Reactions of 1-trifluoromethyl-propyne 1-iminium salts with nitroanilines: synthesis of 4-CF3-nitroquinolines and 1,2,3-trisubstituted-5-CF3-pyrroles

A variety of 4-CF3-quinolines bearing an aryl (or cyclopropyl, tert-butyl, trimethylsilyl) group at C-2 and a nitro group at ring position 6, 7 or 8 have been prepared in good to high yields from 3-substituted 1-CF3-prop-2-yne 1-iminium triflate salts and o-, m- or p-nitroaniline. These reactions include an aza-Michael reaction at room temperature followed by an intramolecular electrophilic aromatic substitution step, which requires additional thermal activation in most cases. In contrast, the conjugate addition of 2,4-dinitroanilines at the acetylenic iminium ions proceeds much more slowly and some of the adducts can be converted thermally into 2-(2,4-dinitrophenyl)-5-CF3-pyrroles. Analogously, 2-(4-pyridyl)-5-CF3-pyrroles were obtained from 3-aryl-1-CF3-propyne iminium salts and 4-aminopyridinium triflate. A novel variation of the Truce-Smiles rearrangement is probably involved in the formation of these pyrroles.

1,3-Bis(trifluoromethyl)prop-2-ene 1-Iminium Salts ‒ Reactions with Alkoxybenzenes and Anilines

1,3-Bis(trifluoromethyl)prop-2-ene 1-iminium triflate salts were prepared for the first time and some synthetic applications as 1,3-biselectrophilic building blocks were established. They were found to react with dimethoxybenzenes or methylene-1,2-dioxybenzenes to furnish vinylogous trifluoroacetylaton products (4-aryl-1,1,1,5,5,5-hexafluoropent-3-en-2-ones) and 1-dialkylamino-1,3-bis(trifluoromethyl)-1H-indenes. With aniline and ring-substituted anilines, 2,4-bis(trifluoromethyl)quinolines were formed. An unusual 4H-pyran, formally a condensation product of the N,N-dimethyl-1,3-bis(trifluoromethyl)prop-2-en-1-iminium ion and its enaminone precursor, is also reported.

Modifications and hybrids of 1,2,3,4-tetrahydropyridinium salts and their antiprotozoal potencies

The antiprotozoal activity of 1-benzyltetrahydropyridin-4-yliden iminium salts is reported. This paper describes the preparation of a series of analogs from dihydropyridines or dihydrothiopyrans as educts. The new compounds were investigated for their activity against Plasmodium falciparum NF54, a causative organism of Malaria tropica and Trypanosoma brucei rhodesiense, the causative organism of Human African Trypanosomiasis (sleeping sickness). Several structure–activity relationships were detected. Both the substituents in ring positions 1 and 4 of the tetrahydropyridinium moiety had a strong impact on the antiprotozoal activities as well as on the cytotoxicity of compounds against L-6 cells (rat skeletal myoblasts). All new compounds were characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. Graphic abstract

Theoretical and Experimental Insights into the Tandem Mannich—Electrophilic Amination Reaction: Synthesis of Safirinium Dyes

Isoxazolo[3,4-b]pyridin-3(1H)-ones are ‘spring-loaded’ compounds that quantitatively react with iminium salts derived from formaldehyde and secondary amines to yield fluorescent Safirinium dyes. The mechanism and energetics of the above tandem Mannich–electrophilic amination reaction have been investigated experimentally and using theoretical methods. The hybrid B3LYP functional with GD3 empirical dispersion and range-separated hybrid functional ωB97XD, both combined with a PCM model, were applied to acquire the energetic profiles of the studied reaction with respect to the structure of secondary amine and isoxazolone used. Diastereoselectivity of the tandem reactions involving iminium salt derived from L-proline has been rationalized theoretically by means of density functional theory calculations.

Electron deficient borane-mediated hydride abstraction in amines: stoichiometric and catalytic processes

Borane mediated hydride abstraction of amines efficiently generates useful iminium salts. This review explores this fascinating reactivity and discusses how the iminium intermediates are utilised in a variety of stoichiometric and catalytic processes.

1-Trifluoromethyl-prop-2-yne 1-iminium salts and 1-imines: reactions with the mesoionic „Nitron“

The heterocyclic mesoionic compound (1,4-diphenyl-1H-1,2,4-triazol-4-ium-3-yl)(phenyl)amide („Nitron“) has recently been found to exist in a prototropic equilibrium with minor amounts of a nucleophilic heterocyclic carbene of the 1,2,4-triazolyl-5-ylidene type. Here we report that Nitron reacts with 1-trifluoromethyl-substituted prop-2-yne iminium salts by conjugate nucleophilic addition of the anionic PhN‒ substituent in the mesoionic tautomer, whereas the nucleophilic triazolylidene form is involved in the reaction with 1-CF3-prop-2-yne imines. 3-(2,3-Dihydro-1H-benzo[c]azepin-5-yl)-1H-1,2,4-triazol-4-ium triflate salts were obtained in the former case and (Z)-9-arylidene-1,2,4,7-tetraazaspiro[4.4]nona-2,7-dienes in the latter.