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The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2)−CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3)−CF3 bonds remains considerably restricted. In this work, we describe an efficient and site‐specific deaminative trifluoromethylation reaction of aliphatic primary amines to afford the corresponding alkyl trifluoromethyl compounds. The reaction proceeds at room temperature with readily accessible N‐anomeric amide (Levin's reagent) and bench‐stable bpyCu(CF3)3 (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Remarkably, the method can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules. Experimental mechanistic studies were conducted, and a radical mechanism is proposed, wherein the dual roles of Grushin's reagent have been elucidated. [ABSTRACT FROM AUTHOR]

The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2)−CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3)−CF3 bonds remains considerably restricted. In this work, we describe an efficient and site‐specific deaminative trifluoromethylation reaction of aliphatic primary amines to afford the corresponding alkyl trifluoromethyl compounds. The reaction proceeds at room temperature with readily accessible N‐anomeric amide (Levin's reagent) and bench‐stable bpyCu(CF3)3 (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Remarkably, the method can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules. Experimental mechanistic studies were conducted, and a radical mechanism is proposed, wherein the dual roles of Grushin's reagent have been elucidated. [ABSTRACT FROM AUTHOR]

We herein describe a protocol to synthesize trifluoromethylated alkyl boronates from alkenes by the mutual activation of the Togni II and the bis(catecholato)diboron reagents in the absence of any catalyst and additives. This reaction enables synthesizing a series of trifluoromethylated alkyl boronates using unactivated alkenes, including natural products and drug derivatives, in a regioselective manner. Moreover, the synthetic utility of the boronic ester present in the product allows access to a range of trifluoromethyl containing compounds. The radical trapping and gas detection experiments reveal that the more Lewis acidic diboron reagent determines the rapid formation of trifluoromethyl and boron centered radicals. [ABSTRACT FROM AUTHOR]

The difunctionalizative trifluoromethylation of unsaturated C−C bonds is a highly useful and efficient method for the synthesis of trifluoromethyl compounds with attractive architectures from simple feedstocks, allowing the introduction of the CF3 group along with a wide variety of substituents either inter‐ or intramolecularly. Given that trifluoromethyl molecules are increasingly used as promising bioactive species in the design of new drugs and agrochemicals, difunctionalizative trifluoromethylation has been extensively studied during the last decade. This review focuses on reactions proceeding via the simultaneous formation of C−heteroatom (O, N, S, Se, B) and C−H bonds, as these reactions provide useful CF3 group‐containing building blocks. To identify the trends and prospects of the evolution of this methodology, we systematically describe the variants of these types of reactions and provide a more general view of reaction conditions, modes, and mechanisms. The presented comprehensive survey enables the categorization of reactions into those that are synthetically mature and those with room for further development. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Trifluoromethyl group is one of the most frequently available and promising functional groups in pharmaceutical, agrochemical as well as material molecules. Developing synthetic methods for the synthesis of trifluoromethyl functionalized compounds by trifluoromethylation reactions occupies significant position in modern organic chemistry. On the other hand, as a typical tool of sustainable synthesis, transition metal‐free synthesis possesses unique advantages in atom economy, easy product purification as well as excellent eco‐tolerance. Consequently, transition metal‐free trifluoromethylation reactions constitute the most important approaches for accessing trifluoromethylated molecules. Herein, the advances in the transition metal‐free C—H trifluoromethylation reactions are reviewed for the first time. According to the updated state‐of‐art, both the catalytic reactions by conventional heating chemistry and the more sustainable photocatalysis are included, covering the trifluoromethylation reactions of C(sp3)–H bond, aromatic C(sp2)–H bond as well as the non‐aromatic C(sp2)–H bond in different substrates over the last five years (2017—2021). [ABSTRACT FROM AUTHOR]

