Synlett

The selective functionalization of C–F bonds in trifluoromethylated arenes (ArCF3) is essential due to the extensive use of fluorinated compounds in pharmaceuticals, agrochemicals, and materials science, alongside emerging regulatory restrictions on trifluoromethyl groups. Here, we report a hybrid palladium-catalyzed strategy for the selective defluorination and functionalization of ArCF3, featuring intermolecular carboamination of linear conjugated dienes or defluorinative cross-coupling with nonactivated alkenes. This methodology enables the 1,4-addition of dienes with exclusive E-selectivity or the defluoroalkylation of (trifluoromethyl)arenes, providing efficient routes to difluoromethylated compounds and addressing key challenges in synthetic fluorine chemistry.

Theaflavins (TFs) contribute greatly to the color and flavor of black tea, and have various bioactivities beneficial to human health. This research compared the activity for TF production from tea polyphenols of recombinant polyphenol oxidase (Malus domestica, GenBank login number LT718523.1, MdPPO2) with that of commercial polyphenol oxidase (Agaricus bisporus, AbPPO) in both free and immobilized forms. Enzyme assays by LC-MS revealed that the production of TFs by the commercial enzyme AbPPO was almost five times as high as that of free recombinant MdPPO2. When immobilized on mesoporous silica, however, the activity of recombinant MdPPO2 increased significantly, whereas AbPPO almost lost its activity. In terms of the relative enzyme activity, the immobilized recombinant MdPPO2 had the highest relative enzyme activity, which was more than six times higher than that of free AbPPO. Among the TFs that were produced, TF3 was the most abundant, followed by TF2a, TF1, and TF2b.

The synthesis of bis(pyrrolo[2,1-a]isoquinolinyl)methanes was achieved through TfOH-catalyzed sequential Friedel–Crafts alkylation of pyrrolo[2,1-a]isoquinoline and aldehyde. A series of highly functionalized bis(pyrrolo[2,1-a]isoquinolinyl)methane derivatives can be obtained in acceptable to excellent yields (11 examples, up to 96% yield). Interestingly, deformylation was observed when treating pyrrolo[2,1-a]isoquinoline-derived aldehyde and indole under the current reaction conditions. Furthermore, the replacement of aldehyde with isatin resulted in the formation of methylene-bridged dimeric pyrrolo[2,1-a]isoquinoline.

A pyrimidinethione candidate carrying pyrazole and thiophene scaffolds was produced by a Biginelli cyclocondensation reaction of a pyrazolecarbaldehyde with pentan-2,4-dione and thiourea. To create some heteroannulated thiazolopyrimidines, the pyrimidinethione was subjected to cyclocondensation reactions with ethyl chloroacetate, 1,2-dibromoethane, chloroacetonitrile, and oxalyl chloride. A DFT simulation was performed for a frontier-orbital analysis to determine the molecular geometry. Among the products, 6-acetyl-7-methyl-5-[1-phen­yl-3-(2-thienyl)-1H-pyrazol-4-yl]-5H-[1,3]thiazolo[3,2-a]pyrimidine-2,3-dione displayed the highest softness and the lowest energy gap in the DFT calculations. Moreover, it had the highest electrophilicity index, suggesting possible biological impacts. The compounds obtained were evaluated against cell lines of breast adenocarcinoma (MCF7) and hepatocellular carcinoma (HepG2) as antiproliferative agents. A simulation of the molecular docking of our compounds with the epidermal growth factor receptor demonstrated the rationality of our design and identified the binding mode. A model pharmacokinetics analysis showed that the products have the expected and desirable drug-like and bioavailability properties.

A simple, quick, and cost-effective protocol is presented herein for the sustainable synthesis of 2-(N-arylamino)benzothiazoles from 2-haloanilines and arylisothiocyanates by using an ionic liquid supported heterogeneous Cu(II) catalyst derived from N-methylimidazole. Compared to the use of homogeneous catalysts and additives, which require long reaction times and high reaction temperatures, this methodology has a broad substrate scope and proceeds in short reaction times to afford compounds in excellent yields under microwave irradiation. In addition, the catalyst can be extracted easily and is recyclable up to five times with no significant loss in catalytic activity.

An indium-catalyzed cyanomethylation of α-alkynyl α,β-unsaturated ketones with 3-azido-2-methylbut-3-en-2-ol is presented. Furan-substituted propanenitriles were produced in yields of 29–97%. The reaction involves a nucleophile addition/cycloisomerization process.

A mild, metal, and photoredox-free direct arylation of alkyl and aryl thiols with aryl iodides using a DMF/KOt-Bu system has been developed. In the absence of an N-heterocyclic carbene (NHC) additive, the reaction proceeds via a benzyne intermediate and was suitable for the substitution of thiols with phenyl, while the presence of an NHC or phenanthroline derivative improves regioselectivity for the reaction of substituted aryl iodides via a radical pathway. This protocol features inexpensive materials and good substrate scope and could be useful in the arylation of aryl and alkyl thiols.

In recent years, formal cycloaddition reactions involving bicyclo[1.1.0]butanes (BCBs) have furnished an array of innovative methodologies and strategies for the efficient synthesis of bicyclo[2.1.1]hexanes (BCHs). Most methods can be broadly classified into two main modes: the radical pathway and the two-electron pathway. This Synpacts article will summarize the recent advancements in Lewis acid catalyzed formal cycloaddition reactions involving BCBs with alkenes, dipolar molecules, and alkynes, spanning the period from 2022 to 2024. Additionally, we introduce the formal cycloaddition reaction of BCBs with ynamides, catalyzed by Sc(OTf)3, which has been recently developed by our group. This approach offers a novel and efficient method for the synthesis of polysubstituted 2-amino-bicyclo[2.1.1]hexenes.1 Introduction2 Lewis Acid Catalyzed Formal Cycloaddition of BCBs with Alkenes and Dipoles3 Lewis Acid Catalyzed Formal Cycloaddition of BCBs with Alkynes4 Conclusion

The furan and thiophene skeleton structures are widely present in natural products and synthetic drugs, and display multiple bioactivities. An effective one-pot three-component reaction to access furan and thiophene derivatives from 2-bromo-5-(dichloromethyl)furan or -thiophene; cyanoacetate esters, cyanoacetamides, or malononitrile; and aliphatic secondary amines has been developed. The multicomponent reaction for the construction of new C–N and C–C bonds in one pot is simple, mild, and efficient, and the yield of the target product is as high as 96%.

We report a catalyst-free intermolecular hydride-transfer reaction to synthesize N-benzylindolines under microwave heating in the absence of a solvent. The reactions are performed by taking indoline (two equivalents) with aryl aldehydes, which give good yields of products. Tetrahydroisoquinoline can also be used in place of indoline to give excellent yields of the expected products. A mechanism has also been proposed. The antioxidant properties of all the N-benzylindolines were tested and compared with that of ascorbic acid, showing that some of them are powerful antioxidants.