Rhodium-catalyzed cycloadditions to construct nitrogen heterocycles and progress towards the synthesis of ionomycin.

摘要

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 alpha,beta-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.