Synlett 2013; 24(6): 727-732
DOI: 10.1055/s-0032-1318432
letter
© Georg Thieme Verlag Stuttgart · New York

Multicomponent Synthesis of N-Carbamoyl Hydantoin Derivatives

Maria Cristina Bellucci
a   Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy
,
Massimo Frigerio
b   Department of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy   Fax: +39(02)23993180   eMail: alessandro.volonterio@polimi.it
,
Tommaso Marcelli
b   Department of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy   Fax: +39(02)23993180   eMail: alessandro.volonterio@polimi.it
,
Alessandro Volonterio*
b   Department of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy   Fax: +39(02)23993180   eMail: alessandro.volonterio@polimi.it
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 21. Dezember 2012

Accepted after revision: 19. Februar 2013

Publikationsdatum:
06. März 2013 (online)


Abstract

A novel, three-component process for the preparation of a small library of unprecedented nonracemic N-carbamoyl hydantoins under very mild conditions, as well as the hypothetic mechanism, are presented.

Supporting Information

 
  • References and Notes


    • For some reviews on MC reactions, see:
    • 1a Armstrong RM, Combs AP, Brown PA, Keating TA. Acc. Chem. Res. 1996; 29: 123
    • 1b Bienaymé H, Hulme C, Oddon G, Schmitt P. Chem. Eur. J. 2000; 6: 3321
    • 1c Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3169
    • 1d Dömling A. Curr. Opin. Chem. Biol. 2000; 4: 318
    • 1e Dömling A. Chem. Rev. 2006; 106: 17
    • 1f Isambert N, Lavilla R. Chem. Eur. J. 2008; 14: 8444
    • 1g Ganem B. Acc. Chem. Res. 2009; 42: 463
    • 1h Ruijter E, Scheffelaar R, Orru RV. Angew. Chem. Int. Ed. 2011; 50: 6234
    • 1i Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083

      For some reviews, see:
    • 2a Orru RV. A, de Greef M. Synthesis 2003; 1471
    • 2b Sunderhaus JD, Martin SF. Chem. Eur. J. 2009; 15: 1300
    • 2c Jiang B, Rajale T, Wever W, Tu S.-J, Li G. Chem. Asian J. 2010; 5: 2318
    • 2d Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
    • 2e Eckert H. Molecules 2012; 17: 1074
    • 3a Ware E. Chem. Rev. 1950; 46: 403
    • 3b Gerona-Navarro G, Gonzalez-Muñiz R, Fernandez-Carvajal A, Gonzalez-Ros JM, Ferrer-Montiel A, Carreño C, Albericio F, Royo M. ACS Comb. Sci. 2011; 13: 458
    • 4a Volonterio A, Ramirez de Arellano C, Zanda M. J. Org. Chem. 2005; 70: 2161
    • 4b Olimpieri F, Volonterio A, Zanda M. Synlett 2008; 3016
    • 4c Marcelli T, Olimpieri F, Volonterio A. Org. Biomol. Chem. 2011; 9: 5156
    • 4d Bellucci MC, Volonterio A. Eur. J. Org. Chem. 2009; 6179
    • 4e Bellucci MC, Marcelli T, Volonterio A. RSC Adv. 2011; 1: 1250
    • 4f Olimpieri F, Bellucci MC, Marcelli T, Volonterio A. Org. Biomol. Chem. 2012; 10: 9538
  • 5 Bellucci MC, Ghilardi A, Volonterio A. Org. Biomol. Chem. 2011; 9: 8379
    • 6a Vazquez J, Garcia-Jareño A, Mondragon L, Rubio-Martinez J, Perez-Paya E, Albericio F. ChemMedChem 2008; 3: 979
    • 6b Jamieson AG, Russell D, Hamilton AD. Chem. Commun. 2012; 48: 3709
    • 6c Sutherell CL, Thompson S, Scott RT. W, Hamilton AD. Chem. Commun. 2012; 48: 9834
  • 7 Characterization of Compound 4a Rf  = 0.43 (hexane–EtOAc, 60:40); [a]D 20 +33.3 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 8.17 (t, J = 5.6 Hz, 1 H), 7.38–6.97 (m, 15 H), 4.83 (dd, J = 5.6, 2.4 Hz, 1 H), 4.62 (dd, J = 14.8, 6.0 Hz, 1 H), 4.52 (d, J = 14.8 Hz, 1 H), 4.50 (dd, J = 14.8, 6.8 Hz, 1 H), 3.70 (dd, J = 14.0, 5.6 Hz, 1 H), 3.30 (dd, J = 14.0, 2.4 Hz, 1 H). 13C NMR (125.7 MHz, CDCl3): δ = 170.5, 155.3, 151.1, 138.0, 133.3, 129.7, 128.7, 128.6, 128.5, 128.2, 128.0, 127.6, 127.4, 59.9, 43.9, 42.4, 34.9. ESI-MS: m/z (%) = 259.1 (100), 436.2 (38) [M+ + H]. Anal. Calcd for C25H23N3O3: C, 72.62, H, 5.61, N, 10.16. Found: C, 72.67, H, 5.64, N, 10.11.
  • 8 Zhang D, Xing X, Cuny GD. J. Org. Chem. 2006; 71: 1750
  • 9 The ee was determined by chiral HPLC (see Supporting Information). In this regard, we would like to acknowledge the referee who suggested we check the ee of the N-carbamoyl hydantoins obtained by our process
  • 10 The starting α-azido esters 1 were prepared from the corresponding α-amino esters by diazotransfer reaction promoted by imidazole-1-sulfonyl azide hydrochloride: Goddard-Borger ED, Stick RV. Org. Lett. 2007; 9: 3797
  • 11 General Procedure for the Preparation of N-Carbamoyl Hydantoins 4 To a stirred solution of α-azido ester 1 (1equiv) and isocyanate 2 (2.5 equiv) in MeCN (0.1 M solution), solid Ph3P (1equiv) was added and the solution stirred at r.t. for 3 h. The solvent was removed under reduced pressure and the crude purified by flash chromatography.
  • 12 Since both N-carbamoyl hydantoins 4a and 4i have ca. 60% ee, we assume that also N-carbamoyl hydantoins 4bf,kl posses the same ee since the process was run under the same conditions, i.e., in MeCN at r.t. for 3 h