Asymmetric Synthesis Of α-Trifluoromethylated α-Propargylamines Induced By (S)-tert-butanesulfinamide And Asymmetric Syntheses Of Anti-HIV Drugs DPC 961

Fluorine-containing compounds have attracted extensive attention due to the unique properties of fluorine atom (high electronegativity, low polarizability, relative small size) which induce modifications of physical properties for these compounds and make them suitable for application in life and material sciences.PartⅠ:A convenient and practical method for the preparation of enantiomerically pureα-trifluoromethylatedα-propargylamines was described. A range of enantiopureα-trifluoromethylatedα-propargyl sulfinamides were obtained by the addition of lithium acetylides generated in situ with n-BuLi and terminal alkynes to the diverse chiral CF3-substituted (S)-N-tert-butanesulfinyl ketimines in moderate to excellent yields (56% to 97%) and with uniformly excellent diastereoselectivities (>99:1) by using Ti(OiPr)4 as catalyst and THF as polar solvent. Optically pureα-trifluoromethylatedα,α-dibranched propargylamines were then readily achieved in excellent yields (87% to 97%) by acidic cleavage of the tert-butanesulfinyl group. PartⅡ:According to the method established as above, asymmetric synthesis of Anti-HIV drug DPC 961 is attempted. Chloroaniline was used as a raw material, and different protective groups were applied to protect the amino group, then the trifluoroacetyl group was introduced into the substrate. Reactions with the chiral (S)-tert-butanesulfinamide were then carried out by using Ti(OiPr)4 as Lewis acid to give CF3-substituted (S)-N-tert-butanesulfinyl ketimine. The final 1,2-addition of cyclopropyl acetylene lithium to the chiral CF3-substituted (S)-N-tert-butanesulfinyl ketimines were attempted under different conditions, but the target compound has not been achieved.