Trifluoromethoxylation of Arenes: Synthesis of ortho‐Trifluoromethoxylated Aniline Derivatives by OCF₃ Migration

Abstract

Aryl trifluoromethoxylation by a two‐step sequence of O‐trifluoromethylation of N‐aryl‐N‐hydroxylamine derivatives and intramolecular OCF3 migration is presented. This protocol allows easy access to a wide range of synthetically useful ortho‐OCF3 aniline derivatives. In addition, it utilizes bench‐stable reagents, is operationally simple, shows high functional‐group tolerance, and is amenable to gram‐scale as well as one‐pot synthesis. A reaction mechanism of a heterolytic cleavage of the NOCF3 bond followed by recombination of the resulting nitrenium ion and trifluoromethoxide is proposed for the OCF3‐migration reaction.

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

“…Since N-hydroxy anilides can be prepared readily by reacting phenylhydroxylamine (12)w ith either acyl chloride or bromide, [23] we turned our attention to testing the possibility of ao ne-pot process for the synthesis of 11 and 8 (Scheme 3). In the one-pot process,2-bromo-2-methylpropanoyl bromide (13;R 2 = R 3 = Me,X 1 = X 2 = Br) was added dropwise to am ixture of 12 and KHCO 3 in ether, with subsequent evaporation of the ether solvent and addition of HFIP.T he reaction mixture was then stirred for another 5hours at room temperature,t hus resulting in the desired product 8a in 68 %y ield.…”

Trifluoromethylation of Allenes: An Expedient Access to α‐Trifluoromethylated Enones at Room Temperature

“…The ubiquity of trifluoromethyl group (-CF 3 ) [1,2] in myriads of pharmaceuticals, agrochemicalsa nd functional materials has inspiredc hemistst od evelop numerous trifluoromethylation strategies over the years. [3,4] Amongd ifferent protocols, trifluoromethylr adicalb ased methods were found to be highly captivating due to their highr eactivity, milder reaction conditions, and easily accessible resources. [5][6][7] In spite of having advantageous features, an umber of important trifluoromethylated scaffold synthesess till remain unaddressed.…”

Regioselective Synthesis of N‐Heteroaromatic Trifluoromethoxy Compounds by Direct O−CF3 Bond Formation

“…Most current routes to trifluoromethoxyc ompounds fall into two main categories:1 )the fluorine atomsa re introducedby chlorine-fluorine exchange, deoxyfluorination of fluoroformates, or oxidative fluorodesulfurization under hazardousa nd harsh reactionc onditions; [7] 2) trifluoromethoxy compounds were synthesized, based on construction of the CÀOCF 3 bond, by nucleophilic trifluoromethoxylation, [8] metal-mediated trifluoromethoxylation, [9] radical addition trifluoromethoxylation, [10] or OCF 3 migration. [11] Although OCF 3 can be introduced to organic molecules, most approaches either suffer from poor substrate scopeo rr equire use of highlyt oxic and/or thermally labile reagents. In addition, in some approaches, regioselectivity is difficult to control.…”

“…, entries[10][11][12]. When the reactiont emperature was increasedt o 100 8Ca nd the reaction time wass hortenedf rom 48 hours to 5h ours, ay ield of 67 %w as obtained(Table 1,entry 13).…”