Download PDF
Synthesis 2012(1): 144-150  
DOI: 10.1055/s-0031-1289631
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of the Indolo[2,3-a]quinolizidine Ring through the Addition of 2-Siloxyfurans to Imines and Intrinsic Reaction Coordinate Calculations

Yaneris Mirabal-Gallardoa, Maria D. P. C. Sorianoa, Julio Caballerob, Jans Alzate-Moralesb, Mario J. Simirgiotisc, Leonardo S. Santos*a
a Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Talca University, P.O. Box 747, Talca, Chile
Fax: +56(71)200448; e-Mail: lssantos@utalca.cl;
b Centre for Bioinformatics and Molecular Simulations, School of Bioinformatics, Talca University, P.O. Box 747, Talca, Chile
c Laboratory of Natural Products, Department of Chemistry, Faculty of Basic Sciences, University of Antofagasta, P.O. Box 170, Antofagasta, Chile
Further Information

Publication History

Received 9 September 2011
Publication Date:
01 December 2011 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

A concise asymmetric diastereoselective strategy for the synthesis of indolo[2,3-a]quinolizidine derivative 1 was developed using diastereoselective addition of 2-siloxyfurans 4 to imine 3 through chiral auxiliary induction. The addition of an ionic liquid as additive in the reaction favored the anti configuration in the major adduct. The stereochemical outcome of the anti/syn (threo/erythro) selectivity was rationalized based on transition state and IRC calculations at DFT (B3LYP) and MP2 theories. MP2 calculations was shown to be the method of choice in these systems, which orbital desymmetrizations were observed in the anti transition state of the addition of 4 to 3 and secondary orbital interactions allowed us to rationalize the production of the major anti-adduct 6. Furthermore, the work also suggested that 2-(triisopropylsiloxy)furan (4a) was the nucleophile of choice in this kind of Mannich reaction. Moreover, the strategy features the use of the Mitsunobu reaction to insert an amino group with the correct configuration into amine 2, key intermediate to achieve 1. The synthetic route can also be applied in the total synthesis of promising aza-β-carboline compounds.

Key words

azaeburnane - β-carbolines - chiral auxiliary - Mitsunobu reaction - intrinsic reaction coordinate calculations

