Brunner, Henri and Schmidt, Peter (2000) Asymmetric catalysis, 131 - Naproxen derivatives by enantioselective decarboxylation. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY (11). pp. 2119-2133. ISSN 1434-193X
Full text not available from this repository. (Request a copy)Abstract
A new catalytic method to synthesize the important anti-inflammmatory agent naproxen [(S)-1] which has to be used as the (S) enantiomer, involves the enantioselective decarboxylation of the 6-methoxynaphth-2-yl derivative 2 of 2-cyanopropionic acid. Compound 2 was stirred in THF at 15 degrees C with catalytic amounts of chiral bases, which abstracted the carboxyl proton. After decarboxylation, reprotonation of the anion of 6 afforded the enantiomerically enriched naproxen nitrile 6, which may be hydrolyzed to naproxen, A variety of bases were screened, and cinchona alkaloids were found to give the best enantioselectivities. Thus, with quinidine 10, up to 34% ee was obtained for (S)-6. The enantiomeric excess could be increased by turning to amides of 9-amino-9-deoxyepicinchona alkaloids. The most successful 2-ethoxybenz- amide 31a of 9-amino-9-deoxyepicinchonine 11 gave up to 71.9% ee (S)-6. Cyclic ethers like THF were suitable solvents, and at a temperature of 15 degrees C, conversion was quantitative within 24 h in most cases. For high enantioselectivities, 5-10 mol- % of chiral base was sufficient, and the catalyst could be fully recycled after decarboxylation. The model compound 2-cyano-2-phenylpropionic acid (40) was decarboxylated with base 31a to the (S) enantiomer of the corresponding nitrile 41 with 60% ee.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONSTEROIDAL ANTIINFLAMMATORY AGENTS; 2-ARYL PROPIONIC ACIDS; MALONIC-ACIDS; 9-AMINO(9-DEOXY)CINCHONA ALKALOIDS; CINCHONA ALKALOIDS; COMBINED NMR; COPPER(I); PROTONATION; ANALOGS; AMIDE; naproxen; asymmetric catalysis; decarboxylation; alkaloids; epicinchonaalkaloid amides |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Anorganische Chemie > Alumni or Retired Professors > Prof. Dr. Henri Brunner |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Apr 2022 10:44 |
| Last Modified: | 26 Apr 2022 10:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42425 |
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