The general goal of the proposed work is to develop reactions discovered in my laboratory which can provide new approaches for asymmetric 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 N-Boc amines, which have been shown in our previous work to provide useful asymmetric synthetic equivalents. The reactions 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 clear 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 |
