Synthesis of N-Aryl-4-trifluoromethylthiazol-2-amines via Insertion/Annulation of Trifluoromethylimidoyl Sulfoxonium Ylides with Sodium Thiocyanate.

An efficient p-TsOH-mediated insertion of sodium thiocyanate into trifluoromethylimidoyl sulfoxonium ylides has been reported, affording annulated N-aryl-4-trifluoromethylthiazol-2-amines in 42-84% yields in a one-pot manner. This protocol encompasses a variety of trifluoromethylimidoyl sulfoxonium ylides with thiocyanate serving as the source of the "S-C═N" moiety of the thiazole ring. The versatile transformations of the resulting pharmacologically important N-aryl-4-trifluoromethylthiazol-2-amines were also demonstrated.

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks.

Trifluoromethylated heterocyclic compounds have played an increasingly significant role in pharmaceuticals, agrochemicals, and materials. This is because the introduction of trifluoromethyl could enhance the lipophilicity, metabolic stability, and pharmacokinetic properties of heterocyclic drug molecules. Therefore, the synthesis of trifluoromethylated heterocyclics has become a major subject of research. The construction of trifluoromethylated heterocyclics via the annulation of trifluoromethyl building blocks with suitable partners has been proved to be a powerful strategy. In this review, we systematically summarize and discuss recent advances in the preparation of trifluoromethyl-containing heterocyclics via trifluoromethyl building block strategies over the period from 2019 to the present.

Solvent-Controlled Enantiodivergent Construction of P(V)-Stereogenic Molecules via Palladium-Catalyzed Annulation of Prochiral N-Aryl Phosphonamides with Aromatic Iodides.

In this work, we describe an efficient and modular method for enantiodivergent accessing P(V)-stereogenic molecules by utilizing the catalytic atroposelective Catellani-type C-H arylation/desymmetric intramolecular N-arylation cascade reaction. The enantioselectivity of this protocol was proved to be tuned by the polarity of the solvent, thus providing a wide range of both chiral P(V)-stereogenic enantiomers in moderate to good yields with good to excellent enantiomeric excesses. Noteworthy is that the strategy developed herein represents an unprecedented example of solvent-dictated inversion of the enantioselectivity of P(V)-stereogenic compounds.

Lithium Bromide-Promoted Formal C(sp3)-H Bond Insertion Reactions of ß-Carbonyl Esters with Sulfoxonium Ylides to Synthesize 1,4-Dicarbonyl Compounds.

A LiBr-promoted formal C(sp3)-H bond insertion reaction between ß-carbonyl esters and sulfoxonium ylides is established. This practical reaction has a wide range of substrate scope for both ß-carbonyl esters and sulfoxonium ylides to give a variety of 1,4-dicarbonyl compounds with 43-94% yields. The reaction features transition-metal-free reaction conditions and exclusive C-alkylation chemselectivity. The use of bench-stable sulfoxonium ylides overcomes previous methods that require transition metal as catalysts and unstable diazo compounds or toxic haloketones as alkylation reagents.

Ingenious fluorescent probes for biogenic amine and their applications in bioimaging and food spoilage detection.

Food safety issues have received much attention. Biogenic amines are considered important markers of food spoilage. Accurate detection of biogenic amines is important for food quality monitoring. Herein, we developed two coumarin-difluoroboron ß-diketonate hybrid probes, 1 and 2, for detection of amines. Both probes possess large conjugated structures and donor-acceptor-donor configuration, exhibiting solvatochromic effects due to intramolecular charge transfer mechanism. Upon reaction with amines, the boron atom in difluoroboron unit can interact with lone pair electrons of nitrogen atom, thus resulting in significant changes in absorption and fluorescence properties. These probes were successfully utilized to image amine in live cells and liver tissues. Moreover, by photographing probe-loaded food extract supernatant, we establish the relationship between color parameters and food storage time, which can easily indicate food spoilage process. This work and its findings hold promise for providing potential strategies for real-time and convenient detection of food freshness.

Palladium-Catalyzed Multicomponent Assembly of (Z)-Alkenylborons via Carbopalladation/Boronation/Retro-Diels-Alder Cascade Reaction.

A palladium-catalyzed multicomponent cascade reaction of aryl iodides, oxanorbornadiene, and diborns to access (Z)-alkenylborons is reported. This transformation proceeds through the sequential carbopalladation/boronation/retro-Diels-Alder domino reaction. The oxanorbornadiene used in this reaction serves as an acetylene surrogate, which is generated via a retro-Diels-Alder reaction. Such a stereoselective and scalable approach has a wide range of functional group tolerance and good substrate universality.