This study reports an oxytrifluoromethylation method for construction of oxazoles and furans motif and the concurrent incorporation of a 2,2,2‐trifluoroethyl group at the aromatic C5‐position. High‐valent copper(III) trifluoromethyl compounds are crucial to this reaction that induces oxy‐trifluoromethylation of alkynes with a pendant amide/enol group functioning as the oxygen‐nucleophile. A wide substrate scope is demonstrated with high efficiency and with broad functional group tolerance. Late‐stage functionalization of dehydrocholic acid, a complex drug compound, is accomplished to show the potential of this method for practical drug design. [ABSTRACT FROM AUTHOR]

A general and selective method is developed that allows direct vinylic C−H bond trifluoromethylation of 1,1‐diarylalkenes by a high‐valent copper(III) trifluoromethyl complex, producing biologically active trifluoromethylated alkenes (as well as trifluoromethylated carbocyclic compounds). This fundamental reactivity of Cu(III)−CF3 compounds has thus far been unknown. The presence of a tertiary amine is crucial to this reaction, acting as both a weak base and a single electron transfer (SET) promoter to abstract the vinylic hydrogen. This method starts from bulk olefins under cost‐effective conditions (without the need for external noble metal photocatalyst or stoichiometric amounts of oxidant), and thus is valuable for practical and sustainable applications. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of vinyl trifluoromethyl compounds from α, β‐unsaturated carboxylic acids and CF3SO2Na has been developed. This electrochemical decarboxylative trifluoro‐methylation was found to be highly stereoselective and afforded products in good yields with wide substrate scope under metal‐free and external chemical oxidant‐free conditions. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Transition-metal-free visible-light-induced trifluoromethylation of imidazopyridines. • Anthraquinone-2-carboxylic acid as the photo-organocatalyst. • Photoredox catalyzed cyclization generate trifluoromethyl radical. Abstract A transition-metal-free, visible-light-induced trifluoromethylation of imidazo[1,2- a ]pyridines has been developed at mild conditions by employing cheap and commercially available anthraquinone-2-carboxylic acid (AQN-2-CO 2 H) as the photo-organocatalyst, and Langlois reagent as the trifluoromethylating reagent. A series of 3-(trifluoromethyl)imidazo[1,2- a ]pyridine derivatives with broad functionalities could be conveniently and efficiently obtained by direct regioselective functionalization. [ABSTRACT FROM AUTHOR]

Direct α‐Trifluoromethylation of acetophenone derivatives was achieved by using trifluoroacetic anhydride (TFAA) as the trifluoromethyl source and pyridine‐N‐oxide (Py−O) as activator and oxidant under visible light irradiation and tris‐(2,2′‐bipyridine)ruthenium(II) hexafluorophosphate (Ru(bpy)3(PF6)2) as the photocatalyst. Different acetophenone derivatives could be converted to the corresponding α‐CF3 derivatives with high selectivity. Extensive mechanistic investigation revealed the formation of vinyl trifluoroacetate as the key intermediate for this transformation. [ABSTRACT FROM AUTHOR]

A simple protocol for the UV light irradiated preparation of heteroaryl trifluoromethyl thioethers from disulfides and inexpensive, environmentally sodium triflinate (CF3SO2Na) has been developed. The features of simple and clean reaction conditions, in moderate to good yields, and broad substrate scope render this new approach synthetically attractive for the preparation of potentially pharmaceutically active compounds. A trifluoromethylation of diheteroaryl disulfides with CF3SO2Na to afford the trifluoromethyl thioethers derivatives. The conversion has good functional group compatibility, without external photocatalyst, generating the corresponding products in moderate to good yields under mild conditions, and the disulfide is fully utilized while constructing two S‐CF3 bonds. [ABSTRACT FROM AUTHOR]

A clean, transition metal‐ and oxidant‐free photochemical protocol was described for the direct trifluoromethylation of coumarins with Togni reagent. The reaction proceeded smoothly under mild condition to afford regioselective 3‐trifluoromethyl coumarins, moreover novel bis‐trifluoromethylated coumarins were formed. Preliminary bioactivity evaluation on some products showed potential antifungal activities. Free, free, free! A clean, transition metal‐ and oxidant‐free photochemical protocol was described for the direct trifluoromethylation of coumarins with mild reaction conditions and good substrate tolerance. [ABSTRACT FROM AUTHOR]

