The primary long-term objective of this research plan is to improve the rational design of efficient chiral catalysts for conjugate copper. This copper-promoted reaction has high applicability to the syntheses of many important bioactive molecules and pharmaceuticals. The specific of this research plan is to study the shifts in electron density that accompany the critical bond-forming step, which should help to distinguish among several proposed mechanisms. Hammett free-energy relationships can help determine if reactants undergo changes in their effective electronic charges en route to their transition state. By placing a series of substituents at various sites at a reactant and by measuring the Hammett p values for these compounds, one can map the flux of electron density within a polarizable molecule during a reaction. The proposed research will study the effect of different substituent on the reaction rates at three key sites in the substrate. These rates will be measured by UV-visible spectrophotometry using a special fiber-optics probe in situ. In addition, the effect of different substituents on the copper catalyst will be examined. The values of an apparent pre-equilibrium constant will be evaluated by the use of analogous that may act as inhibitors for the reaction. The results will be compared with several proposed mechanisms for the reaction.
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