C O M M U N I C A T I O N S
Table 2. Iron-Catalyzed Selective Biaryl Coupling Reactions
roquinoline reacted with mesitylmagnesium bromide at 100 °C to
give the desired product in 82% yield (entry 17). The reaction of
2-thienylmagnesium bromide with 2-chloropyridine did not take
place, but with 2-bromopyridine it smoothly gave 4-thiophen-2-yl
pyridine in 74% yield (entry 18).
Mechanistically, we assume that the fluoride anion coordinating
to the iron center would suppress the formation of a ferrate
complex11 possessing excess aryl groups (such as Ar1Ar2 Fe and
2
Ar1Ar2 Fe) and the consequent nonselective reductive elimination
3
(formation of Ar1-Ar2 and Ar2-Ar2). The fluoride effect is also
observed in cobalt- and nickel-catalyzed cross-coupling reactions
to suppress the homocouplings.12
In summary, we have demonstrated an iron-catalyzed selective
cross-coupling reaction of aryl chlorides with aryl Grignard reagents.
The addition of NHC ligand and fluoride counteranion proved crit-
ical to achieving high yield and selectivity. This method has sev-
eral synthetically attractive features: operational simplicity, rare-metal
free, phosphine free, and minimal byproducts. “Fluoride-tuned”
metal-catalyzed cross-coupling reactions are now being actively
investigated in our laboratory and will be reported in due course.
Acknowledgment. We thank the Ministry of Education, Culture,
Sports, Science, and Technology of Japan for financial support,
and a Grant-in-Aid for Scientific Research on Priority Areas
“Synergistic Effects for Creation of Functional Molecules” (M.N.,
Grant 18064006). Financial support from the Uehara Memorial
Foundation is also acknowledged.
Supporting Information Available: Details of the experimental
procedure, characterization, and physical data of the products. This
References
(1) (a) Corbet, J. P.; Mignani, G. Chem. ReV. 2006, 106, 2651. (b) Holder,
E.; Langeveld, B. M. W.; Schubert, U. S. AdV. Mater. 2005, 17. (c)
Baudoin, O.; Gueritte, F. Stud. Nat. Prod. Chem., Part J 2003, 29 (355),
1109. (d) Ivica, C., Ed. Synthesis of Biaryls; Elsevier Ltd: Oxford, 2004.
(2) (a) de Meijere, A., Diederich, F., Eds. Metal-Catalyzed Cross-coupling
Reactions, 2nd ed.; Wiley-VCH: New York, 2004. (b) Miyaura, N., Ed.
Cross-Coupling Reactions: A Practical Guide; Springer: Berlin, 2002.
(3) Reviews: (a) Fu¨rstner, A.; Rube´n, M. Chem. Lett. 2005, 34, 624. (b) Bolm,
C.; Legros, J.; Le Paih, J.; Zani, L. Chem. ReV. 2004, 104, 6217. (c)
Shinokobu, H.; Oshima, K. Eur. J. Org. Chem. 2004, 2081.
(4) Selected recent papers: (a) Fu¨rstner, A.; Leitner, A.; Me´ndez, M.; Krause,
H. J. Am. Chem. Soc. 2002, 124, 13856. (b) Quintin, J.; Franck, X.;
Hocquemiller, R.; Figade´re, B. Tetrahedron Lett. 2002, 43, 3547. (c)
Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc. 2004,
126, 3686. (d) Nagano, T.; Hayashi, T. Org. Lett. 2004, 6, 1297. (e) Martin,
R.; Fu¨rstner, A. Angew. Chem., Int. Ed. 2004, 43, 3955. (f) Bedford, R.
B.; Bruce, D. W.; Frost, R. M.; Goodby, J. W.; Hird, M. Chem. Commun.
2004, 2822. (g) Nakamura, M.; Ito, S.; Matsuo, K.; Nakamura, E. Synlett
2005, 11, 1794. (h) Sapountzis, I.; Lin, W.; Kofink, C. C.; Despotopoulou,
C.; Knochel, P. Angew. Chem., Int. Ed. 2005, 44, 1654. (i) Itami, K.;
Higashi, S.; Mineno, M.; Yoshida, J.-i. Org. Lett. 2005, 7, 1219.
