K. Sato et al. / Journal of Fluorine Chemistry 125 (2004) 509–515
515
OH
OH
OMOM
I
OMOM
CF2COOEt
F
F
I
MOMO
1, Cu
Me2SO
96%
O
CHO
OMOM
OMOM
24 (11% from 23)
21
22
23
Scheme 10.
F
F
[5] (a) O. Kitagawa, A. Hashimoto, Y. Kobayashi, T. Taguchi, Chem.
Lett. (1990) 1307–1310;
MOMO
Br
Ph3P
+
(b) O. Kitagawa, A. Miura, Y. Kobayashi, T. Taguchi, Chem. Lett.
(1990) 1011–1014;
O
CHO
24
25
F
F
(c) O. Kitagawa, T. Taguchi, Y. Kobayashi, Chem. Lett. (1989) 389–
392;
HO
(d) T. Taguchi, O. Kitagawa, T. Morikawa, T. Nishiwaki, H.
Uehara, H. Endo, Y. Kobayashi, Tetrahedron Lett. 27 (1986) 6103–
6106.
O
20 (39% from 24)
Scheme 11.
[6] R.Q. Brewster, T. Groening, Org. Synthesis Coll. Vol. II (1948)
445–446.
completed the synthesis of 4,4-difluoro-a-tocopherol (20)
(Scheme 11).
[7] K. Sato, R. Kawata, F. Ama, M. Omote, A. Ando, I. Kumadaki,
Chem. Pharm. Bull. 47 (1999) 1013–1016.
[8] M.S. Ashwood, I.F. Cottrell, C.J. Cowden, D.J. Wallace, A.J.
Davies, D.J. Kennedy, U.H. Dolling, Tetrahedron Lett. 50 (2002)
9271–9273.
Our cross-coupling reaction of 1 with an aryl iodide was
successfully applied for the synthesis of 4,4-difluoro-a-
tocopherol (20). This result suggests that this method is
widely applicable for the syntheses of aryldifluoromethylene
compounds.
[9] H. Eto, Y. Kaneko, T. Sakamoto, Chem. Pharm. Bull. 48 (2000)
982–990.
[10] K. Sato, M. Tamura, K. Tamoto, M. Omote, A. Ando, I. Kumadaki,
Chem. Pharm. Bull. 48 (2000) 1023–1025.
[11] (a) T. Itoh, K. Sakabe, K. Kudo, P. Zagatti, M. Renou, Tetrahedron
Lett. 39 (1998) 4071–4074;
3. Concluding remark
(b) T. Itoh, H. Ohara, S. Emoto, Tetrahedron Lett. 36 (1995) 3531–
3534;
(c) T. Morikawa, M. Uejima, Y. Kobayashi, T. Taguchi, J. Fluorine
Chem. 65 (1993) 79–89;
As discussed above, the organocopper complex derived
from ethyl bromodifluoroacetate (1) can be used to introduce
a CF2 group into various molecules. We believe that the
reaction of commercially available 1 in the presence of
copper powder provides useful methods to insert a CF2
functional group.
(d) A. Arnone, P. Bravo, G. Cavicchio, M. Frigerio, F. Viani,
Tetrahedron 48 (1992) 8523–8540;
(e) Z.-Y. Yang, D.J. Burton, J. Chem. Soc. Chem. Commun. (1992)
233–234;
(f) Z.-Y. Yang, D.J. Burton, J. Org. Chem. 56 (1991) 5125–5132.
[12] K. Sato, Y. Ogawa, M. Tamura, M. Harada, T. Ohara, M. Omote,
A. Ando, I. Kumadaki, Coll. Czech. Chem. Commun. 67 (2002)
1285–1295.
References
[13] K. Sato, S. Nakazato, H. Enko, H. Tsujita, K. Fujita, T. Yamamoto,
M. Omote, A. Ando, I. Kumadaki, J. Fluorine Chem. 121 (2003)
105–107.
[1] (a) B.E. Smart, Chem. Rev. 96 (1996) 1555–1823;
(b) G. Resuati, V.A. Soloshnok, Tetrahedron 52 (1996) 1–330;
(c) R. Filler, Y. Kobayashi, L.M. Yagupolskii (Eds.), Organofluorine
Compounds in Medicinal Chemistry and Biomedical Applications,
Elsevier, Amsterdam, 1993;
[14] L.J. Machlin (Ed.), Handbook of Vitamins, Nutritional, Biochemical
and Clinical Aspects, Marcel Dekker, 1984.
[15] (a) T. Yano, S. Yajima, K. Hasegawa, I. Kumadaki, Y. Yano, S.
Otani, M. Uchida, Carcinogenesis 21 (2000) 2129–2133;
(b) M. Koyama, T. Takagi, A. Ando, I. Kumadaki, Chem. Pharm.
Bull. 43 (1995) 1466–1474 (and references therein)
[16] K. Sato, T. Nishimoto, K. Tamoto, M. Omote, A. Ando, I. Kumadaki,
Heterocycles 56 (2002) 403–412.
(d) J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
[2] M.J. Tozer, T.F. Herpin, Tetrahedron 52 (1996) 8619–8683 (a review).
[3] (a) M. Braun, A. Vonderhagen, D. Waldmhller, Liebigs Ann. (1995)
1447–1450;
[17] H.W.J. Cressman, J.R. Thirtle, J. Org. Chem. 31 (1966) 1279–1281.
[18] (a) N. Cohen, R.J. Lopresti, G. Saucy, J. Am. Chem. Soc. 101 (1979)
6710–6716;
(b) E.W. Lang, B. Schaub, Tetrahedron Lett. 29 (1988) 2943–2946;
(c) E.A. Hallinan, J. Fried, Tetrahedron Lett. 25 (1984) 2301–2302.
[4] (a) K. Iseki, Tetrahedron 54 (1998) 13887–13914;
(b) K. Iseki, Y. Kuroki, D. Asada, Y. Kobayashi, Tetrahedron Lett.
38 (1997) 1447–1448;
(b) J.W. Scott, F.T. Bizzarro, D.R. Parrish, G. Saucy, Helv. Chim.
Acta 59 (1976) 290–306;
(c) H. Mayer, P. Schudel, R. Ru¨egg, O. Isler, Helv. Chim. Acta 46
(1963) 650–671.
(c) O. Kitagawa, T. Taguchi, Y. Kobayashi, Tetrahedron Lett. 29
(1988) 1803–1806.