Study On Asymmetric Reactions Of Bis-cyclosulfinamide Chiral Ligands

Chiral sulfinamides and their derivatives are very important compounds in organic synthesis and are widely used as chiral auxiliaries,chiral drugs,catalysts and chiral ligands.In recent years,the use of chiral sulfinamides as ligands has attracted the attention of chemists.Studies have shown that chiral sulfinamides can be used as ligands to complex with a variety of transition metals and applied to asymmetric catalytic reactions.Therefore,the design and synthesis of such chiral ligands has very important scientific value and practical significance.Except that our group recently reported a C₁ symmetric cyclic sulfinamide,all of the chiral sulfinamide ligands used in asymmetric catalysis are acyclic.To our best knowledge,C₂ symmetric rigid bis-cyclic sulfinamide ligands have not been reported.In this dissertation,（S）-2,3-dihydro-1,2-benzisothiazole-1-oxide,which is shortened as cyclic sulfinamide,was obtained by two-step reactions with（R）-tert-butanesulfinamide as the starting material.It is used to synthesize two classes of C₂ symmetric chiral bicyclic sulfinamide ligands.One has a skeleton with two rigid cyclic sulfinamides connected with a flexible alkyl chain.The other has a skeleton with a more rigid butane-di-yl or benzene-di-yl to connect two cyclic sulfinamide blocks.In order to investigate the catalytic activity and enantioselectivity of these ligands,they were used in rhodium-catalyzed asymmetric 1,4-addition of phenylboronic acid with cyclohexenone.By examining this reaction,we screened out the best ligand is（S,S）-1,4-bis（2,3-dihydro-1,2-benzisothiazole-1-oxide）-2-butene,number L₁.To determine the optimal reaction condition for asymmetric 1,4-addition of phenylboronic acid with cyclohexenone with L₁ as ligand,we screened the kind and the amount of rhodium catalyst,the ratio of catalyst and ligand,alkali,solvent and temperature,respectively.The optimized result is that the asymmetric 1,4-addition was performed at 40℃for 4 h,with[Rh（C₂H₄）₂Cl]₂ as a rhodium catalyst,Rh:L₁=1:1,potassium hydroxide as a base,toluene as a solvent.Under the optimized condition,a series of asymmetric conjugate addition reactions of arylboronic acids withα,β-unsaturated cycloalkenones were evaluated.The ee values of all products obtained in the asymmetric catalysis were analyzed by chiral high performance liquid chromatography（HPLC）with Chiralcel OD-H column,Chiralpak AD-H column,Chiralpak AS-H column and Chiralcel OJ-H column as chiral stationary phases.The enantiomeric excess values of the product were up to>99%ee.Through high-resolution mass spectrometry and ¹H NMR of the complex of the ligand L₁ and Rh,it was demonstrated that the ligand L₁ coordinates with the tridentate with Rh（I）.Finally,the products synthesized in the reaction were characterized by optical rotation,melting point,IR,¹H and ¹³C NMR,and high resolution mass spectrometry.