Synthesis of amides from unprotected amino acids by a simultaneous protection-activation strategy using dichlorodialkyl silanes

Tetrahedron Letters

Volumn 43, Issue 50, 2002, Pages 9203-9207

  Van Leeuwen, S H ^a   Quaedflieg, P J L M ^b   Broxterman, Q B ^b   Liskamp, R M J ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

^b DSM Fine Chemicals Austria Nfg GmbH & Co KG   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; AMINO ACID DERIVATIVE; ASPARTIC ACID; BETA AMINO ACID; CARBON; DICARBOXYLIC ACID DERIVATIVE; SILANE DERIVATIVE;

ALKYLATION; AMIDATION; AMINO ACID SYNTHESIS; ARTICLE; CYCLIZATION; PROTON NUCLEAR MAGNETIC RESONANCE; ROOM TEMPERATURE;

EID: 0037049191     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(02)02275-X     Document Type: Article

References (28)

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2. See for example and references cited therein: (a) Pfaender, P.; Kuhnle, E.; Krahl, B.; Backmansson, A.; Gnauck, G.; Blecher, H. Hoppe-Seyler's Z. Physiol. Chem. 1973, 354, 267-285; (b) Katakai, R.; Oya, M.; Uno, K.; Iwakura, Y. J. Org. Chem. 1972, 37, 327-329; (c) Hirschmann, R.; Schwam, H.; Strachan, G.; Schoenewaldt, E. F.; Barkemeyer, H.; Miller, S. M.; Conn, J. B.; Garsky, V.; Veber, D. F.; Denkewalter, R. G. J. Am. Chem. Soc. 1971, 93, 2746-2754.
3. See for example and references cited therein: (a) Pfaender, P.; Kuhnle, E.; Krahl, B.; Backmansson, A.; Gnauck, G.; Blecher, H. Hoppe-Seyler's Z. Physiol. Chem. 1973, 354, 267-285; (b) Katakai, R.; Oya, M.; Uno, K.; Iwakura, Y. J. Org. Chem. 1972, 37, 327-329; (c) Hirschmann, R.; Schwam, H.; Strachan, G.; Schoenewaldt, E. F.; Barkemeyer, H.; Miller, S. M.; Conn, J. B.; Garsky, V.; Veber, D. F.; Denkewalter, R. G. J. Am. Chem. Soc. 1971, 93, 2746-2754.
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7. Dichlorodimethylsilane was used under these conditions by Barlos et al. in the simultaneous protection of the amino and carboxylic acid moiety of histidine in order to protect selectively its imidazole function with a trityl protecting group: (a) Barlos, K.; Papaioannou, D.; Theodoropoulos, D. J. Org. Chem. 1982, 47, 1324-1326; (b) Eleftheriou, S.; Gatos, D.; Panagopoulos, A.; Stathopoulos, S.; Barlos, K. Tetrahedron Lett. 1999, 40, 2825-2828.
8. Dichlorodimethylsilane was used under these conditions by Barlos et al. in the simultaneous protection of the amino and carboxylic acid moiety of histidine in order to protect selectively its imidazole function with a trityl protecting group: (a) Barlos, K.; Papaioannou, D.; Theodoropoulos, D. J. Org. Chem. 1982, 47, 1324-1326; (b) Eleftheriou, S.; Gatos, D.; Panagopoulos, A.; Stathopoulos, S.; Barlos, K. Tetrahedron Lett. 1999, 40, 2825-2828.
9. 2) under a nitrogen atmosphere at ambient temperature (approx. 23°C) and dichlorodimethylsilane (267 μL, 2.2 mmole) was added in one portion. During 2 min the mixture turned clear and the temperature rose from 23 to 28°C. Subsequently, 6 mmole of the selected amine was added (in most cases giving a suspension) and the reaction mixture was stirred for another 16 h and monitored with TLC (using chloroform/methanol/ammonia 60/45/20 v/v/v, sec-butanol/formic acid/water 75/15/10 v/v/v and n-butanol/acetic acid/ethyl acetate/water 1/1/1/1 v/v/v/v). The reaction mixture was concentrated in vacuo and the resulting residue chromatographed on silica gel (eluent: dichloromethane/methanol 100/0 to 95/5 v/v) to furnish the pure L-phenylalanine-amide.
