2346
J . Org. Chem. 1996, 61, 2346-2351
P a lla d iu m -Ca ta lyzed Su zu k i-Typ e Self-Cou p lin g of Ar ylbor on ic
Acid s. A Mech a n istic Stu d y
Marcial Moreno-Man˜as,* Montserrat Pe´rez, and Roser Pleixats
Department of Chemistry, Universitat Auto`noma de Barcelona, Bellaterra, 08193-Barcelona, Spain
Received August 3, 1995X
Symmetrical biaryls are formed from arylboronic acids both under tetrakis(triphenylphosphine)-
palladium and under palladium(II) acetate catalysis. The principal mechanistic features of these
self-couplings have been determined.
In tr od u ction
Palladium-catalyzed cross-coupling between a formal
electrophile C-X (X mainly Br, I, OTf) and an organo-
metallic species C-M (M mainly Mg, Zn, Sn, and B) is a
versatile synthetic method for making C-C bonds.1 The
boron version (Suzuki coupling, Figure 1) has become
increasingly popular since (1) it is compatible with the
presence of electrophilic functional groups, (2) many
boron compounds are stable, (3) several arylboronic acids
are commercially available, (4) the inorganic product of
the reaction can be easily eliminated in water, and (5)
the reaction conditions tolerate aqueous media, which
renders elimination of the boron-containing reaction
products easier.2 The Suzuki coupling was initially used
for C(sp2)-C(sp2) bond forming,2a but recently it was
extended to accommodate carbon atoms in other hybrid-
izations such as sp3.3 A recent improvement of the
Suzuki coupling is the introduction of phosphine-free
catalytic systems.4
F igu r e 1. Palladium(0)-catalyzed Suzuki’s cross-coupling.
Sch em e 1. Ca ta lytic Cycle for th e Su zu k i-Typ e
Cr oss-Cou p lin g
metals such as Mg,5ab Zn,5c and Sn.5d,e The difference is
the inclusion of a step in which a base RO- is introduced
in the coordination sphere of Pd. The reason is that the
presence of a mineral base seems to be fundamental for
the success of the Suzuki-type cross-coupling, which
makes boron-based couplings different from those based
on the other three metals. However, other explanations
have been offered for the fundamental role of the base
in the Suzuki-type cross-coupling; thus, it has been
suggested that the transmetalation step occurs on a
[Ar′B(OH)3]- species rather than on the arylboronic
acid.2d In any case, the presence of mineral base seems
to be essential. Recently it has been reported that
fluoride anion can play the same role.6
From the mechanistic viewpoint Suzuki proposed a
widely accepted catalytic cycle2b that we reproduce in
Scheme 1 for aryl-aryl coupling. The cycle is initiated
by the oxidative addition of the organic halide to the
stabilized Pd(0) species. The transmetalation step trans-
fers the Ar' group from the metal boron to the metal
palladium to generate an intermediate containing Ar, Ar′,
B(OH)2, and RO in the coordination sphere of palladium.
Two reductive eliminations from this intermediate pro-
duce the coupling Ar-Ar′ product and the final boric acid
derivative. In its general trends the cycle is similar to
other cycles proposed for cross-couplings induced by other
The general features of the mechanistic cycle have
received further support since some of the proposed
intermediates have been detected by electrospray ioniza-
tion mass spectrometry.7 However, no RPd(OH)Ln in-
termediate was registered in this study.
In spite of its usefulness, two problems have been
pointed out in some Suzuki-type cross couplings:
1. Marcuccio and co-workers have found that coupling
of arylboronic acid with the phenyl group from the
triphenylphosphine-stabilizing ligand is a side reaction
to the desired coupling of the arylboronic acid with an
X Abstract published in Advance ACS Abstracts, March 1, 1996.
(1) (a) Billington, D. C. Coupling Reactions Between sp3 Carbon
Centers. In Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, Chapter 2.1. (b) Tamao,
K. Coupling Reactions Between sp3 and sp2 Carbon Centers. Ibid. Vol.
3, Chapter 2.2. (c) Knight, D. W. Coupling Reactions Between sp2
Carbon Centers. Ibid. Vol. 3, Chapter 2.3. (d) Sonogashira, K. Coupling
Reactions Between sp2 and sp Carbon Centers. Ibid. Vol. 3, Chapter
2.4.
(2) For fundamental papers and recent reviews see: (a) Miyaura,
N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513. (b) Miyaura,
N.; Yamada, K.; Suginome, H.; Suzuki, A. J . Am. Chem. Soc. 1985,
107, 972. (c) Suzuki, A. Pure Appl. Chem. 1991, 63, 419. (d) Martin,
A. R.; Yang, Y. Acta Chem. Scand. 1993, 47, 221. (e) Suzuki, A. Pure
Appl. Chem. 1994, 66, 213.
(3) See, for instance: (a) Miyaura, N.; Suginome, H.; Suzuki, A.
Tetrahedron Lett. 1984, 25, 761. (b) Ishiyama, T.; Abe, S.; Miyaura,
N.; Suzuki, A. Chem. Lett. 1992, 691. (c) Oh-e, T.; Miyaura, N.; Suzuki,
A. J . Org. Chem. 1993, 58, 2201. (d) Moriya, T.; Furuuchi, T.; Miyaura,
N.; Suzuki, A. Tetrahedron 1994, 50, 7961.
(4) (a) Marck, G.; Villiger, A.; Buchecker, R. Tetrahedron Lett. 1994,
35, 3277. (b) Wallow, T. I.; Novak, B. M. J . Org. Chem. 1994, 59, 5034.
(c) Moreno-Man˜as, M.; Pajuelo, F.; Pleixats, R. J . Org. Chem. 1995,
60, 2396. For a discussion on the benefits of using phosphine-free Pd
catalysts see ref 4b.
(5) (a) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka,
A.; Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem.
Soc. J pn. 1976, 49, 1958. (b) Kumada, M. Pure Appl. Chem. 1980, 52,
669. (c) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okukado,
N. J . Am. Chem. Soc. 1987, 109, 2393. (d) Stille, J . K. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 508. (e) Farina, V.; Krishnan, B. J . Am. Chem.
Soc. 1991, 113, 9585.
(6) Wright, S. W.; Hageman, D. L.; McClure, L. D. J . Org. Chem.
1994, 59, 6095.
(7) Aliprantis, A. O.; Canary, J . W. J . Am. Chem. Soc. 1994, 116,
6985.
0022-3263/96/1961-2346$12.00/0 © 1996 American Chemical Society