Development of new synthetic approaches to alpha-(aminoalkyl)acrylates and alpha-(hydroxyalkyl)acrylates and related analogs has become increasingly important for the synthesis of numerous chemically and biologically important molecules. The application of alpha-(aminoalkyl)acrylates to the design and synthesis of anti cancer drug taxol/taxotere has already provided interesting and promising results. Beta-nonsubstituted (aminoalkyl)acrylates can be synthesized by using the Baylis-Hillman reaction in which there are serious limitations such as slow reaction rate and narrow scope. Since beta-substituted acrylate derivatives do not undergo the Baylis-Hillman reaction, beta-substituted (aminoalkyl)acrylate and alpha-(hydroxyalkyl)acrylate analogs cannot be obtained by use of the Baylis-Hillman process. This proposal is intended to develop novel asymmetric additions of alpha-functionalized vinyl anions to carbonyl derivatives for the synthesis of both beta-nonsubstituted and beta-substituted (aminoalkyl)acrylates and (hydroxyalkyl)acrylates. The new asymmetric processes will be directed by chiral auxiliaries, chiral reagents and catalysts. The push and pull strategies incorporating Bronsted Lewis acids and bases will be applied in the catalyst selections. Reaction conditions such as concentrations of reactants and catalysts, cofactors, solvents or cosolvents, and reaction temperature will be systematically investigated for the proposed project. The new processes will be applied to the design and synthesis of anti cancer drug taxol/taxotere analogs.
