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Synthesis 2003(12): 1851-1855
DOI: 10.1055/s-2003-41030
PAPER
© Georg ThiemeVerlag Stuttgart · New York

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

Hans-Günther Schmalz*, Oliver Kiehl, Ursula Korell, Johann Lex
Institut für Organische Chemie, Universität zu Köln, Greinstrasse4, 50939 Köln, Germany
Fax: +49(221)4703064; e-Mail: Schmalz@uni-koeln.de.;
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Publication History

Received 13 June 2003
Publication Date:
13 August 2003 (online)

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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

  • 1 Bohlmann F. Zdero C. Robinson H. King RM. Phytochemistry  1979,  18:  1675 
    CrossrefGoogle Scholar
  • 2a Ambade NS. Desai DG. Dhanaji G. Mane RB. Indian J. Chem., Sect. B  1981,  20B:  917 
    Google Scholar
  • 2b Bohlmann F. Giencke W. Tetrahedron  1983,  39:  443 
    Google Scholar
  • 2c Kadam AJ. Baraskar UK. Mane RB. Indian J. Chem., Sect. B  2000,  39:  822 
    Google Scholar
  • 3a Tietze LF. Raschke T. Synlett  1995,  597 
    Google Scholar
  • 3b Tietze LF. Raschke T. LiebigsAnn.  1996,  1981 
    Google Scholar
  • 3c Noltemeyer M. Raschke T. Tietze LF. Acta Crystallogr.,Sect.C  1996,  C52:  2256 
    Google Scholar
  • 4a Tietze LF. Schimpf R. Angew.Chem., Int. Ed. Engl.  1994,  33:  1089 
    CrossrefGoogle Scholar
  • 4b Tietze LF. Modi A. Eur. J. Org. Chem.  2000,  1959 
    CrossrefGoogle Scholar
  • Recent work from this laboratory:
  • 5a Dehmel F. Lex J. Schmalz H.-G. Org.Lett.  2002,  4:  3915 
    CrossrefGoogle Scholar
  • 5b Schwarz O. Brun R. Bats JW. Schmalz H.-G. Tetrahedron Lett.  2002,  43:  1009 
    CrossrefGoogle Scholar
  • 5c Dehmel F. Schmalz H.-G. Org. Lett.  2001,  3:  3579 
    CrossrefGoogle Scholar
  • 5d Hörstermann DP. Schmalz H.-G. Kociok-Köhn G. Tetrahedron  1999,  55:  6905 
    CrossrefGoogle Scholar
  • Recent overviews:
  • 6a Schmalz H.-G. Siegel S. In TransitionMetals for Organic Synthesis   Vol. 1:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.550 
    Google Scholar
  • 6b Hegedus LS. Transition Metals inthe Synthesis of Complex Organic Molecules   2nd ed.:  UniversityScience Books; Sausalito CA: 1999.  Chap.10.
    Google Scholar
  • 6c Kündig EP. Pache SH. In Science of Synthesis (Houben-Weyl)   Vol.2:  Imamoto T. ThiemeVerlag; Stuttgart: 2003.  p.155 
    Google Scholar
  • 7 Schmalz H.-G. de Koning CB. Bernicke D. Siegel S. Pfletschinger A. Angew.Chem. Int. Ed.  1999,  38:  1620 
    Google Scholar
  • For reviews on the use of Cr(CO)3-stabilizedbenzylic anions in synthesis, see:
  • 8a Davies SG. Coote SJ. Goodfellow CL. In Advancesin Metal-Organic Chemistry   Vol. 2:  Liebeskind LS. JAI Press; London: 1989.  p.1-57  
    Google Scholar
  • 8b Davies SG. McCarthy TD. In Comprehensive Organometallic Chemistry II   Vol.12:  Abel EW. Stone FGA. Wilkinson G. Hegedus LS. Pergamon; New York: 1995.  p.979-1015  
    Google Scholar
  • This benzylic anion is best representedby a resonance structure where the charge is mainly delocalizedto the metal fragment (see Scheme 3). For a discussion of the electronic structureof Cr(CO)3 complexed benzylic anions, radicals and anions,see:
  • 9a Pfletschinger A. Dargel TK. Schmalz H.-G. Koch W. Chem. Eur. J.  1999,  5:  537 
    CrossrefGoogle Scholar
  • 9b See also: Merlic CA. Walsh JC. Tantillo DJ. Houk KN. J. Am. Chem. Soc.  1999,  121:  3596 
    CrossrefGoogle Scholar
  • 10 Even the more acidic arylic hydrogens ortho to the methoxy group could possiblybe protected by silylation, the benzylic deprotonation would preferentiallytake place at the methylene group meta tothe methoxy substituent because the acidity in para positionis lower for electronic and stereoelectronic reasons; see: Volk T. Bernicke D. Bats JW. Schmalz H.-G. Eur.J. Inorg. Chem.  1998,  1883 ;and references cited therein
    Google Scholar
  • 11a Corey EJ. Helal CJ. Angew.Chem. Int. Ed.  1998,  37:  1987 ;and references cited therein
    CrossrefGoogle Scholar
  • 11b Corey EJ. Helal CJ. TetrahedronLett.  1995,  36:  9153 
    CrossrefGoogle Scholar
  • 13 Schmalz H.-G. Millies B. Bats JW. Dürner G. Angew. Chem., Int.Ed. Engl.  1992,  31:  631 
    Google Scholar
  • 14 Johnstone RAW. Rose ME. Tetrahedron  1979,  35:  2169 
    CrossrefGoogle Scholar
  • 15a Freeman PK. Hutchinson L. J.Org. Chem.  1980,  45:  1924 
    Article in Thieme ConnectGoogle Scholar
  • 15b For the use of LiDBB inarene-Cr(CO)3 chemistry, see: Siwek MJ. Green JR. Synlett  1996,  560 
    Article in Thieme ConnectGoogle Scholar
  • 16a Lombardo L. Tetrahedron Lett.  1982,  23:  4293 
    CrossrefGoogle Scholar
  • 16b Lombardo L. Org.Synth.  1987,  65:  81 
    CrossrefGoogle Scholar
  • 18 Seebach D. Sting AR. Hoffmann M. Angew.Chem., Int. Ed. Engl  1996,  35:  2708 
    CrossrefGoogle Scholar
  • For previous syntheses of calamenenesusing arene chromium chemistry, see:
  • 19a Schmalz H.-G. Arnold M. Hollander J. Bats JW. Angew. Chem., Int. Ed.Engl.  1994,  33:  109 
    CrossrefGoogle Scholar
  • 19b Schmalz H.-G. Hollander J. Arnold M. Dürner G. Tetrahedron Lett.  1993,  34:  6259 
    CrossrefGoogle Scholar
  • 19c Uemura M. In Advances in Metal-Organic Chemistry   Vol.2:  Liebeskind LS. JAIPress; London: 1991.  p.195-245  
    CrossrefGoogle Scholar
12

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

17

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: (+44)1223336033; e-mail: deposit@ccdc.cam.ac.uk.