Rhodium(III)-Catalyzed Coupling of Quinolin-8-carboxaldehydes with CF-Imidoyl Sulfoxonium Ylides by Chelation-Assisted C(sp)-H Bond Activation for the Synthesis of Trifluoromethyl-Substituted Enaminones.

A rhodium(III)-catalyzed aldehydic C(sp)-H imidoylmethylation of quinolin-8-carboxaldehydes with CF-imidoyl sulfoxonium ylides (TFISYs) has been developed for the generation of α-imino ketones, which could be readily tautomerized to enaminones in moderate to excellent yields. In the transformation, TFISYs act as a kind of masked alkenylating reagents for the aldehyde moiety, and the obtained CF-enaminone products have been successfully converted into other useful trifluoromethyl-substituted heterocycles.

Divergent Synthesis of Trifluoromethyl-Substituted 1,2-Dihydroquinoxalines and Diimines by Cascade Reactions of CF-Imidoyl Sulfoxonium Ylides with Azo Compounds.

A base-mediated cascade reaction of CF-imidoyl sulfoxonium ylides and azo compounds has been achieved, allowing for facile access to trifluoromethyl-substituted 1,2-dihydroquinoxalines and diimines in moderate to excellent yields. Noteworthy is that the unusual N-N bond cleavage and rearrangement of azo compounds are involved in the transformations.

Carbonylative Synthesis of Fused Quinoxalinones via Palladium-Catalyzed Cascade Cyclization of 2-Heteroaryl Iodobenzene and NaN.

A facile and straightforward approach for the synthesis of fused quinoxalinones via palladium-catalyzed cascade carbonylative cyclization of 2-heteroaryl iodobenzene and NaN has been achieved. The transformation might undergo cascade carbonylation, formation of acyl azide, a Curtius rearrangement, and an intramolecular cyclization sequence. The obtained heterocycle products can be easily transformed into other structurally diverse valuable compounds, which demonstrates the synthetic utility of the developed protocol.

Construction of trifluoromethyl-containing heterocycles from trifluoroacetimidoyl chlorides and derivatives.

Recent advances in the direct synthesis of trifluoromethyl-containing heterocycles from trifluoroacetimidoyl chlorides (TFAICs) and derivatives, including trifluoroacetimidohydrazides (TFAIHs) and CF-imidoyl sulfoxonium ylides (TFISYs), are systematically summarized and discussed. The cascade annulation reactions of trifluoromethyl-containing synthons with suitable coupling partners have emerged as a powerful and promising tool for the construction of a variety of trifluoromethyl-substituted heterocycles. Compared with other trifluoromethyl-containing building blocks, TFAICs and derivatives have notable merits of easy availability and handling, relative stability and safety, and high reactivity.

Rhodium(III)-catalyzed regioselective C2-alkenylation of indoles with CF-imidoyl sulfoxonium ylides to give multi-functionalized enamines using a migratable directing group.

A rhodium(III)-catalyzed regioselective C2-alkenylation of indoles for the construction of α-CF substituted enamines has been developed, which utilizes CF-imidoyl sulfoxonium ylides (TFISYs) as alkenylating agents for the first time. A wide array of indolyl- and trifluoromethyl-decorated enamine derivatives have been assembled in moderate to good yields.

Radical selenylative cyclization of trifluoromethyl propargyl imines for the synthesis of trifluoromethyl- and seleno-azaspiro[4,5]-tetraenones and quinolines.

A radical selenylative cyclization of trifluoromethyl propargyl imines with diselenides for the regiodivergent construction of diversely functionalized azaspiro[4,5]-tetraenones and quinolines has been developed, which enables dual incorporation of CF and Se groups into heterocycles in a one-pot reaction. When using Oxone as a green oxidant, the reaction proceeds through oxidative dearomative -annulation or intramolecular -annulation exhibiting good regioselectivity. The synthetic utility of this method is demonstrated by a scale-up reaction and further modification of the obtained products.