(5) Heteroaromatic compounds undergo cross-coupling: see ref 4a,b.
(6) Favorable effects of NHC ligands in iron-catalyzed cross-couplings of
haloalkanes were reported. (a) Bica, K.; Gaertner, P. Org. Lett. 2006, 8,
733. (b) Bedford, R. B.; Betham, M.; Bruce, D. W.; Danopoulos, A. A.;
Frost, R. M.; Hird, M. J. Org. Chem. 2006, 71, 1104.
a Reactions were carried out on a 1.0 or 30.0 mmol scale following the
procedure in eq 1 unless otherwise noted. b Isolated yield. c GC yield.
d Treatment of anhydrous FeF3 (3 mol %) and SIPr‚HCl (9 mol %) with
EtMgBr (9 mol %) also gave the active catalyst. e 5 mol % of iron catalyst
was used. f Reaction was carried out in toluene. g 4 mol % of iron catalyst
was used. h 6 mol % of iron catalyst was used.
in 92% yield (entry 6). Fluorine-substituted biaryls, the representa-
tive mesogen structure of liquid crystal molecules, can be synthe-
sized with 4-fluoro-1-chlorobenzene and 3,4-difluoro-1-chloroben-
zene in good yields (entries 7 and 8). While the reactions of o-tolyl-
and mesitylmagnesium bromide were rather slow because of their
steric hindrance, an elevated reaction temperature (80 and 120 °C)
gave the corresponding products in 90 and 93% yields, respectively
(entries 9 and 10). Electron-deficient 4-fluorophenylmagnesium
bromide gave the desired product in 87% yield (entry 11). 1- and
2-naphthylmagnesium bromide took part in the reaction (92 and
96% yields, entries 12 and 13). The dimethylamino and methylthio
groups did not interfere in the cross-coupling (entries 14 and 15).
Note that a small amount of 4,4′′-dimethyl-[1,1′;4′,1′′]terphenyl
(4%) formed via cleavage of the C-S bond, which is often a
problem in the nickel-catalyzed coupling reactions.10 An acetal
remained intact under the conditions used here (entry 16). 2-Chlo-
(7) Other NHC or phosphine ligands are not effective. See Supporting
Information for details.
(8) Fe(acac)3 also gave the homocoupling product 4 as a major product.
(9) In situ generation of NHC ligand, see: Herrmann, W. A. Angew. Chem.,
Int. Ed. 2002, 41, 1290 and references cited therein.
(10) Tiecco, M.; Testaferri, L.; Tingoli, M. Tetrahedron Lett. 1982, 23, 4629.
(11) [Ar4FeIII][Li(THF)3]: (a) Alonso, P. J.; Arauzo, A. B.; Fornie´s, J.; Garcia-
Monforte, M. A.; Martin, A.; Martinez, J. I.; Menjo´n, B.; Rillo, C.; Sa´iz-
Garitaonandia, J. J. Angew. Chem., Int. Ed. 2006, 44, 6707. [Me4FeII]
[Li(OEt2)]2: (b) Fu¨rstner, A.; Krause, H.; Lehmann, C. Angew. Chem.,
Int. Ed. 2006, 45, 440. Fe-F complex: (c) Vela, J.; Smith, J. M.; Yu,
Y.; Ketterer, N. A.; Flaschenriem, C. J.; Lachicotte, R. J.; Holland, P. L.
J. Am. Chem. Soc. 2005, 127, 7857.
(12) The reactions with CoF2‚4H2O and NiF2‚4H2O were carried out according
to the procedure in Table 1: the cobalt and nickel catalysts gave cross-
coupling product 2 in 91 and 93% yields, respectively. Some other catalyst
precursors (Co(acac)3, Ni(acac)2, etc.) produced significant amounts of
homocoupling products 3 and 4 (6-30% yields) and reduced the cross-
coupling product yield.
JA073084L
9
J. AM. CHEM. SOC. VOL. 129, NO. 32, 2007 9845