365-01-5

Upstream product

• 1494-20-8 2,2-difluoro-1,2-diphenylethan-1-ol 
• 5344-88-7 benzil monohydrazone 
• 67-56-1 methanol 
• 501-65-5 diphenyl acetylene 
• 3469-17-8 2-diazo-1,2-diphenylethan-1-one 
• 151416-94-3 (Z)-2,2'-[1,2-(biphenyl)eth-1-ene-1,2-diyl]bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) 
• 109-73-9 N-butylamine 
• 108-86-1 bromobenzene 
• 86340-78-5 2,2-difluoro-1-phenyl-1-trimethylsiloxyethene 
• 451-40-1 phenyl benzyl ketone 
• 530-48-3 1,1-Diphenylethylene 
• 1041934-93-3 C₁₀H₁₁F₂NO₂ 
• 591-51-5 phenyllithium 
• 73183-34-3 bis(pinacol)diborane 

Downstream Products

• 134-81-6 benzil 
• 917988-91-1 2-(tert-butyl)-4,5-diphenyloxazole 
• 26820-94-0 methyl 3-(4,5-diphenyloxazol-2-yl)propanoate 
• 200802-52-4 2-(2-nitrophenyl)-4,5-diphenyloxazole 
• 97015-53-7 2-(4-methoxyphenyl)-4,5-triphenyloxazole 
• 6963-24-2 2,3,5,6-tetraphenyl-1,4-dioxine 
• 66302-37-2 2-(4-chlorophenyl)-4,5-diphenyloxazole 
• 35040-28-9 2-(4-fluorophenyl)-4,5-diphenyloxazole 
• 573-34-2 2,4,5-triphenyloxazole 
• 119-53-9 2-hydroxy-2-phenylacetophenone 
• 720-43-4 2-fluoro-1,2-diphenylethanone 
• 14224-99-8 2-methyl-4,5-diphenyloxazole 
• 1494-20-8 2,2-difluoro-1,2-diphenylethan-1-ol 

Relevant academic research and scientific papers

Kinetics of Electrophilic Fluorinations of Enamines and Carbanions: Comparison of the Fluorinating Power of N-F Reagents

Kinetics of the reactions of enamines and carbanions with commonly used fluorinating reagents, N-fluorobenzenesulfonimide (NFSI), N-fluoropyridinium salts, Selectfluor, and an N-fluorinated cinchona alkaloid, have been investigated in acetonitrile. The reactions follow second-order kinetics, and from the measured rate constants one can derive that the fluorinations proceed via direct attack of the nucleophiles at fluorine, not by SET processes. Correlations of the fluorination rates with the pKaH values of the nucleofugal leaving groups and the calculated fluorine plus detachment energies are discussed. The rate constants for the reactions with deoxybenzoin-derived enamines follow the linear free energy relationship log k2(20 °C) = sN(N + E) which allows the empirical electrophilicity parameters E for these fluorinating agents to be derived from the measured rate constants and the tabulated N and sN parameters for the nucleophiles. Though the deviations of the measured rate constants from those calculated by this relationship are larger than for reactions of Csp2-centered electrophiles with nucleophiles, it is shown that the electrophilicity parameters E reported in this work are able to rationalize known fluorination reactions and are, therefore, recommended as guide for designing new electrophilic fluorinations.

FLUORINATING AGENT AND METHOD FOR PRODUCING FLUORINE-CONTAINING COMPOUNDS

The present invention provides the compound represented in general formula (A1) [Ar1 is a C6-14 aryl group or a C5-14 nitrogen-containing heteroaryl group, substituted with at least two electron-attracting groups; R1 is a C1-30 alkyl group, a C6-14 aryl group, or a C5-14 nitrogen-containing heteroaryl group; the electron-attracting group is a halogen atom, a trihalomethyl group, a cyano group, a nitro group, -CO2R or -CO2N(R)2 (the Rs independently represent C1-30 alkyl groups)].

Bench-Stable Electrophilic Fluorinating Reagents for Highly Selective Mono- and Difluorination of Silyl Enol Ethers

Efficient methods for the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench-stable electrophilic fluorinating reagents were synthesized as N-fluorobenzenesulfonimide (NFSI) substitutes. Reagents obtained by replacing one of the NFSI sulfonyl groups with an acyl group led to the highly selective monofluorination of silyl enol ethers with suppression of undesired overreaction, that is, difluorination. On the other hand, reagents bearing electron-withdrawing substituents at NFSI benzenesulfonyl groups efficiently facilitated the difluorination of silyl enol ethers under base-free conditions. Thus, both mono- and difluorinated target materials were prepared from the same substrate.

