Advances in the Development of Trifluoromethoxylation Reagents

Abstract

This review provides a short summary of the traditional methods for synthesis of CF3-O-containing compounds, followed by a critical overview of known trifluoromethoxylating reagents, focusing on their preparation, synthetic generality and limitations.

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

“…Despite these advances, synthetic challenges still need to be overcome. These synthetic tools are so far still restricted to some fluorinated moieties and extension to other high valueadded fluorinated residues [131,136,[193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208] is of high importance. Besides, in comparison with the functionalization of C(sp 2 ) centers on aromatic and vinylic derivatives, transitionmetal-catalyzed functionalization of C(sp 3 )-H bonds remains largely underexplored to date.…”

Rapid Multikilogram Scale-Up of Di- and Trifluoromethoxy Proline Derivatives

“…Most of these drugs contain fluoroaryl or trifluoromethylaryl moieties, while only a few drugs display difluoromethyl or trifluoromethyl ether functionalities, of which none are aliphatic (Figure ). While there are several methods to prepare fluoromethyl ethers, the direct conversion of chiral aliphatic alcohols to their corresponding di- and trifluoromethoxy counterparts is scarce in the literature. − To the best of our knowledge, no kilogram scale-up of these chiral aliphatic –OCF 2 H or –OCF 3 motifs was reported at the onset of this study.…”

“…5,29−34 Traditional ways for the construction of the O−CF 3 bond rely mainly on (a) activation of alcohol functionality toward intermediates prone to deoxy-or dethiofluorination reactions or (b) direct electrophilic trifluoromethylation of the alcohol (TMSCF 3 , Togni's or Umemoto's reagents). 6 More recently, methods to stabilize the trifluoromethoxy anion have been developed through identification of suitable counterions (e.g., Ag, 35,36 Cs, 37 alkyl ammonium 38 or sulfonium salts, 39 and pyridinium salts 40 ). This has in part enabled the development of nucleophilic functionalization reactions with prefunctionalized starting materials like alkyl halides, 41 boronates, 42 and alkyl silanes 43 (Figure 5c).…”

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

“…There are recent review articles on trifluoromethoxylation reactions in the literature, [19–26] whose classifications are based on types of trifluoromethoxylating reagents, [21,26] types of reactions such as nucleophilic, metal‐assisted or catalytic reactions, [19,22] and methodologies based on direct or indirect methods [25] . A classification of trifluoromethoxylation reactions based on distinct families of organic compounds is pertinent and useful for synthetic organic chemists.…”