Rh(III)-Catalyzed Dual C-H Activation/Cascade Annulation of Benzimidates and CF-Imidoyl Sulfoxonium Ylides for the Synthesis of Trifluoromethyl-Decorated Benzo[][1,8]naphthyridines.

An efficient and straightforward approach for the synthesis of trifluoromethyl-decorated benzo[][1,8]naphthyridines has been achieved via the Rh(III)-catalyzed dual C-H activation and cascade annulation of benzimidates and CF-imidoyl sulfoxonium ylides. The novel transformation involves the formation of four new chemical bonds along with the release of two molecules of dimethyl sulfoxide (DMSO) and one molecule each of ethanol and amine. The optoelectronic properties of the obtained fused aromatic products have been investigated by recording the UV-vis absorption and emission spectra.

Metal-free synthesis of 3-trifluoromethyl-1,2,4-triazoles multi-component reaction of trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate.

A convenient approach for the construction of pharmaceutically valuable 3-trifluoromethyl-1,2,4-triazoles has been developed, which employs the readily available trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate (TFBen) as starting materials. The multi-component reaction features broad substrate scope, high efficiency, and scalability, providing a facile and straightforward route to the biologically important 3-trifluoromethyl-1,2,4-triazole scaffolds in moderate to good yields. Considering its broad-spectrum pharmaceutical activity, the method offers the opportunity for the further study towards the toxicity risk assessment and structure-activity relationship of the pharmaceuticals containing trifluoromethyl-1,2,4-triazole cores.

Ruthenium-Catalyzed Hydroxyl-Directed -Selective C-H Activation and Annulation of 1-Naphthols with CF-Imidoyl Sulfoxonium Ylides for the Synthesis of 2-(Trifluoromethyl)-2,3-dihydrobenzo[]chromen-2-amines.

A ruthenium-catalyzed -selective C-H activation and annulation of 1-naphthols with CF-substituted imidoyl sulfoxonium ylides that uses hydroxyl as a weakly coordinating directing group is disclosed. The strategy provides a facile and practical route to diverse trifluoromethyl-containing 2,3-dihydrobenzo[]chromen-2-amines with high efficiency. Notable advantages of this protocol include readily available materials, excellent regioselectivity, good functional group compatibility, and scalability.

Formal [4+1] Annulation of Azoalkenes with CF-Imidoyl Sulfoxonium Ylides and Dual Double Bond Isomerization Cascade: Synthesis of Trifluoromethyl-Containing Pyrazole Derivatives.

A straightforward strategy for the metal-free construction of trifluoromethyl-containing pyrazole derivatives has been achieved from readily available α-halo hydrazones and CF-imidoyl sulfoxonium ylides. The cascade transformation proceeds through the formal [4+1] cycloaddition followed by an unexpected dual double bond isomerization. The protocol features mild conditions, easy operation, excellent substrate compatibility, and good regioselectivity.

Metal-free photo-induced sulfidation of aryl iodide and other chalcogenation.

A photo-induced C-S radical cross-coupling of aryl iodides and disulfides under transition-metal and external photosensitizer free conditions for the synthesis of aryl sulfides at room temperature has been presented, which features mild reaction conditions, broad substrate scope, high efficiency, and good functional group compatibility. The developed methodology could be readily applied to forge C-S bond in the field of pharmaceutical and material science.

Controllable access to trifluoromethyl-containing indoles and indolines: palladium-catalyzed regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides.

The synthesis of diverse products from the same starting materials is always attractive in organic chemistry. Here, a palladium-catalyzed substrate-controlled regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides has been developed, which provides a direct but controllable access to a variety of structurally diverse trifluoromethyl-containing indoles and indolines. In more detail, with respect to γ,δ-alkenes, 1,1-geminal difunctionalization of unactivated alkenes with trifluoroacetimidoyl chloride enables the [4 + 1] annulation to produce indoles; as for β,γ-alkenes, a [3 + 2] heteroannulation with the hydrolysis product of trifluoroacetimidoyl chloride through 1,2-vicinal difunctionalization of alkenes occurs to deliver indoline products.

