This proposal requests support for a beginning PI at Western Michigan University who is establishing an independent research program in synthetic organic chemistry. Despite the well-known chelation properties of 1,10-phenanthroline and 2,2'-dipyridine, there have been very few reports on their application as ligand templates for asymmetric catalysis. The potential of these dinitrogen ligands can only be realized as synthetic methods for their functionalization emerge. This proposal fills the gap and addresses the synthesis of novel 1,10-phenanthroline derivatives that can be applied as optically active ligands in asymmetric catalysis. The major goal of this proposal is to examine the feasibility of 5,6-dihydrophenanthroline derivatives as a novel class of ligands for asymmetric catalysis. Following is an outline for the synthesis, application and rationale of these novel ligands, addressing important and current aspects of organic chemistry that lie at the interface of organic synthesis, heterocyclic, organometallic, and computational chemistry. ? A. Prepare novel, enantiopure 5,6-dihydrophenanthroline ligands: Dihydrophenanthroline derivatives with chiral groups attached in the 2,3,8- and/or 9 position(s) are known to serve as effective ligands in Pd-mediated allylation reactions (up to 81% ee). An efficient approach is described for the synthesis of 5,6-disubstituted 5,6-dihydro-l,10-phenanthrolines as novel, tunable ligands for asymmetric catalysis. Nucleophilic ring opening of 1,10-phenanthroline-5,6-epoxide, a key intermediate, allows for the introduction of new functionalities (X and Y) and stereogenic centers in the 5- and 6-positions. Methods for the preparation of enantiopure phenanthroline derivatives are discussed. ? B. Apply tailored ligands to asymmetric catalysis reactions: Asymmetric allylic alkylation reactions offer the advantage of forming many different types of carbon-carbon and carbon-heteroatom bonds and have emerged as powerful methods for the construction of chiral, non-racemic intermediates for organic synthesis. In order to understand the relationship of ligand structure, catalyst reactivity, and selectivity, the PI proposes first to study the catalytic performance of new phenanthroline ligands during allylation reactions with palladium as the testing ground. A long-term goal is to test these new ligands in other catalytic processes. ? C. Study stereoselectivity trends for different substituents in the 5,6-positions: The PI proposes a multifaceted approach to study ligand properties and performance that provides mechanistic insight. The influence of substituents will be examined by determining reaction enantioselectivities and conformational preferences for all new ligands. X-Ray diffraction analysis will furnish solid-state structural data and nuclear magnetic resonance studies will provide pivotal information for conformational preferences in solution. These experimental approaches will be complemented with computational ligand design based on molecular mechanics tools. ? ?
| Kohler, Lars; Schoffers, Elke; Driscoll, Erin et al. (2012) First isolation of disubstituted cis-5,6-dihydro-1,10-phenanthrolines. Lipase-mediated resolution of cis- and trans-phenoxy alcohol isomers and assignment of absolute stereochemistry via CD and NMR spectroscopy. Chirality 24:245-51 |
| Schoffers, Elke; Kohler, Lars (2009) Efficient alcoholysis of 5,6-dihydro-1,10-phenanthroline-5,6-epoxide with ytterbium(III) triflate and subsequent enantioselective transesterification with lipases. Tetrahedron Asymmetry 20:1879-1902 |
