Aryl Trifluoromethyl Ethers Research Articles

Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers.

Increased interest in the trifluoromethoxy group in organic synthesis and medicinal chemistry has induced a demand for new, selective, general, and faster methods applicable to natural products and highly functionalized compounds at a later stage of hit-to-lead campaigns. Applying pyrylium tetrafluoroborate, we have developed a mechanochemical protocol to selectively substitute the aromatic amino group with the OCF3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected SNAr products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.

Electrochemical O-trifluoromethylation of electron-deficient phenols

A simple and sustainable one-step strategy for the preparation of electron-deficient aryl trifluoromethyl ethers (ArOCF3) from the corresponding phenols by electrochemical synthesis is presented. Anodic oxidation of trifluoromethane sulfinate (Langlois reagent) leads to direct O-trifluoromethylation of phenol-derivatives bearing fluorine, chlorine, bromine and nitrile substituents under mild conditions in yields up to 75% and in gram-scale. This electrochemical protocol provides an economic and green synthesis for an otherwise inaccessible class of molecules without the need for expensive or toxic reagents, oxidants or metal catalysts.

Sequential Xanthalation and O-Trifluoromethylation of Phenols: AProcedure for the Synthesis of Aryl Trifluoromethyl Ethers.

Molecules containing trifluoromethoxyaryl groups are of interest in pharmaceutical, agrochemical, and materials science research, due to their unique physical and electronic properties. Many of the known methods to synthesize aryl trifluoromethyl ethers require harsh reagents and highly controlled reaction conditions and rarely occur when heteroaromatic units are present. The two-step O-trifluoromethylation of phenols via aryl xanthates is one such method that suffers from these drawbacks. Herein, we report a method for the synthesis of aryl trifluoromethyl ethers from phenols by the facile conversion of the phenol to the corresponding aryl and heteroaryl xanthates with newly synthesized imidazolium methylthiocarbonothioyl salts and conversion of these xanthates to the trifluoromethyl ethers under mild reaction conditions.

Radical Trifluoromethoxylation of Arenes Triggered by a Visible-Light-Mediated N-O Bond Redox Fragmentation.

A simple trifluoromethoxylation method enables non-directed functionalization of C-H bonds on a range of substrates, providing access to aryl trifluoromethyl ethers. This light-driven process is distinctly different from conventional procedures and occurs through an OCF3 radical mechanism mediated by a photoredox catalyst, which triggers an N-O bond fragmentation. The pyridinium-based trifluoromethoxylation reagent is bench-stable and provides access to synthetic diversity in lead compounds in an operationally simple manner.

Fluorodecarboxylation: Synthesis of aryl trifluoromethyl ethers (ArOCF3) and thioethers (ArSCF3)

Fluorodecarboxylation of aryloxydifluoroacetic acid (ArOCF2CO2H) and arylmercaptodifluoroacetic acid (ArSCF2CO2H) towards ArXCF3 (X=O, S) using silver (I) salts in the presence of Selectfluor in a biphasic system with trifluoroacetic acid additive is discussed.

O-Trifluoromethylation of Phenols: Access to Aryl Trifluoromethyl Ethers by O-Carboxydifluoromethylation and Decarboxylative Fluorination.

A new strategy for the synthesis of aryl trifluoromethyl ethers (ArOCF3) by combining O-carboxydifluoromethylation of phenols and subsequent decarboxylative fluorination is reported. This protocol allows easy construction of functionalized trifluoromethoxybenzenes and trifluoromethylthiolated arenes (ArSCF3) in moderate to good yields. Moreover, it utilizes accessible and inexpensive reagents sodium bromodifluoroacetate and SelectFluor II and, thus, is practical for O-trifluoromethylation of phenols. The potential application of this method is demonstrated with the preparation of a plant-growth regulator, Flurprimidol.

ChemInform Abstract: Silver‐Mediated Oxidative Trifluoromethylation of Phenols: Direct Synthesis of Aryl Trifluoromethyl Ethers.

