Two-step synthesis of vicinal trifluoromethyl primary amines from α-(trifluoromethyl)styrenes and phthalimide.

A novel two-step synthesis of ß-trifluoromethyl primary amines from readily available α-(trifluoromethyl)styrenes and phthalimide is developed. The first step involves a hydroamination between α-(trifluoromethyl)styrenes and phthalimide (PhthNH) with the assistance of a base. Next, the hydrazinolysis of the resulting N-(ß-trifluoromethyl-ß-arylethyl)phthalimides with hydrazine hydrate affords the desired N-(ß-trifluoromethyl-ß-arylethyl)amines.

Solvent-free base-controlled addition reaction of H-phosphonates and H-phosphine oxides to α-CF3 styrenes: facile synthesis of ß-CF3-substituted phosphonates and phosphine oxides.

A practical and efficient solvent-free synthesis of ß-trifluoromethyl-substituted phosphonates and phosphine oxides via hydrophosphonylation and hydrophosphinylation of α-(trifluoromethyl)styrenes with H-phosphonates and H-phosphine oxides, respectively, was developed. The reaction proceeded smoothly within 2 h at room temperature without the cleavage of the rather fragile C-F bond in α-(trifluoromethyl)styrenes and afforded a wide variety of structurally diverse and valuable ß-trifluoromethyl-containing phosphonates and phosphine oxides in moderate to good yields. This protocol features mild conditions, wide substrate scope, simple manipulation, and excellent functional group compatibility.

Controllable Synthesis of Trifluoromethyl- or gem-Difluorovinyl-containing Analogues of Neonicotinoids by the Reaction of α-(Trifluoromethyl)styrenes with 2-Nitroimino-imidazolidine.

A simple and straightforward addition or defluorination of α-(trifluoromethyl)styrenes with 2-nitroimino-imidazolidine (2a), 2-(nitromethylene)imidazolidine (2b), 2-cyanoimino-thiazolidine (2c), and (E)-1-methyl-2-nitroguanidine (2d), in a controlled manner, was developed. The hydroamination of α-(trifluoromethyl)styrenes with 2a, 2b, 2c, and 2d was completed in the presence of DBN at room temperature within 0.5-6 h, affording structurally diverse ß-trifluoromethyl-ß-arylethyl analogues of neonicotinoids in moderate to good yields. The γ,γ-difluoro-ß-arylallyl analogues of neonicotinoids were also successfully synthesized via defluorination of α-(trifluoromethyl)styrenes, with 2a and 2c using NaH as base at an elevated temperature together with a prolonged reaction time of 12 h. The method features simple reaction setup, mild reaction conditions, broad substrate scope, high functional group compatibility, and easy scalability.

Highly Regioselective Synthesis of N-ß-trifluoromethyl 2-pyridones via anti-Markovnikov Hydroamination of α-(trifluoromethyl)styrenes with 2-pyridones.

A novel and facile method for the synthesis of N-ß-CF3 -substituted 2-pyridones via hydroamination of α-(trifluoromethyl)styrenes with 2-pyridones was described. The reaction proceeded smoothly at room temperature, affording a variety of N-(ß-trifluoromethyl-ß-arylethyl)pyridin-2(1H)-ones in moderate to good yields with excellent N-regioselectivity.

Fe-catalyzed hydroxytrifluoromethylation of α-(trifluoromethyl)styrenes with CF3SO2Na: facile access to α,ß-bistrifluoromethyl tertiary alcohols.

A mild and practical Fe-catalyzed hydroxytrifluoromethylation of α-(trifluoromethyl)styrenes with CF3SO2Na in the presence of K2S2O8 and air was developed. The reaction proceeded efficiently at room temperature without ß-fluoride elimination and afforded the corresponding α,ß-bistrifluoromethyl tertiary alcohols in good to excellent yields.

