Asymmetric Organocatalytic Carbon-Heteroatom Bond Formation Reaction

In recent years, asymmetric organocatalysis is a rapidly growing field and now has been as the third general approach to the catalytic production of enantiomerically pure organic compounds between the extremes of enzymatic transformations and transition metal catalysis. Moreover, the construction of chiral carbon-heteroatom bond, either of the foundation of the research methodology, or the synthesis of important drug molecules and natural products, is of practical significance and application value, also this will be a long-term attention and research hot spot for organic chemist. This dissertation mainly focuses on the design and research of asymmetric organocatalytic carbon-heteroatom bond formation reaction, which is divided into four parts.Part I:We have successfully developed the enantioselective sulfenylation of?-keto phosphonates and constructed the chiral C-S bond under the catalysis of?,?-diaryl-L-prolinols. At 0?, the?-sulfenylated?-keto phosphonates with a quaternary stereocenter were obtained in good yields and with excellent enantioselectivities (up to 92%ee) for various?-keto phosphonates and N-(arylthio)-phthalimides in hexane. The absolute configuration of the product was determined to be R by means of comparison of the CD spectrum. And on the basis of the results, the activation mode of the reaction may be attributed to a molecular interaction rather than a covalent bond.Part?:We have provided a highly efficient organocatalytic enantioselective C-S bond formation reaction between simple alkyl thiols and Morita-Baylis-Hillman (MBH) carbonates under the catalysis of a cinchona alkaloid derivative chiral tertiary amine. At 10?, the optically active?-methylene?-mercapto esters could be obtained in good yields with excellent enantioselectivities (up to 97%ee) for a wide range of alkyl thiols and MBH carbonates in 1,4-dioxane. And the absolute configuration of the product was determined to be S by means of an X-ray crystallographic analysis, the broad scope and simple operation makes this methodology very practical.Part III:We have provided a highly efficient asymmetric amination reaction of Morita-Baylis-Hillman (MBH) carbonates with benzophenone imine and constructed the chiral C-N bond under the catalysis of the catalysis of a cinchona alkaloid derivative chiral tertiary amine. At room temperature, the a-methylene-?-amino esters were obtained in good yields with excellent enantioselectivities (up to 99%ee) for a wide range of MBH carbonates in 1,4-dioxane. Furthermore, the unprotected a-methylene-?-amino esters were easily obtained with retentive enantioselectivities via one-step acidic hydrolysis protocol for the first time.Part IV:We have described the enantioselective Friedel-Crafts alkylation reaction between indoles and 2,2,2-trifluoroacetophenones under the catalysis of a chiral bifuncational catalyst derivated from cinchona alkaloid. At 5?, the chiral trifluoromethyl substituted tertiary alcohols with a quaternary stereocenter were obtained in good yields with moderate to good enantioselectivies in DCE.