The Asymmetric Synthetic Conversion Of The Trifluoromethyl-substituted N-Tert-Butylsulfinylimines

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.Part I:The asymmetric aza-Morita-Baylis-Hillman reaction (aza-MBH reaction) is an atom economic carbon-carbon bond formation reaction to afford chiral a-methylene-β-aminocarbonyl compounds which were valuable intermediate in organic synthesis. However, the aza-MBH reaction has shortcomings such as solw reaction rate, low yield and low stereoselectivity. This dissertation innovatively applied trifluoromethyl substituted N-tert-butanesulfinylimine and α, β-unsaturated carbonyl compounds in the asymmetric aza-Morita-Baylis-Hillman reaction catalyzed by triethylenediamine (DABCO) and Ti(O’Pr)4. It is noteworthy that this novel aza-MBH reaction could proceed smoothly to generate the desired products in up to97%yields and up to99:1dr value. The aza-MBH adducts can further transferred into optical pure a-methylene-β-trifluorornethyl-β-lactams after deprotection and cyclization.Part II:According to the method established by our group, asymmetric synthesis of anti-Aids drug DPC961is investigated. Starting from5-chloro-2-nitrobenzaldehyde,5-chloro-2-nitrotrifluoroacetylbenzene was obtained after trifluoromethylation with TMSCF; in the presence of tetrabutylammonium fluoride(TBAF) and oxidation by iodobenzene diacetate (BA1B) and2,2,6.6-tetramethyl-l-piperidinyloxy (TEMPO). Reaction of5-chloro-2-nitrotrifluoroacetylbenzene with the (S)-tert-butanesulfinamide catalyzed by Ti(O’Pr)4gave CF3-substituted (S)-N-tert-butanesulfinyl ketimine. The final1,2-addition of cyclopropyl acetylene lithium to the CF3-substituted (S)-N-tert-butanesulfinyl ketimine were then attempted, but the desired product has not been achieved.