Baylis-Hillman Reaction：Baylis-Hillman反应.ppt

The Baylis–Hillman Reaction and Related Modifications Literature meeting Presented by Josée Philippe Prof André B. Charette October 4th, 2005 Content What is the Baylis–Hillman Reaction? Activation of the Reaction Enantioselective Reaction Intramolecular Reaction Aza–Baylis–Hillman Reaction Application of Baylis–Hillman Reaction in the Synthesis of Natural Products such as Salinosporamide A. About Baylis–Hillman Reaction In 1968, Morita reported the reaction between acetaldehyde and ethyl acrylate in the presence of a tertiary phosphine. Four years later, Baylis and Hillman developed the same transformation, but in the presence of a tertiary amine, DABCO, which is less toxic and cheaper. Reaction works with aliphatic as well as aromatic aldehydes. Carbon-carbon bond formation involving Michael-type addition. What Kind of Substrates Are Used in BH Reaction? Activated alkenes Electrophile Catalyst Amine (BH Rxn) Phosphine (MBH Rxn) General Mechanism of BH Reaction New Interpretation of the Mechanism RDS is the elimination product and not the 1,2-Addition The rate law is second order in aldehyde and first order in catalyst and in methyl acrylate New Interpretation of the Mechanism Tertiary Amines and PhosphinesUsed in the BH or MBH Reaction What Can Be Used to Activate the Reaction? Different methods have been used so far to enhance the rate of the reaction. Use of DBU as catalyst or DMAP Mixture of water and organic solvent has been shown to increase the rate of reaction Solvent dependant: Dioxane and methanol are also used Use of stoichiometric amount of catalyst Use of co-catalyst in the reaction: LiClO4 with DABCO, proline with imidazole, DABCO with CaH2 These modifications are often substrate dependant and vary in yield and in time: usually between 0.5 h and 6 days or more!!! Question: Are there more efficient conditions for the BH-reaction? Activation of the BH Reaction Catalysis by Ionic Liquid Immobilized Quinuclidine Activation of th