With this Research in Undergraduate Institutions (RUI) award, the Organic Synthesis Program supports Professor Thomas Shawe's studies in the Department of Chemistry at Bucknell University of the asymmetric synthesis of cycloalkenones. Alkylation of chiral enaminones followed by Grignard reagent addition affords access to cycloalkenones with good stereocontrol. The role of chiral auxiliaries in the transfer of chirality is assessed through modification of the chelate ring size and number of chelate sites provided by the chiral auxiliary, alteration of the nature of the chiral auxiliary, and examination of additive effects. Addition of other organometallic nucleophiles in place of Grignard reagents permits further synthetic generality, while the use of metal hydrides offers promise for the formation of cycloalkenones unsubstituted in the 3-position. The products of these reactions are elaborated synthetically, both to permit unambiguous assignment of stereochemistry and to generate intermediates for further synthetic applications. Preparation of molecules of demonstrated or potential biological activity often requires control over the three-dimensional arrangement of atoms or groups of atoms in the target molecules. In particular, one often desires a molecule which differs from another only in the manner by which a right hand differs from a left hand, namely as non-superimposable mirror images. Professor Shawe develops new chemical approaches for the selective synthesis of such molecules through the use of sequential addition of reagents to precursor molecules bearing chemically-attached `auxiliaries` which direct incoming reagents to the desired position for reaction. The resulting compounds offer promise as synthetic building blocks for further elaboration into molecules displaying important biological activity, such as the prostaglandins.
