Communications
respectively, using lower catalyst loadings (Table 3, entries 11
Keywords: homogeneous catalysis · hydrolysis · hydroxylation ·
palladium · phenols
.
and 12). Previously, all attempts to hydroxylate aryl halides
possessing a CF3 substituent at elevated temperatures failed
because of the hydrolysis of the CF3 group. Under the present
set of conditions both para- and ortho-aryl halides possessing
CF3 groups were coupled successfully at room temperature in
good yields (Table 3, entries 13–15). In addition, a hetero-
cyclic derivative, such as 4-chloro-2-methylquinoline, is
smoothly transformed into the corresponding phenol in
quantitative yield (Table 3, entry 17). With regard to limita-
tions of the present method, we found that CO2H and OH
groups are not tolerated presumably because of the formation
poorly soluble salts.
[1] a) Patai Series: The Chemistry of Functional Group. The
Chemistry of Phenols (Ed.: Z. Rappoport), Wiley, Chichester,
2003; b) J. H. P. Tyman, Studies in Organic Chemistry 52.
Synthetic and Natural Phenols, Elsevier, Amsterdam, 1996.
[2] For polyphenols in wine, see: G. J. Soleas, E. P. Diamandis, D. M.
[3] For typical methods for the preparation of phenols, see:
reference [1] and D. A. Whiting in Comprehensive Organic
Chemistry. The Synthesis and Reactions of Organic Compounds,
Vol. 1 (Eds.: D. Barton, W. D. Ollis), Pergamon Press, Oxford,
1979, pp. 717 – 730.
The novel protocol was also successfully applied for the
hydroxylation of various non-activated aryl bromides includ-
ing bromobenzene, ortho- and para-substituted halobenzenes,
and 1-halonaphthalenes to give substituted phenols in 70–
93% yields (Table 3, entries 1–9). Bromo- and chloronaph-
thalenes smoothly reacted at room temperature affording
naphthols in 75–87% yields (Table 3, entries 7–9). Bromo-
benzene and 4-bromotoluene were somewhat less reactive
and required a reaction temperature of 508C (Table 3,
entries 5–6). The introduction of one or two methyl groups
in ortho positions of halobenzenes increased the reactivity of
the halides, allowing the reaction again to proceed at room
temperature with excellent yields (Table 3, entries 1–4). For
example, bromomesitylene and 2-bromotoluene furnished
phenols in 93% and 92% yields, respectively. Hydroxylation
of similar chloro derivatives also proceeded under the same
conditions (Table 3, entries 2 and 4). Acceleration of the
reaction by ortho substituents in haloarenes, as well as the
similar reactivity of aryl bromides and aryl chlorides, makes it
likely that reductive elimination is the rate limiting step for
[4] For a highlight of the palladium-catalyzed synthesis of phenols,
[5] S. Mann, C. Incarvito, A. L. Rheingold, J. F. Hartwig, J. Am.
[7] K. W. Anderson, T. Ikawa, R. E. Tundel, S. L. Buchwald, J. Am.
[8] T. Schulz, C. Torborg, B. Schꢀffner, J. Huang, A. Zapf, R.
[9] For overview of palladium-catalyzed arylation of phenols and
alcohols, see: a) J. F. Hartwig in Handbook of Organopalladium
Chemistry for Organic Synthesis, Vol. 1 (Eds.: E.-i. Negishi, A.
de Meijere), Wiley, New York, 2002, pp. 1097 – 1106; b) A. Zapf,
M. Beller, T. Riermeier in Transition Metals for Organic
synthesis. Building Blocks and Fine Chemicals, Vol. 1 (Eds.: M.
Beller, C. Bolm), Wiley, Weinheim, 2004, pp. 231 – 256.
[10] For room temperature arylation of alcohols using Pd/Q-Phos,
see: a) Q. Shelby, N. Kataoka, G. Mann, J. Hartwig, J. Am. Chem.
[11] Hydroxylation of activated aryl halides such as ortho-halonitro-
benzenes was carried out in the presence of Pd/PtBu3 at 25–508C
(see reference [6]).
[12] In addition to the main product some minor side-products were
formed (5–10%), which could not be removed by recrystalliza-
tion. Reaction with [Pd(TMEDA)(Me)2] gave a mixture of
[Pd(L3)(2,4,6-Me3C6H2)(Br)] (1) and [Pd(TMEDA)(2,4,6-
Me3C6H2)(Br)] in the 2.57:1 ratio.
[14] B. P. Fors, D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am.
À
this hydroxylation reaction. Indeed, it is known that carbon
heteroatom bond-forming reductive elimination from aryl-
palladium complexes is accelerated by ortho substituents in
aryl halides.[27] However, we found that the further increase in
the steric bulk of the ortho substituents, for example, from
methyl to iso-propyl decelerates the reaction. Hence, room
temperature hydroxylation of 2-bromo-iso-propylbenzene
proceeded only to 10% conversion, whereas the reaction of
2,4,6-triiso-propylbromobenzene did not occur at all and led
to decomposition of the catalyst.
This effect of the different ortho substituents on the rate
of the hydroxylation may imply a change of the rate-
determining step.
[15] CCDC 728525 (1) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
In summary, we demonstrated for the first time that all
steps of the catalytic cycle of the palladium-catalyzed
hydroxylation of aryl chlorides and bromides can proceed at
room temperature. Based on these findings, the catalytic
synthesis of phenols occurs under unprecedented mild con-
ditions. The key to the success is the combination of the novel
palladium precursor [Pd(cod)(CH2SiMe3)2] and the imida-
zole-based ligand L3, which should be useful for numerous
other catalytic coupling reactions as well.
[16] Four-membered P,N-chelates were also observed in palladium
and platinum complexes of 2-(dialkylphosphino)-1-methyl-1H-
imidazoles: a) D. B. Grotjahn, Y. Gong, L. N. Zakharov, J. A.
b) D. B. Grotjahn, Y. Gong, A. G. DiPasquale, L. N. Zakharov,
[17] Complex 1 exhibits no dynamic behavior in the temperature
range of 25–(À80)8C as evidenced by the 1H and 31P{1H } NMR
spectra in [D8]THF (see the Supporting Information).
[18] In contrast to 1, oxidative addition palladium complexes bearing
related biphenyl ligands show equilibrium between two forms,
where one of them exhibits interaction of palladium atom and
second arene ring of the biphenyl ligand, see reference [14] and
Received: April 21, 2009
Revised: August 7, 2009
Published online: September 8, 2009
7598
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 7595 –7599