Catalytic Asymmetric Addition Of3-En-1-ynes To Trifluoromethyl Ketoimines&Nucleophilic Addition Of Formaldehyde N-tert-butyl Hydrazone To Cyclic Ketoimines

Part one: Chiral propargyl amines are important building blocks for the totalsynthesis of pharmaceuticals and complex natural products. The development ofpractical methods for the preparation of chiral propargyl amines continues to attractsynthetic chemists. The direct enantioselective addition of alkynes to ketoimines,using organometallic reagents generated in situ from alkynes and suitable metalprecursors, represents one of the most convenient and efficient approach to thesynthesis of these compounds.In this thesis, an effective method for enantioselective addition of3-en-1-ynes to-trifluoromethylketoimines has been developed via a Me2Zn/BINOL catalyzedprocess. Variation of reaction paramemeters (ligand, solvent and temperature) hasbeen investigated. Under the optimum reaction condition, a series of eneynylatedadducts were synthesized in80%–99%yields with91%–97%ee. Additionally,-trifluoromethylated amino alcohol derivatives were easily prepared via reduction ofthe obtained products in the presence of LiAlH4.Part two: Formaldehyde hydrazones posses an enhanced nucleophilic character dueto the smaller steric factors of the azomethine carbon atom that enables the reactionswith a much broader variety of electrophiles. In this paper, a base-mediatednucleophilic addition of formaldehyde N-tert-butylhydrazine to cyclic N-acyltrifluoromethylketoimines has been developed, and trifluoromethyl-substituted azocompounds have also been synthesized with this method. The effects of base andsolvents were investigated. Under the optimized reaction condition, a series ofadducts were synthesized in80%–99%yields. In addition, the obtained adducts weretransformed into N-tert-butyl hydrazones by a simple TFA-catalyzed isomerization.