Efficient cross-coupling of aryl chlorides with aryl grignard reagents (Kumada reaction) mediated by a palladium/imidazolium chloride system [10]

Full text of DOI:10.1021/ja991703n

J. Am. Chem. Soc. 1999, 121, 9889-9890
9889
Table 1. Cross-Coupling of Chlorotoluene with Phenylmagnesium
Bromide under Various Conditions
Efficient Cross-Coupling of Aryl Chlorides with Aryl
Grignard Reagents (Kumada Reaction) Mediated by
a Palladium/Imidazolium Chloride System
Jinkun Huang and Steven P. Nolan*
Department of Chemistry, UniVersity of New Orleans
New Orleans, Louisiana 70148
ReceiVed May 24, 1999
entry
L
solvent
temp (°C) time (h) yielda (%)
Palladium-catalyzed cross-coupling reactions of aryl halides
or halide equivalents with organometallic reagents have been
demonstrated to be a highly effective and practical method for
the formation of C-C bonds.1 The use of aryl chlorides as
chemical feedstock in coupling chemistry has proven difficult but
would economically benefit a number of industrial processes.2,3
In 1972, Kumada and Tamao4 and Corriu5 reported independently
that the reaction of Grignard reagents with alkenyl or aryl halides
(Kumada reaction) could be catalyzed by Ni(II) complexes. The
Pd-catalyzed Kumada reaction was first reported by Murahashi6
in 1975. To the best of our knowledge, no successful coupling
has ever been reported involving unactivated aryl chlorides and
an aryl Grignard reagent.7 Several reports have recently appeared
dealing with phosphine-modified palladium- or nickel-mediated
coupling reactions which employ inexpensive aryl chlorides as
substrates.8
1
2
3
4
5
6
7
IMes Et2O/THF
45
45
80
80
80
80
80
20
20
20
5
3
3
35
97
10
86
0
41
99
IPr
IPr
IPr
Et2O/THF
toluene/THF
THF
none dioxane/THF
IMes dioxane/THF
IPr
dioxane/THF
3
a Isolated yields are the average of two runs.
the catalyst to yield the bulk metal.10 The use of these ligands in
palladium-catalyzed Heck reactions,11 rhodium carbene complexes
in hydrosilylation12 and ruthenium carbene catalysts in olefin
metathesis,13,14a has opened new opportunities in catalysis.
Recently, we examined the solution calorimetry of transition
metal centered ligand substitution involving nucleophilic N-
heterocyclic carbenes.14 This class of ligands exhibits a consider-
able stabilizing effect in organometallic systems.10,15 An under-
standing of ligand stereoelectronic effects provided by the
thermochemical investigations led to the use of this ligand class
in a ring-opening/closing metathesis system.14a This ligand class
has recently been employed by Herrmann and co-workers in
Suzuki cross-coupling involving aryl bromides and activated aryl
chlorides.16 We recently reported the Suzuki cross-coupling
reactions of aryl chlorides and arylboronic acids employing Pd2-
(dba)3 or Pd(OAc)2/imidazolium salts as the catalyst system.17
Considering that aryl boronic acids and other organometallic
reagents used in this type of C-C coupling are generally made
from the corresponding Grignard or lithium reagents,18 it would
prove valuable to find a general method for Kumuda coupling.
Herein, we wish to report the first successful example of Kumada
coupling using a variety of aryl chlorides as substrates.
Nucleophilic N-heterocyclic carbenes, or so-called “phosphine-
mimics”, have attracted considerable attention as possible alterna-
tives for the widely used phosphine ligands in homogeneous
catalysis.9,10 The primary advantage of these ligands appears to
be that they do not dissociate from the metal center, as a result
an excess of the ligand is not required to prevent aggregation of
* Corresponding author. FAX: (504)-280-6860. E-mail: snolan@uno.edu.
(1) (a) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G., Abel, E. W., Eds.; Pergamon: Oxford,
1982; Vol. 8, pp 799-938. (b) Heck, R. F. Palladium Reagents in Organic
Syntheses; Academic Press: New York, 1985. (c) Tsuji, J. Palladium Reagents
and Catalysts; Wiley: Chichester, 1995. (d) Tsuji, J. Synthesis 1990, 739-
749.
