Novel Asymmetric Routes to 2-Oxetanones and Their Application

Texas A&M Research Foundation, College Station TX

Investigators

Abstract

This project will continue work on the development of concise methods for the asymmetric synthesis of novel beta-lactones (2-oxetanones) via organocatalysis. In particular, further development of Lewis base-promoted, aldol-lactonizations (net cycloadditions) that construct a C-C bond and a C-O bond simultaneously will be pursued to access these versatile strained heterocycles. In addition to studies of novel Lewis-base promoters, mechanistic studies will be undertaken to gain further insights into the overall reaction pathway including a potential acyl substitution proceeding via an SN2 pathway. In addition, novel transformation of these heterocycles including ring expansions by way of dyotropic rearrangements of bicyclic and tricyclic beta-lactones will be explored further. Hypothesis driven studies of novel reaction pathways involving ammonium enolates and including extended and interrupted Morita-Baylis-Hillman processes will be pursued. The utility of the methods and processes developed will be highlighted by applications to the total synthesis of spongiolactone and curcumalactone. With respect to educational objectives, the translation of laboratory research into the teaching laboratory will continue along with further development of multimedia approaches for conveying the societal relevance of organic synthesis. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Daniel Romo of the Department of Chemistry at Texas A&M University. Professor Romo's research efforts revolve around the development of catalytic, asymmetric methods for the synthesis of beta-lactones and their application in synthesis including natural product total synthesis. The results of this research will contribute significantly to further use and application of these underutilized heterocycles, which possess a diverse array of reactivity modes making them highly versatile intermediates for organic synthesis. Successful development of the proposed methods will have an impact on organic synthesis in the pharmaceutical and agricultural industries as the methods being developed are robust and "user friendly." In addition, synthesis of the targeted natural products will have broader impacts in enabling the further understanding of fundamental cellular processes.