TFBen (Benzene-1,3,5-triyl triformate): A Powerful and Versatile CO Surrogate.

Carbonylative reactions by the using of CO surrogates constitute a facile avenue for the assembly of valuable carbonyl-containing compounds due to the colorless, toxic, flammable, and not easy-handing character of carbon monoxide gas. Recent advances in the carbonylative transformations with TFBen (benzene-1,3,5-triyl triformate) as a safe and convenient CO precursor are systematically summarized and discussed, which can be divided into three parts based on the patterns of the obtained products. This Review focuses on the discussion of the application of TFBen in carbonylative synthesis of various carbonyl-containing compounds.

The cascade coupling/iodoaminocyclization reaction of trifluoroacetimidoyl chlorides and allylamines: metal-free access to 2-trifluoromethyl-imidazolines.

A metal-free cascade coupling/iodoaminocyclization reaction for the rapid assembly of 2-trifluoromethyl-imidazolines has been disclosed. The transformation applies readily accessible trifluoroacetimidoyl chlorides, allylamines and N-iodosuccinimides as the starting substrates, achieving an efficient and straightforward pathway to construct diverse imidazoline derivatives. Excellent efficiency of the reaction is observed (higher than 90% isolated yield for half of the examples), and the obtained imidazoline products bearing a pendent iodomethyl group could be easily transformed into other synthetically valuable compounds.

Synthesis of 3-1,2,4-Triazol-3-ones via NiCl-Promoted Cascade Annulation of Hydrazonoyl Chlorides and Sodium Cyanate.

A nickel-promoted cascade annulation reaction for the facile synthesis of 3-1,2,4-triazol-3-ones from readily available hydrazonoyl chlorides and sodium cyanate has been developed. The transformation occurs through a cascade nickel-promoted intermolecular nucleophilic addition-elimination process, intramolecular nucleophilic addition, and a hydrogen-transfer sequence. The method has been successfully applied for the construction of the core skeleton of the angiotensin II antagonist.

Silver-Mediated [3 + 2] Cycloaddition of Azomethine Ylides with Trifluoroacetimidoyl Chlorides for the Synthesis of 5-(Trifluoromethyl)imidazoles.

A silver-mediated [3 + 2] cycloaddition of azomethine ylides with trifluoroacetimidoyl chlorides for the rapid assembly of 5-(trifluoromethyl)imidazoles has been developed. Notable features of the reaction include readily accessible reagents, a broad substrate scope, and high efficiency. The protocol can be successfully applied to construct the analogue of the specific allosteric modulator of GABA receptors.

Palladium-Catalyzed Cascade Carbonylative Synthesis of 1,2,4-Triazol-3-ones from Hydrazonoyl Chlorides and NaN.

A palladium-catalyzed three-component carbonylative reaction for the synthesis of 3-1,2,4-triazol-3-ones from hydrazonoyl chlorides and NaN has been achieved. The reaction presumably proceeds through a cascade carbonylation, acyl azide formation, Curtius rearrangement, and intramolecular nucleophilic addition sequence. A wide variety of structurally diverse 3-1,2,4-triazol-3-ones were constructed in moderate to excellent yields.

FeCl-Mediated Synthesis of 2-(Trifluoromethyl)quinazolin-4(3)-ones from Isatins and Trifluoroacetimidoyl Chlorides.

An FeCl-mediated cascade coupling/decarbonylative annulation reaction for the efficient construction of 2-(trifluoromethyl)quinazolin-4(3)-ones has been developed. This transformation employs readily available isatins and trifluoroacetimidoyl chlorides as the starting materials, providing a facile and practical route to diverse biologically relevant quinazolin-4(3)-one derivatives. A plausible reaction pathway has been proposed based on the mechanistic observations.

Carbonylative synthesis of heterocycles involving diverse CO surrogates.