AbstractAg(I)‐mediated conversion of structurally diverse phenols to their CF3‐ethers is achieved using CF3‐SiMe3 as commercially available CF3‐nucleophile.

Synthesis of Trifluoromethoxylated (Hetero)Arenes via OCF3 Migration.

Incorporation of the OCF3 group into organic molecules, especially aromatic and heteroaromatic compounds, is recognized as one of the major challenges in synthetic organic chemistry. Although many attempts have been made to develop efficient trifluoromethoxylation strategies, most of the current approaches still require use of highly toxic, thermally unstable reagents, or impractical reaction conditions. Herein, we highlight a recent contribution from our group towards the synthesis of (hetero)aryltrifluoromethyl ethers. Our protocol is scalable, operationally simple, and allows an easy access to a wide range of synthetically useful ortho-OCF3 aniline derivatives, as well as functionalized trifluoromethoxylated pyridines and pyrimidines under mild reaction conditions.

Silver‐Mediated Oxidative Trifluoromethylation of Phenols: Direct Synthesis of Aryl Trifluoromethyl Ethers

AbstractAryl trifluoromethyl ethers (ArOCF3) are prevalent in pharmaceuticals, agrochemicals, and materials. However, methods for the general and efficient synthesis of these compounds are extremely underdeveloped and limited. Herein, we describe a highly efficient and general procedure for the direct O‐trifluoromethylation of unprotected phenols through a silver‐mediated cross‐coupling reaction using CF3SiMe3 as the CF3 source and exogenous oxidants. This novel oxidative trifluoromethylation provides access to a wide range of aryl trifluoromethyl ethers from simple phenols. The mild process was also applied to the late‐stage trifluoromethylation of a medicinally relevant compound.

Silver-Mediated Oxidative Trifluoromethylation of Phenols: Direct Synthesis of Aryl Trifluoromethyl Ethers.

Aryl trifluoromethyl ethers (ArOCF3 ) are prevalent in pharmaceuticals, agrochemicals, and materials. However, methods for the general and efficient synthesis of these compounds are extremely underdeveloped and limited. Herein, we describe a highly efficient and general procedure for the direct O-trifluoromethylation of unprotected phenols through a silver-mediated cross-coupling reaction using CF3 SiMe3 as the CF3 source and exogenous oxidants. This novel oxidative trifluoromethylation provides access to a wide range of aryl trifluoromethyl ethers from simple phenols. The mild process was also applied to the late-stage trifluoromethylation of a medicinally relevant compound.

Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.

A silver-mediated cross-coupling of trifluoromethoxide with aryl stannanes and arylboronic acids to give aryl trifluoromethyl ethers is reported. This is the first report of a transition-metal-mediated C(aryl)-OCF(3) bond formation.

Chemistry in hydrogen fluoride. 7. A novel synthesis of aryl trifluoromethyl ethers

Chemistry in hydrogen fluoride. 7. A novel synthesis of aryl trifluoromethyl ethers

Substituent effects on the 13C 19F coupling constants of substituted benzotrifluorides, aryl trifluoromethyl ethers, and aryl trifluoromethyl sulfides

The 13C- 19F coupling constants of a series of ortho-, meta- and para-substituted benzotrifluorides and of several para-substituted aryl trifluoromethyl ethers and sulfides were found to correlate with substituent electronic effects according to the dual substituent parameter equation of Taft using the σ R + scale.

A study of the infrared spectra of aryl trifluoromethyl ethers

1. The infrared spectra of seven aryl trifluoromethyl ethers have been obtained and the attribution of the trifluoromethoxy group absorption is discussed. The intense 1262±5 cm−1 (υCarom), 1178±10 cm−1 (νC-F), 1222±4 cm−1 (νc-f), and 925 cm−1 bands can be used in analysis for determining the presence of an OCF3 group in the benzene ring. 2. The shifts in the frequencies of theC-F valence vibrations show that transmission of the electron effects of the para substituent on the C-F bond via the ring-heteroatom system diminishes in the order-S->-O->-SO2-.