(2) Cornils, B.; Herrmann, W. A., Eds. Applied Homogeneous Catalysis
with Organometallic Compounds; VCH: Weinheim, 1996.
(3) (a) Chem. Eng. News 1998, June 1, . 24. (b) Chem. Eng. News 1998,
July 13, 71.
(4) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94,
4374-4376.
(5) Corriu, R. J. P.; Masse, J. P. Chem. Soc., Chem. Commun. 1972, 144.
(6) Yamamura, M.; Moritani, I.; Murahashi, S. J. Organomet. Chem. 1975,
91, C39-C42.
(7) More examples for Kumada reaction: (a) Tamao, K.; Kiso, Y.; Sumitani,
K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 9268-9269. (b) Sekiya, A.;
Ishikawa, N. J. Organomet. Chem. 1976, 118, 349-354. (c) Tamao, K.;
Sumitani, K.; Kisa, Y.; Zambayashi, M.; Fujioka, A.; Kodama, A.; Nakajima,
I.; Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49, 1958-1969. (d)
Widdowson D. A.; Zhang, Y.-Z. Tetrahedron 1986, 42, 2111-2116. (e)
Minato, A.; Tamao, K.; Hayashi, T.; Suzuki, K.; Kumada, M. Tetrahedron
Lett. 1981, 22, 5319-5322. (f) Hayashi, T.; Konishi, M.; Fukushima, M.;
Mise, T.; Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc. 1982,
104, 180-186. (g) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.;
Higuchi, T.; Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158-163. (h) Sofia,
A.; Karlstrom, E.; Itami, K.; Backvall, J.-E. J. Org. Chem. 1999, 64, 1745-
1749 (i) Busacca, C. A.; Eriksson, M. C.; Fiaschi, R. Tetrahedron Lett. 1999,
40, 3101-3104. (j) Miller, J. A.; Farrell, R. P. Tetrahedron Lett. 1998, 39,
7275-7278. (k) For a review, see: Kumada, M. Pure Appl. Chem. 1980, 52,
669-679.
(8) For more examples dealing with coupling of aryl chlorides: (a) Old,
D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722-
9723. (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. Engl. 1998, 37,
3387-3388. (c) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120,
7369-7370. (d) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 481-483. (e) Littke, A. F.; Fu, G. C. J. Org. Chem.
1999, 64, 10-11. (f) Bei, X.; Guram, A. S.; Turner, H. W.; Weinburg, W. H.
Tetrahedron Lett. 1999, 40, 1237-1241. (g) Bei, X.; Guram, A. S.; Turner,
H. W.; Weinburg, W. H. Tetrahedron Lett. 1999, 40, 3855-3858. (h) Indolese,
A. F. Tetrahedron Lett. 1997, 38, 3513-3516. (i) Saito, S.; Oh-tani, S.;
Miyaura, N. J. Org. Chem. 1997, 62, 8024-8030. (j) Saito, S.; Sakai, M.;
Miyaura, N. Tetrahedron Lett. 1996, 37, 2993-2996.
(9) Applications of phosphine ligands in homogeneous catalysis: (a)
Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and
Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, CA, 1987. (b) Parshall, G. W.; Ittel, S. Homogeneous
Catalysis; J. Wiley and Sons: New York. 1992. (c) Pignolet, L. H., Ed.
Homogeneous Catalysis with Metal Phosphine Complexes; Plenum: New
York, 1983.
(10) (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725-728. (b)
Arduengo, A. J., III; Krafczyk, R. Chem. Ztg. 1998, 32, 6-14. (c) Herrmann,
W. A.; Ko¨cher, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2163-2187.
(11) (a) Herrmann, W. A.; Elison, M.; Fisher, J.; Ko¨cher, C.; Autus, G. R.
J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2371-2373. (b) Herrmann, W. A.;
Fischer, J.; Elison, M.; Ko¨cher, C.; Autus, G. R. J. Chem. Eur. J. 1996, 2,
772-780. (c) McGuinness, D. S.; Green, M. J.; Cavell, K. J.; Skelton, B. W.;
White, A. H. J. Organomet. Chem. 1998, 565, 165-178.
