Development and Application of Trifluoromethoxylating Reagents

Abstract

Comprehensive Summary The trifluoromethoxy functional group has received increasing attention in recent years due to its distinctive properties such as good metabolic stability, appropriate lipophilicity and special electrical properties. Thus, the development of new reagents and new strategies of direct trifluoromethoxylation are attracting the enthusiasm of many fluorine chemical workers. At present, nucleophilic and radical trifluoromethoxylating reagents have made major breakthroughs, greatly promoting the development of trifluoromethoxy chemistry. This review is mainly divided into two parts: nucleophilic and radical types, focusing on the development history, characteristics and applications of various trifluoromethoxylating reagents.

Review and Theoretical Analysis of Fluorinated Radicals in Direct CAr−H Functionalization of (Hetero)arenes

“…The trifluoromethoxy (OCF 3 ) group has emerged as a valuable functional group in various fields of chemical research. [82,83] Notably, the OCF 3 group in aryl trifluoromethylethers, unlike its methoxy analogue (OCH 3 ), lies orthogonal to the arene ring due to the poor conjugation of the oxygen lone pair in the aromatic ring owing to its delocalization in the adjacent CÀ F bond. [84][85][86] Traditionally, aryl trifluoromethylethers were obtained by electrophilic trifluoromethylation of phenols.…”

Transition-metal-catalyzed straightforward synthesis of N-trifluoromethyl indoles from 2-alkynylaryl isothiocyanates or 2-alkynylanilines

“…Incorporation of the trifluoromethyl (CF 3 ) group into organic molecules has been a subject of intense research in the fields of medicinal chemistry 1 and materials science 2 due to their specific physicochemical properties such as higher metabolic stability, stronger lipophilicity and greater bioavailability. 3 Although trifluoromethylation coupled with C -CF 3 , S -CF 3 , and O -CF 3 bond formation has made remarkable progress over the past decade, 4 N -trifluoromethylation remains scarcely investigated as a result of lack of efficient reagents and methods for the construction of the trifluoromethylamino (NCF 3 ) moiety. 5 Traditional synthetic methods for the NCF 3 moiety suffer from tedious procedures or the use of hazardous reagents (SF 4 , BrF 3 , or HF), including the halogen–fluorine exchange reaction of N -trihalomethyl and deoxy-(sulfur)-fluorination of N -thiocarbonyl.…”

Design, Synthesis and Antifungal Activities of Novel Pyrazole Analogues Containing the Aryl Trifluoromethoxy Group

“…The fungicides with a pyrazole moiety have been applied to manage a variety of diseases in crops, fruits, and vegetables. The installation of OCF3 into the proper positions of agrochemicals would lead to efficiently enhanced chemical and metabolic stability as well as improved lipophilicity and bioavailability [21]. Moreover, as the OCF3 group is attached to an aromatic ring, a unique and stable conformation where the dihedral angle of the C=C-O-CF3 bond is close to 90° would be set [22].…”