The goal of this project is the discovery and development of new cascade reactions involving N-heterocyclic carbene catalysts. Currently, research has led to the discovery of a new Michael- Benzoin cascade for the formation of functionalized cyclopentanones in high yield and excellent diastereoselectivity and enantioselectivity. This cascade reaction uses both a secondary amine catalyst and a chiral triazolium salt developed in our labs. Higher yields and selectivity are achieved using this cascade methodology as opposed to a traditional, two-reaction protocol. In addition, this methodology has been applied towards the synthesis of Crescentin IV. This compound has been used in folk medicines of several cultures. We believe a concise and selective synthesis of this compound can be achieved using this new cascade methodology. This synthetic route should lend itself to the syntheses of related, bioactive compounds. The knowledge gained from the development of this reaction will then be applied to the discovery of new cascade reactions. Accomplishments in this field will then lead to the quick, efficient syntheses of medicinally important compounds.
Cascade catalysis is a growing field in organic chemistry that allows the efficient synthesis of complex compounds using multiple catalysts. We have applied this principle in the construction of complex cyclopentanones using simple starting materials. This new methodology will provide access to medicinally important molecules in a quick and selective manner.
|White, Nicholas A; Ozboya, Kerem E; Flanigan, Darrin M et al. (2014) Rapid Construction of (-)-Paroxetine and (-)-Femoxetine via N-Heterocyclic Carbene Catalyzed Homoenolate Addition to Nitroalkenes. Asian J Org Chem 3:442-444|