Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers

Abstract

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 OCF 3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected S N Ar products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.

Mechanochemical Defluorinative Arylation of Trifluoroacetamides: An Entry to Aromatic Amides

“…In this perspective, mechanochemically induced transformations as solvent-free and energy-efficient processes have gained substantial interest. − Of note, the employment of trifluoroacetamides in carbamoylation reactions can be considered as an effort toward environment remedy as organofluorine compounds are long-lived and persistent in the environment. In view of the above and in pursuit of our research efforts in the chemistry of fluorinated organic compounds, , herein, we report a facile protocol for defluorinative coupling of trifluoroacetamides with four different arylating agents, namely, arylboronic acids, trimethoxyphenylsilanes, diaryliodonium salts, and dimethyl­(phenyl)­sulfonium salts (Scheme ), yielding a wide variety of substituted amides.…”

Trifluoromethoxylation Reactions of (Hetero) arenes, Olefinic Systems and Aliphatic Saturated Substrates

“…Silver-mediated trifluoromethoxylations of aryl stannanes and aryl boronic acids (II, Figure 5) with reagent 2 (Figure 3) have been reported for the trifluoromethoxylation of arenes. [54,55] Nucleophilic reagent 5 (Figure 3) has recently been employed in the substitution of TMS group (III, Figure 5) with CF 3 O moiety towards the syntheses of trifluoromethyl aryl ethers. [46] Reagent 7B [56] (Figure 3) has recently been used in the nucleophilic [57] trifluoromethoxylation of anilines (IV, Figure 5).…”

Bio‐Inspired Deaminative Hydroxylation of Aminoheterocycles and Electron‐Deficient Anilines

“…Beyond deaminative hydroxylation of aminoheterocycles, electron‐deficient anilines were also explored (Figure 4A) [31] . Phenols bearing one or two nitro groups could be easily obtained using the same strategy ( 40 , 41 and 42 ).…”

“…[30] Beyond deaminative hydroxylation of aminoheterocycles, electron-deficient anilines were also explored (Figure 4A). [31] Phenols bearing one or two nitro groups could be easily obtained using the same strategy (40, 41 and 42). The observed moderate yields result from the slow condensation of the pyrylium salt 1 with the poorly nucleophilic aniline.…”