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Synlett 2008(19): 3016-3020  
DOI: 10.1055/s-0028-1087352
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Three-Component, One-Pot Sequential Synthesis of 1,3-Disubstituted 5-Arylhydantoins

Francesca Olimpieria, Alessandro Volonterio*a,b, Matteo Zanda*b
a Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
Fax: +39(02)23993080; e-Mail: alessandro.volonterio@polimi.it;
b C.N.R., Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘A. Quilico’, Via Mancinelli 7, 20131 Milano, Italy
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Publication History

Received 6 August 2008
Publication Date:
12 November 2008 (online)

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Abstract

Reaction of carbodiimides with α-Br(Cl)-aryl acetic acids produces N,N′-substituted 5-arylhydantoins under very mild conditions and high yields. When the carbodiimides are generated in situ by Staudinger reaction, the process becomes a one-pot, three-component sequential synthesis of libraries of differently substituted 5-arylhydantoins.

Key words

heterocycles - multicomponent reactions - combinatorial chemistry - carbodiimides - sequential synthesis

    References and Notes

  • 1a Comprehensive Organic Synthesis   Vol. 1-9:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991. 
    Google Scholar
  • 1b Encyclopedia of Reagents for Organic Synthesis   Vol. 1-8:  Paquette LA. Wiley and Sons; New York: 1995. 
    Google Scholar
  • For recent reviews, see:
  • 2a Tietze LF. Chem. Rev.  1996,  96:  115 
    Google Scholar
  • 2b Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
    Google Scholar
  • 2c Winkler JD. Chem. Rev.  1996,  96:  167 
    Google Scholar
  • 2d Ryu I. Sonoda N. Curran DP. Chem. Rev.  1996,  96:  177 
    Google Scholar
  • 2e Parsons PJ. Penkett CS. Shell AJ. Chem. Rev.  1996,  96:  195 
    Google Scholar
  • 2f Wang KK. Chem. Rev.  1996,  96:  207 
    Google Scholar
  • 2g Padwa A. Weingarten MD. Chem. Rev.  1996,  96:  223 
    Google Scholar
  • 2h Malacria M. Chem. Rev.  1996,  96:  289 
    Google Scholar
  • 2i Molander GA. Harris CR. Chem. Rev.  1996,  96:  307 
    Google Scholar
  • 2j Tietze LF. Beifuss U. Angew. Chem. Int. Ed. Engl.  1993,  32:  131 
    Google Scholar
  • 2k Ho T.-L. Tandem Organic Reactions   Wiley and Sons; New York: 1992. 
    Google Scholar
  • For an overview of multicomponent reactions, see:
  • 3a Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 3b Multicomponent Reactions, In Tetrahedron Symposium-in-Print No 114   Vol. 61:  Marek I. Elsevier; Amsterdam: 2005.  p.11309-11519  
    Google Scholar
  • 4 Andraos J. Org. Process Res. Dev.  2005,  9:  149 
    CrossrefGoogle Scholar
  • For recent reviews, see:
  • 5a Orru RVA. de Greef M. Synthesis  2003,  1471 
    Google Scholar
  • 5b Balme G. Bossharth E. Monteiro N. Eur. J. Org. Chem.  2003,  4101 
    Google Scholar
  • 5c Dömling A. Chem. Rev.  2006,  106:  17 
    Google Scholar
  • 6a Brouillette WJ. Jestkov VP. Brown ML. Akhtar MS. DeLorey TM. Brown GB. J. Med. Chem.  1994,  37:  3298 
    Google Scholar
  • 6b Matsugi K. Kageyama M. Nishimura K. Giles H. Shirasawa E. Eur. J. Pharm.  1995,  275:  245 
    Google Scholar
  • 6c Osz E. Somsak L. Szilagyi L. Kovacs L. Docsa T. Toth B. Gergely P. Bioorg. Med. Chem. Lett.  1999,  9:  1385 
    Google Scholar
  • 6d Schelkum RM. Yuen PW. Sperpa K. Meltzer LT. Wise LD. J. Med. Chem.  2000,  43:  1892 
    Google Scholar
  • 6e Stilz HU. Guba W. Jablonka B. Just M. Klingler O. Konig W. Wehner V. Zoller G. J. Chem. Med.  2001,  44:  1158 
    Google Scholar
  • 7a Yokozeki K. Kubota K. Agric. Biol. Chem.  1987,  51:  721 
    Google Scholar
  • 7b Yamada H. Shimizu S. Biocatalysis in Organic Synthesis   Tramper J., van der Plas H. C. Elsevier; Amsterdam: 1985.  p.19 
    Google Scholar
  • 8 Matthews J. Rivero RA. J. Org. Chem.  1997,  62:  6090 
    CrossrefGoogle Scholar
  • 9 Beller M. Eckert M. Moradi WA. Neumann H. Angew. Chem. Int. Ed.  1999,  38:  1454 
    CrossrefGoogle Scholar
  • 10a Volonterio A. Ramirez de Arellano C. Zanda M.
    J. Org. Chem.  2005,  70:  2161 
    Google Scholar
  • 10b Volonterio A. Zanda M. Org. Lett.  2007,  5:  841 
    Google Scholar
11

The reaction was carried out in dioxane because carbodiimide 2f was insoluble in CH2Cl2.

12

The lower yields obtained with N,N′-dialkylcarbodiimides in the three-component process are probably due to lower yields in the Staudinger reaction.