Synthesis 2011(10): 1587-1594  
DOI: 10.1055/s-0030-1260012
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Diversity-Oriented Silver(I)-Mediated Synthesis of Spiro-2-aminoimidazoles

Olga P. Pereshivkoa, Vsevolod A. Peshkova, Denis S. Ermolat’ev*a, Sofie Van Hovea, Kristof Van Heckeb, Luc Van Meerveltb, Erik V. Van der Eycken*a
a Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax: +32(16)327990; e-Mail: [email protected]; e-Mail: [email protected];
b Biomolecular Architecture, Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Further Information

Publication History

Received 21 February 2011
Publication Date:
19 April 2011 (online)

Abstract

A diversity-oriented protocol giving access to a novel class of spiro-cyclic guanidine derivatives is described. The copper(I)-catalyzed, three-component coupling of a ketone, an alkyne and a primary amine (KA²-coupling) provides the required secondary propargylamines and assures the generation of diversity. The key step of the protocol, a silver(I)-mediated tandem guanylation of secondary propargylamines followed by an intramolecular heterocyclization, provides the target bis-Boc-protected-2-iminoimidazolines spiro-fused with a five-, six- or seven-membered (heterocyclic) ring, which could, in most cases, be further deprotected to the spiro-2-aminoimidazoles.

