A Tuneable Ge-based Linker that Enables Application-led Solid Phase Synthesis Optimisation - Towards a Robust Iterative Synthesis of Oligothiophenes

Synlett

Volumn , Issue 1, 2004, Pages 111-115

  Spivey, Alan C ^c   Turner, David J ^a   Turner, Michael L ^a   Yeates, Stephen ^b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b Avecia Biologics Limited   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Combinatorial chemistry; Cross coupling; Electrophilic aromatic substitutions; Heterocycles; Solid phase synthesis

Indexed keywords

CARBON; GERMANIUM; THIOPHENE DERIVATIVE;

ARTICLE; CHEMICAL BOND; CHEMICAL MODIFICATION; PRECURSOR; SOLID; SYNTHESIS;

EID: 0346340914     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2003-43363     Document Type: Article

References (28)

1. Beck-Sickinger, A.; Weber, P. Combinatorial Strategies in Biology and Chemistry; Wiley: Chichester, 2002.
2. Guillier, F.; Orain, D.; Bradley, M. Chem. Rev. 2000, 100, 2091.
3. Congreve, M. S.; Ley, S. V.; Scicinski, J. J. Chem.-Eur. J. 2002, 8, 1768.
4. James, I. W. Tetrahedron 1999, 55, 4855.
5. Spivey, A. C.; Turner, D. J.; Turner, M. L.; Yeates, S. Org. Lett. 2002, 4, 1899.
6. Reviews: (a) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359. (b) Dimitrakopoulos, C. D.; Mascaro, D. J. IBM J. Res & Dev. 2001, 45, 11.
7. Reviews: (a) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359. (b) Dimitrakopoulos, C. D.; Mascaro, D. J. IBM J. Res & Dev. 2001, 45, 11.
8. (a) Spivey, A. C.; Diaper, C. M.; Rudge, A. J. Chem. Commun. 1999, 835.
9. (b) Spivey, A. C.; Diaper Adams, H. C. M.; Rudge, A. J. Org. Chem. 2000, 65, 5253.
10. (c) Spivey, A. C.; Srikaran, R.; Diaper, C.; Turner, D. J. Org. Biomol. Chem. 2003, 1, 1638.
11. 4Ge but the reaction is less selective (57% yield after distillation): Kraus, C. A.; Brown, C. L. J. Am. Chem. Soc. 1930, 52, 3690.
12. 2: 371. 9739; found: 371.9749.
13. 2: 484.1458; found: 484, 1446.
14. For the analogous 'activation' of an arylsilane linker precursor see: Woolard, F. X.; Paetsch, J.; Ellman, J. A. J. Org. Chem. 1997, 62, 6102.
15. Tour, J. M.; Wu, R. Macromolecules 1992, 25, 1901.
16. (a) Benkeser, R. A.; Krysiak, H. R. J. Am. Chem. Soc. 1954, 76, 6353.
17. (b) Eaborn, C.; Moore, R. C. J. Chem. Soc. 1959, 3640.
18. (15) Hexylthiophene immobilisation (2b→11b) proceeded smoothly in all cases except for the para-fluorophenyl case, which gave a complex mixture of products, tentatively ascribed to fragmentation pathways following nucleophilic attack at the carbon ipso to the fluorine substituent.
19. The insensitivity of Ge cf. Si towards steric shielding has been noted previously and attributed to longer Ge-C vs SiC bond lengths: Eaborn, C. J. Organomet. Chem. 1975, 100, 43.
20. (17) Quadragel™-OH (Avecia Ltd.) is a DVB crosslinked PS-based resin with hydroxyl-terminated PEG grafts containing 4 oxyethyl repeat units.
21. Galvao, D. S.; Dos Santos, D. A.; Laks, B.; Dos Santos, M. C. Synth. Met. 1991, 43, 3521.
22. 3): δ = 17.6, 21.8, 24.9, 25.2, 25.5, 25.7, 26.0, 31.7, 37.4, 41.6, 67.0, 67.3, 67.6, 67.9, 68.2, 71.7, 72.2, 128.9.
23. 2), 6.10-6.70 (ArH), 6.70-7.30 (ArH), 7.56 (d, J = 4.5 Hz, ArH).
24. 2), 6.10-6.80 (ArH), 6.80-7.30 (ArH), 7.53 (d, J = 4.5 Hz, ArH).
25. 2), 6.10-7.30 (ArH), 7.44 (d, 7 = 4.5 Hz, ArH), 7.50-7.55 (SCH).
26. 2), 6.10-7.30 (ArH), 7.42 (d, J = 4.5 Hz, ArH).
27. 3): δ = 14.5, 17.3, 18.6, 21.9, 22.9, 23.0, 26.8, 29.6, 29.7, 30.0, 31.1, 31.7, 32.0, 32.2, 40.9, 44.3, 67.9, 70.2, 71.1, 71.2, 114.6, 115.0, 126.1, 128.4, 128.8, 129.1, 129.5, 129.6, 130.5, 133.6, 134.2, 135.0, 135.1, 135.5, 137.4, 138.7, 139.2, 139.5, 140.1, 140.6, 141.6, 145.7, 151.4, 157.3.
28. 2O + 0.1% formic acid, R, 22.4 min). Spectroscopic data identical to that previously reported.18