The goal of this research is to significantly improve synthetic methodology. The proposed work is based on the hypothesis that the complex induced proximity effect provides the basis for discovering and developing efficient and convenient methodology with organolithium chemistry. The pathways of asymmetric syntheses applicable to chemotherapeutic and bioactive compounds. The chemistry of a number of organolithium-chiral ligand complexes which play key roles in diastereoselective and enantioselective syntheses will be studied. Recent discoveries made in the PI's laboratory with alpha- hetero atom and benzylic organolithium intermediates will be developed. New chiral ligands will be prepared based on promising preliminary results and assessed for their effectiveness in asymmetric inductions. Asymmetric deprotonations, demonstrated to provide highly enantioenriched alpha-lithioamine synthetic equivalents, will be extended to new systems. Asymmetric substitutions of organolithium intermediates in the presence of selected chiral ligands will be carried out with a focus on asymmetric carbon-carbon bond formation. These studies of asymmetric syntheses will be extended beyond the activated systems recently discovered to a number of new organolithium intermediates useful for syntheses of large and different classes of compounds. Further understanding of these reactions will be sought by mechanistic studies in order to provide rational improvements in the synthetic methodology.
| Lee, Suk Joong; Beak, Peter (2006) Asymmetric synthesis of 4,5,6- and 3,4,5,6-substituted azepanes by a highly diastereoselective and enantioselective lithiation-conjugate addition sequence. J Am Chem Soc 128:2178-9 |
