New fluoride-labile linkers for solid-phase organic synthesis

Tetrahedron Letters

Volumn 38, Issue 47, 1997, Pages 8287-8290

  Routledge, Anne ^a   Stock, H Thijs ^a   Flitsch, Sabine L ^a   Turner, Nicholas J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALUMINUM FLUORIDE; AMINOPYRIDINE DERIVATIVE; BENZOIC ACID DERIVATIVE; BENZOTRIAZOLE DERIVATIVE; CYANAMIDE; FLUORIDE; RESIN; SILANE DERIVATIVE;

ARTICLE; CHEMICAL REACTION; HYDROLYSIS; SOLID STATE; SYNTHESIS;

EID: 0030698249     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10169-1     Document Type: Article

References (22)

1. Backes, B.J.; Ellman, J.A., Current Opinion in Chemical Biology, 1997, 1, 86-93.
2. Terrett, N.K.; Gardner, M.; Gordon, D.W.; Kobylecki, R.J.; Steele, J., Tetrahedron, 1995, 51, 8135-8173.
3. (ii) Hermkens, P.H.H.; Ottenheijem, H.C.J.; Rees, D., Tetrahedron, 1996, 52, 4527-4554.
4. Recent photolabile linkers (i) Holmes, C.P.; Jones, D.G., J. Org. Chem., 1995, 60, 2318-2319.
5. (ii) Routledge, A.; Abell, C., Balasubramanian, S., Tetrahedron Lett., 1997, 38, 1227-1230.
6. Rich, D.H.; Guwara, S.K., J. Am. Chem. Soc., 1975, 97, 1575-1579.
7. (i) Ramage, R.; Barron, C.A.; Bielecki, S.; Holden, R.; Thomas, D.W., Tetrahedron, 1992, 48, 499-514.
8. (ii) Chao, H-G.; Bernatowicz, M.S.; Reiss, P.D.; Klimas, C.E.; Matsueda, G.R., J. Am. Chem. Soc., 1994, 116, 1746-1752.
9. 2 and squeezing the swollen resin between two NaCl plates, the spectra was acquired as for a normal thin film FTIR
10. Purchased from Aldrich (1 mmol/g, 2% divinylbenzene).
11. -1) 1693 (C=O).
12. Bordeau, M.; Villeneuve, P.; Bennetau, B.; Dunogues, J., J Organomet, Chem., 1987, 331, 169-174.
13. Purchased from Novabiochem (0.44 mmol/g, 100-200 mesh, 1% divinylbenzene)
14. 3), 75.77(COH).
15. -1) 1718 (C=O).
16. Determined by elemental analysis for bromine. All elemental analyses were performed by MEDAC LTD, Department of Chemistry, Brunel University, Uxbridge, U.K.
17. TFA= 12300) by TBAF and determination of yield by UV spectroscopy. Resin 4 (13.1 mg, 0.006 mmol of resin-bound 4-bromobenzoic acid) was swollen in anhydrous DMF (0.1 ml), TBAF (12.0 μl, 0.012 mmol, 1M in THF) was added and the reaction was allowed to stand at ambient temperature for 1h. The resin was filtered, washed with DMF (3×;1 ml) and the filtrate concentrated under reduced pressure. The residue was dissolved in methanol (Spectroscopic grade, 5 ml), 1 μl of acetic acid was added then 200 μl of the acidified methanolic solution were removed and further diluted with methanol (Spectroscopic grade, 5 ml). The absorbance at 240 nm was measured on either an ATI UNICAM UV/VIS spectrometer or a CECIL CE 1020S scanning UV spectrometer.
18. Procedure for the release of 4-bromobenzoic acid by CsF and determination of yield by UV spectroscopy. Resin 4 (19.2 mg, 0.009 mmol of resin-bound 4-bromobenzoic acid) was swollen in anhydrous DMF (0.1 ml), CsF (11.9 mg, 0.078 mmol.) was added and the reaction was allowed to stand at ambient temperature for 24h. Work up as for ref. 14.
19. For both linkers the yield of released 4-bromobenzoic acid appeared to reach a maximum value, but inspection of the FTIR spectra of the resin after cleavage showed no discernible ester carbonyl and acidolysis with 50% TFA gave almost quantitative release. This suggests the apparent plateau in cleavage yield is not due to 4-bromobenzoic acid being irreversibly bound to the resin via ester formation directly onto hydroxymethyl polystyrene (present as a by-product on the commercial formyl polystyrene or from hydrolysis of Merrifield resin.).
20. -1) 1761 (C=O).
21. Determined by elemental analysis for nitrogen.
22. The addition of molecular sieves had be shown to be beneficial for the cleavage of SEM ethers. Kan, T.; Hashimoto, M.; Yanagiya, M.; Shirahama, H., Tetrahedron Lett., 1988, 29, 5417-5418.