    References

  • 1a Berlinck RGS. Burtoloso ACB. Trindade-Silva AE. Romminger S. Morais RP. Bandeira K. Mizuno CM. Nat. Prod. Rep.  2010,  27:  1871 
  • 1b Berlinck RGS. Burtoloso ACB. Kossuga MH. Nat. Prod. Rep.  2008,  25:  919 
  • 1c Berlinck RGS. Kossuga MH. Nat. Prod. Rep.  2005,  22:  516 
  • 1d Berlinck RGS. Nat. Prod. Rep.  2002,  19:  617 ; and references cited therein
  • For anti-biofilm activity of 2-aminoimidazoles, see:
  • 2a Huigens RW. Richards JJ. Parise G. Ballard TE. Zeng W. Deora R. Melander C. J. Am. Chem. Soc.  2007,  129:  6966 
  • 2b Rogers SA. Melander C. Angew. Chem. Int. Ed.  2008,  47:  5229 ; Angew. Chem. 2008, 120, 5307
  • 2c Ballard TE. Richards JJ. Wolf AL. Melander C. Chem. Eur. J.  2008,  14:  10745 
  • 3a Malamas MS. Erdei J. Gunawan I. Turner J. Hu Y. Wagner E. Fan K. Chopra R. Olland A. Bard J. Jacobsen S. Magolda RL. Pangalos M. Robichaud AJ. J. Med. Chem.  2010,  53:  1146 
  • 3b Malamas MS. Erdei J. Gunawan I. Barnes K. Johnson M. Hui Y. Turner J. Hu Y. Wagner E. Fan K. Olland A. Bard J. Robichaud AJ. J. Med. Chem.  2009,  52:  6314 
  • 4a Coleman RS. Campbell EL. Carper DJ. Org. Lett.  2009,  11:  2133 
  • 4b Nodwell M. Pereira A. Riffell JL. Zimmermann C. Patrick BO. Roberge M. Andersen RJ. J. Org. Chem.  2009,  74:  995 
  • 5a Jin Z. Nat. Prod. Rep.  2003,  20:  584 
  • 5b Jin Z. Nat. Prod. Rep.  2005,  22:  196 
  • 5c Jin Z. Nat. Prod. Rep.  2006,  23:  464 
  • 5d Jin Z. Nat. Prod. Rep.  2009,  26:  382 
  • 5e Weinreb SM. Nat. Prod. Rep.  2007,  24:  931 
  • 5f Sullivan JD. Giles RL. Looper RE. Curr. Bioact. Compd.  2009,  5:  39 
  • 5g Hoffmann H. Lindel T. Synthesis  2003,  175 
  • 5h Koswatta PB. Lovely CJ. Nat. Prod. Rep.  2010,  28:  511 ; and references cited therein
  • 6a Dunbar DC. Rimoldi JM. Clark AM. Kelly M. Hamann MT. Tetrahedron  2000,  56:  8795 
  • 6b Crews P. Clark DP. Tenney K. J. Nat. Prod.  2003,  66:  177 
  • 6c Hassan W. Edrada R. Ebel R. Wray V. Berg A. Van Soest R. Wiryowidagdo S. Proksch P. J. Nat. Prod.  2004,  67:  817 
  • 7a Fu X. Barnes JR. Do T. Schmitz FJ. J. Nat. Prod.  1997,  60:  497 
  • 7b Gross H. Kehraus S. König GM. Woerheide G. Wright AD. J. Nat. Prod.  2002,  65:  1190 
  • 8a Carmely S. Kashman Y. Tetrahedron Lett.  1987,  28:  3003 
  • 8b Carmely S. Ilan M. Kashman Y. Tetrahedron  1989,  45:  2193 
  • 9 Fu X. Schmitz FJ. Tanner RS. Kelly-Borges M.
    J. Nat. Prod.  1998,  61:  384 
  • 10a Akee RK. Carroll TR. Yoshida WY. Scheuer PJ. Stout TJ. Clardy J. J. Org. Chem.  1990,  55:  1944 
  • 10b Carroll AR. Bowden BF. Coll JC. Aust. J. Chem.  1993,  46:  1229 
  • 10c Mancini I. Guella G. Debitus C. Pietra F. Helv. Chim. Acta  1995,  78:  1178 
  • 10d Plubrukarn A. Smith D. Cramer R. Davidson B. J. Nat. Prod.  1997,  60:  712 
  • 11 Edrada RA. Stessman CC. Crews P. J. Nat. Prod.  2003,  66:  939 
  • For original isolation, see:
  • 12a Kinnel RB. Gehrken HP. Scheuer PJ. J. Am. Chem. Soc.  1993,  115:  3376 
  • 12b Kinnel RB. Gehrken HP. Swali R. Skoropowski G. Scheuer PJ. J. Org. Chem.  1998,  63:  3281 
  • 12c For structural reassignment, see: Buchanan MS. Carroll AR. Quinn RJ. Tetrahedron Lett.  2007,  48:  4573 
  • 12d For total synthesis, see: Seiple IB. Su S. Young IS. Lewis CA. Yamaguchi J. Baran PS. Angew. Chem. Int. Ed.  2010,  49:  1095 ; and references cited therein
  • 13 For a review on the synthesis of alkaloids from the Oroidin family, see: Arndt HD. Riedrich M. Angew. Chem. Int. Ed.  2008,  47:  4785 
  • 14a Sivappa R. Koswatta P. Lovely CJ. Tetrahedron Lett.  2007,  48:  5771 
  • 14b Sivappa R. Hernandez NM. He Y. Lovely CJ. Org. Lett.  2007,  9:  3861 
  • 14c Lovely CJ. Du H. He Y. Dias HVR. Org. Lett.  2004,  6:  735 
  • 15 Iwagawa T. Miyazaki M. Okamura H. Nakatani M. Doe M. Takemura K. Tetrahedron Lett.  2003,  44:  2533 
  • 16 Capon RJ. Rooney F. Murray LM. Collins E. Sim ATR. Rostas JAP. Butler MS. Carroll AR. J. Nat. Prod.  1998,  61:  660 
  • For synthetic efforts towards dragmacidin E, see:
  • 17a Feldman KS. Ngernmeesri P. Org. Lett.  2005,  7:  5449 
  • 17b Huntley RJ. Funk RL. Org. Lett.  2006,  8:  4775 
  • 17c Feldman KS. Ngernmeesri P. Org. Lett.  2010,  12:  4502 
  • 18 Giles RL. Sullivan JD. Steiner AM. Looper RE. Angew. Chem. Int. Ed.  2009,  48:  3116 
  • 19a Ermolat’ev DS. Babaev EV. Van der Eycken EV. Org. Lett.  2006,  8:  5781 
  • 19b Ermolat’ev DS. Alifanov VL. Rybakov VB. Babaev EV. Van der Eycken EV. Synthesis  2008,  2083 
  • 19c Ermolat’ev DS. Van der Eycken EV. J. Org. Chem.  2008,  73:  6691 
  • 19d Ermolat’ev DS. Svidritzky EP. Babaev EV. Van der Eycken E. Tetrahedron Lett.  2009,  50:  5218 
  • 19e Modha SG. Mehta VP. Ermolat’ev DS. Balzarini J. Van Hecke K. Van Meervelt L. Van der Eycken E. Mol. Diversity  2010,  14:  767 
  • 20 Ermolat’ev DS. Bariwal JB. Steenackers HPL. De Keersmaecker SCJ. Van der Eycken EV. Angew. Chem. Int. Ed.  2010,  49:  9465 
  • 21 Ermolat’ev DS. PhD Thesis   Katholieke Universiteit Leuven; Belgium: 2008. 
  • 22 For the synthesis of secondary propargylamines, see: Bariwal JB. Ermolat’ev DS. Van der Eycken EV. Chem. Eur. J.  2010,  16:  3281 
  • 23 For a description of the KA²-coupling, see: Pereshivko OP. Peshkov VA. Van der Eycken EV. Org. Lett.  2010,  12:  2638 
  • 24 During the preparation of this manuscript, the rhodium(II)-catalyzed 6-endo-dig-selective hydroamination of propargylguanidines was reported, see: Gainer MJ. Bennett NR. Takahashi Y. Looper RE. Angew. Chem. Int. Ed.  2011,  50:  684 
  • 25 For the addition of lithium acetylides and n-BuLi to six-membered ketimines, see: Ma Y. Lobkovsky E. Collum DB. J. Org. Chem.  2005,  70:  2335 
26

Differences in R f values allow both minor and major products to be isolated through gradient-elution column chromatography.

27

See Supporting Information for details.

28

CCDC-801762 contains the supplementary crystallographic data for this paper and can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:+44(1223)336033; or [email protected]).