Application of Cascade Processes for the Synthesis of Polycyclic Ring Systems

Emory University, Atlanta GA

Investigators

Abstract

With this award, the Chemical Synthesis Program is supporting the research of Professor Albert Padwa of the Department of Chemistry at Emory University. Professor Padwa's research efforts revolve around the use of novel cascade sequences for the assemblage of complex target molecules. Synthetic methods that combine transformations of different reaction types significantly broaden the scope of such procedures in synthetic chemistry. One of the immediate goals is to develop a new approach toward piperidine synthesis that employs a tandem reaction sequence using various oximes with 2,3-bis(phenylsulfonyl)-1,3-diene. Formation of an aza-oxabicyclic ring cycloadduct involves conjugate addition of the oxime onto the diene to give a transient nitrone which then undergoes a subsequent intramolecular dipolar cycloaddition reaction. The research goals also call for a formal synthesis of the novel marine alkaloid halichlorine using a related series of reactions. The intramolecular Diels-Alder cycloaddition/rearrangement cascade of 2-amido substituted furans represents a very effective strategy for the preparation of a variety of naturally occurring alkaloids. Another goal will be to explore the synthetic power of the tandem cyclization/cycloaddition sequence of rhodium carbenoids toward the synthesis of several Vinca alkaloids. alpha-Diazo-dicarbonyl compounds are appealing as synthetic intermediates in that they are readily accessible, are reasonably robust and leave functionality in the cyclized product that is useful for further synthetic transformation. In terms of broader impacts, the work is expected to have wide application to the field of organic synthesis. The novel cascade sequences being developed under this grant have potential application for the production of key target molecules in the pharmaceutical and agricultural sectors. The research outlined in the proposal also represents ideal training for undergraduate, graduate and postdoctoral students, which is in keeping with NSF's goals of research and education. Students trained during the performance of this research will use this knowledge to make important future contributions in pharmaceutical and academic research.