Recent advances in the carbonylative synthesis of heterocycles by using diverse CO surrogates as sources of CO are summarized and discussed. The merger of carbonylative transformations involving CO surrogates with heterocyclic compound syntheses provides a powerful and promising tool for the construction of a series of carbonyl-containing heterocyclic compounds. In contrast to toxic and flammable gaseous carbon monoxide, most of the CO surrogates are readily available, bench-stable, harmless and easy to handle.

Palladium-Catalyzed Four-Component Carbonylative Cyclization Reaction of Trifluoroacetimidoyl Chlorides, Propargyl Amines, and Diaryliodonium Salts: Access to Trifluoromethyl-Containing Trisubstituted Imidazoles.

A palladium-catalyzed four-component carbonylative cyclization reaction for the expeditious construction of trifluoromethyl-containing trisubstituted imidazoles has been achieved. With readily accessible trifluoroacetimidoyl chlorides, propargyl amines, and diaryliodonium salts as the starting materials, the carbonylative transformation proceeds smoothly under mild conditions to enable the formation of multifunctionalized imidazole molecules in a one-pot, one-step manner. Diaryliodonium salts serve as both oxidants and aryl sources in the reaction.

Redox-Neutral Rhodium(III)-Catalyzed Annulation of Arylhydrazines with Sulfoxonium Ylides To Synthesize 2-Arylindoles.

A rhodium-catalyzed redox-neutral reaction of arylhydrazines with sulfoxonium ylides to construct 2-arylindole derivatives in one pot has been developed. The transformation proceeds efficiently under mild conditions and involves tandem C-H activation and an intramolecular dehydration annulation sequence, providing a straightforward pathway to access pharmaceutically and biologically valuable 1-aminoindole derivatives.

Synthesis of Aryl Trimethylstannane via BF·OEt-Mediated Cross-Coupling of Hexaalkyl Distannane Reagent with Aryl Triazene at Room Temperature.

BF·OEt-mediated cross-coupling of (SnMe) with aryl triazene offers a new strategy for the synthesis of aryl stannane. A variety of synthetically useful aryl trimethylstannanes were produced in moderate to good yields with this metal-free approach. One-pot sequential Stille cross-coupling with different aryl bromides provides a short entry to both symmetrical and unsymmetrical biaryl compounds.

Cobalt-Catalyzed Aerobic Oxidative C-H/C-H Cross-Coupling of Unactivated Arenes for the Synthesis of Biaryls.

A mild and efficient protocol for the synthesis of 2,2'-difunctional biaryls from readily available benzamides and oximes by Co(OAc)·4HO catalysis has been developed. The catalytic cycle that includes aerobic oxidation of Co(I) to Co(III) is successfully achieved for the first time through dual-chelation-assisted C-H/C-H coupling with the assistance of catalytic Mn(acac). The catalytic system exhibits powerful reactivity and tolerates a large number of sensitive functional groups.

Transition-Metal-Free Arylation and Alkylation of Diarylmethyl p-Tolyl Sulfones with Zinc Reagents.

The transition-metal-free synthesis of unsymmetrical and highly functionalized triarylmethanes through arylation of the situ generated o-QMs from diarylmethyl p-tolyl sulfones with aryl zinc reagents is described. Alkyl zinc reagents are also well tolerated in this reaction. Additionally, the straightforward synthesis of the analogue of the antituberculosis agent A and the key precursor of the anti-breast-cancer agent B are achieved by this strategy.

1,2-Gold Carbene Transfer Empowers Regioselective Synthesis of Polysubstituted Furans.

A gold-catalyzed cascade cycloisomerization/ring-opening reaction of allenyl ketones bearing a cyclopropyl moiety with a wide variety of alcohols or ketones is developed. This reaction involves an unprecedented 1,2-gold carbene transfer to provide regioselective and modular access to tri- or tetrasubstituted furans in moderate to high yields and with broad substrate tolerability.