Study On Cyclopropanation And Mechanism Of Olefins Catalyzed By Metalloporphyrins

Cyclopropane modules as an important organic synthetic materials and reaction intermediates, is widely distributed in varieties of active substances in nature. Introducing trifluoromethyl groups into small-ring modules has profound effects on their physical and chemical properties of pharmaceutical agents. Consequently, there is considerable interest in the development of trifluoromethyl-substituted cyclopropanes in the medicinal chemistry laboratory.In this paper, the cyclopropanation of styrene with trifluoroethylamine hydrochloride catalyzed by metalloporphyrin was systematically studied, including the influence factors in the reaction, expansion of reaction system and the mechanism of the metalloporphyrin-catalyzed cyclopropanation system. The details are summarized as follows:1. Seven metalloporphyrins were synthesized, and their catalytic performances for the cyclopropanation of styrene with trifluoroethylamine hydrochloride were investigated. We found that metalloporphyrin showed better catalytic activity for styrene cyclopropanation than other catalyst. Especially when the catalyst was TPFPPFeCl, the highest yield of trifluoromethyl-substituted adducts reached up to 88%.2. The qualitative and quantitative analysis of the styrene cyclopropantion were studied by GC-MS?GC methods and column chromatography. The reaction catalyzed by metalloporphyrins generated cyclopropanes with high diastereoselectivity and more trans-adducts.3. A systematic study on the styrene cyclopropanation catalyzed by TPFPPFeCl was carried out. The effects of reaction time, reaction temperature, reaction solvent, amount of catalyst and molar ratio of styrene with trifluoroethylamine hydrochloride were examined. The optimized reaction conditions is shown as follow:the volume of styrene was 35?L, the loading of TPFPPFeCl was 1.05 mg, the amount of trifluoroethylamine hydrochloride was 90 mg, the amount of sodium nitrite was 55 mg, the volume of water was 2.8 mL, the reaction time was 14 h, and the reaction temperature was 25?. Under this optimized condition, the yields of cyclopropanes were 88%.4. The scope of cyclopropanation of alkenes with trifluoroethylamine hydrochloride catalyzed by TPFPPFeCl was investigated. The aromatic terminal olefins, including the electron withdrawing and the electron-donating were good substrates for this transformation. Compared with electron withdrawing substrates, the styrene with electron donating groups afforded good diastereoselectivity and yield.5. Combining the related literatures with our preliminary research on the role of metalloporphyrin, we proposed a possible mechanism of metalloporphyrin-catalyzed cyclopropanation of styrene with trifluoroethylamine hydrochloride, which involved an iron-nitrogen transition state examined by kinetic datas and UV spectrophotometer.