Complete functionalisation of small and large diameter bromopolystyrene beads; applications for solid-supported reagents, scavengers and diversity-oriented synthesis

Organic and Biomolecular Chemistry

Volumn 2, Issue 12, 2004, Pages 1679-1681

  Thomas, Gemma L ^a   Ladlow, Mark ^a   Spring, David R ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOLS; BROMINE COMPOUNDS; CARBOXYLIC ACIDS; COLUMN CHROMATOGRAPHY; COPOLYMERIZATION; FILTRATION; MAGNESIUM PRINTING PLATES; OXIDATION; SILANES; SUBSTITUTION REACTIONS; SYNTHESIS (CHEMICAL);

BROMOPOLYSTYRENE BEADS; DIVERSITY ORIENTED SYNTHESIS; METALLATION; SOLID SUPPORTED REAGENTS;

POLYSTYRENES;

LETHRINIDAE;

EID: 3042717144     PISSN: 14770520     EISSN: None     Source Type: Journal    
DOI: 10.1039/b406488g     Document Type: Article

References (24)

1. S. L. Schreiber, Science, 2000, 287, 1964; D. R. Spring, Org. Biomol. Chem., 2003, 1, 3867; M. D. Burke and S. L. Schreiber, Angew. Chem., M. Ed., 2004, 43, 46.
2. S. L. Schreiber, Science, 2000, 287, 1964; D. R. Spring, Org. Biomol. Chem., 2003, 1, 3867; M. D. Burke and S. L. Schreiber, Angew. Chem., M. Ed., 2004, 43, 46.
3. S. L. Schreiber, Science, 2000, 287, 1964; D. R. Spring, Org. Biomol. Chem., 2003, 1, 3867; M. D. Burke and S. L. Schreiber, Angew. Chem., Int. Ed., 2004, 43, 46.
4. S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer and S. J. Taylor, J. Chem. Soc., Ferkin Trans. 1, 2000, 3815.
5. Derivatized polystyrene can be synthesized either by copolymerization (styrene, divinylbenzene & functionalized styrene) or, more divergently, by functionalization of a polystyrene starting material.
6. Beads smaller than 75 μm have the advantage that chemical reaction rates on polymer-supported substrates are faster relative to larger beads; however, they have the major disadvantages that they are more difficult to handle (filtration, flow characteristics, relative avoidance of the effects of static, ease of compartmentalization into porous capsules and cartridges) and have a much lower capacity of functionality per bead.
7. G. Thomas and D. R. Spring, unpublished results. Bead sizes for previous metallation procedures are given in refs. 6 and 7. Suzuki-Miyaura cross-coupling is successful with large beads (see ref. 10).
8. T. M. Fyles and C. C. Leznoff, Can. J. Chem., 1976, 54, 935 (38-75 μm polystyrene).
9. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
10. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
11. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
12. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
13. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
14. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
15. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
16. Lithium-bromine exchange: M. J. Farrall and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 (38-75 μm); G. D. Darling and J. M. J. Fréchet, J. Org. Chem., 1986, 51, 2270 (38-75 μm); P. A. Tempest and R. W. Armstrong, J. Am. Chem. Soc., 1997, 119, 7607 (38-75 μm); R. J. Kell, P. Hodge, M. Nisar and R. T. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 3403; magnesium-bromine exchange: S. Itsuno, G. D. Darling, H. D. H. Stöver and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4645 (38-75 μm); M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer and P. Knochel, J. Org. Chem., 2000, 65, 4618 (75-150 μm); calcium-bromine exchange; R. A. O'Brien, T. Chen and R. D. Rieke, J. Org. Chem., 1992, 57, 2667 (38-75 μm); zinc-iodine exchange: Y. Kondo, T. Komine, M. Fujinami, M. Uchiyama and T. Sakamoto, J. Comb. Chem., 1999, 1, 123.
17. The use of copolymerized bromopolystyrene (styrene, divinylbenzene & 4-bromostyrene) ensures that the bromine functionalisation occurs uniformly throughout the polymer bead. Commercially available polymers are available in a range of bead sizes, from 38-75 μm (400-200 mesh) to 500-600 μm (35-30 mesh).
18. K. Kitagawa, A. Inoue, H. Shinokubo and K. Oshima, Angew. Chem., Int. Ed., 2000, 39, 2481.
19. 2), before addition of the electrophile. In Scheme 2 the cuprate was made before addition of allyl bromide.
20. F. X. Woolard, J. Paetsch and J. A. Ellman, J. Org. Chem., 1997, 62, 6102; J. A. Tallarico, K. M. Depew, H. E. Pelish, N. J. Westwood, C. W. Lindsley, M. D. Shair, S. L. Schreiber and M. A. Foley, J. Comb. Chem., 2001, 3, 312; P. A. Clemons, A. N. Koehler, B. K. Wagner, T. G. Sprigings, D. R. Spring, R. W. King, S. L. Schreiberand M. A. Foley, Chem. Bid., 2001, 8, 1183.
21. F. X. Woolard, J. Paetsch and J. A. Ellman, J. Org. Chem., 1997, 62, 6102; J. A. Tallarico, K. M. Depew, H. E. Pelish, N. J. Westwood, C. W. Lindsley, M. D. Shair, S. L. Schreiber and M. A. Foley, J. Comb. Chem., 2001, 3, 312; P. A. Clemons, A. N. Koehler, B. K. Wagner, T. G. Sprigings, D. R. Spring, R. W. King, S. L. Schreiberand M. A. Foley, Chem. Bid., 2001, 8, 1183.
22. F. X. Woolard, J. Paetsch and J. A. Ellman, J. Org. Chem., 1997, 62, 6102; J. A. Tallarico, K. M. Depew, H. E. Pelish, N. J. Westwood, C. W. Lindsley, M. D. Shair, S. L. Schreiber and M. A. Foley, J. Comb. Chem., 2001, 3, 312; P. A. Clemons, A. N. Koehler, B. K. Wagner, T. G. Sprigings, D. R. Spring, R. W. King, S. L. Schreiberand M. A. Foley, Chem. Bid., 2001, 8, 1183.
23. The theoretical maximum silicon content in product polymer = 5.2%.
24. Ethoxytrimethylsilane (bp = 75°C), ethanol (bp = 79°C), pyridine (bp = 115°C) and trimethylsilyl fluoride (bp = 16°C) can all be removed under reduced pressure.