Use of a convertible isocyanide for generation of Ugi reaction derivatives on solid support: Synthesis of α-acylaminoesters and pyrroles

Tetrahedron Letters

Volumn 37, Issue 8, 1996, Pages 1149-1152

  Strocker, Ali M ^a   Keating, Thomas A ^a   Tempest, Paul A ^a   Armstrong, Robert W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; PYRROLE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030063277     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00012-3     Document Type: Article

References (16)

1. For a recent, comprehensive review, see: Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251.
2. For a recent, comprehensive review, see: Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401.
3. For a discussion of MCC reactions for library synthesis, see: Ugi, I.; Dömling, A.; Hörl, W. Endeavour 1994, 18, 115-123.
4. (a) Ugi, I.; Lohberger, S.; Karl, R. In Comprehensive Organic Synthesis; B. M. Trost and I. Fleming, Eds.; Pergamon: New York, 1991; Vol. 2; pp 1083-1109.
5. (b) Gokel, G.; Lüdke, G.; Ugi, I. In Isonitrile Chemistry; I. Ugi, Ed.; Academic: New York, 1971; pp 145-199.
6. Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc. 1995, 117, 7842-7843.
7. Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc. submitted for publication.
8. For an earlier strategy, see: (a) Geller, J.; Ugi, I. Chem. Scr. 1983, 22, 85-89.
9. (b) Ugi, I. Angew. Chem., Int. Ed. Engl. 1982, 21, 810-819.
10. Tempest, P. A.; Brown, S. D.; Armstrong, R. W. Angew. Chem., Int. Ed. Engl. in press.
11. Rink, H. Tetrahedron Lett. 1987, 28, 3787. Fmoc-protected Rink resin (100-200 mesh, 0.56 mmol/g) was purchased from Advanced ChemTech, and was deprotected with a 20% piperidine solution.
12. Wang, S.-S. J. Am. Chem. Soc. 1973, 95, 1328. Wang resin (100-200 mesh, 0.9 mmol/g) was purchased from Advanced ChemTech.
13. In our initial efforts, deprotected Rink resin was used as the amine input for the Ugi 4CC. While this reaction proceeds smoothly (see reference 8), subsequent conversions of the type presented here failed to result in appreciable yields of expected product. We postulate that the münchnone 13 in this system, bearing a positive charge on nitrogen, cleaves itself off the resin, in much the same manner as protonation by TFA would operate. A mixture of products in the resin washes supports this. (figure presented)
14. Potts, K. T. In 1,3-Dipolar Cycloaddition Chemistry; A. Padwa, Ed.; Wiley-Interscience: New York, 1984; Vol. 2; pp 1-82.
15. Huisgen, R.; Gotthardt, H.; Bayer, H. O.; Schaefer, F. C. Angew. Chem., Int. Ed. Engl. 1964, 3, 136-137.
16. The results presented here employ only DMAD as the acetylenic dipolarophile in the formation of pyrroles. We have accomplished the corresponding cycloaddition with a variety of other acetylenes in solution (see reference 6), and are working to extend this methodology to solid support.