Asymmetric Synthesis Of Indole-thiopyrano Derivatives Catalyzed By Chiral Tertiary Amine-thiourea Bifunctional Catalyst

At the beginning of the twenty-first Century, chiral catalysis, especially chiral molecular catalysis, has made great progress. By the use of chiral tertiary amine-thiourea bifunctional catalyst derivatived from the cinchona alkaloids and 1,2-diphenylethane-1,2-diamine(DPEN), this thesis focused on asymmetric tandem [3+3] Michae-cyclization reaction between indoline-2-thiones and 2-benzylidenemalononitrile or 1-azadiene.In the first part of the thesis, a series of small organicmolecular amine thiourea catalysts has been synthesized by cinchona alkaloids and DPEN as the chiral starting materials.The second part of the this thesis, asymmetric Michael tandem reaction between indoline-2-thiones and 2-benzylidenemalononitriles has been successfully realized in the presence of tertiary amine-thiourea catalyst derived from chiral DPEN skeleton. After optimization of reaction conditions, a series of indole-thiopyrano heterocyclic compounds was obtained in high yields with excellent enantioselectivities. With the aim of explaining the higher reactivity of indoline-2-thione with 2-benzylidenemalononitrile than that of hydroxyindole, we carried out the density functional theory(DFT) calculations.The third part of this thesis, asymmetric tandem [3+3] Michae-cyclization reaction between indoline-2-thione and 1-azadiene has been studied. It was disclosed that chiral tertiary amine-thiourea catalyst derived from cinchona alkaloids was a potent organocatalyst for this transformation, which provided the desired products in excellent yields with excellent enantioselectivities. The desired spiro heterocyclic compounds contain sulfonyl imide motifs and indole-thiopyran skeletons, which is always endowed with potential physiological activity or pharmacological activity.