Synthesis of Novel 2,3-Dihydroimidazo[2,1-b][1,3]oxazoles Through Intramolecular Nucleophilic ipso-Substitution in 2-Alkylsulfonylimidazoles

Pilar Moreno; Montserrat Heras; Miguel Maestro; José M. Villalgordo

doi:10.1055/s-2002-35982

PAPER

Synthesis of Novel 2,3-Dihydroimidazo[2,1-b][1,3]oxazoles Through Intramolecular Nucleophilic ipso-Substitution in 2-Alkylsulfonylimidazoles

Pilar Moreno^a, Montserrat Heras^a, Miguel Maestro^b, José M. Villalgordo*^a
^a Departament de Química, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain
Fax: +34(97)2418150; e-Mail: jose.villalgordo@udg.es;
^b Servicios Xerais de Apoio a Investigación, Universidade da Coruña, Campus da Zapateira s/n, 15071, A Coruña, Spain

Abstract

All articles of this category

Abstract

Readily available 2-(benzylsulfanyl)imidazoles 6, were studied as potential precursors toward the synthesis of novel diversely substituted 2,3-dihydroimidazo[2,1-b][1,3]oxazoles. Thus, the reaction between enolates derived from 6 and different electrophiles as well as the addition of Grignard reagents to the carbonyl group in 6 were explored. The formation of the fused imidazoxazoles 20 under mild conditions was successfully accomplished taking advantage of the key role played by the 2-alkylsulfonyl moiety in 19 as an efficient leaving group in intramolecular nucleophilic ipso-substitution reactions.

Key words

alkylsulfonyl groups - leaving groups - intramolecular nucleophilic ipso-substitution - imidazoles - 2,3-dihydroimidazo[2,1-b][1,3]oxazoles

Full Text

References

1 Shepard RG. Fedrik JF. Adv. Heterocycl. Chem. 1965, 4: 145

2 Vecchietti V. Dredi E. Lauria F. J. Chem. Soc., C 1971, 2554

3 Franco F. Greenhouse R. Muchowski JM. J. Org. Chem. 1982, 47: 1682

4 Zumbrunn A. Synthesis 1998, 1357

5 Grimmett MR. Adv. Heterocycl. Chem. 1970, 12: 103

6 Grimmett MR. Adv. Heterocycl. Chem. 1980, 27: 241

7 Preston PN. Chem. Rev. 1974, 74: 279

8 Brown DJ. Ford PW. J. Chem. Soc. C 1967, 568

9 Barlin GB. Brown WV. J. Chem. Soc. C 1967, 2473

10 Heras M. Ventura M. Linden A. Villalgordo JM. Synthesis 1999, 1613

11 Jarosinski MA. Anderson WK. J. Org. Chem. 1991, 56: 4058

12 Obrecht D. Villalgordo JM. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular Weight Compound Libraries, Tetrahedron Organic Chemistry Series Vol. 17: Pergamon; Oxford: 1998.

13 Obrecht D. Grieder A. Abrecht C. Villalgordo JM. Helv. Chim. Acta 1997, 80: 65

14 Chucholowski A. Masquelin T. Obrecht D. Stadlwieser J. Villalgordo JM. Chimia 1996, 50: 525

15 Villalgordo JM. Methods Find. Exp. Clin. Pharmacol. 1997, 19 (Suppl. A): 37

16 Villalgordo JM. Obrecht D. Chucholowski A. Synlett 1998, 1405

17 Font D. Heras M. Villalgordo JM. Synthesis 2002, 1813

18 Kaminski JJ. Bristol JA. Puchalski C. Lovey RG. Elliot AJ. Guzik H. Solomon DM. Conn DJ. Domalski MS. Wong S.-C. Gold EH. Long JF. Chiu PJS. Steinberg M. McPhail AT. J. Med. Chem. 1985, 28: 876

19 Fos E. Bosca F. Mauleon D. Garganico G. J. Heterocycl. Chem. 1993, 30: 473

20 Stefancich G. Silvestri R. Artico M. J. Heterocycl. Chem. 1993, 30: 529

21 Shawcross A. Stanforth SP. J. Heterocycl. Chem. 1993, 30: 563

22 Aldabbagh F. Bowman WR. Tetrahedron Lett. 1993, 38: 3793

23 Aldabbagh F. Bowman WR. Mann E. Tetrahedron Lett. 1997, 38: 7937

24 Hua DH. Zhang F. Chen J. Robinson PD. J. Org. Chem. 1994, 59: 5084

25 Johnson CK. ORTEP II. Report ORNL-5138 Oak Ridge National Laboratory; Tennessee: 1976.

26

Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-187224 (Compound 24). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 122 3336033; e-mail: deposit@ccdc.cam.ac.uk).

27 Sheldrick GM. SHELXS-97, Program for Crystal Structure Solution University of Göttingen; Göttingen, Germany: 1997.

28 Sheldrick GM. M. SHELXS-97, Program for the Refinement of Crystal Structures form Diffraction Data University of Göttingen; Göttingen, Germany: 1997.