Studies On A Novel Chiral N,N'-Dioxide Applying To Asymmetric Silylcyanation Of Ketones And Henry Reaction

In the last two decades, asymmetric synthesis focused on the C-C bond formation, thereinto, asymmetric silycyanation and Henry (nitroaldol) reaction were two important organic synthesis methods.Cyanohydrins and nitroalcohols are versatile intermediates in the context of organic synthesis, especially, in asymmetric synthesis. The addition of TMSCN and nitromethane to carbonyl compounds is the most direct, efficient, and prevailing strategy. In this dissertation, the efforts were focused on asymmetric cyanation of acitive ketones and asymmetric Henry reaction. A series of useful and creative results have been obtained.A series of novel C₂-symmetric chiral N,N '-dioxide catalyst were synthesized and evaluated for the enantioselective addition of TMSCN to acitive ketones. The electronic and spatial effects of the substitutes on chiral N, N '-dioxide ligands impacting on the enantioselectivity and reactivity of this reaction were systematically studied. Under the optimized conditions, in-situ-generated N,N '-dioxide from the corresponding amide (10 mol%) and m-CPBA (20 mol%) retained the same asymmetric catalytic activity and enantioselectivity, and most of the aromatic,α,β-unsaturated, heterocyclic, aliphatic and steric hindrance ketones could be converted into the corresponding cyanohydrin trimethylsilyl ethers in up to 99% yield and 93% ee.Supported by the control experiments and ¹H NMR studies, N,N'-dioxide was approved as a bifunctional organocatalyst containing amide hydrogen as Br(?)nsted acid to activate the carbonyl group of the substrate and iV-oxide as Lewis base to activate TMSCN. Moreover, the ee values between the ligand and the product are linearly correlated.The chiral N,N'-dioxide copper complexes were firstly successfully applied in asymmetric Henry reaction of aldehydes andα-keto esters. We investigated several factors in detail that affect the enatioselectivity, such as the structure of the ligands (steric and electronic effects), central metal, molar ratio of chiral ligands to metal, solvent, different amount of catalyst, reaction temperature and so on. Under the optimized conditions, most of aldehydes and a-keto esters could be converted into the corresponding nitroalcohols in up to 99% yield with 98% ee in the presence of 5-10 mol% N,N '-dioxide -CuOTf complex and 4A MS as additive.According to the control experiments and the experiment phenomena, a possible catalytic cycle is rationally proposed to illustrate the experimental observations for the two reactions. All of these results offer some important reference to asymmetric cyanation and Henry reaction of carbonyl compounds with C₂-symmetric chiral N,N'-dioxide as catalyst or ligand systemically investigated in the future.