Organocatalytic Enantioselective Vinylogous Aldol And Micheal Addition Reaction

Asymmetric organocatalysis is another thriving method for the synthesis of chiral compounds after enzyme catalysis and organometallic catalyzed yet, and it has been a hot field of organic synthetic chemistry in 21 st century. Because it has less environmental pollution, simple operation, mild reaction conditions, and high selectivity, and so on into the decade of the 21 st century it rapidly gained world wide many medicinal chemists and organic chemist's concern and attention, and it has also been a rapid development. It has had a wide application in the synthesis of chiral drugs and many complex natural products, and has become an integral part of the method to synthesize the chiral compounds. Based on the organic catalyst, two classical reactions were studied in this paper.1 Organocatalytic Enantioselective Vinylogous Aldol Reaction of Allyl Aryl Ketones to Activated Acyclic KetonesFirst, this paper was based on the direct vinylogous aldol reaction of allyl ketones to activated acyclic ketones, the reaction conditions was determine through the screening of the kinds of catalysts, reaction temperature, common solvent and additives of the reaction, and we have developed the first simple direct organocatalysis asymmetric vinylogous aldol reaction of activated allyls to activated acyclic ketones. We get a series of chiral electron-withdrawing group-functionalized tertiary hydroxy-based addition products in good yields(up to 98%) and satisfactory enantioselectivity(ee up to 99%) with(R, R)-1,2-diamine-derived five-membered ring thiourea bifunctional organocatalyst as chiral catalyst, Na3PO4 or K2HPO4 as additives, tert-butyl benzene as a solvent and under the temperature of-10 oC or-20 oC. By further modifying the synthesized compounds, we synthesized a series of chiral electron-withdrawing group-functionalized tertiary hydroxy-based carboxylic acids(EWG-THCAs), for example Mosher's aicd, which are important element and intermediates for many pharmaceutical and chemical raw materials.2 Chiral Bicylic Guanidine-Catalyzed Conjugate Addition of ?-Fluoro-?-Ketoesters to Cyclic EnonesSecond, by utilising a chiral bicyclic guanidine as catalyst and triethylamine as additive, the first asymmetric Michael addition of ?-fluoro-?-ketoesters to various cyclic enones has been successfully developed, affording a variety of Michael adducts with potential synthetic utilities with satisfactory yield(up to 95%) and stereoselectivity(up to 94% ee and 4.3 : 1 dr).