Essential to our ability to discover novel compounds of biological and medicinal value is our ability to design and synthesize organic molecules. The development of efficient, versatile and predictable synthetic methods is therefore vital to biomedical research. This research plan aims to develop a conceptually novel and synthetically powerful metal-catalyzed imine-yne metathesis reaction. Based on inspiration from Bergman's work with group (IV) imido complexes and considerations of the electronic and steric properties of imines, nine metallocene complexes are proposed for investigation as catalysts for achieving a general imine-yne metathesis. Experiments designed to probe the synthetic utility of the imine-yne metathesis are outlined. In addition, the regio- and stereoselectivity for both the inter- and intramolecular variants of this reaction are discussed and predicted. If successful, these studies will enrich our understanding of the structure and reactivity of metal-heteroatom complexes. This new methodology will also represent a significant advancement over the current technologies available for the synthesis of alpha,beta-unsaturated imines and enones - fundamental building blocks in organic synthesis. Moreover, the intramolecular variant of this reaction should be applicable to the synthesis of heterocycles, carbocycles, and macrocycles, which are structural architectures prevalent in compounds of medicinal interest.
| Dong, Vy M; Fiedler, Dorothea; Carl, Barbara et al. (2006) Molecular recognition and stabilization of iminium ions in water. J Am Chem Soc 128:14464-5 |
