Enantiomerically pure α-fluoroalkyl-α-amino acids: Synthesis of (R)-α-difluoromethyl-alanine and (S)-α-difluoromethyl-serine

Tetrahedron Asymmetry

Volumn 7, Issue 8, 1996, Pages 2321-2332

  Bravo, Pierfrancesco ^a   Capelli, Silvia ^a   Meille, Stefano V ^a   Seresini, Paolo ^a   Volonterio, Alessandro ^a   Zanda, Matteo ^a  

^a POLITECNICO DI MILANO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA DIFLUOROMETHYLALANINE; ALPHA DIFLUOROMETHYLSERINE; AMINO ACID DERIVATIVE; ORGANOFLUORINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; PRIORITY JOURNAL; REACTION ANALYSIS; X RAY ANALYSIS;

EID: 0030220446     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/0957-4166(96)00287-X     Document Type: Article

References (49)

1. 1. (a) See for example: Silverman, R. B.; Bichler, K. A.; Leon, A. J. J. Am. Chem. Soc. 1996, 118, 1241-1252. Ibid. J. Am. Chem. Soc. 1996, 118, 1253-1261.
2. 1. (a) See for example: Silverman, R. B.; Bichler, K. A.; Leon, A. J. J. Am. Chem. Soc. 1996, 118, 1241-1252. Ibid. J. Am. Chem. Soc. 1996, 118, 1253-1261.
3. (b) Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic Chemistry; John Wiley & Son Inc: New York, 1991.
4. (c) Filler, R.; Kobayashi, Y.; Yagupolskii, L.M. Biomedical Aspects of Fluorine Chemistry, Elsevier: Amsterdam, 1993.
5. (d) Welch, J. T.; Gyenes, A.; Jung, M. J. "General Features of Biological Activity of Fluorinated Amino Acids: Design, Pharmacology and Biochemistry". In Fluorine Containing Amino Acids; Kukhar, V.P.; Soloshonok, V.A. Eds.; John Wiley & Son Inc: New York, 1994; pp. 311-331.
6. 2. For an excellent review see the first four chapters of the book cited in ref 1c; pp. 1-219. Kukhar, V. P.; Yagupol'skii, Yu. L.; Soloshonok, V. A. Russ. Chem. Rev. 1990, 59, 149-175. See also Osipov, S. N.; Golubev, A.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Synlett 1995, 1270-1271. Osipov, S. N.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Tetrahedron Lett. 1996, 37, 615-618.
7. 2. For an excellent review see the first four chapters of the book cited in ref 1c; pp. 1-219. Kukhar, V. P.; Yagupol'skii, Yu. L.; Soloshonok, V. A. Russ. Chem. Rev. 1990, 59, 149-175. See also Osipov, S. N.; Golubev, A.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Synlett 1995, 1270-1271. Osipov, S. N.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Tetrahedron Lett. 1996, 37, 615-618.
8. 2. For an excellent review see the first four chapters of the book cited in ref 1c; pp. 1-219. Kukhar, V. P.; Yagupol'skii, Yu. L.; Soloshonok, V. A. Russ. Chem. Rev. 1990, 59, 149-175. See also Osipov, S. N.; Golubev, A.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Synlett 1995, 1270-1271. Osipov, S. N.; Sewald, N.; Kolomiets, A. F.; Fokin, A. V.; Burger, K. Tetrahedron Lett. 1996, 37, 615-618.
9. 3. (a) Kukhar, V. P.; Resnati, G.; Soloshonok, V. A. "Asymmetric Synthesis of Fluorine-Containing Amino Acids". In the book cited in ref 1c; pp. 221-241.
10. (b) Bravo, P.; Capelli, S.; Meille, S. V.; Viani, F.; Zanda, M.; Kukhar, V. P.; Soloshonok, V. A. Tetrahedron: Asymmetry 1994, 5, 2009-2018.
11. (c) Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron 1996, 52, 233-244.
12. (d) Sting, A. R.; Seebach, D. Tetrahedron 1996, 52, 279-290.
13. (e) Soloshonok, V. A.; Hayashi, T. Tetrahedron Lett. 1994, 35, 2713-2716.
14. 4. (a) Davis, F. A.; Portonovo, P. S.; Reddy, R. E.; Chiu, Y. J. Org. Chem. 1996, 61, 440-441 and references therein quoted.
15. (b) Williams, R. M. Organic Chemistry Series Volume 7: Synthesis of Optically Active α-Amino Acids; Baldwin, J. E.; Magnus, P. D. eds.; Pergamon Press: Oxford, 1989; pp. 208-229.
16. c) Duthaler, R. O. Tetrahedron 1994, 50, 1539-1650.
17. 5. The reaction is also reported to occur via formation of an α-hydroxy-amine, which reacts with the cyanide affording the final α-aminonitrile. For a review on the synthesis of α-aminonitriles see: Shafran, Yu. M.; Bakulev, V. A.; Mokrushin, V. S. Russ. Chem. Rev. 1989, 58, 148-162.
18. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
19. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
20. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
21. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
22. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
23. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
24. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
25. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
26. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
27. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
28. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
29. 6. Tolman, V. "Synthesis of Fluorine-Containing Amino Acids by Method of Classical Amino Acid Chemistry". In the book cited in ref. 1c; pp. 15-21. Sewald, N.; Burger, K. "Synthesis of β-Fluorine-containing Amino Acids". In the book cited in ref. 1c; pp. 176-178. See also: Koos, M.; Mosher, H. S. Tetrahedron 1993, 49, 1541-1546. For some examples of Strecker and Bucherer-Bergs reactions in the synthesis of FAAs see: Kollonitsch, J.; Patchett, A. A. Eur. Pat. 1980, 7 600; Chem. Abstr. 1980, 93, 11497. Christensen, H. N.; Oxender, D. L. Biochim. Biophys. Acta 1963, 74, 386-391. Dingwall, J. G. Eur. Pat. 1989, 298 029; Chem. Abstr. 1989, 111, 115172. Sletzinger, M.; Plainfield, N.; Gaines, W. A. US Pat. 1962, 3 046 300; Chem. Abstr. 1960, 57, 16740. Lontz, J. F.; Raasch, M. S. US Pat. 1953, 2 662 915; Chem. Abstr. 1954, 48, 12795.
30. 7. Unpublished results from these laboratories.
31. 8. (a) Bravo, P.; Crucianelli, M.; Zanda, M. Tetrahedron Lett. 1995, 36, 3043-3046.
32. (b) Arnone, A.; Bravo, P.; Capelli, S.; Fronza, G.; Meille, S. V.; Zanda, M.; Cavicchio, G.; Crucianelli, M. J. Org. Chem. 1996, in press.
33. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
34. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
35. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
36. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
37. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
38. 9. Enantiomerically enriched (-)-(S)-α-difluoromethyl-alanine has been already obtained, though with very low e.e.: Kolb, M.; Barth, J. Liebigs Ann. Chem. 1983, 1668-1688. For other approaches to this racemic amino acid see: Bey, P.; Vevert, J.-P.; Van Dorsselaer, V.; Kolb, M. J. Org. Chem. 1979, 44, 2732-2742. Bey, P.; Vevert, J.-P. Tetrahedron Lett. 1978, 19, 1215-1218. Taylor, J. S.; Deutsch, C. Biophys. J. 1983, 261-267. To the best of our knowledge α-difluoromethyl-serine has never been described. For racemic α-fluoromethyl-serine see: Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 793-796. For both enantiomers of e.p. α-trifluoromethyl-serine see: Bravo, P.; Viani, F.; Zanda, M.; Soloshonok, V. A. Gazz. Chim. Ital. 1995,125, 149-150.
39. 2P(O)CN see Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett. 1979, 20, 4663-4666.
40. 2P(O)CN see Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett. 1979, 20, 4663-4666.
41. 2P(O)CN see Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett. 1979, 20, 4663-4666.
42. 2P(O)CN see Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett. 1979, 20, 4663-4666.
43. 11. Arnone, A.; Bravo, P.; Bruché, L.; Crucianelli, M.; Vichi, L.; Zanda, M. Tetrahedron Lett. 1995, 36, 7301-7304. The sulfenamide trifluoroacetate 6 was not isolated, but only detected by TLC.
44. 12. Johnson, C.K. 1976, ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee.
45. 13. Park, H., Vela, M. A., Kohn, H. J. Am. Chem. Soc. 1994, 116, 471-478.
46. 19F NMR signals of the syn diastereoisomers are at higher fields than the signals of the anti isomers. For a similar attribution of stereochemistry to another series of γ-fluoro-β-aminosulfoxides see ref. 3b.
47. 15. Altomare, A.; Cascarano, G.; Giacovazzo, G.; Guagliardi A. J. Appl. Cryst. 1993, 26, 343-350.
48. 16. Sheldrick, G.M. 1993, SHELXL93, Program for the Refinement of Crystal structures, University of Göttingen, Germany.
49. 17. Flack, H.D. Acta Cryst. 1983, A 39, 876-880.