Transition-Metal-, Additive-, and Solvent-Free [3 + 3] Annulation of RCF2-Imidoyl Sulfoxonium Ylides with Cyclopropenones to Give Multifunctionalized CF3-Pyridones.

An efficient and practical strategy was developed to synthesize 1,3,4-triaryl-6-trifluoromethylpyridones from CF3-imidoyl sulfoxonium ylides and cyclopropenones in good to excellent yields. This stepwise [3 + 3] annulation reaction was carried out under transition-metal-, additive-, and solvent-free conditions, generating 1 equiv of dimethyl sulfoxide as byproduct and tolerating a series of functional groups.

Transition Metal-Free C-H Thiolation via Sulfonium Salts Using ß-Sulfinylesters as the Sulfur Source.

We disclose a direct C(sp)-, C(sp2)-, and C(sp3)-H thiolation reaction using ß-sulfinylesters as the versatile sulfur source. The key step of this protocol is chemoselective C-S bond cleavage of the sulfonium salts that are formed in situ from the corresponding alkenes, alkynes, and 1,3-dicarboxyl compounds with ß-sulfinylesters. The successful capture of the acrylate byproduct supports a retro-Michael reaction mechanism.

Annulation of CF3-Imidoyl Sulfoxonium Ylides with 1,3-Dicarbonyl Compounds: Access to 1,2,3-Trisubstituted 5-Trifluoromethylpyrroles.

A lithium-bromide-promoted nucleophilic substitution/annulation cascade reaction between CF3-imidoyl sulfoxonium ylides and 1,3-dicarbonyl compounds has been established, and the corresponding 1,2,3-trisubstituted 5-trifluoromethylpyrroles have been obtained in 27-78% yield. This reaction features a broad substrate scope and generates dimethyl sulfoxide and H2O as byproducts.

Base-Promoted Stereoselective Hydrogenation of Ynamides with Sulfonyl Hydrazide to Give Z-Enamides.

A base-mediated semihydrogenation of ynamides using p-toluenesulfonyl hydrazide as an inexpensive and easy-to-handle hydrogen donor is reported. This transition-metal-free protocol avoids overhydrogenation and reduction of other functional groups, generating the thermodynamically unfavorable Z-enamides exclusively.

Regioselective Synthesis of 2,4-Diaryl-6-trifluoromethylated Pyridines through Copper-Catalyzed Cyclization of CF3-Ynones and Vinyl Azides.

A novel copper-catalyzed cyclization of readily available vinyl azides with CF3-ynones is steadily achieved under mild conditions to furnish the versatile 2,4-diaryl-6-trifluoromethylated pyridine products, which are of great interest in medicinal chemistry. The generation of the vinyl iminophosphorane intermediates from vinyl azides through the Staudinger-Meyer reaction ensures the subsequent 1,4-addition process with CF3-ynones in this transformation.

Palladium-Catalyzed Chemoselective Synthesis of 2-Aminocinnamyl Esters via Sequential Amination and Olefination of Aryl Iodides.

We report a highly chemoselective palladium-catalyzed Catellani-type amination of aryl iodides terminated by the Heck reaction using allylic esters as terminating reagents. 2-Aminocinnamyl esters were formed exclusively via ß-H elimination rather than ß-OAc elimination without the assistance of a silver salt. This protocol represents a useful extension of Catellani-type transformations.

Rhodium(II)-catalyzed multicomponent assembly of α,α,α-trisubstituted esters via formal insertion of O-C(sp3)-C(sp2) into C-C bonds.

The direct cleavage of C(CO)-C single bonds, delivering otherwise inaccessible compounds, is a significant challenge. Although the transition metal-catalyzed insertion of functional groups into C(CO)-C bonds has been studied, strained ketone substrates or chelating assistance were commonly required. In this article, we describe a rhodium(II)-catalyzed three-component reaction of 1,3-diones, diazoesters, and N,N-dimethylformamide (DMF), leading to an unusual formal insertion of O-C(sp3)-C(sp2) into unstrained C(CO)-C bonds. This procedure provides a rapid entry to a gamut of otherwise inaccessible α,α,α-trisubstituted esters/amide from relatively simple substrates in a straightforward manner. 55 examples of highly decorated products demonstrate the broad functional group tolerance and substrate scope. The combination of control experiments and isotope-labeling reactions support that O, C(sp3), and C(sp2) units derive from 1,3-diones, diazoesters, and DMF, respectively.

