Synthesis and thermal cyclization of an enediyne-sulfonamide

Tetrahedron

Volumn 60, Issue 5, 2004, Pages 1087-1092

  Klein, Michael ^a   König, Burkhard ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

Author keywords

Carbene rearrangement; Enediyne; Thermal cyclization; Yne amine

Indexed keywords

ALKYNE; AMMONIUM DERIVATIVE; CARBENOID; FLUORIDE; SULFONAMIDE;

ARTICLE; CHEMICAL REACTION KINETICS; CYCLIZATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; SYNTHESIS; TEMPERATURE DEPENDENCE;

EID: 0347600556     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2003.11.078     Document Type: Article

References (36)

1. For one of the first experimental reports of electronic effects on the Bergman cyclization, see: Schmittel M., Kiau S. Chem. Lett. 1995;953-954.
2. Jones G.B., Warner P.M. J. Am. Chem. Soc. 123:2001;2134-2145.
3. Plourde G.W. II, Warner P.M., Parrish D.A., Jones G.B. J. Org. Chem. 67:2002;5369-5374.
4. Kim C.S., Russell K.C. J. Org. Chem. 63:1998;8229-8234.
5. Kim C.S., Diez C., Russell K.C. Chem. Eur. J. 6:2000;1555-1558.
6. Nath M., Huffmann J.C., Zaleski J.M. Chem. Commun. 2003;858-859.
7. For a recent report on computer design of new enediyne based anticancer drugs, see: Kraka E., Cremer D. J. Am. Chem. Soc. 122:2000;8245-8264.
8. Effect of ortho-substituents in benzannelated enediynes: (a) Alabugin I.V., Manoharan M., Kovalenko S.V. Org. Lett. 4:2002;1119-1122.
9. Alabugin I.V., Manoharan M. J. Phys. Chem. A. 107:2003;3363-3371.
10. Koga N., Morokuma K. J. Am. Chem. Soc. 113:1991;1907-1911.
11. Prall M., Wittkopp A., Fokin A.A., Schreiner P.R. J. Comput. Chem. 22:2001;1605-1614.
12. Wenk H.H., Balster A., Sander W., Hrovat D.A., Borden W.T. Angew. Chem. Int. Ed. 40:2001;2295-2298.
13. Amino-enediynes show a little lower reactivity than the parent system in calculations. Because ammonium has no π-donor and only σ-acceptor properties, the ammonium-enediyne has a relatively low barrier for cyclization and an almost thermoneutral reaction energy as predicted from calculations. Doubly substituted bis-ammonium-enediynes are far less reactive, because of the repulsion of the positively charged groups of the ortho-ammonium substituents in the cyclization product. See Ref. 7 for a systematic computational study.
14. For a recent report on synthesis and thermal cyclization of structurally related 3-aza-3-ene-1,5-dienes, see: (a) Nadipuram A.K., David W.M., Kumar D., Kerwin S.M. Org. Lett. 4:2002;4543-4546.
15. The nitrogen atom in these enediynes is part of a imidazole ring and therefore of different electronic influence. Enediynes with amide or amine not adjacent to the alkyne termini: (b) Banfi L., Guanti G., Rasparini M. Eur. J. Org. Chem. 2003;1319-1336.
16. Basak A., Mandal S., Das A.K., Bertolasi V. Bioorg. Med. Chem. Lett. 12:2002;873-877.
17. Brandsma L. Preparative Acetylenic Chemistry. 2nd ed. 1988;Elsevier, Amsterdam. p 187ff.
18. Brandsma L. Recl. Trav. Chim. Trav. Chim. Pays-Bas. 90:1971;1098-1100.
19. Witulski B., Stengel T. Angew. Chem. Int. Ed. Engl. 37:1998;489-492.
20. The positive charge of the ammonium group should contribute to the σ-acceptor properties of the substituents. This effect is missing in sulfonamides. Their activation effect on the enediyne system is therefore expected to be smaller.
21. Frederick M.O., Mulder J.A., Tracey M.R., Hsung R.P., Huang J., Kurtz K.C.M., Shen L., Douglas C.J. J. Am. Chem. Soc. 125:2003;2368-2369.
22. Witulski B., Stengel T. Angew. Chem. Int. Ed. Engl. 38:1999;2426-2430.
23. The alkyne was synthesized in two steps from TMS-ethynyl-phenyliodonium triflate and N-Ts,N-Bz-amine, followed by deprotection of the TMS group with fluoride. See supporting information for details. Synthesis of the TMS-ethynyl-phenyliodonium triflate, see: (a) Stang P.J., Zhdankin V.V. Chem. Rev. 96:1996;1123-1178.
24. Stang P.J. Stang P.J., Diederich F. Modern Acetylene Chemistry. 1995;67-98 VCH, Weinheim.
25. Huynh C., Linstrumelle G. Tetrahedron. 44:1988;6337-6344.
26. Other conditions were tried: TBAF in THF/water gave only very slow conversion and even poorer yield.
27. Theory predicts a significantly reduced thermal reactivity for a bis-ammonium enediyne, because of strong repulsion of the ortho ammonium moieties in the cyclization product. In the case of a bis-sulfonamide at least the contribution from charge to repulsion is omitted.
28. Compound 7 may have been obtained from 9 by one addition of a lithium amide and rearrangement to the alkyne amide. The second iodoniumphenyl moiety was hydrolyzed upon work up.
29. The analytical method follows previously described procedures: (a) Choy N., Kim C.-S., Ballestero C., Artigas L., Diez C., Lichtenberger F., Shapiro J., Russell K.C. Tetrahedron Lett. 41:2000;6955-6958.
30. Wisniewski Grissom J., Calkins T.L., McMillen H.A., Jiang Y. J. Org. Chem. 59:1994;5833-5835.
31. Kim C.-S., Russell K.C. J. Org. Chem. 63:1998;8229-8234.
32. The derived rate constant describes the thermal conversion of 7 . HPLC analyses showed that the Bergman cyclisation product is the main product of the thermolysis. HPLC-MS shows side products in minor amounts.
33. For a recent study on the effect of the steric influence of functional groups at the termini of acylic enediynes on the Bergman cyclization temperature, see: Rawat D.S., Zaleski J.M. Chem. Commun. 2000;2493-2494.
34. Roesler A., Pfleiderer W. Helv. Chim. Acta. 80:1997;1869-1881.
35. Hellwinkel D., Lenz D.R. Chem. Ber. 118:1985;66-85.
36. Buzniak J., Skulksi L., Wybraniec-Bugaj J. Pol. J. Chem. 55:1981;1923-1927.