Synthesis of Fluorinated Amide Derivatives via a Radical N-Perfluoroalkylation–Defluorination Pathway

Abstract

A one-pot approach to fluorinated hydroxamic acid, amide, and thioamide derivatives is reported. The reaction proceeds via an N-perfluoroalkylation of nitrosoarenes with perfluoroalkanesulfinates, resulting in labile N-perfluoroalkylated hydroxylamines. By the addition of suitable additives, a controllable oxy/thiodefluorination of the fluorinated hydroxylamine intermediates was achieved. The method highlights N-perfluoroalkylated amines as versatile intermediates for further synthesis.

Dehydrative Ring‐Opening of gem‐Difluorocyclopropyl Carbinols to Allylic Trifluoromethyl and Difluorohalomethyl Derivatives Promated by Titanium Tetrahalide

“…The imide 7 was unexpectedly formed when acetonitrile was employed as the solvent (entry 11). The formation of 7 is possibly ascribable to a defluorinative hydrolysis process, in which the nitrile rather than the fluoride ion is involved in the initial nucleophilic ring‐opening of the gem ‐difluoromethyl group to form an unstable intermediate which, in turn, undergoes facile hydrolysis of its difluoromethyl and nitrile moieties Therefore, we conclude that the conditions shown in entry 6 are optimal and were subsequently used in the general procedure.…”

Radical Perfluoroalkylation of Aliphatic Substrates

“…The authors 156 Xiao, Ko, and colleagues 157 reported the photocatalytic amidation and esterification with perfluoroalkyl iodides toward the construction of perfluoroalkyl amides and esters. The scope of the transformation is depicted in Scheme 62.…”

“…Zheng, Selander, and colleagues reported a one-pot N -perfluoroalkylation reaction of nitrosoarenes for the synthesis of fluorinated hydroxamic acids, amides, and thioamides via an N -perfluorinated hydroxylamine intermediate. The scope of the transformation is illustrated in Scheme .…”

Stable and Storable N(CF3)2 Transfer Reagents

“…In contrast to perfluoroalkyl and perfluoroalkoxy groups, the chemistry of related perfluoroalkyl nitrogen substituents has been studied to a much lesser extent. Some synthetic strategies towards N ‐trifluoromethylamines and related N ‐perfluoroalkylnitrogen derivates have been developed in recent years [28–38] . Efficient strategies towards N , N ‐bis(perfluoroalkyl)nitrogen compounds remain scarce, presumably, because of the lack of suitable starting materials [18,39–40] .…”

“…Some synthetic strategies towards N ‐trifluoromethylamines and related N ‐perfluoroalkylnitrogen derivates have been developed in recent years. [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] Efficient strategies towards N , N ‐bis(perfluoroalkyl)nitrogen compounds remain scarce, presumably, because of the lack of suitable starting materials. [ 18 , 39 , 40 ] Especially the N , N ‐bis(trifluoromethyl)amino group is of interest as its organic derivatives are known to exhibit high stability, for example against acids and bases,[ 1 , 41 ] and because its potential as substituent in pharmaceuticals was demonstrated, earlier.…”