The general goal of the proposed work is the discovery and development of reactions which can provide new strategies for syntheses of biologically active compounds. Prototypical reactions for the creation of asymmetric carbon-carbon bonds by lithiation substitution sequences in the presence of a chiral ligand will be investigated. The focus of the application is on elaboration of derivatives of amines, a class of compounds which is over-represented among medicinal agents. The reaction sequences to be studied have the potential for providing a strategic approach for asymmetric syntheses. The methodology and fundamental understanding to be provided should be of such obvious advantage that synthetic schemes will be designed around this methodology. The proposed work provides convenient, efficient, asymmetric syntheses which would be useful for the preparation of chemotherapeutic agents on the discovery, development and manufacturing scale.
| 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 |
