenic center were obtained in good yields (up to 90%) merely upon the illumination of two starting materials in 1,2-dichloroethane solution at room temperature. This work provides facile access to spiroindolenines bearing a trifluoromethyl group enabled by visible light.

A photocatalytic decarboxylative/defluorinative [4 + 3] annulation of o-hydroxyphenylacetic acids and trifluoromethyl alkenes: synthesis of fluorinated dihydrobenzoxepines

A photocatalytic decarboxylative/defluorinative [4 + 3] annulation of o-hydroxyphenylacetic acids and trifluoromethyl alkenes was developed. The reaction led to fluorinated dihydrobenzoxepines through two consecutive C–F substitutions in a CF3 group.

A four-component radical cascade trifluoromethylation reaction of alkenes enabled by an electron-donor-acceptor complex.

An efficient four-component radical cascade reaction of alkenes, enabled by an EDA complex between Togni's reagent and Hantzsch ester, has been reported. This operationally simple protocol demonstrates excellent selectivity, which is dominated by the innate polar effect, providing facile access to important δ-CF3 carbonyls under mild conditions. To further demonstrate the wide synthetic utility of this method, a three-step synthesis of CF3-naftidrofuryl has been successfully conducted.

Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies.

Two synergistic approaches to the facile assembly of complex α-trifluoromethyl alkenes are described. Using α-trifluoromethyl-β-silyl alcohols as masked trifluoromethyl alkenes, cross-coupling or related functionalization processes at distal electrophilic sites can be executed without inducing Peterson elimination. Subsequent Lewis acidic activation affords functionalized α-trifluoromethyl alkenes. Likewise, the development of a novel α-trifluoromethylvinyl trifluoroborate reagent complements this approach and allows a one-step cross-coupling of (hetero)aryl halides to access a broad array of complex α-trifluoromethyl alkenes.

Enantioselective α-C-H functionalization of amides with indoles triggered by radical trifluoromethylation of alkenes: Highly selective formation of C[sbnd]CF3 and C[sbnd]C bonds

A dual copper/chiral phosphoric acid-catalyzed asymmetric tandem remote C(sp3)-H/unactivated alkene functionalization reaction triggered by radical trifluoromethylation of unactivated alkenes for the concomitant construction of CCF3 and CC bonds was described. This approach provided an efficient method for the synthesis of valuable chiral trifluoromethylated indole derivatives with excellent regio-, chemo-, and good enantioselectivity.

Trifluoroethoxy-Coated Subphthalocyanine affects Trifluoromethylation of Alkenes and Alkynes even under Low-Energy Red-Light Irradiation.

Photoredox chemical reactions induced by visible light have undergone a renaissance in recent years. Polypyridyl dyes such as Ir(ppy)3 and Ru(bpy)3 are key catalysts in this event, and blue‐ or white‐light irradiation is required for the chemical transformations. However, it remains a challenge to achieve reactions under the lower energy of red light. We disclose, herein, that trifluoroethoxy‐coated subphthalocyanine realizes the red‐light‐driven trifluoromethylation of alkenes and alkynes with trifluoromethyl iodide in good‐to‐high yields. Perfluoroalkylations were also achieved under red light. The reaction mechanism is discussed with the support of UV/Vis spectroscopy and cyclic voltammetry of trifluoroethoxy‐coated subphthalocyanine. Light irradiation/dark study also supports the proposed mechanism.

Synthesis of gem-Difluoroallylboronates via FeCl2-Catalyzed Boration/β-Fluorine Elimination of Trifluoromethyl Alkenes.

The first ferrous chloride catalyzed boration/β-fluorine elimination of trifluoromethyl alkenes is described. Thus, a full range of gem-difluoroallylboronates were obtained in high yield under mild conditions. As an important fluorinated building block, gem-difluoroallylboronate can be readily converted into diverse difluoro-substituted species.

Metal-free di- and tri-fluoromethylation of alkenes realized by visible-light-induced perylene photoredox catalysis.

