An Enantioselective Approachto Cytotoxic Norcalamenenes via Electron-Transfer-Driven BenzylicUmpolung of an Arene Tricarbonyl Chromium Complex

Abstract

An efficient enantioselective total synthesis of (R)-1-isopropenyl-6-methoxy-7-methyl-1,2,3,4-tetrahydronaphthalene,the dehydro-analog of the cytotoxic norsesquiterpene (R)-7-demethyl-2-methoxycalamenene, wasachieved in seven steps starting from 6-methoxytetralone. The synthesisexploits the specific reactivity and stereochemistry of planar chiral η⁶-arene-Cr(CO)₃ complexes.In a key step, a Cr(CO)₃-complexed benzylic anion, regioselectively generatedby means of electron- transfer-driven benzylic umpolung, is diastereoselectivelyalkylated with acetyl chloride.

Key words

arene complexes - asymmetric synthesis - chromium - electron-transfer - natural products

References

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The enantiomeric excess was determinedby HPLC on a Daicel Chiralcel OJ column (hexane-i-PrOH) using a racemic sample as reference.

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The crystallographic data (excludingstructure factors) have been deposited with the Cambridge CrystallographicData Centre as supplementary publication no. CCDC 154574. Copiesof the data may be obtained from: The Director of the CambridgeCrystallographic Centre, 12 Union Road, GB-Cambridge CB2 1EZ, UK;Fax: [phone]; e-mail: [e-mail].