10. The silyl intermediate probably easily decomposes at higher temperatures.
11. Besides pyridine the following solvents were tried in the coupling reaction of L-phenylalanine with benzylamine using dichlorodimethylsilane: THF, dichloromethane, N,N-dimethyl-acetamide (DMA), N,N-dimethylformamide, N-methylpyrrolidone (NMP), 1,4-dioxane, 1,2-dichloroethane, acetone, DMSO, chloroform, acetonitrile and sulpholane; the maximum L-phenylalanine-benzylamide yield obtained was 25% (using DMA and NMP). When triethylamine (2 equiv. based on L-phenylalanine) was added before the addition of dichlorodimethylsilane, the yields in these solvents significantly increased (for instance to 80% in DMA and NMP, to 50% in acetonitrile and 48% when triethylamine was used as the solvent itself) but they were still lower than in pyridine (98%).
12. 5 in dichloromethane; in pyridine this compound rapidly polymerized.
13. +] 306.
14. 2) under a nitrogen atmosphere at ambient temperature (approx. 23°C) and 2.2 mmole of the dichlorodialkylsilane was added in one portion. After 1 min 3-5 equiv. of benzylamine was added and the reaction mixture was stirred for another 16 h, monitored with TLC and worked up (as above).
15. The same experimental procedure was applied as given in Ref. 6 .
16. See for example and references cited therein: (a) Zuckermann, R. N.; Martin, E. J.; Spellmeyer, D. C.; Stauber, G. B.; Shoemaker, K. R.; Kerr, J. M.; Figliozzi, G. M. D.; Goff, A.; Siani, M. A.; Simon, R. J.; Banville, S. V.; Brown, E. G.; Wang, L.; Richter, L. S.; Moos, W. H. J. Med. Chem. 1994, 37, 2678-2685; (b) Nguyen, J. T.; Turck, C. W.; Cohen, F. E.; Zuckermann, R. N.; Lim, W. A. Science 1998, 282, 2088-2092; (c) Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banville, S.; Ng, S.; Wang, L.; Rosenberg, S.; Marlowe, C. K. D.; Spellmeyer, C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Barlett, P. A. Proc. Natl. Acad. Sci. USA 1992, 89, 9367-9371; (d) Kruijtzer, J. A. W.; Hofmeyer, L. J. F.; Heerma, W.; Versluis, C.; Liskamp, R. M. J. Chem. Eur. J. 1998, 4, 1570-1580.
17. See for example and references cited therein: (a) Zuckermann, R. N.; Martin, E. J.; Spellmeyer, D. C.; Stauber, G. B.; Shoemaker, K. R.; Kerr, J. M.; Figliozzi, G. M. D.; Goff, A.; Siani, M. A.; Simon, R. J.; Banville, S. V.; Brown, E. G.; Wang, L.; Richter, L. S.; Moos, W. H. J. Med. Chem. 1994, 37, 2678-2685; (b) Nguyen, J. T.; Turck, C. W.; Cohen, F. E.; Zuckermann, R. N.; Lim, W. A. Science 1998, 282, 2088-2092; (c) Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banville, S.; Ng, S.; Wang, L.; Rosenberg, S.; Marlowe, C. K. D.; Spellmeyer, C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Barlett, P. A. Proc. Natl. Acad. Sci. USA 1992, 89, 9367-9371; (d) Kruijtzer, J. A. W.; Hofmeyer, L. J. F.; Heerma, W.; Versluis, C.; Liskamp, R. M. J. Chem. Eur. J. 1998, 4, 1570-1580.
18. See for example and references cited therein: (a) Zuckermann, R. N.; Martin, E. J.; Spellmeyer, D. C.; Stauber, G. B.; Shoemaker, K. R.; Kerr, J. M.; Figliozzi, G. M. D.; Goff, A.; Siani, M. A.; Simon, R. J.; Banville, S. V.; Brown, E. G.; Wang, L.; Richter, L. S.; Moos, W. H. J. Med. Chem. 1994, 37, 2678-2685; (b) Nguyen, J. T.; Turck, C. W.; Cohen, F. E.; Zuckermann, R. N.; Lim, W. A. Science 1998, 282, 2088-2092; (c) Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banville, S.; Ng, S.; Wang, L.; Rosenberg, S.; Marlowe, C. K. D.; Spellmeyer, C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Barlett, P. A. Proc. Natl. Acad. Sci. USA 1992, 89, 9367-9371; (d) Kruijtzer, J. A. W.; Hofmeyer, L. J. F.; Heerma, W.; Versluis, C.; Liskamp, R. M. J. Chem. Eur. J. 1998, 4, 1570-1580.
