ORGN 521 |
| 1,8-naphthyridines provide an important scaffold for a variety of compounds of unique biological activities. Our recent findings demonstrated that they also serve as a key structure for highly efficient chain breaking antioxidant (30 times stronger than α-tocopherol, nature's the most powerful antioxidant). As a methodology for the preparation of gem-dialkyl 1,8-naphthyridine, the addition of n-alkyllithiums to α,α'-disubstituted-1,8-naphthyridines was investigated. High yields were obtained only in non-polar solvents such as ether/hexanes mixture. In more polar solvents, such as THF, alkyllithium acts as a base rather than a nucleophile. Regioselective addition of n-alkyllithiums to α,α'-disubstituted-1,8-naphthyridines was achieved through a cyclic chelation with co-chelating group. Five-membered chelation by TBS protected alcohol moiety turned out to be the most successful. In contrast, six-membered chelation gave marginal regioselectivity. This methodology was successfully incorporated to the synthesis of nitrogen analogs of PMC, an α-tocopherol derivative with 2,2-dimethyl substituents. |
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New Reactions, Methodology, Total Synthesis, Physical Organic Chemistry
8:00 PM-10:00 PM, Tuesday, 15 March 2005 Convention Center -- Sails Pavilion, Poster
Division of Organic Chemistry |