Abstract: The diastereoselective trifluoromethylation of chiral α,β‐unsaturated N‐tert‐butanesulfinyl ketimines with Ruppert‐Prakash reagent (TMSCF3) has been attained, which provided a convenient and straightforward method for the asymmetric synthesis of structurally diverse α‐tertiary trifluoromethyl allylic amines in high yields and with excellent diastereoselectivities (dr up to > 99:1). The stereochemical outcome of the present diastereoselective trifluoromethylation of the α,β‐unsaturated N‐tert‐butanesulfinyl ketimines suggested that a cyclic six‐membered transition state is involved in the reaction, which is remarkably different from that of the trifluoromethylation of N‐tert‐butanesulfinyl aldimines. [ABSTRACT FROM AUTHOR]

Abstract: Organo halides and their derivatives have received much attention in both the design and development of new synthetic reagents, drugs, and functional materials. In this review, we provide a comprehensive summary of recent advances and strategies in the halo‐functionalization of diazo compounds, including halogenation, dihalogenation, dihaloolefination, trifluoromethylation, trifluoromethylthiolation, and trifluoromethoxylation, using diverse halogenating agents. Special emphasis is placed on the challenges and achievements of these halogenation strategies. For selected examples, mechanisms leading to unusual reactivities and selectivities are discussed in detail to show the impressive and unique properties of these halogenation reactions. Furthermore, we hope to encourage the scientific community to explore the benefits of using diazo compounds as a straightforward and step‐economic alternative approach to the construction of carbon‐halogen bonds. [ABSTRACT FROM AUTHOR]

Trifluoromethylation enabled by photochemistry enriched the toolbox of synthetic chemists, to allow the simple and efficient installation of CF3 groups in organic molecules. Herein, we report a cascade addition/annulation reaction of 2‐isocyanobiphenyls towards the synthesis of 6‐trifluoromethylphenanthridines. It is proposed that this reaction is triggered by the CF3 radical generated from photoexcited 2,3‐butanedione (diacetyl) and sodium triflinate. In contrast to classical aromatic trifluoromethylations, this work does not require any additives and features formation of a C–CF3 bond with concomitant construction of an aromatic scaffold. [ABSTRACT FROM AUTHOR]

Abstract: A new protocol has been developed for the synthesis of α-trifluoromethyl ketones via organocatalyzed decarboxylative trifluoromethylation of β-ketoacids with Togni’s reagent. Among various simple amine catalysts, primary amines and secondary amines were identified to be more effective than tertiary amines, with piperazine being the most effective. Mechanistic investigations suggested that the primary or secondary amine-catalyzed reactions proceed mainly through trifluoromethylation of an enamine intermediate, which is more effective than the tertiary amine-catalyzed pathway that involves an enol intermediate. By using piperazine as the optimal organocatalyst, various β-ketoacids, including the sterically hindered α,α-disubstituted ones, were converted into the corresponding α-trifluoromethyl ketones in good yields. This research not only provides a useful strategy for the efficient synthesis of a wide range of α-trifluoromethyl ketones under mild conditions, but also constitutes one of the few studies on decarboxylative alkylation of β-ketoacids, which can intrigue further exploitation on organocatalyzed asymmetric decarboxylative alkylation reactions.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Abstract: While acid fluorides can readily be made from widely available or biomass‐feedstock‐derived carboxylic acids, their use as functional groups in metal‐catalyzed cross‐coupling reactions is rare. This report presents the first demonstration of Pd‐catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF3). The strategy relies on a Pd/Xantphos catalytic system and the supply of fluoride for transmetalation through intramolecular redistribution to the the Pd center. This strategy eliminated the need for exogenous and detrimental fluoride additives and allows Xantphos to be used in catalytic trifluoromethylations for the first time. Our experimental and computational mechanistic data support a sequence in which transmetalation by R3SiCF3 occurs prior to decarbonylation. [ABSTRACT FROM AUTHOR]

The copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes as the fluoride sources for the synthesis of trifluoromethylated or trifluoromethylthiolated compounds are reviewed. Compared with the ordinary fluoride reagents, the addition of reactant species in the reaction systems of copper trifluoromethyl or trifluoromethylthio complexes were less, so the reaction systems are relatively simple and easy to operate. In most cases, the trifluoromethylated or trifluoromethylthiolated products were obtained in moderate to excellent yields. GRAPHICAL ABSTRACT: SYNOPSISThis mini-review highlights recent developments in trifluoromethylation or trifluoromethylthiolation using copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes, such as (phen) $$\hbox {CuCF}_{3}$$ , (phen) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , (bpy) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , $$(\hbox {Ph}_{3}\hbox {P})_{3}\hbox {CuCF}_{3}$$ , and (bpy) $$\hbox {CuSCF}_{3}$$ . [ABSTRACT FROM AUTHOR]

The first example of a magnesium-catalyzed direct trifluoromethylation of 3-substituted oxindoles using an electrophilic hypervalent iodine reagent is reported. The reaction proceeds under unprecedented mild conditions leading to the formation of an all-carbon quaternary center in oxindoles in high chemical yield and demonstrates excellent functional group tolerance. In addition to trifluoromethyl, other perfluoroalkyl groups can be introduced with similar level of efficacy. Mechanistic investigations are consistent with the involvement of a radical pathway. The chemical versatility of the obtained products is further illustrated through their conversion in situ into valuable organofluorine building blocks, making the protocol more widely applicable. [ABSTRACT FROM AUTHOR]

Disclosed herein is a novel, redox-neutral protocol for the visible-light-induced radical alkynylation of unactivated olefins. The intramolecular migration of an alkynyl group, by cleaving an inert C−C σ bond, is realized for the first time. A wide range of synthetically useful trifluoroethylated linear alkynes are readily obtained under mild reaction conditions. [ABSTRACT FROM AUTHOR]

The reaction of hexafluoropropene trimers with Ruppert-Prakash (CF 3 SiMe 3 ) reagent gave highly congested perfluoroolefins such as the mono-trifluoromethylation products F -2,4-dimethyl-3-isopropyl-2-pentene ( P1 ) and E - and Z -forms of F -4,4-dimethyl-3-isopropyl-2-pentene ( 2 E and 2 Z ), and the bis-trifluoromethylation product F -2,4,4-trimethyl-3-isopropyl-2-pentene ( 3 ). The E -form of 2 was also comprised of two rotamers. Various aprotic polar solvents were surveyed for this reaction, and it was found that the aprotic solvent DMI has a unique solvent effect to selectively give the mono-trifluoromethylated perfluoroolefin P1 , a precursor for the persistent perfluoroalkyl radical F -3-isopropyl-2,4-dimethyl-3-pentyl, in very high yield. [ABSTRACT FROM AUTHOR]

In the presence of trifluoromethylsulfonium reagents, boronate complexes derived from 2-lithio furan and non-racemic secondary and tertiary alkyl or aryl boronic esters undergo deborylative three-component coupling to give the corresponding 2,5-disubstituted furans with excellent levels of enantiospecificity. The process proceeds via the reaction of boronate complexes with a trifluoromethyl radical, which triggers 1,2-metallate rearrangement upon single-electron oxidation. Alternative electrophiles can also be used in place of trifluoromethylsulfonium reagents to effect similar three-component coupling reactions. [ABSTRACT FROM AUTHOR]

The introduction of fluorine groups to pharmaceutical compounds can have a dramatic effect on the lipophilicity and metabolic stability of the molecule in vivo. Around 20 % of drugs contain at least one fluorine atom. The trifluoromethyl group is known to have beneficial effects and can dramatically affect the biological activity when substituted for a methyl group, for example. In any case, the direct and late-stage introduction of a trifluoromethyl group is a powerful transformation in the tool box of the medicinal chemist. The use of methyl fluorosulfonyldifluoroacetate (MFSDA) as a relatively inexpensive reagent for trifluoromethylation was first reported in 1989; however, in our opinion it has been somewhat underutilised. Herein, a comprehensive review of trifluoromethylation using MFSDA is reported, which we hope will further expose readers to this useful reagent. [ABSTRACT FROM AUTHOR]

