Studies On Enantioselective Allylation Of Ketones Catalyzed By A Novel Chiral N,N'-Dioxide Indium (Ⅲ) Complexes

The enantioselective allylation of carbonyl compouds is one of the most valuable methods to furnish chiral homoallylic alcohols, which are widely used in the syntheses of many natural products and biologically active compounds. The development of efficient synthetic methods for the preparation of chiral homoallylic alcohols has attracted considerable attention. In recent years, several new procedures with either metal complexes or organocatalysts have been developed to the allylation of aldehydes. However, allylation of ketones is still challenging, due to their reduced reactivities and lower binding affinity to metals.N-oxides, a series of strong electronic donors, have long been recognized as suitable entities for ligand design. As a coin, the application of chiral N-oxides has two sides. One is metal-free catalytic transformations, and the other is as ligands in metal complex catalysts. N,N′-dioxides as a highly efficient organocatalyst have been successfully used in the cyanosilylation of aldehydes, aldimines, ketones and ketoimines. However, use of N-oxides in metal-mediated asymmetric synthesis have been limited.In this dissertation, the efforts were focused on the enantioselective allylation of ketones catalyzed by (S)-pipecolic acid-derived N,N′-dioxides and Indium (III) bromide complexes, which delivered good yields and enantioselectivities. A novel chiral N,N'-dioxide of twenty-four ligands were synthesized, as well as three achiral N-oxides, one chiral (S)-2,2',3,3'-tetrahydro-1,1'-spiro-bi-[indene]-7,7'-di ol ligand and other sixteen imine and amide ligands. The chiral N,N'-dioxide Indium complexes which were prepared from N,N'-dioxide and InBr3 at the ratio of 2:1 were successfully applied in asymmetric allylation of 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. The results revealed that 52-In(III) showed an excellent chiral induction in this reaction. We investigated several factors in detail that affected the enatioselectivity, such as the structure of the ligands (steric and electronic effects), central metal, molar ratio of chiral ligands to InBr3, solvent, concentration of substrate, different amount of catalyst, reaction temperature and so on. Under the optimized conditions, A variety of aromatic ketones were found to be suitable substrates in the presence of 30 mol% 52-In(III) complex, and afforded the corresponding homoallylic alcohols with good enantioselectivites (up to 83% ee) and moderate to high yields (up to 94%).And based on the experimental results, the 1H NMR spectra of the ligand 52 and the 52-In(III) complex and the nonlinear effect for the reaction, a possible catalytic cycle including a transition state has been proposed to explain the origin of the reactivity and asymmetric inductivity, and a bifunctional catalyst was described with Lewis base N-oxide activating tetraallyltin and Lewis acid indium activating ketone. All of these results offer some important reference to asymmetric allylation of carbonyl compounds with chiral N,N'-dioxide ligands systemically investigated in the future.