Enantioselective Synthesis Of Trifluoromethyl Substituted Heterocyclic Compounds Catalyzed Via N-heterocyclic Carbene

Due to cyclic motifs are widespread in natural products and pharmaceuticals, the construction of cyclic compounds is an important topic in organic synthesis and the construction of chiral cyclic compounds is more defiant. The Lewis bases, such as, amines, phosphines and N-heterocyclic carbenes, can catalyze various reactions under mild reaction conditions for the rapid construction of cyclic compounds. In the meantime, as the incorporation of fluorine into drug can bring notable change in physical and chemical properties and changes the drug activity, the design of fluorine medicine has became a hot area of research for seveval years. Base on the above mentioned, in the thesis we focused on N-heterocyclic carbenes catalyzed cyclization of trifluoromethyl substituted azadienes and trifluoromethyl substituted ketones with aldehydes for synthesis a series of trifluoromethyl substituted heterocyclic compounds which may have potential drug activity for curing cancer and antibacterial and so on.In the first part, the N-heterocyclic carbene-catalyzed [4+2] cyclocondensation of a-chloroaldehydes and trifluoromethyl N-Boc azadienes was reported. It was demonstrated that N-heterocyclic carbene could efficiently catalyzed the cyclization of a-chloroaldehydes with trifluoromethyl N-Boc azadienes to give the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities. Further chemical trans formation afforded the corresponding dihydropyridinone without protective group which has no erosion of the ee value.In the second part, The N-heterocyclic carbene-catalyzed [3-3] cycloaddition of bromoenals and ketones with trifluoromethyl group had been reported. It was founded that the N-heterocyclic carbene catalyst could catalyzed the annulations reaction of bromoenals and ketones with trifluoromethyl group, giving the corresponding enol lactones in good yields with good to excellent enantioselectivities. The reaction also could be scaled up without apparent loss of yield and enantioselectivity.