The Application Of Chiral Ligands In The Asymmetric Catalysis Reaction

Chirality is an important characteristic of life, and enantiomers usually have different or even opposite physiological activity, thus it is extremely significant to synthesize the compounds which have very high enantioselectivity. Recent research indicates that the asymmetric reaction conducted by chiral ligand is the most direct and efficient way to obtain high optical active compounds, so the application of novel ligand in asymmetric catalysis reactionis is still necessary and may stand as hot topics in organic chemistry. In this paper, based on existing ligands of the previous work, the further application of L1、 L76、L93can hope to explore the relationship between the molecular structure and catalytic performance and achieve excellent results in Henry reaction、Alkylation、Total synthesis of marine sponge natural product and Arylation of sulfones and amides.Chiral nitroalcohols are important organic intermediates, which are widely used in medicine, pesticide and others. Therefore, we investigated systematically the catalytic properties of the ligands L73-80in the asymmetric Henry reaction of zinc aldehyde with nitromethane, and ligand L76is applied in catalytic asymmetric Henry reaction finally. The experimental results show that the ligands afforded corresponding nitroalcohol products in good to high yields and enantioselectivities, for the4-methylbenzaldehyde84%ee was obtained.Chiral propargyl alcohols are the important intermediates of many fine chemicals, and natural products, so we applied the Zinc-Amino alcohols system in the highly enantioselective addition of1,3-diynes to aldehydes and investigated the effect of different reaction conditions such as ligand structure, reaction temperature and solvent on the catalytic results. Under the optimal reaction conditions identified, we studied a variety of substituted1,3-diynes to aldehydes which gave excellent results, most products of propargyl alcohol’s ee values were more than90%, in which the best95%ee was obtained. In addition, by using the chiral propargyl alcohol products as the key intermediate, the total asynthesis of marine sponge natural product was developed. The long-chainunsaturated aldehydes were synthesized through coupling reaction, reduction, oxidation and a series of high yield reaction firstly, then the alkynol fragment was prepared by the method of asymmetric alkynylation of above unsaturated aldehydes, finally with the help of potassium carbonate to removethe protectiving group, the target product was achieved. This route is short and the total yield is higher, although the ee of addition product is only81-82%, after recrystallization, the ee value could be increased to95%.Furthermore, this paper also studied systematically the palladium catalyzed arylation of methyl sulfone with bromobenzene. Under the nitrogen atmosphere, using toluene as the solvent and Pd (OAc)2as Pd source, methyl sulfone can smoothly react with bromobenzene, providing the arylated products in70-90%yield and the ratio of mono-to bis-arylation was well controlled (10-20:1) in the reactions. It provides a convient method to synthesize sulfone compounds.Finally, an efficient system for the direct catalytic intermolecular alpha-arylation of acetamide derivatives with aryl halides is presented, which provides the arylated amides in up to95%yield. Excellent chemoselectivities (up to50:1) in the mono-and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and other conditions. We demonstrated the catalyst exhibited excellent reactivity in intramolecular arylation in the synthesis of oxindoles as well.