(12) Herrmann, W. A.; Goossen, L. T.; Ko¨cher, C.; Autus, G. R. J. Angew.
Chem., Int. Ed. Engl. 1996, 35, 2805-2807.
(13) (a) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann, W.
A. Angew. Chem., Int. Ed. Engl. 1998, 37, 2490-2493. (b) Scholl, M.; Trnka,
T. M.; Morgan, J. P.; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247-2250.
(14) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am. Chem.
Soc. 1999, 121, 2674-2678. (b) Huang, J.; Schanz, H.-J.; Stevens, E. D.;
Nolan, S. P. Organometallics 1999, 18, 2370-2375.
(15) Voges, M. H.; Rømming, C.; Tilset, M. Organometallics 1999, 18,
529-533.
(16) Herrmann, W. A.; Reisinger, C.-P.; Spiegler, M. J. Organomet. Chem.
1998, 557, 93-96.
(17) (a) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem.
1999, in press. (b) Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P.
Manuscript submitted for publication.
(18) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
10.1021/ja991703n CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/08/1999

9890 J. Am. Chem. Soc., Vol. 121, No. 42, 1999
Communications to the Editor
Scheme 1
Table 2. Palladium/Imidazolium Salt-Catalyzed Cross-Coupling
Based on our recent success with IMesHCl14,19 (IMes ) bis-
(1,3-(2,4,6-trimethylphenyl))imidazol-2-ylidene) in Suzuki cou-
pling of aryl chlorides with arylboronic acids,17 we employed a
similar protocol for Kumada coupling. In our initial experiment,
Pd2(dba)3/IMesHCl (2) was used as the catalyst precursor. In
Suzuki coupling, the carbene ligand IMes (1) can be generated
in situ by use of a strong base, Cs2CO3. The presence of
phenylmagnesium bromide (1.0 M solution in THF) in Kumada
coupling allows for use of a slight excess of the Grignard reagent
to form 1 from 2. When 4-chlorotoluene is reacted with
phenylmagnesium bromide using this catalytic system in Et2O at
45 °C for 20 h, the product 4-phenyltoluene is isolated in 35%
yield (Table 1, entry 1).
Since the use of bulky ligands may improve catalytic perfor-
mance in this C-C coupling procedure,7c,g,8b,c,e,17 a new carbene
salt, IPrHCl (3, IPr ) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidene), recently explored in our lab,20 was employed in this
reaction. When the same reaction is carried out with 3, the
coupling product 4-phenyltoluene is isolated in 99% yield (Table
1, entry 2). This result is consistent with Arduengo’s21 and our
studies14,20 which explain the ligand steric and electronic properties
of this family of ligands. The ligands are excellent donors and
therefore facilitate the oxidative addition of aryl halides and the
sterics at the ortho position of the imidazolyl aryl groups cause
a destabilization of the groups ready to reductively eliminate.
Further study showed that using dioxane as the cosolvent and
heating the reaction mixture at 80 °C gave excellent yield of
product in 3 h (Table 1, entry 7), while the reaction in toluene/
THF and THF required longer reaction time and led to lower
yields (Table 1, entries 3 and 4).
