66865-75-6

Upstream product

• 104-87-0 4-methyl-benzaldehyde 
• 624-31-7 4-tolyl iodide 
• 106-43-4 para-chlorotoluene 
• 195062-57-8 p-tolylboronic pinacol ester 
• 56228-54-7 2-((difluoromethyl)sulfonyl)-4,6-dimethylpyrimidine 
• 6140-17-6 4-methylbenzotrifluoride 
• 1493-03-4 iododifluoromethane 
• 5720-05-8 4-methylphenylboronic acid 
• 1511-62-2 bromodifluoromethane 
• 106-38-7 para-bromotoluene 
• 1219454-89-3 2-((difluoromethyl)sulfonyl)pyridine 
• 15106-88-4 di(p-tolyl)zinc 
• 52693-87-5 4-methylbenzaldehyde hydrazone 
• 3429-52-5 2,2,3-trimethyl-2-silabutane 

Relevant academic research and scientific papers

Arylsulfur trifluorides: Improved method of synthesis and use as in situ deoxofluorination reagents

Building on recent results of Umemoto and Winter, an improved method of synthesis of arylsulfur trifluorides, including the excellent, new deoxofluorination reagent Fluolead, is hereby reported. The method utilizes Br2 and KF as oxidizing and fluorinating reagents for efficient, high yield conversion of aryl disulfides and mercaptans to arylsulfur trifluorides. It has also been shown that both Fluolead and mesitylsulfur trifluoride may be generated in acetonitrile and used as in situ deoxofluorination reagents for conversion of either aldehydes or ketones to their respective gem-difluoro compounds. An analysis of the probable mechanism of action, including computational efforts, allows postulation of a rationale for the highly variable reactivities of different arylsulfur trifluorides as deoxofluorination reagents.

Iron-Catalyzed Fluoroalkylation of Arylborates with Sulfone Reagents: Beyond the Limitation of Reduction Potential

The iron-catalyzed alkyl–aryl coupling reaction between sulfones and arylboron compounds has remained a challenge. We report the first iron-catalyzed radical difluoroalkylation of arylborates with N-heteroaryl sulfones. The coordination between the iron catalyst and the nitrogen atom of N-heteroaryl sulfones was identified to be important in overcoming the reduction potential limitation of sulfones in the intermolecular single-electron-transfer process, which enables both fluoroalkyl N-heteroaryl sulfones (with relatively high reduction potentials) and nonfluorinated alkyl N-heteroaryl sulfones (with low reduction potentials) to serve as powerful alkylation reagents.

A NEW METHOD OF 18F LABELLING AND INTERMEDIATE SALTS

Disclosed herein is a salt of formula I: where R1, X, n, R, R1, Y, m, p, q, Z and o are as defined herein. Also disclosed herein are methods of using said salts in chemical synthesis, such as to prepare compounds isotopically enriched in 18F for use in PET imaging, as well as methods to make the compounds of formula I.

METHOD AND REAGENT FOR DEOXYFLUORINATION

A safe, simple, and selective method and reagent for deoxyfluorination is disclosed. With the method and reagent disclosed herein, organic compounds such as carboxylic acids, carboxylates, carboxylic acid anhydrides, aldehydes, and alcohols can be fluorinated by using the most common nucleophilic fluorinating reagents and electron deficient fluoroarenes as mediators under mild conditions, giving corresponding fluoroorganic compounds in excellent yield with a wide range of functional group compatibility and easy product purification. For example, directly utilizing KF for deoxyfluorination of carboxylic acids provides the most economical and the safest pathway to access acyl fluorides, key intermediates for syntheses of peptide, amide, ester, and dry fluoride salts.

Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups

Single fluoride substitution in trifluoromethylarenes is an ongoing synthetic challenge that often leads to "over-reaction", where multiple fluorides are replaced. Development of this reaction would allow simple access to a vast range of difluoromethyl derivatives of current interest to pharmaceutical, agrochemistry, and materials sciences. Using a catalytic frustrated Lewis pair approach, we have developed a generic protocol that allows a single substitution of one fluoride in trifluoromethyl groups with neutral phosphine and pyridine bases. The resulting phosphonium and pyridinium salts can be further functionalized via nucleophilic substitution, photoredox coupling, and electrophilic transfer reactions allowing the generation of a vast array of difluoromethyl products.

Precatalyst Effects on Pd-Catalyzed Cross-Coupling Difluoromethylation of Aryl Boronic Acids

The Pd-catalyzed difluoromethylation of aryl boronic acids with difluoroiodomethane is shown to provide the difluoromethyl compounds in high to moderate yields by Pd(PPh3)2/DPEphos catalyst in H2O/toluene. Mechanistic studies show that the oxidative addition by Pd(PPh3)4 rather than Pd2(dba)3 precatalyst to difluoroiodomethane provides a square-planar trans-(PPh3)2Pd(II)(CF2H)I complex defined by X-ray crystallographic analysis. The trans-(PPh3)2Pd(CF2H)I complex is transformed to cis-(PPh3)2Pd(CF2H)Ph detected by low temperature NMR analysis, via transmetalation with phenylboronic acids. The reductive elimination occurs via ligand exchange to DPEphosPd(CF2H)Ph to give Ph-CF2H (t1/2 = 144.7 min at 20 °C) with formation of the Pd(0)(PPh3)2/DPEphos catalyst.

Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2-Pyridyl Sulfone

We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C-S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the involvement of radical species in this iron-catalyzed difluoromethylation process.

Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature

Methods for the direct synthesis of difluoromethylated arenes are sparse, despite the importance of the difluoromethyl group in medical, agro-, and materials chemistry. A palladium-catalyzed decarbonylative cross-coupling reaction of acid chlorides with a difluoromethyl zinc reagent is achieved to access difluoromethylated compounds. The transformation proceeds at room temperature and shows broad functional group tolerance, thus providing a general and efficient method for decarbonylative difluoromethylation of a wide range of aromatic carboxylic acids.

Metallaphotoredox Difluoromethylation of Aryl Bromides

Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl-radical-mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late-stage functionalization of several drug analogues.

Synthesis of Aryldihalomethanes by Denitrogenative Dihalogenation of Benzaldehyde Hydrazones

We report a denitrogenative dihalogenation reaction of phenyldiazomethanes in which the hypervalent iodine reagents PhICl2 and TolIF2 act as surrogates for elemental chlorine and fluorine. Halogen transfer from iodane to aryldiazomethane is described, as is a tandem oxidative dihalogenation reaction between iodane and hydrazone. This is the first use of non-α-stabilized diazo compounds in this reaction, which provided an efficient synthesis of aryldifluoromethane (ArCHF2) and aryldichloromethane (ArCHCl2) derivatives. (Figure presented.).