We report an efficient oxidative radical desulfur-fragmentation and reconstruction of enol triflates for the synthesis of α-CF3 ketones. Preliminary mechanistic studies disclosed that oxidative fragmentation to release a CF3 radical from the triflyl group of enol triflate and subsequent addition of the CF3 radical to another enol triflate form the desired α-CF3 ketones. This method provides a new approach to α-CF3 ketones, featuring the utilization of catalytic amount of oxidants, broad substrate scope, and potential to control the regioselectivity. [ABSTRACT FROM AUTHOR]

A novel method for the conversion of vinyl triflates into α-trifluoromethylated ketones in the absence of external trifluoromethyl sources is described. This process accomplishes an efficient migration of the trifluoromethyl group of the triflate to the α-position in the ketone through a radical process. The reaction proceeds by the addition of a trifluoromethyl radical to the vinyl triflate and subsequent fragmentation of the trifluoromethane sulfonyl radical. Based on this reaction, a one-pot two-step procedure for the trifluoromethylation of ketones was developed. The method presented herein also allows the transfer of perfluoroalkyl groups from vinyl perfluoroalkanesulfonates, which are readily accessible from alkynes and perfluoroalkanesulfonic acids. [ABSTRACT FROM AUTHOR]

Reported herein is the one-pot synthesis of trifluoromethylated amines at room temperature using the bench-stable (Me4N)SCF3 reagent and AgF. The method is rapid, operationally simple and highly selective. It proceeds via a formal umpolung reaction of the SCF3 with the amine, giving quantitative formation of thiocarbamoyl fluoride intermediates within minutes that can readily be transformed to N-CF3. The mildness and high functional group tolerance render the method highly attractive for the late-stage introduction of trifluoromethyl groups on amines, as demonstrated herein for a range of pharmaceutically relevant drug molecules. [ABSTRACT FROM AUTHOR]

A series of trifluoromethyl-containing heterocycles, like indene and dihydroquinolinone or dihydrocoumarin-fused tetracyclic compounds have been prepared using copper-catalyzed cascade reaction of benzene-tethered 1,7-enynes. A study of the mechanism indicated that radical trifluoromethylation and sequential 6-exo-dig/ 5-endo-trig bicyclization processes were involved in this protocol. Moreover, some selected products showed certain fungicidal activities against 14 kinds of plant fungi which means that these functionalized tetracyclic compounds might be used in the agrochemical field. [ABSTRACT FROM AUTHOR]

A direct and convenient method has been developed for the synthesis of optically active pyrrolidines bearing a quaternary stereogenic center containing a CF3 group at the C-3 position of the pyrrolidine ring. The synthesis system, CuI/Si-FOXAP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with β-CF3-β,β-disubstituted nitroalkenes, provides pyrrolidines with high diastereoselectivities (up to >98:2 d.r.) and excellent enantioselectivities (up to >99.9 ee) and performs well for a broad scope of substrates under mild conditions. [ABSTRACT FROM AUTHOR]

Photocatalytic radical trifluoromethylation strategies have impacted the synthesis of trifluoromethyl-containing molecules. However, mechanistic aspects concerning such transformations remain poorly understood. Here, we describe in detail the mechanism of the visible-light photocatalytic trifluoromethylation of N-methylpyrrole with gaseous CF3I in flow. The use of continuous-flow microreactor technology allowed for the determination of different important parameters with high precision (e.g., photon flux, quantum yield, reaction rate constants) and for the handling of CF3I in a convenient manner. Our data indicates that the reaction occurs through a reductive quenching mechanism and that there is no radical chain process present. [ABSTRACT FROM AUTHOR]

