The Asymmetric Synthesis Of Trifluoromethylated Aziridine Andγ-Trifluoromethylated α,β-Unsaturated δLactone

Many biologically active compounds contain the CF3groups as the essential motif. As a result, much attention has been paid to the development of new synthetic methods for the introduction of the CF3groups into diverse organic compounds. In this dissertation, a new methods for the asymmetric synthesis of trifluoromethylated aziridines was developed. In addition, the design and synthesis of the trifluoromethylated α,β-unsaturated8lactone was investigated. This work was divided into two parts:Part Ⅰ:The reaction of sulfur ylide with (S)-N-tet-butanesulfinyl imines gave trifluoromethylated aziridines3in moderate to excellent yields (45-93%) and excellent diastereoselectivities (86:14to>99:1) by screening sulfur ylides, temperature, solvents and charging sequence. A convenient and practical route to optical active trifluoromethylated aziridines was developed. Trifluoromethylated cyclopropylamine4was readily achieved in good yields (80%) by acidic cleavage of the tert-butanesulfinyl group, and then the ring-opening product6can be aquired.Part Ⅱ:The design and synthesis of the trifluoromethylated α,β-unsaturated δ lactone was explored. Firstly, The aliphatic aldehyde12was prepared from L-glutamic acid after7steps. And the chiral auxiliary20was prepared from (S)-phenylalanine methyl ester hydrochloride via aminolysis and condensation reaction. Then the electrophilic trifluoromethylation Togni II reagent24was also made by methyl2-iodobenzoate after Grignard reaction, oxidation reaction, and substitution reaction. Unfortunately, the electrophilic trifluoromethylation of aldehyde12with Togni Ⅱ reagent24in the presence of20failed.