Trifluoroacetimidoyl halides: a potent synthetic origin

Abstract

In the review, recent advances in the synthetic applications of trifluoroacetimidoyl halides have been summarized.

Halogen‐Imparted Reactivity in Lithium Carbenoid Mediated Homologations of Imine Surrogates: Direct Assembly of bis‐Trifluoromethyl‐β‐Diketiminates and the Dual Role of LiCH2I

“…Regardless the position on the aromatic ring (ortho, meta, para), also the potentially exchangeable bromo analogues reacted in high yield giving the homologated substrates 4 and 5. An analogous outcome was observed when chlorinated (6)(7)(8), monofluoro (9), difluoro (10) or trifluoromethyl (11) TFAICs derivatives were employed. Genuine chemoselectivity was deducted when multi-electrophilic TFAICs were tested, thus demonstrating the chemical integrity of nitrile (12) and esters [t-Bu (13) and Et (14)].…”

“…Notably, the nature of the halogen (Cl, Br, I) did not influence the outcome of the process. Later in 2019, we introduced the concept of telescoped homologation of imine surrogates for accessing—via trivial stoichiometric control—mono‐ or di‐homologated CF 3 ‐aziridines starting from trifluoromethylated imine surrogates (trifluoroacetimidoyl chlorides, TFAICs) [8b, 9] . The hypothesized reaction mechanism based on the experimental evidence points out that after the first homologation event conducting to tetrahedral intermediate (TI) I , a selective cyclization of the lithium amide on the installed chloromethyl‐fragment took place, giving the mono‐homologated α‐chloro‐aziridine ( II ) [8b] .…”

A Convenient FeCl3‐Mediated Synthesis of 5‐Trifluoromethyl‐1,2,4‐triazoles from Trifluoroacetimidoyl Chlorides and Hydrazides

“…In recent years, the synthetic protocol employing different trifluoromethyl synthons and suitable reactive partners has been emerged as a mainstream and attractive pathway to build trifluoromethyl‐containing heterocyclic compounds. In this context, trifluoroacetimidoyl halides have been frequently applied as versatile building blocks in synthetic organofluorine chemistry [9] . Very recently, our group reported an iodine‐mediated annulation reaction of trifluoroacetimidoyl chlorides and hydrazones to prepare a variety of 5‐trifluoromethyl‐1,2,4‐triazoles in good yields (Scheme 1e) [10] .…”

“…In this context, trifluoroacetimidoyl halides have been frequently applied as versatile building blocks in synthetic organofluorine chemistry. [9] Very recently, our group reported an iodine-mediated annulation reaction of trifluoroacetimidoyl chlorides and hydrazones to prepare a variety of 5-trifluoromethyl-1,2,4-triazoles in good yields (Scheme 1e). [10] Nevertheless, the hydrazones derived from aliphatic aldehydes were not applicable to the reaction, so 3-alkyl-fluorinated 1,2,4-triazoles could not be furnished.…”

“…Optimization of reaction conditions. [a] , entries[6][7][8][9][10]. Further examination towards reaction temperature demonstrated that the low temperature was detrimental to the reaction and the elevated temperature had a marginal influence on the reaction with the slight decrease of the reaction efficiency(Table 1, entries[11][12][13].…”