Trifluoromethylation reactions have recently received increased attention because of the beneficial effect of the trifluoromethyl group on the pharmacological properties of numerous substances. A common method to introduce the trifluoromethyl group employs the Ruppert-Prakash reagent, that is, Si(CH3)3CF3, together with a copper(I) halide. We have applied this method to the trifluoromethylation of aromatic alkynes and used electrospray-ionization mass spectrometry to investigate the mechanism of these reactions in tetrahydrofuran, dichloromethane, and acetonitrile as well as with and without added 1,10-phenanthroline. In the absence of the alkyne component, the homoleptic ate complexes [Cu(CF3)2]− and [Cu(CF3)4]− were observed. In the presence of the alkynes RH, the heteroleptic complexes [Cu(CF3)3R]− were detected as well. Upon gas-phase fragmentation, these key intermediates released the cross-coupling products R−CF3 with perfect selectivity. Apparently, the [Cu(CF3)3R]− complexes did not originate from homoleptic cuprate anions, but from unobservable neutral precursors. The present results moreover point to the involvement of oxygen as the oxidizing agent. [ABSTRACT FROM AUTHOR]

A direct regioselective C sp2 –H trifluoromethylation of pyrimidinones and pyridinones using CF 3 SO 2 Na/Mn(OAc) 3 to afford 5-trifluoromethyl pyrimidinones and 3-trifluoromethyl pyridinones in moderate to good yields was described. The reaction showed that the steric hindrance due to bulky groups adjacent to the position of attack by the trifluoromethyl radical had important influence on the yield. [ABSTRACT FROM AUTHOR]

A copper-catalyzed cascade reaction involving trifluoromethylation of acrylamides coupled with ring closure and indole dearomatization is reported. This facile transformation was highly regioselective and proceeded under mild conditions, allowing efficient access to trifluoromethyl-substituted spiro[indole-3,3′-pyrrolidine] derivatives, which are of increasing interest to the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] ( 1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] ( 2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter ( ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state. [ABSTRACT FROM AUTHOR]

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3-dimethyl-1-(trifluoromethyl)-1 λ3,2-benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S-centred nucleophile thiophenol, their free energies of activation, Δ F≠, lying between 9 and 15 kcal mol−1. We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1, thus generating negative charge on the sulfur atom in the rate-determining step. The formation of a CF3 radical can be thermally induced by internal dissociative electron transfer, its activation energy, Δ F≠, amounting to as little as 10.8 and 2.8 kcal mol−1 for reagent 1 and its protonated form 2, respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion. [ABSTRACT FROM AUTHOR]

The trifluoromethylation of enamines of ethyl 3-oxocarboxylates catalyzed by Fenton reagent with CF 3 I was investigated. Trifluoromethylation followed by acid hydrolysis provided 3-oxo-2-(trifluoromethyl)carboxylates in 64–94% yields, which were greater than those obtained by the trifluoromethylation of 3-oxocarboxylates as reported previously. Enamines trifluoromethylated at the 2-position were isolated as intermediates. Hydrolysis and successive decarboxylation of the obtained 3-oxo-2-(trifluoromethyl)carboxylates under acidic conditions provided (2,2,2-trifluoroethyl)ketones in satisfactory yields. [ABSTRACT FROM AUTHOR]

First evidence for the existence of free trifluoromethyl anion CF3- has been obtained. The 3D-caged potassium cation in [K(crypt-222)]+ is inaccessible to CF3-, thus rendering it uncoordinated ("naked"). Ionic [K(crypt-222)]+ CF3- has been characterized by single-crystal X-ray diffraction, solution NMR spectroscopy, DFT calculations, and reactivity toward electrophiles. [ABSTRACT FROM AUTHOR]

A mild and efficient procedure for the silver-catalyzed tandem trifluoromethylation and cyclization of aryl isonitriles with the Langlois reagent (sodium triflinate) is developed. A series of trifluoromethylated phenanthridines is prepared in moderate to good yields from a cheap and stable trifluoromethyl source. [ABSTRACT FROM AUTHOR]

The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl was achieved via the reaction of the corresponding alkyloxydiphenylphosphine and CuCF 3 , generated in situ from methyl fluorosulfonyldifluoroacetate and CuI, under mild conditions. A plausible mechanism was proposed on the basis of experimental results. [ABSTRACT FROM AUTHOR]

