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 CF3 and Se groups into heterocycles in a one-pot reaction. When using Oxone as a green oxidant, the reaction proceeds through oxidative dearomative ipso-annulation or intramolecular ortho-annulation exhibiting good regioselectivity. The synthetic utility of this method is demonstrated by a scale-up reaction and further modification of the obtained 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.

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 GABAA receptors. The silver species could be recycled by a simple operation.

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.

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 BF3·OEt2-Mediated Cross-Coupling of Hexaalkyl Distannane Reagent with Aryl Triazene at Room Temperature.

BF3·OEt2-mediated cross-coupling of (SnMe3)2 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.

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.

Catalyst-Controlled Chemodivergent Modification of Indoles with 2-Furylcarbinols: Piancatelli Reaction vs Cross-Dehydrative Coupling Reaction.

A divergent synthetic strategy to functionalize the indole nucleus with readily available 2-furylcarbinols was developed. It was found that the 3-(4-oxo-2-cyclopentenyl)indoles were obtained in moderate to good yields (up to 89%) through Piancatelli reaction catalyzed by ZnCl2, whereas employment of Brønsted acid TFA afforded directly coupled product 3-(2-furyl)indoles in moderate to good yields (up to 87%) via the deprotonation-rearomatization route.

Strain-Promoted Nitration of 3-Cyclopropylideneprop-2-en-1-ones and the Application for the Synthesis of Pyrroles.

The tunable nucleophilic nitration of 3-cyclopropylideneprop-2-en-1-ones with cheap sodium nitrite is described. This transformation proceeds with the assistance of a strained cyclopropane ring and allows for a divergent route to various synthetically useful ß,γ-dinitro or γ-mononitro adducts in high yields with exclusive regio- and stereoselectivity. Additionally, a wide array of valuable functionalized N-unprotected pyrroles is achieved from the resulting ß,γ-dinitro compounds via reductive cyclization strategy.

Base-mediated diastereoselective [4 + 3] annulation of in situ generated ortho-quinone methides with C,N-cyclic azomethine imines.

An efficient [4 + 3] annulation of 2-(1-tosylalkyl)phenols with C,N-cyclic azomethine imines via in situ generation of ortho-quinone methides (o-QMs) under mild basic reaction conditions is disclosed, furnishing biologically interesting seven-membered heterocyclic compounds with moderate to good yields and excellent diastereoselectivities. A gram-scale reaction is performed to demonstrate the potential in industrial application and two transition states are proposed to rationalize the outstanding diastereoselectivity.

1-Hydroxybenzotriazole-Assisted, N-Heterocyclic Carbene Catalyzed ß-Functionalization of Saturated Carboxylic Esters: Access to Spirooxindole Lactones.

A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct ß-functionalization of saturated carboxylic esters is disclosed. This formal [3 + 2] annulation reaction of carboxylic esters with isatins affords optically pure spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A dual role of HOBt is proposed based on controlled experiments to rationalize the enhancement of diastereoselectivity and enantioselectivity.

Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with ß-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols.

Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with ß-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis.

Metal-free C-N- and N-N-bond formation: synthesis of 1,2,3-triazoles from ketones, N-tosylhydrazines, and amines in one pot.

A novel synthetic approach toward 1,4-disubstituted 1,2,3-triazoles by C-N- and N-N-bond formation has been established under transition-metal-free conditions. Complete control of the regioselectivity was successfully achieved. Commercially available anilines, ketones, and N-tosylhydrazine were treated with molecular iodine in one pot to allow the regioselective generation of 1,4-disubstituted 1,2,3-triazoles in high yields without the use of azides.

Efficient synthesis of 1,2,3-triazoles by copper-mediated C-N and N-N bond formation starting from N-tosylhydrazones and amines.

An effective copper-mediated synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30 mol % amino acid is added into the reaction mixture. This methodology exhibits many notable features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and N-N bond formation process.

CuI-catalyzed aerobic oxidative α-aminaton cyclization of ketones to access aryl or alkenyl-substituted imidazoheterocycles.

CuI-catalyzed aerobic oxidative synthesis of imidazoheterocycles has been achieved. Four hydrogen atoms were removed in one step. This protocol was compatible with a broad range of functional groups, and it has been also successfully extended to unsaturated ketones, bringing about the formation of alkenyl-substituted imidazoheterocycles, which were difficult to prepare by previous means. Preliminary mechanistic studies indicated that this reaction was most likely to proceed through a catalytic Ortoleva-King reaction. By using this method, the marketed drug Zolimidine could be prepared with 90% yield on a gram scale from commercially available materials.

Carbonylative Synthesis of Fused Quinoxalinones via Palladium-Catalyzed Cascade Cyclization of 2-Heteroaryl Iodobenzene and NaN3.

A facile and straightforward approach for the synthesis of fused quinoxalinones via palladium-catalyzed cascade carbonylative cyclization of 2-heteroaryl iodobenzene and NaN3 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 CF3-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 CF3-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-CF3 substituted enamines has been developed, which utilizes CF3-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.

Divergent Synthesis of Trifluoromethyl-Substituted 1,2-Dihydroquinoxalines and Diimines by Cascade Reactions of CF3-Imidoyl Sulfoxonium Ylides with Azo Compounds.

A base-mediated cascade reaction of CF3-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.

Ruthenium-Catalyzed Hydroxyl-Directed peri-Selective C-H Activation and Annulation of 1-Naphthols with CF3-Imidoyl Sulfoxonium Ylides for the Synthesis of 2-(Trifluoromethyl)-2,3-dihydrobenzo[de]chromen-2-amines.

A ruthenium-catalyzed peri-selective C-H activation and annulation of 1-naphthols with CF3-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[de]chromen-2-amines with high efficiency. Notable advantages of this protocol include readily available materials, excellent regioselectivity, good functional group compatibility, and scalability.