SPECIAL TOPIC
Ortho-Selective Cross-Coupling of Fluorobenzenes with Grignard Reagents
2649
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H NMR (400 MHz, CDCl ): d = 2.02 (br s, 1 H), 4.53 (s, 2 H), 7.08
Quéguiner, G. J. Org. Chem. 2002, 67, 8991.
3
(
5
t, J = 8.4 Hz, 2 H), 7.24 (dd, J = 7.2, 1.6 Hz, 1 H), 7.31 (dd, J = 8.4,
(d) Dankwardt, J. W. J. Organomet. Chem. 2005, 690, 932.
(e) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem.
Soc. 2005, 127, 17978. (f) Ackermann, L.; Born, R.; Spatz,
J. H.; Meyer, D. Angew. Chem. Int. Ed. 2005, 44, 7216.
(g) Guan, B.-T.; Xiang, S.-K.; Wu, T.; Sun, Z.-P.; Wang,
B.-Q.; Zhao, K.-Q.; Shi, Z.-J. Chem. Commun. 2008, 1437.
(6) (a) Widdowson, D. A.; Wilhelm, R. Chem. Commun. 1999,
.6 Hz, 2 H), 7.33–7.38 (m, 2 H), 7.50 (dd, J = 6.8, 2.0 Hz, 1 H).
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¢,5-Difluorobiphenyl-2-ol (21)18
White solid; purified by preparative TLC (silica gel, Et O–hexane,
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1
1
:4); mp 67.2–68.3 °C.
H NMR (400 MHz, CDCl ): d = 4.98 (s, 1 H), 6.85–6.95 (m, 2 H),
3
2211. (b) Baleizão, C.; Corma, A.; García, H.; Leyva, A.
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4
.92 (d, J = 8.4 Hz, 1 H), 7.16 (t, J = 8.6 Hz, 2 H), 7.42 (dd, J = 8.6,
J. Org. Chem. 2004, 69, 439. (c) Schaub, T.; Backes, M.;
Radius, U. J. Am. Chem. Soc. 2006, 128, 15964.
.8 Hz, 2 H).
(
7) (a) Ishii, Y.; Chatani, N.; Yorimitsu, S.; Murai, S. Chem.
Lett. 1998, 157. (b) Cahiez, G.; Lepifre, F.; Ramiandrasoa,
P. Synthesis 1999, 2138. (c) Kim, Y. M.; Yu, S. J. Am.
Chem. Soc. 2003, 125, 1696. (d) Widdowson, D. A.;
Wilhelm, R. Chem. Commun. 2003, 578. (e) Mikami, K.;
Miyamoto, T.; Hatano, M. Chem. Commun. 2004, 2082.
Acknowledgment
This work was partly supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘Advanced Molecular Transformation
of Carbon Resources’ from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
(
f) Bahmanyar, S.; Borer, B. C.; Kim, Y. M.; Kurtz, D. M.;
Yu, S. Org. Lett. 2005, 7, 1011. (g) Saeki, T.; Takashima,
Y.; Tamao, K. Synlett 2005, 1771. (h) Wang, T.; Alfonso,
B. J.; Love, J. A. Org. Lett. 2007, 9, 5629. Site-selective
cross-coupling of polyfluoropyridines: (i) Braun, T.; Perutz,
R. N.; Sladek, M. I. Chem. Commun. 2001, 2254.
References
(
1) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.;
de Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
(
8) Preferential reactions of an alkyl fluoride over an alkyl
chloride were observed in nickel- or copper-catalyzed cross-
coupling with Grignard reagents: (a) Terao, J.; Ikumi, A.;
Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125,
2004.
(
2) Examples of site-selective cross-coupling of dibromo- and
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Chanteau, S.; Kosynkin, D. V.; Tour, J. M. Tetrahedron
5646. (b) For transition-metal-catalyzed cross-coupling at a
fluoro group in the presence of a bromo group, see ref. 7h.
2
001, 57, 5109. (c) Ackermann, L.; Althammer, A. Angew.
(
9) Ishikawa, S.; Manabe, K. Chem. Lett. 2007, 36, 1302.
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(
(
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(
(
3) Examples of site-selective cross-coupling of
polyhalogenated heteroarenes have been reviewed:
(
2
a) Schröter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61,
245. (b) Fairlamb, I. J. S. Chem. Soc. Rev. 2007, 36, 1036.
(
13) Saeki and Tamao et al. assumed a chelating effect of
o-difluorobenzene in their cross-coupling with a Grignard
See also: (c) Legault, C. Y.; Garcia, Y.; Merlic, C. A.; Houk,
K. N. J. Am. Chem. Soc. 2007, 129, 12664.
4) (a) Ishikawa, S.; Manabe, K. Chem. Lett. 2007, 36, 1304.
7
g
reagent. The ortho selectivity in our system may be
attributable to a similar chelating effect.
(
(
(
(
14) Haga, N.; Takayanagi, H. J. Org. Chem. 1996, 61, 735.
15) Shimizu, H.; Manabe, K. Tetrahedron Lett. 2006, 47, 5927.
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Firooznia, F.; Hu, Q.-Y. WO 2007024945, 2007; Chem.
Abstr. 2007, 146, 295923.
(
b) Ishikawa, S.; Manabe, K. Org. Lett. 2007, 9, 5593.
(
5) Examples of cross-coupling of fluorobenzenes with
Grignard reagents: (a) Tamao, K.; Sumitani, K.; Kiso, Y.;
Zembayashi, M.; Fujioka, A.; Kodama, S.-i.; Nakajima, I.;
Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49,
(
(
1
958. (b) Böhm, V. P. W.; Gstöttmayr, C. W. K.; Weskamp,
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(
Synthesis 2008, No. 16, 2645–2649 © Thieme Stuttgart · New York