Stereoselective Functionalization of Hydrocarbons using oxaziridines
Most small, bioactive organic compounds interact specifically with a particular enzyme through a series of oxygen- and nitrogen-containing "functional groups." The specificity and strength of this interaction depends on the overall shape of the molecule and on the arrangement of its functional groups in space (i.e., its "stereochemistry"). The discovery of new compounds with the ability to fight disease or otherwise modulate the behavior of a biological system thus relies on the existence of methods for the synthesis of densely functionalized, well-defined organic molecules. In this regard a particularly important goal of synthetic organic chemistry is the discovery of new transformations that convert simple, widely available hydrocarbon starting materials into complec, functionalized molecules with high levels of control over their stereochemistry. We are investigating the utility of small, oxygen- and nitrogen- rich compounds called "oxaziridines", (2) fundamentally different reactions will be observed using different catalysts, and (3) these catalysts will have the ability to contol the stereochemistry of the resulting value-added products. The proposed research will test these hypotheses in the context of three parallel project areas. First, we will develop copper-catalyzed reactions of oxaziridines for the construction of stereochemically well-defined 1,2-aminoalcohol structures ("aminohydroxylation reatctions"). Second, we will develop titanium-catalyzed reactions of oxaziridines for the construction of 1,3-aminoalcohol-containing structues with similarly high leveles of stereochemical fidelity ("nitrone cycloadditions"). Third, we will invesitgate the ability of oxaziridines to selectively insert nitrogen into unreactive C-H bonds on simple alkane substrates. Successful realization of our project goals will constitute a significant contribution to the field of synthetic organic chemistry and provide a set of powerful tools for the discovery of new drugs, new biological probes, and new materials.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.