A novel synthetic pathway leads to 4-fluoropyridines bearing aryl substituents in positions 2 and 6 and possibly an additional alkyl group in position 3. 2-Fluoroallylic alcohols were esterified with N-benzoylalanine or N-aroylphenylglycines and the resulting esters were transformed to give 4-(2-fluoroallyl)oxazol-5(4H)-ones in a Steglich-type, Ireland-Claisen rearrangement. The latter compounds gave either N-aroyl-substituted 2-amino-4-fluoro-2-methyl-or 2-amino-4-fluoro-2-phenylalk-4-enoic acids in excellent yields by hydrolysis or substituted 2-aryl-4-fluoro-6-phenylpyridines in a cascade reaction initiated by an aza-Cope rearrangement to form thermally unstable 2-(2-fluoroallyl)oxazol-5(2H)-ones. Succeeding extrusion of carbon dioxide, intramolecular cyclopropanation of the fluorinated double bond with the formed carbene, ring-opening with formation of a fluorinated dihydropyridine, and final oxidative aromatization gave the title compounds in moderate yields.
2008Halogenated carboxylic acids and esters P 0260
Synthesis of Optically Active 2-Fluoroalk-1-en-3-yl Esters and Chirality Transfer in Their Claisen-Type Rearrangements. -Chiral esters (V) and (VIII) are efficiently prepared via kinetic resolution of the racemic alcohol (I) and used for the synthesis of chiral acids (VI) and (IX) by Ireland-Claisen rearrangement. -(MARHOLD, M.; WITTMANN, U.; GRIMME, S.; TAKAHASHI, T.; HAUFE*, G.; J. Fluorine
Succeeding Ireland-Claisen and Aza-Cope Rearrangements as KeySteps. -A novel pathway to 2,6-diaryl-4-fluoropyridines is presented. The process involves a cyclization of esters (III) to intermediary oxazoles which undergo spontaneous Ireland-Claisen rearrangement followed by thermolysis of the resulting oxazolones (IV). Hydrolysis of the latter affords amino acids of type (V). -(WITTMANN, U.; TRANEL, F.; FROEHLICH, R.; HAUFE*, G.; Synthesis 2006Synthesis , 13, 2085Synthesis -2096 Org.-Chem. Inst., Westfael. Wilhelms Univ., D-48149 Muenster, Germany; Eng.) -Mais 45-141
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