Trifluoroacetimidoyl chlorides

Trifluoroacetimidoyl chlorides reacted with compounds containing an active methylene group to give enamines that thermally cyclized in cumene to 2-trifluoromethylquinolines (89TL4821). With N.N -disubstituted trifluoroacetamidines, the N-group determined whether cyclization gave triazoles or quinazolones (90TL2717). 

N-Substituted trifluoroacetimidoyl chlorides react with sodium azide to give 1-substituted 5-trifluoromethyltetrazoles (76T1995). 

Trifluoroacetonitrile (62JOC2085, 62JOC3248), trifluoroacetimidoyl chlorides (90TL2717), and trifluoroacetimidoyl fluorides (66JOC789) react with sodium azide or alkyl azides to give 5-trifluoromethyltetrazoles (Scheme 32). 

Trifluoroacetimidoyl chlorides"" and trifluorohydroxyimino chlorides (e. g., 54) react with nitrogen nucleophiles to give the substitution products (e. g., 55) in excellent yields. 

Base-induced cycloaddition of diethyl isocyanomethylphosphonate 1326 to trifluoroacetimidoyl chlorides 1327 produces 1-substituted diethyl 5-trifluoromethylimidazole-4-phosphonates 1328 with high regioselectivity (Scheme 339) <19968511>. 

The gem-difluoroalkenylphosphonate (183) has been synthesised by reaction of lithiated diethyl methylphosphonate with a-trifluoromethylstyrene. 1-Substituted 5-trifluoromethyliniidazole-4-phosphonates (185) have been prepared in moderate yield by the reaction of isocyanomethylphosphonate carbanions with trifluoroacetimidoyl chlorides (184). Diphosphono-alkylation of nucleophiles has been achieved in one pot by sequential treatment of phosphonate carbanions with alkyl dichlorophosphates and the conjugate acid of the appropriate nucleophile (Scheme 23). ... 

Reaction of imidoyl chlorides with azide ion produces tetrazoles through an imidoyl azide intermediate. Thus, A -substimted trifluoroacetimidoyl chlorides undergo facile nucleophilic displacement with azide ion and subsequently cyclize to give 1 -substimted-5-trifloromethyltetrazoles (Fig. 3.99). The acetimidoyl chlorides are readily prepared by refluxing a mixmre of trifluoroacetic acid and primary amine in carbon tetrachloride in the presence of triethylamine and triphenylphosphine. 

Three synthetic approaches toward 3-trifluoromethylpyrazole 41 are summarized in Scheme 12.5, all of which involve [2 + 3] cycloaddition. Either combinations of diazotrifluoroethane 39 with acetylene 40 or trifluoroacetimidoyl chloride 43 with ethyl vinyl ether leads to 41. However, cycloaddition of a zwiterionic intermediate 45 with norbornadiene affords 47 (after removal of norbornene fragment), but only as a minor product. Intermediate 45 is generated by the dehydrobromination of imi-doylbromide 44 with triethylamine. 

A Rh -catalyzed tandem one-pot coupling cycUzation reaction with TMSA and trifluoroacetimidoyl chlorides delivers 2-trifluoromethylated quinolines with good regioselectivity (eq45). i... 

Chloro-2-trifluoromethyl quinolines 95 can be obtained from the corresponding N-aryl trifluoroacetimidoyl chlorides through the Rh(I)-catalyzed intramolecular cyclizations with the alkyne moieties (Scheme 39) [60,61],... 

Amii H, Kishikawa Y, Uneyama K (2001) Rh(I)-catalyzed coupling cycUzation of N-aryl trifluoroacetimidoyl chlorides with alkynes one-pot synthesis of fluorinated quinoUnes. Org Lett 3 1109-1112... 

Although generation and reactions of 1,1,1-trifluorobiacetyl was reported as early as in 1957, the compound was not isolated in this work [637], Trifluoromelhyl-substituted derivatives 1071 were obtained via trifluoroacetylation of hydrazones 1070 [638, 639], acylation of (trifluoroacetimidoyl)lithium derivatives 1075 [640], or condensation of trifluoroacetimidoyl chlorides 1077 with aromatic aldehydes in presence of sodium hydride [641] (Scheme 230). These methodologies were also used for the synthesis of trifluoromethyl glyoxal equivalents 1064 [640,642]. 

After the report on the visible-light-induced [4-f2] benzannulation of biaryl-diazonium salts and alkynes [31], Zhou and coworkers [32] also demonstrated the radical cyclization of trifluoroacetimidoyl chlorides with alkynes, yielding various 2-trifluoromethyl quinolones (Scheme 13.15). It is worth noting that this is the first example where the activation of sp C-Cl bonds by a photoredox catalyst... 

Scheme 25 Cul-catalyzed synthesis of 2-trifluoromethyl substituted benzimidazoles from ]V-(2-haloaryl)trifluoroacetimidoyl chlorides...

Zhang et al. designed a tandem C-N bond formation reaction for the assembly of 2-trifluoromethyl substituted benzimidazoles 71 from A-(2-haloaryl) trifluoroacetimidoyl chlorides 70 (Scheme 25) [57]. Cul/TMEDA-catalyzed cross coupling of 70 with primary amines following by intramolecular condensation produced 71 with 62-98% yields. 

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