Regioselective amino-difluoromethylation of aromatic alkenes via C(sp3)-CF2H and C(sp3)-N bond formation with the C[double bond, length as m-dash]C moiety has been achieved in a single operation by visible-light photoredox catalysis. The combination of a shelf-stable and easy-to-handle sulfonium salt, S-difluoromethyl-S-di(p-xylyl)sulfonium tetrafluoroborate, and perylene catalysis is the key to the successful transformation. Furthermore, this noble metal-free protocol allows for the photocatalytic trifluoromethylation of alkenes.

Phosphine-catalyzed remote α-C–H bond activation of alcohols or amines triggered by the radical trifluoromethylation of alkenes: reaction development and mechanistic insights

An efficient radical protocol for concomitant functionalization of both alkenes and remote α-C–H bonds of alcohols or amines via 1,5(6,7)-HAT was realized in a highly controlled site-selective manner.

The dual role of thiourea in the thiotrifluoromethylation of alkenes.

Alkenes substituted with a thiourea undergo C-CF3 followed by intramolecular C-S bond formation with the Togni reagent and trifluoroacetic acid (TFA) at room temperature; thiols and thioamides are not suitable S-sources for this reaction. This anti-addition process involves a CF3 radical, and affords CF3-substituted thiazolines and thiazines for medicinal applications. A metal or photoredox catalyst is not required as the thiourea acts as a reductant, as well as serving as an S-source capable of adding to a C-centered radical. Mechanistic work comparing the reactivity of thiourea, urea, thioamide and thiol in the context of alkene trifluoromethylation demonstrates that in this series, the thiourea is unique for its ability to release CF3 radical from the Togni reagent, and to orchestrate trifluoromethylation followed by S-cyclization with both activated and unactivated alkenes.

ChemInform Abstract: Copper‐Catalyzed Trifluoromethylation of Alkenes with Redox‐Neutral Remote Amidation of Aldehydes.

AbstractSubstrates containing aldehyde and alkene functionalities undergo trifluoromethylation and amidation under mild conditions in an one‐pot manner.

Copper-Catalyzed Trifluoromethylation of Alkenes with Redox-Neutral Remote Amidation of Aldehydes.

A room-temperature and one-pot synthesis of ε-CF3-substituted amides via the copper-catalyzed trifluoromethylation of alkenes with redox-neutral remote amidation of aldehydes is described. This reaction is featured by an unprecedented 1,5-H atom abstraction from aldehydic C-H bonds by α-CF3-alkyl radicals resulting from the radical trifluoromethylation of alkenes, thus enabling a new possibility of the trifluoromethylation-initiated remote sp(2) C-H functionalization.

ChemInform Abstract: NMP and O2 as Radical Initiator: Trifluoromethylation of Alkenes to Tertiary β‐Trifluoromethyl Alcohols at Room Temperature.

AbstractA novel strategy is developed to trigger CF3 radicals by using in situ generated peroxide in NMP under O2 or air as the radical initiator.

ChemInform Abstract: Trifluoromethylation of Aromatic Alkenes by Visible‐Light‐Driven Photoredox Catalysis: Direct Conversion of Alkenes to 3‐Trifluoromethyl‐1‐propenyl and 1,3‐Bis(trifluoromethyl)‐1‐propenyl Derivatives.

Abstract Photoredox-catalyzed trifluoromethylation of alkenes using Umemoto's reagent as a CF3 source under visible light irradiation has been developed. A Ru photocatalyst, [Ru(bpy)3](PF6)2 (bpy = 2,2′-bipyridine), is useful for the present trifluoromethylation and preferable formation of 3-trifluoromethyl-1-propenyl derivatives is observed. Use of an excess amount of Umemoto's reagent readily induces double trifluoromethylation of electron-rich alkenes, resulting in 1,3-bis(trifluoromethyl)-1-propenyl skeleton.

ChemInform Abstract: Product Control in Alkene Trifluoromethylation: Hydrotrifluoromethylation, Vinylic Trifluoromethylation, and Iodotrifluoromethylation Using Togni Reagent.

AbstractThree distinct products, e.