Olefin metathesis has been widely explored in recent years and has emerged as a highly useful and often employed synthetic process. In contrast, the area of metathesis involving carbon-heteroatom (in particular carbon-nitrogen) multiple bonds has been largely ignored. Carbon-nitrogen double bond (imine) metathesis has enormous potential for use in synthetic chemistry, given the number of molecules of biological and medicinal significance that contain carbon-nitrogen bonds. To become synthetically useful, many aspects of imine metathesis require further investigation, including the mechanism of the reaction and the role of the metal, both of which are unclear in certain cases. The feasibility of a new reaction of fundamental importance, a metal-catalyzed ring-closing metathesis between an imine an alkene, will be studied in an effort to develop a novel, facile, and practical method for the generation of cyclic imines for use as synthetic building blocks. A series of ene-imines with varying functionality will be prepared and investigated in this reaction to examine the scope of the reaction. After the initial demonstration of principle, more challenging (i.e., highly functionalized) substrates will be investigated in route to a variety of naturally occurring and/or biologically interesting molecules, such as proline analogs, which are constituents of many medicinal agents, pyrrolidine alkaloids, and (-)-indolactam V, a PKC modulator. Finally, in addition to the synthetic aspects, the mechanism of the reaction will be explored sing kinetic analysis, to establish metal involvement and to determine the preferred pathway in the reaction, since the catalyst can react with both the imine and alkene moieties.
