Download PDF
Synthesis 2011(15): 2423-2430  
DOI: 10.1055/s-0030-1260114
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Synthesis of a Cyclopentannulated Pyrrolidine Derivative

Faiz Ahmed Khan*, Sarasij K. Upadhyay
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
Fax: +91(512)2597436; e-Mail: faiz@iitk.ac.in;
Further Information

Publication History

Received 21 April 2011
Publication Date:
14 July 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A racemic cyclopentannulated pyrrolidine derivative was synthesized utilizing ruthenium oxidation and borane reduction as the key steps. Ruthenium oxidation reaction of the 1,2-dibromoalkene moiety in an N-Boc-protected tetrabromonorbornyl derivative afforded a tricyclic α-hydroxy ketone, which on alkaline hydrogen peroxide cleavage furnished a bicyclic lactam in excellent yield. Borane reduction of the N-Boc-protected bicyclic lactam gave an unexpected product as a single diastereomer resulting from the reduction of not only the lactam and ester moieties but also the ketal to the corresponding methyl ether. A plausible mechanism involving an oxocarbenium ion is discussed.

Key words

bicyclic pyrrolidine - ruthenium oxidation - borane reduction - Diels-Alder cycloaddition - hydrodehalogenation

    References

  • 1a Ranatunga S. Valle JRD. Tetrahedron Lett.  2009,  50:  2464 
    Google Scholar
  • 1b Obst U. Betschmann P. Lerner C. Seiler P. Diederich F. Helv. Chim. Acta  2000,  83:  855 
    Google Scholar
  • 1c Kolodziej SA. Nikiforovich GV. Skeean R. Lignon M.-F. Martinez J. Marshall GR. J. Med. Chem.  1995,  38:  137 
    Google Scholar
  • 2a Martín R. Alcón M. Pericás MA. Riera A. J. Org. Chem.  2002,  67:  6896 
    Google Scholar
  • 2b Sebahar PR. Williams RM. J. Am. Chem. Soc.  2000,  122:  5666 
    Google Scholar
  • 2c Denhart DJ. Griffith DA. Heathcock CH. J. Org. Chem.  1998,  63:  9616 
    Google Scholar
  • 2d Overman LE. Tellew JE. J. Org. Chem.  1996,  61:  8338 
    Google Scholar
  • 2e Sisko J. Henry JR. Weinreb SM. J. Org. Chem.  1993,  58:  4945 
    Google Scholar
  • 3a Lombardo M. Fabbroni S. Trombini C. J. Org. Chem.  2001,  66:  1264 
    Google Scholar
  • 3b Dondoni A. Perrone D. Tetrahedron Lett.  1999,  40:  9375 
    Google Scholar
  • 3c Blanco M.-J. Sardina FJ. J. Org. Chem.  1998,  63:  3411 
    Google Scholar
  • 3d Wong C.-H. Provencher L. Porco JA. Jung S.-H. Wang Y.-F. Chen L. Wang R. Steensma DH. J. Org. Chem.  1995,  60:  1492 
    Google Scholar
  • 3e Lundt I. Madsen R. Daher SA. Winchester B. Tetrahedron  1994,  50:  7513 
    Google Scholar
  • 3f Thompson DK. Hubert CN. Wightman RH. Tetrahedron  1993,  49:  3827 
    Google Scholar
  • 3g Liu KKC. Kajimoto T. Chen L. Zhong Z. Ichikawa Y. Wong CH. J. Org. Chem.  1991,  56:  6280 
    Google Scholar
  • 3h Card PJ. Hitz WD. J. Org. Chem.  1985,  50:  891 
    Google Scholar
  • 4a Bunch L. Nielsen B. Jensen AA. Bräuner-Osborne H. J. Med. Chem.  2006,  49:  172 
    Google Scholar
  • 4b Ennis MD. Hoffman RL. Ghazal NB. Old DW. Mooney PA. J. Org. Chem.  1996,  61:  5813 
    Google Scholar
  • 4c Yan M. Jacobsen N. Hu W. Gronenberg LS. Doyle MP. Colyer JT. Bykowski D. Angew. Chem. Int. Ed.  2004,  43:  6713 
    Google Scholar
  • 4d Feldman KS. Iyer MR. J. Am. Chem. Soc.  2005,  127:  4590 
    Google Scholar
  • Reviews of the use of pyrrolidine derivatives in enamine catalysis, see:
