Rhodium-catalyzed cycloadditions to construct nitrogen heterocycles and progress towards the synthesis of ionomycin
Date
2014
Authors
Oberg, Kevin Martin, author
Rovis, Tomislav, advisor
Kennan, Alan J., committee member
Ferreira, Eric M., committee member
Neilson, James R., committee member
Kanatous, Shane B., committee member
Journal Title
Journal ISSN
Volume Title
Abstract
The ability to construct molecules in a rapid, atom-economical fashion is a major goal of organic chemistry. This work describes four topics; pyridone synthesis, mechanistic understanding in [2+2+2] cycloadditions, pyrimidinone synthesis, and progress towards ionomycin. The first chapter describes the synthesis of 4,6-substituted 2-pyridones and 3,5-substituted 4-pyridones from the rhodium-catalyzed [2+2+2] cycloaddition of two alkynes and an isocyanate. Our group demonstrated that an enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and alkynes generates indolizidinone and quinolizidinone products. Although trends for product and regioselectivity were established, the underlying mechanism was unclear. The second chapter describes X-ray analysis of rhodium·phosphoramidite complexes in conjunction with other mechanistic work to elucidate a theory that explains product and regioselectivity in this reaction. This system is amazing in that it illuminates the factors contributing to oxidative cycloadditions in a spectacular fashion by delivering two different products. The third chapter describes the enantioselective synthesis of pyrimidinones from a rhodium-catalyzed [4+2] cycloaddition of α, β-unsaturated imines and isocyanates. The final chapter describes our group's progress toward the synthesis of ionomycin using rhodium-catalyzed desymmetrization of anhydrides with zinc nucleophiles.