Synthesis Of Chiral Phosphonate Functional Molecules Catalyzed By Nitrogen Heterocyclic Carbene And Study Of Their Pesticide Activit

Organic phosphines are indispensable class of organic compounds in living organisms.Phosphonate-containing molecules exhibit ubiquitous biological activities with proven applications in medicines and agriculture chemicals.It was found thatα-aminophosphonates andα-hydroxyphosphonates have anti-plant virus,anti-tumor,anti-thrombosis,anti-bacteria,anti-oxidation and other biological activities.The development and use of chiral phosphonates can not only improve the drug economy,but also effectively reduce the environmental impact.Asymmetric synthesis of phosphine-containing functional molecules is still a challenge and attracts much attention.N-Heterocyclic Carbene（abbreviated as NHC）as an important class of small-molecule catalysts have been applicated in the reaction of umpolung of carbonyl compounds which reacted with nucleophilic or electrophilic reagents,and efficient access to chiral skeletons that cannot be constructed by traditional synthesis methods.In this paper,the readitional synthesis methods ofα-hydroxyphosphonates andα-amino phosphonates and their application in pesticides were described.The activation of enaldehyde sp³γ-carbon actalyzed by NHC is introduced.We successfully achieved the asymmetric synthesis ofα-hydroxophosphonate andα-aminophosphonate by employed NHC catalysts,In addition,carried out preliminary tests on the antibacterial activity and anti-virus activity of chiral phosphonates with high optical purity obtained by[4+2]cycloaddition model.In addition,we applied the method of synthesis of chiral phosphonates to the study of synthesis of complex structure polycyclic lactone compounds,and this kind of method has been successfully applied.The main results of our findings emanating from the present study are outlined below.1.The asymmetric[4+2]cycloaddition reaction betweenβ-methyl cinnamaldehyde andα-carbonyl phosphonate catalyzed by NHC under oxidation conditions was successfully developed.A variety of chiral 2-pyranylphosphonates were afforded with excellent enantioselectivities.These chiral 2-pyranylphosphonates compounds were tested for their antibacterial（X.oryzae pv.oryzae）and anti-Tobacco Mosaic virus（TMV）.Several of the optically enriched phosphonate compounds exhibited anti-bacterial and anti-viral activities in our preliminary studies.For example,products I-3f（54.2%,60.8%）and I-3u（44.4%,59.9%）exhibited a similar inhibitory rate against X.oryzae pv.oryzae when compared to the commercially available bactericide bismerthiazol（47.1%,72.7%）at the concentrations of both 100mg m L^-1 and 200 mg m L^-1.The against TMV activities of chiral2-pyranylphosphonates compared with the commercially available anti-viral drug of ningnanmycin（curative effects 45.5%,protective effects 44.6%）,products I-3i（curative effects 44.8%）,I-3o（curative effects 43.1%）and I-3u（curative effects50.4%）showed similar curative effects,and products I-3p（44.8%）and I-3r（44.4%）showed comparable protective effects.2.The asymmetric[4+2]cycloaddition reaction for preparation of chiralα-amino phosphonates catalyzed by NHC under oxidation conditions was developed.A variety of substitutedα-aminophosphonates bearing sophisticated multi-cyclic scaffolds were afforded in generally good to excellent yields with excellent enantioselectivities.The synthetic chiralα-aminophosphonate compounds and some intermediates were tested for their antibacterial and anti-Tobacco Mosaic virus（TMV）activities,Several of the optically enriched phosphonate compounds exhibited anti-bacterial and anti-viral activities.products II-3e（45.6%%,80.0%）and II-3l（69.3%,88.8%）exhibited a similar inhibitory rate against X.oryzae pv.oryzae when compared to the commercially available bactericide bismerthiazol（44.6%,73.6%）at the concentrations of both 100 mg m L^-1 and 200 mg m L^-1.The against TMV activities of chiralα-aminophosphonates compared with the commercially available anti-viral drug of ningnanmycin(curative effects 45.5%,protective effects（44.6%）,products II-3c（49.5%）,II-3e（46.8%）,II-3g（59.4%）,II-3h（46.5%）,II-3j（47.8%）,II-3k（53.1%）showed similar curative effects,and products II-3c（43.9%）,II-3e（52.1%）、II-3g（56.6%）、II-3h（55.4%）、II-3j（44.7%）and II-3k（46.9%）showed comparable protective effects.3.The asymmetric[4+2]cycloaddition reaction ofβ-methyl cinnamaldehyde with five-membered cyclic imines by NHC catalyzed was developed.The reaction gives chiral quaternaryα-amino phosphonates bearing tetrasubstituted carbon centers with excellent enantioselectivities.Due to the imine substrates can be generated in situ from the corresponding amines under an oxidative condition.Therefore,NHC catalyzed a one-pot Cross-Dehydrogenative-Coupling（abbreviated as CDC）reaction between enals and amines is also realized with high enantioselectivity remaining.4.A NHC-promoted cascade reaction betweenβ-methyl enal and dienone is developed for quick access to multicyclic lactone molecules bearing quaternary chiral carbon centers.Our study constitutes the first 1,6-addition of the acylazolium vinyl enolateγ-carbon via NHC catalysis and provides rapid access to complex lactone molecules that are otherwise difficult to prepare.The structurally sophisticated lactone products bearing up to four fused ring structures are afforded in up to quantitative yields with good to excellent enantioselectivities.