Development of New Phenanthroline-Based Chiral Ligands, Asymmetric Additions to Lactams, and the Completion of the Synthesis of Trichostatin A

1,10-Phenanthroline derivatives are important for a variety of synthetic applications and serve as effective ligands in a wide selection of reactions. While a variety of syntheses have been put forward for building a range of these ligands, the previous routes are quite lengthy and involve a number of low yielding steps. Therefore, only a limited number of chiral 1,10-phenanthroline derivatives have been synthesized and used in asymmetric reactions. This thesis outlines work done towards the development of a new method for synthesizing chiral phenanthroline-based ligands through a samarium diiodide-mediated coupling. The addition of stabilized anions to Ì_å±,Ì_å_-unsaturated 2-piperidinones has been underdeveloped in organic chemistry. Therefore, we have sought to make a contribution in this area by developing Mukiayama-Michael reaction conditions using bis(oxazoline) ligands in the asymmetric addition of ketene thioacetals to Ì_å±,Ì_å_-unsaturated Ì_å«-lactams. Through the use of bis(oxazoline) ligands we have been successful in setting benchmarks for enantio- and diastereoselectivity in developing this new chemistry. This methodology is ready to be extended to the use of the phenanthroline ligands developed in the Helquist lab. In tandem with developing this method, we have also pursued the synthesis of an analogue of PG-883347. The key step of the synthesis employs an asymmetric addition of a ketene thioacetal to an Ì_å±,Ì_å_-unsaturated 2-pyrrolidone to install a stereocenter on C2 of the thioester fragment of the compound. Finally, the Helquist lab has been pursuing a gram-scale synthesis of the naturally occurring compound, trichostatin A. While previous members of our group have made significant contributions to this synthesis, additional work is required to improve the synthesis, particularly the separation of the E and Z isomers of trichostatic acid. The final chapter of this thesis will detail the efforts made towards finishing this synthetic route.