Studies On The Annulation And Addition Reactions Of Trifluoromethyl Ketimines And Trifluorodiazoethane

The chemical transformations based on various trifluoromethyl-containing building blocks have been established as important strategies to construct trifluoromethyl-containing compounds,which are playing a key role in the fields of pharmaceuticals,agrochemicals and materials.This dissertation focuses on the annulation reactions of cyclic N-acyl trifluoromethylketimines with allenoates or MBH carbonates and the asymmetric 1,2-addition reaction of 2,2,2-trifluorodiazoethane with aldehydes,delivering a variety of neotype trifluoromethyl-containing compounds.The main achievements are listed as follows:1)Organic Lewis base-triggered annulation of allenoates and MBH carbonates is one of the most efficient and straightforward synthetic methods for the construction of highly functionalized carbocycle or heterocycle structural motifs,which are present in a wide range of bioactive natural products and medicinally important substances.With the aim of constructing trifluoromethyl-containing polycyclic compounds,four kinds of Lewis bases were employed as efficient catalysts for the reactions of allenoates with cyclic N-acyl trifluoromethylketimines.With PPh3,[3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields.While promoted by DPPP,sequential [3 + 2]/[3 + 2] annulations were realized,leading to the formation of N-fused tetracyclic compounds with excellent regio-and diastereoselectivities.Under the catalysis of DABCO,[2 + 2] annulations occurred,producing azetidine derivatives in good to high yields.However,in the presence of pyridine,?,?'-disubstituted allenoates were obtained in high yields via aza-MBH reactions.Moreover,the dihydropyrrole derivatives and ?,?'-disubstituted allenoates can be transformed to N-fused tetracyclic compounds via DPPP-triggered annulations with allenoates.Subsequently,we developed a highly regio-and diastereoselective PBu3-catalyzed [3 + 2] annulation of MBH carbonates with cyclic N-acyl trifluoromethylketimines.With this methodology,a series of N-fused tricyclic products were generated in excellent yields under mild conditions.It is worth mentioning that cyclic methyl-or phenylketimines were not able to proceed the reactions aforementioned,indicating that the strong electron-withdrawing trifluoromethyl group is critical for the occurance of these annulation reactions.2)The highly reactive 2,2,2-trifluorodiazoethane has emerged as an attractive C2 synthon or 1,3-dipole for the synthesis of structurally diverse trifluoromethyl-containing compounds.In view of the active hydrogen of trifluorodiazoethane,we developed the asymmetric 1,2-addition reaction of 2,2,2-trifluorodiazoethane with various aldehydes.With ZnEt2 as the base and quinine as the chiral lagand,a series of optically active trifluoromethyl-containing ?-diazoalcohols were successfully synthesized with good yields(69-92%)and enantioselectivities(68-92% ee).Furthermore,the products can be transformed to trifluoroethyl-containing alcohols and trifluoromethyl-containing hydrazones by hydrogenation,expanding the further application of 2,2,2-trifluorodiazoethane.