81577-07-3

Upstream product

• 1421521-60-9 (1-(4-chlorophenyl)-2,2-difluorovinyl)triethylsilane 
• 15183-58-1 O-(4-chlorobenzyl) S-methyl carbonodithioate 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 129946-88-9 Umemoto's reagent 
• 680-15-9 2,2-difluoro-2-(fluorosulfonyl)acetate 
• 910212-97-4 4-chlorobenzyl diphenylphosphinite 
• 106-43-4 para-chlorotoluene 
• 1680206-12-5 Grushin’s reagent 
• 637-87-6 1-Chloro-4-iodobenzene 
• 353-83-3 1,1,1-trifluoro-2-iodoethane 
• 104-88-1 4-chlorobenzaldehyde 
• 887144-94-7 Togni's reagent II 
• 52372-80-2 (4-chlorobenzylidene)hydrazine 
• 1679-18-1 4-Chlorophenylboronic acid 

Downstream Products

• 81577-16-4 1-(1-bromo-2,2,2-trifluoroethyl)-4-chlorobenzene 
• 394-54-7 1-chloro-1-(4-chlorophenyl)-2,2,2-trifluoroethane 

Relevant academic research and scientific papers

Nickel-Catalyzed Direct Trifluoroethylation of Aryl Iodides with 1,1,1-Trifluoro-2-Iodoethane via Reductive Coupling

A nickel-catalyzed direct trifluoroethylation of aryl iodides with an industrial raw material CF3CH2I has been developed, demonstrating high efficiency, excellent functional-group compatibility, especially with large sterically hindered groups. The key to success is the combination of nickel with readily available nitrogen and phosphine ligands. The powerful potential of this strategy is further demonstrated by the late-stage modification of several derived bioactive molecules. (Figure presented.).

Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2-Trifluoroethyl)arenes

Reacting hydrazones of arylaldehydes with Togni's CF3-benziodoxolone reagent, in the presence of potassium hydroxide and cesium fluoride, induces a denitrogenative hydrotrifluoromethylation event to produce (2,2,2-trifluoroethyl)arenes. This novel reaction was tolerant to many electronically-diverse functional groups and substitution patterns, as well as naphthyl- and heteroaryl-derived substrates. Advantages of this process include the easy access to hydrazone precursors on a large scale, speed and operational simplicity, and being transition metal-free.

Csp3-Csp3 Bond-Forming Reductive Elimination from Well-Defined Copper(III) Complexes

Carbon-carbon bond-forming reductive elimination from elusive organocopper(III) complexes has been considered the key step in many copper-catalyzed and organocuprate reactions. However, organocopper(III) complexes with well-defined structures that can undergo reductive elimination are extremely rare, especially for the formation of Csp3-Csp3 bonds. We report herein a general method for the synthesis of a series of [alkyl-CuIII-(CF3)3]- complexes, the structures of which have been unequivocally characterized by NMR spectroscopy, mass spectrometry, and X-ray crystal diffraction. At elevated temperature, these complexes undergo reductive elimination following first-order kinetics, forming alkyl-CF3 products with good yields (up to 91%). Both kinetic studies and DFT calculations indicate that the reductive elimination to form Csp3-CF3 bonds proceeds through a concerted transition state, with a ΔH? = 20 kcal/mol barrier.

Aqueous Benzylic C-H Trifluoromethylation for Late-Stage Functionalization

The installation of trifluoromethyl groups has become an essential step across a number of industries such as agrochemicals, drug discovery, and materials. Consequently, the rapid introduction of this critical functional group in a predictable fashion would benefit current practitioners in those fields. This communication describes a mild trifluoromethylation of benzylic C-H bonds with high selectivity for the least hindered hydrogen atom. The reaction provides monotrifluoromethylation and proceeds in an environmentally friendly acetone/water solvent system. The method can be used to install benzylic trifluoromethyl groups on highly functionalized drug molecules.

Copper-Mediated Trifluoromethylation of Benzylic Csp3?H Bonds

Trifluoromethyl-containing compounds play a significant role in medicinal chemistry, materials and fine chemistry. Although direct C?H trifluoromethylation has been achieved on Csp2?H bonds, direct conversion of Csp3?H bonds to Csp3?CF3 remains challenging. We report herein an efficient protocol for the selective trifluoromethylation of benzylic C?H bonds. This process is mediated by a combination CuIII?CF3 species and persulfate salts. A wide range of methylarenes can be selectively trifluoromethylated at the benzylic positions. A combination of experimental and theoretical mechanistic studies suggests that the reaction involves a radical intermediate and a CuIII?CF3 species as the CF3 transfer reagent.

Synthesis of trifluoromethylated compounds from alcohols via alkoxydiphenylphosphines

The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl was achieved via the reaction of the corresponding alkyloxydiphenylphosphine and CuCF3, generated in situ from methyl fluorosulfonyldifluoroacetate and CuI, under mild conditions. A plausible mechanism was proposed on the basis of experimental results.

Switchable 2,2,2-trifluoroethylation and gem-difluorovinylation of organoboronic acids with 2,2,2-trifluorodiazoethane

The transition-metal-free 2,2,2-trifluoroethylation and gem-difluorovinylation of arylboronic acids were developed. By employing different reaction conditions, these transformations provide both (2,2,2-trifluoroethyl)arenes and gem-difluorovinylarenes fro

Efficient synthesis of silylated 2,2-difluorostyrene derivatives through Suzuki-Miyaura cross-coupling of 2,2-difluoro-1-iodo-1-silylethenes

We report a new synthetic sequence for the preparation of silylated 2,2-difluorostyrene derivatives. This new route has numerous advantages over the previous one including enhanced scope, higher yields, ease of purification, and significant reduction of the amount of desilylated side-products. An unexpected transformation of a silylated 2,2-difluorostyrene derivative is also presented.

Copper-mediated deoxygenative trifluoromethylation of benzylic xanthates: Generation of a C-CF3 bond from an O-based electrophile

The conversion of an alcohol-based functional group, into a trifluoromethyl analogue is a desirable transformation. However, few methods are capable of converting O-based electrophiles into trifluoromethanes. The copper-mediated trifluoromethylation of benzylic xanthates using Umemoto's reagent as the source of CF3 to form C-CF3 bonds is described. The method is compatible with an array of benzylic xanthates bearing useful functional groups. A preliminary mechanistic investigation suggests that the C-CF3 bond forms by reaction of the substrate with in situ generated CuCF3 and CuOTf. Further evidence suggests that the reaction could proceed via a radical cation intermediate. Highly compatible and useful: The copper-mediated trifluoromethylation of benzylic xanthates using Umemoto's reagent as the source of CF3 to form C-CF3 bonds is described (see scheme). The method is compatible with an array of benzylic xanthates bearing useful functional groups. A preliminary mechanistic investigation suggests that the C-CF3 bond forms by reaction of the substrate with in situ generated CuCF3 and CuOTf. Copyright

Study on the addition of hydrogen fluoride to 2',2'-difluorostyrenes

2,2,2-Trifluoroethylarenes were obtained in good yield from the addition of KF to 2',2'-difluorostyrenes in the presence of crown ether. A linear regression line obtained from correlation between log(reaction rate) and Hammett constants with slope of +4.28 suggested that this addition process is very sensitive to the substituents on the phenyl ring.