Development of homobimetallic and heterobimetallic catalysts for the enantioselective conjugate addition of cyanide to alpha,beta-unsaturated imides

I. Development of a homobimetallic catalyzed enantioselective conjugate addition of cyanide to alpha,beta-unsaturated imides. (Salen)Al-Cl complex 1a catalyzes the asymmetric conjugate addition of hydrogen cyanide to alpha,beta-unsaturated imides in high yields and enantioselectivities. The cyanide adducts are readily converted into a variety useful chiral building blocks, including alpha-substituted-beta-amino acids and beta-substituted-gamma-aminobutyric acids. A second-order dependence on catalyst concentration and a positive non-linear correlation of catalyst ee to product ee suggest a cooperative bimetallic mechanism involving both nucleophile and electrophile activation.*; II. Cooperative heterobimetallic catalysis: Application to the highly enantioselective conjugate addition of cyanide to alpha,beta- unsaturated imides. Cooperative heterobimetallic catalysis was used as a design principle to improve the reactivity of the homobimetallic conjugate addition of hydrogen cyanide to alpha,beta-unsaturated imides. A dual catalyst pathway involving (salen) aluminum chloride complex 1a and (i-propyl pybox) erbium chloride complex 4 provides measurable improvements in the rates and enantioselectivities relative to complex 1a alone. Mechanistic studies indicate the presence of competing heterobimetallic and homobimetallic pathways.; To develop a system that operates by a purely heterobimetallic mechanism, each catalyst was optimized for single-component activation. A second-generation dual catalyst system involving a mu-oxo (salen) aluminum complex 1b and (i-propyl pybox) erbium chloride complex 4 provides a significant improvement relative to both the homobimetallic and the first generation dual catalyst systems. Mechanistic investigations indicate that the reaction proceeds through a heterobimetallic pathway, presumably one in which a mu-oxo (salen) aluminum complex 1b activates the imide and (i-propyl pybox) erbium chloride complex 4 activates hydrogen cyanide.*; *Please refer to dissertation for diagrams.