Synthesis of β-amino-α,α-difluoroketones by reactions of 1,1-difluorovinyl methyl ethers with N-acyliminium intermediates

Tetrahedron Letters

Volumn 37, Issue 7, 1996, Pages 1061-1064

  Kodama, Yoshitoshi ^a   Okumura, Masato ^a   Yanabu, Noriko ^a   Taguchi, Takeo ^a  

^a TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCES   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID DERIVATIVE; KETONE; ORGANOFLUORINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030031231     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02348-8     Document Type: Article

References (24)

1. a) Welch, J. T. Tetrahedron 1987, 43, 3123.
2. b) "Selective Fluorination in Organic and Bioorganic Chemistry", Welch, J. T. Ed.; ACS Symposium Series 456, ACS; Washington DC, 1991.
3. Fluoroalkyl ketones serve as ideal mimics of the tetrahedral transition state for peptide or ester bond hydrolysis. For examples: a) Gelb, M. H.; Svaren, J. P.; Ables, R. H. Biochemistry 1985, 24, 1813.
4. b) Thaisrivongs, S.; Pals, D. T.; Kati, W. M.; Turner, S. R.; Thamasco, L. M.; Watt, W. J. Med. Chem. 1986, 29, 2080.
5. c) Gelb, M. H. J. Am. Chem. Soc, 1986, 108, 3146.
6. a) Welch, J. T.; Eswarakrishnan, S. In Fluorine-Containing Molecules; Structure, Reactivity, Synthesis, Liebman, J. F.; Greenberg, A.; Dolbier, Jr., W.R. Eds.; VCH publisher; New York, 1988, p123.
7. b) Ishihara, T. J. Synth. Org. Chem. Jpn. 1992, 50, 347 and references cited therein.
8. c) Howarth, J.; Martin Owton, W.; Percy, J. M. J. Chem. Soc. Chem. Commun. 1995, 757.
9. Methods involving conversion of a carbonyl group to difluoride by DAST are also reported. For example: Dreyer, G. B.; Metcalf, B. W. Tetrahedron Lett. 1988, 29, 6885.
10. a) Shah, N. V.; Cama, L. D. Heterocycles 1987, 25, 221.
11. b) Whitten, J. P.; Barney, C. L.; Huber, E. W.; Bey, P.; McCarthy, J. R. Tetrahedron Lett. 1989, 30, 3649.
12. Imine-condensation of difluoroacetate: Taguchi, T.; Kitagawa, O.; Suda, Y.; Ohkawa, S.; Hashimoto, A.; Iitaka, Y.; Kobayashi, Y. Tetrahedron Lett. 1988, 29, 5291.
13. Kodama, Y.; Yamane, H.; Okumura, M.; Shiro, M.; Taguchi, T. Tetrahedron 1995, 51, 12217.
14. Although biscarbamate 2 can be prepared by mixing aldehyde and ethyl carbamate (2 equiv), N-acylimine 3a is prepared via N-trimethylsilyl imine obtained by reaction of aldehyde with lithium hexamethyldisilazide [LiN(TMS)2].
15. We could not obtain the condensation product by reaction of 1 with imines derived from aldehydes and primary amines in the presence of a variety of Lewis acids.
16. a) "Iminium Salts in Organic Chemistry", Bohme, H.; Viehe, H. G. Eds.; Wiley, New York, 1979.
17. b) Weinreb, S. M.; Levin, J. I. Heterocycles 1979, 12, 949.
18. c) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367.
19. d) Yamamoto, Y.; Nakada, T.; Nemoto, H. J. Am. Chem. Soc. 1992, 114, 121.
20. 4 or TMSOTf, were not effective and gave only low yield of product(s) along with decomposition of the vinyl ether 1.
21. Fluorine-substituent strongly destabilizes β-carbonium ion. For example: Fried, J.; Hallinan, E. A.; Szwedo, Jr., M. J. J. Am. Chem. Soc. 1984, 106, 3871.
22. 10d
23. 2 (liq.) are discussed on the basis of NMR spectra, a) Olah, G. A.; Kreinbuhl, P. J. Am. Chem. Soc. 1967, 89, 4756.
24. b) Krow, G. R.; Pyun, C.; Leitz, C.; Marakowski, J.; Ramey, K. J. Org. Chem. 1974, 39, 2449. See also ref. 10d.