    References

  • For asymmetric Pictet-Spengler reactions, see:
  • 1a Raheem IT. Thiara PS. Peterson EA. Jacobsen EN. J. Am. Chem. Soc.  2007,  129:  13404 
    Search in Google Scholar
  • 1b Cox ED. Cook JM. Chem. Rev.  1995,  95:  1797 
    Search in Google Scholar
  • 1c Chrzanowska M. Rozwadowska MD. Chem. Rev.  2004,  104:  3341 
    Search in Google Scholar
  • 1d Allin SM. Gaskell SN. Elsegood MRJ. Martin WP. Tetrahedron Lett.  2007,  48:  5669 
    Search in Google Scholar
  • 1e Wanner MJ. van der Haas RNS. de Cuba KR. van Maarseveen JH. Hiemstra H. Angew. Chem. Int. Ed.  2007,  46:  7485 
    Search in Google Scholar
  • For reviews on the use of siloxyfurans, see:
  • 2a Casiraghi G. Rassu G. Synthesis  1995,  607 
  • 2b Rassu G. Zanardi F. Battistini L. Casiraghi G. Chem. Soc. Rev.  2000,  29:  109 
    Search in Google Scholar
  • 3a Hermange P. Dau METH. Retailleau P. Dodd RH. Org. Lett.  2009,  11:  4044 
    Search in Google Scholar
  • 3b Martin SF. Corbett JW. Synthesis  1992,  55 
  • 3c Morimoto Y. Nishida K. Hayashi Y. Shirahama H. Tetrahedron Lett.  1993,  34:  5773 
    Search in Google Scholar
  • 3d Pichon M. Figadere B. Cave A. Tetrahedron Lett.  1996,  37:  7963 
    Search in Google Scholar
  • 3e Morimoto Y. Iwahashi M. Synlett  1995,  1221 
  • 3f Zanardi F. Battistini L. Rassu G. Pinna L. Mor M. Culeddu N. Casiraghi G. J. Org. Chem.  1998,  63:  1368 
    Search in Google Scholar
  • 3g Martin SF. Barr KJ. Smith DW. Bur SK. J. Am. Chem. Soc.  1999,  121:  6990 
    Search in Google Scholar
  • 3h D’Oca MGM. Pilli RA. Vencato I. Tetrahedron Lett.  2000,  41:  9709 
    Search in Google Scholar
  • 4a Soriano MDPC. Shankaraiah N. Santos LS. Tetrahedron Lett.  2010,  51:  1770 
    Search in Google Scholar
  • 4b de Oliveira MCF. Santos LS. Pilli RA. Tetrahedron Lett.  2001,  42:  6995 
    Search in Google Scholar
  • 4c Santos LS. Pilli RA. Tetrahedron Lett.  2001,  42:  6999 
    Search in Google Scholar
  • 4d Shankaraiah N. Pilli RA. Santos LS. Tetrahedron Lett.  2008,  49:  5098 
    Search in Google Scholar
  • 5 Ducrot P. Rabhi C. Thal C. Tetrahedron  2000,  56:  2683 
    Search in Google Scholar
  • 6a Lopez I. Diez A. Rubiralta M. Tetrahedron  1996,  52:  8581 
    Search in Google Scholar
  • 6b Melnyk P. Legrand B. Gasche J. Ducrot P. Thal C. Tetrahedron  1995,  51:  1941 
    Search in Google Scholar
  • 7 Santos LS. Pilli RA. J. Braz. Chem. Soc.  2003,  14:  982 
    Search in Google Scholar
  • 8a Kim SS. Rajagopal G. Song DH. J. Organomet. Chem.  2004,  689:  1734 
    Search in Google Scholar
  • 8b Razet R. Thomet U. Furtmuller R. Jursky F. Sigel E. Sieghart W. Dodd RH. Bioorg. Med. Chem. Lett.  2000,  10:  2579 
    Search in Google Scholar
  • 8c Kim SS. Lee JT. Lee SH. Bull. Korean Chem. Soc.  2005,  26:  993 
    Search in Google Scholar
  • 8d Onaka M. Higuchi K. Sugita K. Izumi Y. Chem. Lett.  1989,  1393 
  • 8e Wilkinson HS. Grover PT. Vandenbossche CP. Bakale RP. Bhongale NN. Wald SA. Senanayake CH. Org. Lett.  2001,  3:  553 
    Search in Google Scholar
  • 8f Yamaguchi K. Imago T. Ogasawara Y. Kasai J. Kotani M. Mizuno N. Adv. Synth. Catal.  2006,  348:  1516 
    Search in Google Scholar
  • 9a Duran-Lara EF. Shankaraiah N. Geraldo D. Santos LS. J. Braz. Chem. Soc.  2009,  20:  813 
    Search in Google Scholar
  • 9b Gozzo FC. Santos LS. Augusti R. Consorti CS. Dupont J. Eberlin MN. Chem. Eur. J.  2004,  10:  6187 
    Search in Google Scholar
  • 10 Yoon NM. Brown HC. J. Am. Chem. Soc.  1968,  90:  2927 
    Search in Google Scholar
  • 11 ¹H NMR for compound 2 is in accordance with: Wasserman HH. Kuo GH. Tetrahedron  1992,  48:  7071 
    Search in Google Scholar
  • 12a Bombrun A. Casi G. Tetrahedron Lett.  2002,  43:  2187 
    Search in Google Scholar
  • 12b Frohner W. Monse B. Braxmeier TM. Casiraghi L. Sahagun H. Seneci P. Org. Lett.  2005,  7:  4573 
    Search in Google Scholar
  • 12c Tholander J. Bergman J. Heterocycles  1999,  51:  1275 
    Search in Google Scholar
  • 12d Iyer MS. Palomo M. Schilling KM. Xie Y. Formanski L. Zembower DE. J. Chromatogr., A  2002,  944:  263 
    Search in Google Scholar
  • 12e Morita N. Krause N. Eur. J. Org. Chem.  2006,  4634 
  • 12f Roush WR. Straub JA. Brown RJ.
    J. Org. Chem.  1987,  52:  5127 
    Search in Google Scholar
  • ¹H and ¹³C NMR are in accordance with that described in the literature:
  • 13a Melnyk P. Ducrot P. Demuynck L. Thal C. Tetrahedron Lett.  1993,  34:  5085 
    Search in Google Scholar
  • 13b Lee YS. Cho DJ. Kim SN. Choi JH. Park H. J. Org. Chem.  1999,  64:  9727 
    Search in Google Scholar
  • 14 Overman reported the Mitsunobu reaction with hydrazoic acid to install an azide group in similar systems. See: Cohen F. Overman LE. J. Am. Chem. Soc.  2006,  128:  2594 
    Search in Google Scholar
  • 15a Schlesinger HI. Brown HC. Finholt AE. Gilbreath JR. Hoekstra HR. Hyde EK. J. Am. Chem. Soc.  1953,  75:  215 
    Search in Google Scholar
  • 15b Brown CA. J. Org. Chem.  1970,  35:  1900 
    Search in Google Scholar
  • 15c Hoffer LJE. Schultz J. Panson RD. Anderson RB. Inorg. Chem.  1964,  3:  1783 
    Search in Google Scholar
  • 15d Seltzman HH. Berrang BD. Tetrahedron Lett.  1993,  34:  3083 
    Search in Google Scholar
  • 15e Santos LS. Pilli RA. Synthesis  2002,  87 
  • 16 Shankaraiah N. Markandeya N. Espinoza-Moraga M. Arancibia C. Kamal A. Santos LS. Synthesis  2009,  2163 
  • 17 Schmitt P. Melnyk P. Bourde O. Demuynck L. Pujol J.-F. Thal C. Med. Chem. Res.  1993,  3:  24 
    Search in Google Scholar
  • 18a Fukui K. Acc. Chem. Res.  1981,  14:  363 
    Search in Google Scholar
  • 18b Gonzalez C. Schlegel HB. J. Chem. Phys.  1989,  90:  2154 
    Search in Google Scholar
  • 18c Gonzalez C. Schlegel HB. J. Chem. Phys.  1990,  94:  5523 
    Search in Google Scholar
  • 19 Bur SK. Martin SF. Org. Lett.  2000,  2:  3445 
    Search in Google Scholar