Trifluoromethylthiolation, Trifluoromethylation, and Arylation Reactions of Difluoro Enol Silyl Ethers

This study reports a new application area of difluoro enol silyl ethers, which can be easily obtained from trifluoromethyl ketones. The main focus has been directed to the electrophilic fluoroalkylation and arylation methods. The trifluoromethylthiolation of difluoro enol silyl ethers can be used for the construction of a novel trifluoromethylthio-α,α-difluoroketone (-COCF2SCF3) functionality. The -CF2SCF3 moiety has interesting properties due to the electron-withdrawing, albeit lipophilic, character of the SCF3 group, which can be combined with the high electrophilicity of the difluoroketone motif. The methodology could also be extended to difluoro homologation of the trifluoromethyl ketones using the Togni reagent. In addition, we presented a method for transition-metal-free arylation of difluoro enol silyl ethers based on hypervalent iodines.

Development and Mechanistic Investigations of a Base-Free Suzuki-Miyaura Cross-Coupling of α,α-Difluoroacetamides via C-N Bond Cleavage

This study describes the development and understanding of a palladium-catalyzed cross-coupling of fluoroacetamides with boronic acids, under base-free conditions, to selectively give valuable α,α-difluoroketone derivatives. Detailed mechanistic studies were conducted to assess the feasibility of each elementary step, that is, C(acyl)-N bond oxidative addition, followed by base-free transmetallation and reductive elimination. These investigations allowed the structural characterization of palladium(II)fluoroacyl intermediates derived from C-N bond oxidative addition of an amide electrophile. They also revealed the high reactivity of these intermediates for transmetallation with boronic acids without exogenous base. The mechanistic studies also provided a platform to design a practical catalytic protocol for the synthesis of a diversity of α,α-difluoroketones, including CF2H-ketones. Finally, the synthetic potential of this fluoroacylation methodology is highlighted in sequential, orthogonal C-Br and C-N bond functionalization of an α-bromo-α,α-difluoroacetamide with a focus on compounds of potential biological relevance.

Lewis acid-mediated defluorinative [3+2] cycloaddition/aromatization cascade of 2,2-difluoroethanol systems with nitriles

The properties of C?F bonds, including high thermal and chemical stability, make derivatization of organic fluorine-containing compounds by the activation of the C?F bond and subsequent functionalization quite challenging. We herein report a Lewis acid-mediated defluorinative cycloaddition/aromatization cascade of 2,2-difluoroethanols with nitriles as a novel synthetic method for the preparation of 2,4,5-trisubstituted oxazoles. This reaction, which involves cleavage of two C?F bonds and the consecutive formation of C?O and C?N bonds in a one-pot fashion, features a broad substrate scope and moderate to high reaction yields. Mechanistic studies revealed that the reaction is initiated by the Lewis acid-mediated ring closure of the 2,2-difluoroethanol to produce the fluoroepoxide intermediate. (Figure presented.).

Visible-light-initiated difluoromethylation of arene diazonium tetrafluoroborates

A mild and efficient method for the radical addition of α-aryl-β,β-difluoroenol silyl with arene diazonium tetrafluoroborates at room temperature has been disclosed, which involves an innate radical long chain cycle, so only a small amount (0.05 mol%) of photocatalyst and a short light exposure time are required as radical initiators. A proposed mechanism for the transformation is also illustrated based on the results of control experiments and quantum calculations. A variety of α-aryl-α,α-difluoroketones were formed in moderate to high yields, and can be easily further transformed into various difluoromethylarenes under basic conditions.

FLUORINATING AGENT

An object of the present invention is to provide a novel substance that has a high reactivity as a fluorinating agent, is effectively used in various fluorination reactions, and is safely handled even in air. As the solution for achieving this object, the present invention provides a complex obtained by reacting bromine trifluoride with at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals in a nonpolar solvent. This complex serves as a fluorinating agent that provides excellent fluorination performance and that is stable in air.

Synthesis of18F-Difluoromethylarenes from Aryl (Pseudo) Halides

A general method for the synthesis of [18F]difluoromethylarenes from [18F]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay-corrected) from 10 to 60 %. The18F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven18F-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [18F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design.

Pd-catalyzed α-arylation of α,α-difluoroketones with aryl bromides and chlorides. A route to difluoromethylarenes

We report the Pd-catalyzed α-arylation of α,α- difluoroketones with aryl and heteroaryl bromides and chlorides catalyzed by an air- and moisture-stable palladacyclic complex containing P(t-Bu)Cy2 as ligand. The combination of this Pd-catalyzed arylation and base-induced cleavage of the acyl-aryl C-C bond within the α-aryl-α,α- difluoroketone constitutes a one-pot, two-step procedure to synthesize difluoromethylarenes from aryl halides. A broad range of electronically varied aryl and heteroaryl bromides and chlorides underwent these two transformations, providing α-aryl-α,α-difluoroketones, difluoromethylarenes, and difluoromethylheteroarenes in high yields.