Synthesis 2006(21): 3575-3584  
DOI: 10.1055/s-2006-942511
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Modular Approach for the Synthesis of Dibenzoazepine Derivatives

Gerhard Hilt*, Fabrizio Galbiati, Klaus Harms
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein Straße, 35043 Marburg, Germany
Fax: +49(6421)2825677; e-Mail: Hilt@chemie.uni-marburg.de;
Further Information

Publication History

Received 28 March 2006
Publication Date:
25 July 2006 (eFirst)

Abstract

A straightforward reaction sequence consisting of a Sonogashira­ coupling of protected propargylic amines, a cobalt-catalysed­ neutral Diels-Alder reaction, DDQ oxidation of the dihydroaromatic intermediate, a sodium borohydride reduction and an acid induced Friedel-Crafts-type cyclisation approach incorporating four simple starting materials leads to polyfunctionalised polycyclic products. Based on the electronic, steric and structural preconditions either seven-membered dibenzoazepine derivatives or alternatively six- or eight-membered isoindoline derivatives are formed.

    References

  • Selected references for biologically activities of isoindole derivatives, see:
  • 1a De Clercq E. J. Med. Chem.  1995,  38:  2491 
  • 1b Ferland JM. Demerson CA. Humber LG. Can. J. Chem.  1985,  63:  361 
  • 1c Linden M. Hadler D. Hofmann S. Hum. Psychopharmacol.  1997,  12:  445 
  • 1d Zhuang ZP. Kung MP. Mu M. Kung HF. J. Med Chem.  1998,  41:  157 
  • 1e Norman MH. Minick DJ. Rigdon GC. J. Med. Chem.  1996,  39:  149 
  • 1f Li S. Wang X. Guo H. Chen L. Yiyano Gongye  1985,  16:  543 ; Chem. Abstr. 1986, 105, 6378n
  • 1g inventors; Laboratori Baldacci S.p.A. Japanese Patent  5,946,268.  1984; Chem. Abstr. 1984, 101, 54922
  • 1h Lippmann W. inventors; U.S. Patent  4,267,189.  1981; Chem. Abstr. 1981, 95, 61988m
  • 1i Achinami K, Ashizawa N, and Kobayasui F. inventors; Japanese Patent  03,133,955.  1991; Chem. Abstr. 1991, 115, 255977j
  • 2a Govindachari TR. Ravindranath KR. Viswanathan N. J. Chem. Soc., Perkin Trans. 1  1974,  1215 
  • 2b Pendrack I. Barney S. Wittrock R. Lambert DM. Kingsbury WD. J. Org. Chem.  1994,  59:  2623 
  • 2c Taylor EC. Zhou P. Jenning LD. Mao Z. Hu B. Jun JG. Tetrahedron Lett.  1997,  38:  521 
  • 2d Fuska J. Fuskova A. Proksa B. Zb. Pr. Chemickotechnol. Fak. SVST  1979-1981 (pub. 1986),  285-291  ; Chem. Abstr. 1987, 106, 95582k
  • 2e Egbertson MS. Hartman GD. Gould RJ. Bednar RA. Cook JJ. Gaul SL. Holahan MA. Libby LA. Lynch RJ. Sitko GR. Stranieri MT. Vassallo LM. Bioorg. Med. Chem. Lett.  1996,  6:  2519 
  • 3a Brever E. Zbaida Z. Tetrahedron Lett.  1975,  31:  499 
  • 3b Inubushi Y. Tsuda Y. Konita T. Matsumoto S. Chem. Pharm. Bull.  1964,  12:  749 
  • 3c Inubushi Y. Tsuda Y. Konita T. Matsumoto S. Chem. Pharm. Bull.  1968,  16:  1014 
  • 3d Abramovitch RA. Shinkai I. Mavunkel BJ. More KM. O’Connor S. Ooi GH. Pennington WT. Srinivason PC. Stowers JR. Tetrahedron  1996,  52:  3339 
  • 3e Pigeon P. Decroix B. Tetrahedron Lett.  1997,  38:  2985 
  • 3f Heaney H. Shuhaibar KF. Synlett  1995,  47 
  • 3g Othman M. Decroix B. Synth. Commun.  1996,  2803 
  • 3h Othman M. Pigeon P. Decroix B. Tetrahedron  1997,  53:  2495 
  • 3i Boger DL. Lee JK. Goldberg J. Jin Q. J. Org. Chem.  2000,  65:  1467 
  • 4 Hilt G. Galbiati F. Synlett  2005,  829 
  • 6a Pesquet A. Daïch A. Decroix B. Van Hijfte L. Org. Biomol. Chem.  2005,  3:  3937 
  • 6b Cul A. Daïch A. Decroix B. Sanz G. Van Hijfte L. Heterocycles  2004,  64:  33 
  • 6c Decroix B. Daïch A. Marchalín Š. Sikoraiová J. Tetrahedron Lett.  2002,  43:  4747 
  • 6d Decroix B. Jilale A. Daïch A. Chihab-Eddine A. Heterocycles  2002,  58:  449 
  • 6e Decroix B. Daïch A. Hucher N. J. Org. Chem.  2001,  66:  4695 
  • 6f Decroix B. Daïch A. Hucher N. J. Heteroat. Chem.  1998,  35:  1477 
  • 6g Decroix B. Pigeon P. Marchalin Š. Daïch A. Tetrahedron Lett.  1998,  39:  9187 
  • 6h Decroix B. Pigeon P. Tetrahedron Lett.  1998,  39:  8659 
  • 6i Decroix B. Pigeon P. Othman M. Tetrahedron  1998,  54:  8737 
  • 7 Decroix B. Pigeon P. Tetrahedron Lett.  1997,  38:  2985 
5

The starting materials for the cobalt-catalysed Diels-Alder reactions are easily accessed by a nucleophilic substitution/Sonogashira reaction sequence in good to excellent yields under standard reaction conditions.

8

The compounds 5f, 5i and 5j exhibit additional stereogenic centres and are therefore obtained as mixtures of diastereomers.