Solvent-controlled base-free synthesis of bis(trifluoromethyl)-cyclopropanes and -pyrazolines via cycloaddition of 2-trifluoromethyl-1,3-enynes with 2,2,2-trifluorodiazoethane.

A highly efficient solvent-controlled synthesis of bis(trifluoromethyl)cyclopropanes and bis(trifluoromethyl)pyrazolines via a [2 + 1] or [3 + 2] cycloaddition reaction of 2-trifluoromethyl-1,3-conjugated enynes with CF3CHN2 was developed. The reactions of 2-trifluoromethyl-1,3-conjugated enynes with CF3CHN2 proceeded smoothly under transition-metal and base-free conditions, affording the expected cycloaddition products in good to excellent yields. When DMAc (N,N-dimethylacetamide) was used as the solvent, bis(trifluoromethyl)pyrazolines were obtained; however, in contrast, bis(trifluoromethyl)cyclopropanes were formed by changing the solvent from DMAc to DCE (1,2-dichloroethane).

DBN-Mediated Addition Reaction of α-(Trifluoromethyl)styrenes with Diazoles, Triazoles, Tetrazoles, and Primary, Secondary, and Secondary Cyclic Amines.

A mild and efficient DBN-mediated addition reaction of α-(trifluoromethyl)styrenes with diazoles, triazoles, tetrazoles, and primary, secondary, and secondary cyclic amines was developed. This practical protocol provided a robust method for the synthesis of various ß-trifluoromethyl nitrogen-containing heterocycles and ß-trifluoromethyl amines.

Synthesis of CF3-Containing Linear Nitriles from α-(Trifluoromethyl)styrenes.

Four unprecedented base-catalyzed/mediated nucleophilic additions of TMSCN to α-(trifluoromethyl)styrenes and 2-trifluoromethyl enynes were developed. The reaction proceeded smoothly at room temperature under mild and transition-metal-free conditions without affecting the trifluoromethyl group and afforded the corresponding CF3-containing alkyl, alkynyl, and butadienyl nitriles in moderate to excellent yields in a highly regioselective manner, respectively.

Chemo- and regioselective synthesis of polysubstituted 2-aminothiophenes by the cyclization of gem-dibromo or gem-dichloroalkenes with ß-keto tertiary thioamides.

A facile and practical method for the synthesis of 2,3,4-trisubstituted 2-aminothiophenes by the cyclization of gem-dibromoalkenes or gem-dichloroalkenes with ß-keto tertiary thioamides has been developed. The cyclization reaction proceeded chemoselectively and regioselectively under metal-catalyst-free conditions, providing various structurally diverse 2,3,4-trisubstituted N,N'-dialkyl 2-aminothiophenes in good to excellent yields.

Design, synthesis and insecticidal activity of novel analogues of flubendiamide containing alkoxyhexafluoroisopropyl groups.

Flubendiamide has received considerable attention in the agriculture field due to its novel mode of action and excellent insecticidal activity. However, the high cost and toxicity to aquatic invertebrates associated with flubendiamide limit its agronomic utility. On the basis of the structure of the lead compound, flubendiamide, we designed and synthesized a series of novel analogues of flubendiamide bearing a alkoxyhexafluoroisopropyl moiety using 2-methyl-4-(2-alkoxyhexafluoroisopropyl) anilines as the key intermediates. Their insecticidal activities against the oriental armyworm (Mythimna separata Walker) were evaluated. The results indicated that most of the target compounds exhibited high insecticidal activities. Specifically, compound 8h showed the best insecticidal activity against the armyworm and its insecticidal activity reached 70% at 0.156 mg L-1. The LC50 value of compound 8h (0.0512 mg L-1) is nearly the same as the corresponding commercial product flubendiamide (0.0412 mg L-1). Furthermore, the acute toxicity test showed that the 48 h LC50 values of compound 8h and flubendiamide against Daphnia magna Straus were 0.0066 and 0.0021 mg L-1, respectively. The toxicity of compound 8h is obviously lower than flubendiamide.