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Molecular Diversity

, Volume 3, Issue 3, pp 161–171 | Cite as

Use of silica gels and mesoporous molecular sieves as supports for the solid-phase Claisen rearrangement

  • Irving Sucholeiki
  • Michael R. Pavia
  • Charles T. Kresge
  • Sharon B. McCullen
  • Andre Malek
  • Suzanne Schramm
Article

Abstract

A series of silica gels and mesoporous molecular sieves differing in both the range of particle size and mean pore size were derivatized with the p-[(R,S)-α-[1-(9H-fluoren-9-yl)-methoxyformamido]-2,4-dimethoxybenzyl]-p henoxyacetic acid linker and their loading capacities were measured. Loading capacities ranging between 0.4–0.6 mmol Fmoc/g were achieved. Several of these silica based materials were derivatized with the hydroxymethyl benzoic acid linker and used as supports for the solid phase Claisen rearrangement of a support bound phenyl allyl ether. Both the silica gel and mesoporous supports were heated at 225 °C for 3 h to effect the Claisen rearrangement. The results showed that, compared to the same reaction run homogeneously, the silica gel support achieved similar total product yields and ratios for two Claisen products. The mesoporous supports were found to selectively produce one of the Claisen products over the other. Analysis shows that the molecules bound to the mesoporous support are physically further separated from each other as compared to those bound to the silica gel support. A mechanism is presented which accounts for the selectivity of the mesoporous support in forming one Claisen product over the other. The Claisen product was further derivatized to the resulting phenyl ethyl ether through a solid phase Mitsunobu reaction on the mesoporous support.

mesoporous silica solid-phase Claisen rearrangement solid-phase synthesis support 

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References

  1. 1.
    Terret, N.K., Gardner, M., Gordon, D.W., Kobylecki, R.J. and Steele, J., Combinatorial synthesis - The design of compound libraries and their application to drug discovery, Tetrahedron, 51 (1995) 8135–8173.CrossRefGoogle Scholar
  2. 2.
    Fruchtel, J.S. and Jung, G., Organic chemistry on solid supports, Angew Chem., Int. Ed. Engl., 35 (1996) 17–42.CrossRefGoogle Scholar
  3. 3.
    Tabell, D.S., The Claisen Rearrangement, In Adams, R. (Ed.) Organic Reactions, Vol. 2, JohnWiley & Sons, New York, NY, 1944, pp. 1–48.Google Scholar
  4. 4.
    Fráter, Gy. and Schmid, H., Ñber den Mechanismus der thermichen cis, trans- Isomerisierung von 2-crotylphenolen, Helv. Chim. Acta, 49 (1966) 1957–1962.CrossRefGoogle Scholar
  5. 5.
    Schmid, E., Fráter, Gy., Hansen, H.J. and Schmid, H., Eine neue 2-allylphenol-cumaran-umlagerung, Helv. Chim. Acta, 55 (1972) 1625–1674.CrossRefGoogle Scholar
  6. 6.
    Jurd, L., Stevens, K. and Manners, G., Acid-catalyzed and thermal rearrangements of obtusaquinol and related 3,3-diarylpropenes, Tetrahedron, 29 (1973) 2347–2353.CrossRefGoogle Scholar
  7. 7.
    Barany, G. and Merrifield, R.B., Solid Phase Peptide Synthesis, In Gross, E. and Meienhofer, J., (Eds.) The Peptides, Vol. 2, Academic Press, New York, NY, 1980, pp. 1–284.Google Scholar
  8. 8.
    Ellis, T.S., Karasz, F.E. and Brinke, G.T., The influence of thermal properties on the glass transition temperature in styrene/divinylbenzene network-dilutent systems, J. Appl. Polym. Sci., 28 (1983) 23–32.CrossRefGoogle Scholar
  9. 9.
    Keana, J.F.W., Shimizu, M. and Jernstedt, K.K., Functionalized silica gel as a support for solid-phase organic synthesis, J. Org. Chem., 51 (1986) 1641–1644.CrossRefGoogle Scholar
  10. 10.
    Beck, J.S., Vartuli, J.C., Roth, W.J., Leonowicz, M.E., Kresge, C.T., Schmitt, K.D., Chu, C.T-W., Olson, D.H., Sheppard, E.W., McCullen, S.B., Higgins, J.B. and Schlenker, J.L., A new family of mesoporous molecular sieves prepared with liquid crystal templates, J. Am. Chem. Soc., 114 (1992) 10834–10843.CrossRefGoogle Scholar
  11. 11.
    Green, J. and Bradley, K., Studies on the acylation of hydroxyfunctionalized resins using Fmoc amino acids activated using diisopropylcarbodiimide/HOBT or as acid fluorides, Tetrahedron, 49 (1993) 4141–4146.CrossRefGoogle Scholar
  12. 12.
    The natural neoflavanoid latifolin, incorporating four alkoxy groups, was shown to rearrange while simple mono-alkoxy derivatives were found not to rearrange: Kumari, D., Mukerjee, S.K. and Seshadri, T.R., A novel rearrangement of the latifolin skeleton, Tetrahedron Lett., 13 (1967) 1153–1156.CrossRefGoogle Scholar
  13. 13.
    Jurd, L., Cinnamyl alcohol - Polyphenol condensations in aqueous solutions, Tetrahedron, 25 (1969) 1407–1416.CrossRefGoogle Scholar
  14. 14.
    Tundo, P., Functionalization of inorganic supports, In Tundo, P. (Ed.), Continuous Flow Methods In Organic Synthesis, Ellis Horwood Ltd, West Sussex, U.K., 1991, pp. 66–67.Google Scholar
  15. 15.
    Kresge, C.T., Leonowicz, M.E., Roth, W.J., Vartuli, J.C. and Beck, J.S., Order mesoporous molecular sieves synthesized by a liquid crystal template mechanism, Nature, 359 (1992) 710–712.CrossRefGoogle Scholar
  16. 16.
    The unfunctionalized samples were vacuum dried at 300 °C. The derivatized silica based supports were vacuum dried at 100 °C in order to avoid decomposition.Google Scholar
  17. 17.
    Average spacing = [surface area (Å2/g)/loading capacity (molecules/g)]. Example calculations for hydroxymethyl mesoporous support 11e: 0:95 mmol=g D 5.719 x 1020 molecules/g 1083 m2=g D 1:083 x 1023 Å2/g 14 Å (1:083 x 1023/5:719 x 1029)Google Scholar
  18. 18.
    As part of the synthesis of the mesoporous supports there is a calcination procedure requring heating at elevated temperatures ~540 °C), a process which might have resulted in the dehydration of some of the silanols.Google Scholar
  19. 19.
    Sample spinning = 4.0- 4.5 kHz, recycle time = 800 s, tetramethylsilane was used as external standard.Google Scholar
  20. 20.
    Krchñ ák, V., Flegelová, Z., Weichsel, A.S. and Lebl, M., Polymer-supported Mitsunobu ether formation and its use in combinatorial chemistry, Tetrahedron Lett., 36 (1995) 6193–6196.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Irving Sucholeiki
    • 1
  • Michael R. Pavia
    • 1
  • Charles T. Kresge
    • 2
  • Sharon B. McCullen
    • 2
  • Andre Malek
    • 2
  • Suzanne Schramm
    • 2
  1. 1.Sphinx Pharmaceuticals, A Division of Eli Lilly and CompanyCambridgeU.S.A
  2. 2.Mobil Technology Company–Strategic Research CenterPaulsboroU.S.A

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