Modular and Stereoselective Synthesis of C-Aryl Glycosides via Catellani Reaction.

In this work, we describe a Catellani-type C-H glycosylation to provide rapid access to various highly decorated α-C-(hetero)aryl glycosides in a modular and stereoselective manner (>90 examples). The termination step is flexible, which is demonstrated by ipso-Heck reaction, hydrogenation, Suzuki coupling, and Sonogashira coupling. Application of this methodology has been showcased by preparing glycoside-pharmacophore conjugates and a dapagliflozin analogue. Notably, the technology developed herein represents an unprecedented example of Catellani-type alkylation involving an SN1 pathway.

Catalytic Enantioselective [2+2] Cycloaddition of α-Halo Acroleins: Construction of Cyclobutanes Containing Two Tetrasubstituted Stereocenters.

A catalytic enantioselective formal [2+2] cycloaddition between α-halo acroleins and electronically diverse arylalkenes is described. In the presence of (S)-oxazaborolidinium cation as the catalyst, densely functionalized cyclobutanes containing two vicinal tetrasubstituted stereocenters were produced in high yields and high diastereoselectivities with excellent enantioselectivities. Mechanistic studies revealed that the cis isomer could be transformed into the trans isomer via an enantiocontrolled process. A gram-scale reaction of this catalytic method was used to demonstrate its synthetic potential.

Synthesis of 3-(2-quinolyl) chromones from ynones and quinoline N-oxides via tandem reactions under transition metal- and additive-free conditions.

A novel method for the synthesis of 3-(2-quinolyl) chromones through a tandem [3+2] cycloaddition/ring-opening/O-arylation from ynones and quinoline N-oxides has been developed. This protocol proceeds under transition metal- and additive-free conditions and can be amplified to the gram level in 91% yield. 3-(1-Isoquinolyl) and 3-(2-pyridyl) chromones are also successfully synthesized using isoquinoline and pyridine N-oxides under basic conditions. Various heteroarene-contaning chromones were afforded in 30-98% yields, which are difficult to be obtained and are compounds of interest in pharmaceutical chemistry and chemical biology.

Ruthenium(II)-Catalyzed Construction of Isocoumarins via Dual C-H/C-C Activation of Sulfoxonium Ylides.

A ruthenium(II)-catalyzed annulation between two molecules of sulfoxonium ylides is achieved, generating a variety of substituted isocoumarins in reasonable yields. This strategy features dual C-H/C-C activation in one pot and has a wide substrate scope and good functional group tolerance.

Ruthenium(ii)-catalyzed chemoselective deacylative annulation of 1,3-diones with sulfoxonium ylides via C-C bond activation.

The first successful example of deacylative annulation of 1,3-diones with sulfoxonium ylides was achieved through Ru(ii)-catalyzed C-C bond activation. The excellent chemoselectivity and broad substrate scope render this method a practical and versatile approach for the preparation of (hetero)aryl and alkenyl substituted furans, which are valuable units in many biologically active compounds and functional materials. A preliminary mechanistic study reveals that this process involves a deacylative α-ruthenation to generate key alkyl Ru(ii) intermediates with the release of a benzoic acid fragment.

Copper-Catalyzed Three-Component Cascade Michael Addition/Heck-Type Alkylation/Annulation: Accessing Fully Substituted 1,3-Dihydro-2H-pyrrol-2-ones.

We report a highly efficient copper-catalyzed three-component reaction of alkylamines, acetylenedicarboxylates, and α-bromocarbonyls for the assembly of fully substituted 1,3-dihydro-2H-pyrrol-2-ones. A variety of alkylamines and ammonium salt are functionalized with acetylenedicarboxylates and α-bromocarbonyls. N-aryl enaminoesters are also successfully alkylated with α-bromocarbonyls. This protocol is understood to proceed through radical Heck-type coupling of in-situ-generated bulky trisubstituted alkenes with bulky tertiary alkyl bromides, which is realized for the first time.

Palladium-Catalyzed Regioselective Heck Coupling of Alkynes with Aryl Iodides for the Synthesis of Trisubstituted Allenes.

A utility approach toward trisubstituted allenes through Pd-catalyzed alkynyl Heck coupling reaction of alkynes and aryl iodides is reported. This process proceeded via regioselective carbopalladation of 1-aryl-1-alkynes to give alkenyl palladium species, which undergo ß-hydride elimination to provide 1,1-diarylallenes in 25-71% yields. This method features unique regioselectivity and high functional group compatibility.