Catalytic Asymmetric Tandem Conjugate Addition/Electrophilic Fluorination Of Isoxazolidinone To Nitroolefins&Conjugate Addition Of Alkylzinc To Vinyl Sulfones

Part one: As the introduction of fluorine atom into the organic moleculars willgreatly influence their physical and chemical properties, the application oforganofluorine compounds has received extensive attention in the area ofpharmaceutical industry, agrochemistry and materials science. Catalytic asymmetrictandem process has been an efficient approach in the construction of chiral complexmolecule. Although the direct asymmetric conjugate addition reaction and theasymmetric conjugate addition two-component tandem reation of nitroolefins hasbeen investigated extensively, asymmetric conjugate addition/electrophilicfluorination of nitroolefins has not been reported.In this work, a series of chiral glycosyl thiourea catalysts had been designed andsynthesised and applied to catalyze asymmetric tandem conjugateaddition/electrophilic fluorination of isoxazolidinone to nitroolefins. Some changeinvolving the catalysts and its loading, additives, temperature, and solvent, werecarried out to optimize the reaction conditions. The results showed that in the modeltandem reaction,1,2-diphenylethylenediamine-derived thiurea18p delivered thetandem product in94%yield with92%ee and99/1dr. Nineteen novel organofluorinecompounds were synthesised, and the absolute configuration of the product wasdetermined by the X-ray structural analysis.Part two: Owing to the easy removal of sulfonyl group, sulfones have beenwidely employed in organic synthesis and medicinal chemistry. At present, someprogress has been made in the organocatalytic asymmetric conjugate addition ofaldehyde and ketones nucleophiles into vinyl sulfones. However,transition-metal-catalyzed asymmetric conjugate addition of organometallic reagentsinto vinyl sulfones has not been reported so far. In this section, Cu-catalyzedasymmetric conjugate addition of diethylzinc to vinyl sulfones was developed byusing BINOL-derived bulky phosphoramidite ligands designed by our group.Different chiral ligands and solvents were screened to optimize the reaction conditions. It was found that in the presence of (S)-3,3’-bis{4-[3,5-bis(trifluoromethyl) phenyl]phenyl}-1,1’-binaphthyl phosphoramidite, Cu-catalyzed asymmetric conjugateaddition of diethylzinc to1-[2,2-bis(phenyl sulfonyl) vinyl] benzene and itsderivatives have been successfully performed, and a variety of desired adducts wereobtained in up to75%yield with93%ee.