Design Of Novel Chiral Sulfoxide Ligands And Their Applications In Asymmetric Catalysis And Heterocycle Synthesis

Asymmetric catalysis as one of the most efficient and powerful methods for obtaining enantiopure compounds has seen tremendous advances in the past decades, and the design and synthesis of chiral ligands are key in asymmetric catalysis.Based on the concept of chiral ligand development,"rational combination of two privileged backbones into one molecule", in this dissertation, we designed and synthesized two novel chiral sulfoxide ligands and applied them in the copper and palladium catalyzed asymmetric catalysis and heterocycle’s construction. The detailed work are listed below:First, we developed a new class of chiral sulfoxide-Schiff base ligands for the first time by rational combination of two privileged architectures, using commercially available chiral amino alcohol as starting materials. These sulfoxide-Schiff base hybrids were found to be highly efficient for the Cu-catalyzed asymmetric Henry reaction, furnishing the corresponding products with excellent yields (up to98%) and high enantioselectivities (up to96%ee).To furhter extend the use of our ligand design concept, we synthesized a new kind of chiral sulfoxide-phosphine ligands by rational combination of chiral sulfoxide-amino scaffold and soft basic phosphine group. These new ligands exhibited excellent catalytic efficiency in the Pd-catalyzed asymmetric allylic alkylation reactions, affording the corresponding alkylated products with high yields (up to97%) and enantioselectivities (up to>99%ee). Importantly, one of the products can be successfully applied in a convenient synthesis of chiral cyclopentene derivatives by ring-closing metathesis without any loss of enantiomeric excess.In addition, an unprecedented copper-catalyzed enantioselective Friedel-Crafts alkylation/N-hemiacetalization cascade of substituted indoles with β,γ-unsaturated a-ketoesters has been reported. This mild strategy provides a new access to various synthetically and biologically important2,3-dihydro-lH-pyrrolo[1,2-a]indoles in a highly enantioselective manner (67-97%yields, up to97:3d.r. and>99%ee). More importantly, this methodology can be applied in the formal total synthesis of flinderoles B and C analoges.At last, we have developed an efficient Br(?)nsted acid-catalysed one-pot, multicomponent reactions of aldehydes, aniline and2-vinyl indoles. The chemo-and regioselectivity of the reaction can easily be tuned by changing the protecting group of the2-vinyl indole component with two kinds of structurally different products obtained in good yields, providing a practical approach for obtaining the synthetically and biologically important tetrahydro-y-carboline and tetrahydroquinoline derivatives. The structures of these products were determined by X-ray analysis, and a possible transition state was proposed.