A survey of catalytic cross-coupling of arylhalides with
arylmagnesium bromides using IPrHCl (3) is provided in Table
2. Reactions were faster for aryl bromides and iodides (Table 2,
entries 3, 8, and 10) than that of aryl chlorides. As in similar
coupling reactions, the significant challenge in the practical
Kumada reaction is the tolerance of a variety of functional
groups.22,7j Those halides bearing methoxy (Table 2, entries 4 and
10-14) or even hydroxy23 (Table 2, entries 8 and 9) groups react
with Grignard reagents to form biaryls in excellent yields. When
methyl 4-bromobenzoate was used, methyl 4-phenylbenzoate was
isolated in 69% yield (Table 2, entry 7), although more compli-
cated byproducts are formed when the less reactive chloro
analogue was used. Although sterically hindered substrates are
often problematic,8h,i,17 the ortho-substituted 2-fluoro- or 2,4,6-
trimethyl phenylmagnesium bromides coupled with 4-chloroani-
sole without any difficulty. When ortho substituents were present
in aryl chlorides, good yields were obtained by using a slight
excess of Grignard reagent (1.8 instead of 1.2 equiv). However,
the coupling of 2-chloro-m-xylene or 2-bromomesitylene with
mesitylmagnesium bromide failed because of steric congestion
around both reactive centers. Homocoupling products of Grignard
Aryl Halides with Aryl Grignard Reagentsa
entry
Ar-X
Ar′
time (h) yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
4-MeC6H4-Cl
4-MeC6H4-Cl
4-MeC6H4-Br
4-MeOC6H4-Cl
2, 5-(Me)2C6H3-Cl
2, 6-(Me)2C6H3-Cl
4-MeO2CC6H4-Br
4-HOC6H4-I
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-MeC6H4
3-MeC6H4
2-FC6H4
2,4,6-(Me)3C6H2
2,4,6-(Me)3C6H2
3
3
1
3
3
5
5
3
5
1
3
3
3
3
24
24
99
96c
99
97
85
87d
69
96e
95e
98
99
83
99
95
0
4-HOC6H4-Cl
6-MeO-Np-2-Br
4-MeOC6H4-Cl
4-MeOC6H4-Cl
4-MeOC6H4-Cl
4-MeOC6H4-Cl
2,6-(Me)2C6H3-Cl
2,4,6-(Me)3C6H2-Br 2,4,6-(Me)3C6H2
0
a The reactions were carried out according to the conditions indicated
by the above equation; 1.2 equiv of PhMgBr (1.0 M solution in THF)
used unless otherwise stated. b Isolated yields (average of two runs)
after flash chromatography. c 2.0 mol % of Pd(OAc)2 used instead of
1.0 mol % of Pd2(dba)3. d 1.8 equiv of phenylmagnesium bromide was
used. e 2.5 equiv of phenylmagnesium bromide was used.
reagent were observed in all other reactions as minor products
with the exception of mesitylmagnesium bromide where no
homocoupling is observed.
While the mechanism remains to be elucidated, it seems
apparent at least that diarylpalladium intermediates are involved
in this reaction.7i At some point the steric bulk of the ligand
becomes more important than its electron donor contribution, as
IPr is a poorer donor24 than IMes but results in more effective
couplings.
In conclusion, we present a general methodology for the
Kumada reaction. The methodology proves effective for unacti-
vated aryl chlorides, aryl bromides, and aryl iodides by simply
employing Pd(0) or Pd(II) and an imidazolium chloride as the
catalytic precursor. Development of improved protocols for this25
and related C-C bond coupling reactions is ongoing.
Acknowledgment. The National Science Foundation is gratefully
acknowledged for partial support of this research.
Supporting Information Available: Experimental procedures (PDF).
This material is available free of charge via the Internet at http://pubs.acs.org.
JA991703N
(19) Arduengo, A. J., III; Dias, H. V. R.; Harlow, R. L.; Kline, M. J. Am.
Chem. Soc. 1992, 114, 5530-5534.
(24) This donor trend has been quantified by solution calorimetry in the
Cp*RuCl(L) system, where enthalpies of reaction of both IMes (∆H ) -15.6
kcal/mol) and IPr (∆H ) -11.1 kcal/mol) are compared: Jafarpour, L.;
Stevens, E. D.; Nolan, S. P. Manuscript in preparation.
(25) While this manuscript was being reviewed, we determined that 1 equiv
of the IPr‚HCl salt could be used leading to similar isolated yields in
approximately half the time. A full report of this improvement is forthcoming.
(20) Detailed preparation of 3 is described in the Supporting Information.
(21) Arduengo, A. J., III; Dias, H. V. R.; Calabrese, J. C.; Davidson, F. J.
J. Am. Chem. Soc. 1992, 116, 4391-4393.
(22) Stanforth, S. P. Tetrahedron 1998, 54, 263-303.
(23) Jendralla, H.; Chen, L.-J. Synthesis 1990, 827-833.