19. See for example and references cited therein: (a) Zuckermann, R. N.; Martin, E. J.; Spellmeyer, D. C.; Stauber, G. B.; Shoemaker, K. R.; Kerr, J. M.; Figliozzi, G. M. D.; Goff, A.; Siani, M. A.; Simon, R. J.; Banville, S. V.; Brown, E. G.; Wang, L.; Richter, L. S.; Moos, W. H. J. Med. Chem. 1994, 37, 2678-2685; (b) Nguyen, J. T.; Turck, C. W.; Cohen, F. E.; Zuckermann, R. N.; Lim, W. A. Science 1998, 282, 2088-2092; (c) Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banville, S.; Ng, S.; Wang, L.; Rosenberg, S.; Marlowe, C. K. D.; Spellmeyer, C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Barlett, P. A. Proc. Natl. Acad. Sci. USA 1992, 89, 9367-9371; (d) Kruijtzer, J. A. W.; Hofmeyer, L. J. F.; Heerma, W.; Versluis, C.; Liskamp, R. M. J. Chem. Eur. J. 1998, 4, 1570-1580.
20. See for example: (a) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071; (b) Seebach, D.; Ciceri, P.; Overhand, M.; Juan, B.; Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer, H. Helv. Chim. Acta 1996, 79, 2043; (c) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (d) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574; (e) Wang, X.; Espinosa, J. F.; Gellman, S. H. J. Am. Chem. Soc. 2000, 122, 4821.
21. See for example: (a) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071; (b) Seebach, D.; Ciceri, P.; Overhand, M.; Juan, B.; Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer, H. Helv. Chim. Acta 1996, 79, 2043; (c) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (d) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574; (e) Wang, X.; Espinosa, J. F.; Gellman, S. H. J. Am. Chem. Soc. 2000, 122, 4821.
22. See for example: (a) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071; (b) Seebach, D.; Ciceri, P.; Overhand, M.; Juan, B.; Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer, H. Helv. Chim. Acta 1996, 79, 2043; (c) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (d) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574; (e) Wang, X.; Espinosa, J. F.; Gellman, S. H. J. Am. Chem. Soc. 2000, 122, 4821.
23. See for example: (a) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071; (b) Seebach, D.; Ciceri, P.; Overhand, M.; Juan, B.; Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer, H. Helv. Chim. Acta 1996, 79, 2043; (c) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (d) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574; (e) Wang, X.; Espinosa, J. F.; Gellman, S. H. J. Am. Chem. Soc. 2000, 122, 4821.
24. See for example: (a) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071; (b) Seebach, D.; Ciceri, P.; Overhand, M.; Juan, B.; Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer, H. Helv. Chim. Acta 1996, 79, 2043; (c) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (d) Appella, H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574; (e) Wang, X.; Espinosa, J. F.; Gellman, S. H. J. Am. Chem. Soc. 2000, 122, 4821.
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28. For the coupling experiments with L-aspartic acid, a similar experimental procedure as given in Ref. 6 was used. The α-product (α-L-aspartic acid-benzylamide) and the β-product (β-L-aspartic acid-benzylamide) were determined on HPLC by comparison of the peak areas with those of reference solutions of known concentration.