A novel electron-donor-acceptor (EDA) complex-mediated direct CH trifluoromethylation of arenes with Umemoto's reagent has been developed. This transformation has been enabled by an unprecedented EDA complex formed by Umemoto's reagent and an amine, which was supported by experiments and theoretical calculations. The radical-based methodology presented here allows to access highly-functionalized trifluoromethyl arenes in up to 81 % chemical yield. [ABSTRACT FROM AUTHOR]

An efficient copper-catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni's reagent has been developed. This strategy, accompanied by a double-bond migration, leads to various branched CF3-substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β-H elimination is prohibited, CF3-containing oxetanes are isolated as the sole product. [ABSTRACT FROM AUTHOR]

A variety of vinylic bromides and iodides undergo smooth trifluoromethylation and pentafluoroethylation with RfH-derived CuRf (Rf = CF3, C2F5) to give the corresponding fluoroalkylated olefins. These reactions employing the low-cost CuRf reagents occur in high yield with excellent chemo- and stereoselectivity under mild conditions (23-80 °C). Crystal structures of one trifluoromethyl and one pentafluoroethyl derivative have been determined. [ABSTRACT FROM AUTHOR]

AuI/CuI-co-catalyzed tandem 1,3-acyloxy migration/trifluoromethylation reaction of propargyl esters to give α-trifluoromethyl enones in moderate yields and with excellent stereoselectivity is described. It is proposed that the reaction proceeds through the 1,3-acyloxy migration of the propargyl esters catalyzed by AuI to produce an allenic intermediate, followed by its trifluoromethylation to give the final product. [ABSTRACT FROM AUTHOR]

The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. [ABSTRACT FROM AUTHOR]

The incorporation of a trifluoromethyl (CF3) group into organic compounds is of great importance in pharmaceutical, agricultural, and materials science. Trifluoromethylation based on radical intermediates, as a valuable alternative transformation using the inexpensive and stable solid sodium trifluoromethanesulfinate (CF3SO2Na; Langlois' reagent), has attracted much attention and has become a hot research field. This review examines recent advances in radical trifluoromethylation reactions with CF3SO2Na as CF3 source. [ABSTRACT FROM AUTHOR]

A range of benzotrifluorides are conveniently accessible in high yields from widely available (hetero)aromatic amines and the inexpensive trifluoromethylating agent TMSCF3 through a copper-mediated Sandmeyer trifluoromethylation reaction. Two practical procedures are presented. In the first, the diazonium salts are preformed in an extra reaction step, in the second approach the diazotization and the trifluoromethylation are combined into a one-pot procedure. [ABSTRACT FROM AUTHOR]

A novel strategy for aromatic trifluoromethylation by converting amino into trifluoromethyl groups via a Sandmeyer-type reaction is reported. The transformation involves diazotization of the aromatic amines with tert-butyl nitrite and hydrochloric acid to form aryldiazonium chlorides, followed by trifluoromethylation with trifluoromethylsilver at low temperature. Various readily available aromatic amines are smoothly converted under mild conditions. [ABSTRACT FROM AUTHOR]

A new efficient strategy for the synthesis of 3-trifluoromethyl-indoles was developed through tandem cyclization/trifluoromethylation of 2-alkynylanilines and Umemoto's reagent under effect of CuBr. The reaction features the use of cheap copper salt, mild reaction conditions and high yield of products. The preliminary mechanism study indicates the solvent dimethylacetamide acts as the role of dealkylation. [ABSTRACT FROM AUTHOR]

Difluoromethylene phosphobetaine (Ph3P+CF2CO2−, PDFA), a known difluorocarbene reagent, was found to be able to efficiently trifluoromethylate terminal alkynes in the presence of Cu(I) and potassium fluoride. The transformation proceeded smoothly to afford the corresponding trifluoromethylated acetylenes in moderate yields. [ABSTRACT FROM AUTHOR]

The development of efficient methods for accessing fluorinated functional groups is desirable. Herein, we report a twostep method that utilizes catalytic copper for the decarboxylative trifluoromethylation of propargyl bromodifluoroacetates is described. This protocol affords a mixture of propargyl trifluoromethanes and trifluoromethyl allenes. [ABSTRACT FROM AUTHOR]