  • 5a Mukherjee S. Yang JW. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
    Google Scholar
  • 5b Notz W. Tanaka F. Barbas CF. Acc. Chem. Res.  2004,  37:  580 
    Google Scholar
  • 5c List B. Acc. Chem. Res.  2004,  37:  548 
    Google Scholar
  • 6 Khan FA. Das BP. Dash J. J. Prakt. Chem.  2000,  342:  512 ; and references therein
    CrossrefGoogle Scholar
  • 7a Khan FA. Prabhudas B. Dash J. Sahu N. J. Am. Chem. Soc.  2000,  122:  9558 
    Google Scholar
  • 7b Khan FA. Sahu N.
    J. Catal.  2005,  231:  438 
    Google Scholar
  • For selected list of publications on the applications of norbornyl derivatives from our laboratory, see:
  • 8a Khan FA. Rao CN. Tetrahedron Lett.  2006,  47:  7567 
    Google Scholar
  • 8b Khan FA. Dash J. Sudheer Ch. Sahu N. Parasuraman K.
    J. Org. Chem.  2005,  70:  7565 
    Google Scholar
  • 8c Khan FA. Dash J. Eur. J. Org. Chem.  2004,  2692 
    Google Scholar
  • 8d Khan FA. Dash J. Sudheer Ch. Chem. Eur. J.  2004,  10:  2507 
    Google Scholar
  • 8e Khan FA. Satapathy R. Dash J. Savitha G. J. Org. Chem.  2004,  69:  5295 
    Google Scholar
  • 8f Khan FA. Dash J. Sahu N. Sudheer Ch.
    J. Org. Chem.  2002,  67:  3783 
    Google Scholar
  • 8g Khan FA. Sahu N. Dash J. Prabhudas B. J. Indian Inst. Sci.  2001,  81:  325 
    Google Scholar
  • 9a Khan FA. Rout B. J. Org. Chem.  2007,  72:  7011 
    Google Scholar
  • 9b Khan FA. Rout B. Tetrahedron Lett.  2006,  47:  5251 
    Google Scholar
  • 10 Khan FA. Upadhyay SK. Tetrahedron Lett.  2008,  49:  6111 
    CrossrefGoogle Scholar
  • 11 Köhling P. Schmidt AM. Eilbracht P. Org. Lett.  2003,  5:  3213 
    CrossrefGoogle Scholar
  • 12 Khan FA. Prabhudas B. Tetrahedron Lett.  1999,  40:  9289 
    CrossrefGoogle Scholar
  • 13a Anastasia M. Allevi P. Ciuffreda P. Fiecchi A. Scala A. J. Chem. Soc., Perkin Trans. 1  1986,  2117 
    Google Scholar
  • 13b Borch RF. Bernstein MD. Durst HD. J. Am. Chem. Soc.  1971,  93:  2897 
    Google Scholar
  • 15 Hwu JR. Jain ML. Tsay S.-C. Hakimelahi GH. Tetrahedron Lett.  1996,  37:  2035 
    CrossrefGoogle Scholar
  • 16a Brown HC. Murray KJ. Tetrahedron  1986,  42:  5497 
    Google Scholar
  • 16b Maryanoff BE. McComsey DF. Nortey SO. J. Org. Chem.  1981,  46:  355 
    Google Scholar
  • 17 Rathore R. Weigand U. Kochi JK. J. Org. Chem.  1996,  61:  5246 
    CrossrefGoogle Scholar
  • 18 Fleming B. Bolker HI. Can. J. Chem.  1974,  52:  888 
    CrossrefGoogle Scholar
  • 19a Fu Y.-Q. Li Z.-C. Ding L.-N. Tao J.-C. Zhang S.-H. Tang M.-S. Tetrahedron: Asymmetry  2006,  17:  3351 
    Google Scholar
  • 19b Tzeng Z.-H. Chen H.-Y. Reddy RJ. Huang C.-T. Chen K. Tetrahedron  2009,  65:  2879 
    Google Scholar
  • 20 Perrin DD. Armarego WLF. Perrin DR. Purification of Laboratory Chemicals   2nd ed.:  Pergamon Press; Oxford: 1980. 
    Google Scholar
14

The original endo/exo ratio in 11 was slightly altered in favor of exo product perhaps due to epimerization of aldehyde group in 10 under reaction conditions. On the other hand, addition of relatively bulky groups such as allyl to 10 with similar endo/exo composition exclusively furnished the endo addition product due to the unfavorable steric interaction of the syn-OMe group of the ketal offsetting the balance in favor of the endo product8e via epimerization of aldehyde group.