General and efficient catalytic amination of aryl chlorides using a palladium/bulky nucleophilic carbene system

Article abstract of DOI:10.1021/ol990987d

(matrix prensented) A combination of palladium and an imidazolium chloride has been used as catalyst precursor in the amination of aryl chlorides. The imidazolium salt IPrHCI (4, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) was found to provide the most efficient transformation rates in this catalytic system. This new system proves general and efficient for aryl chlorides as well as aryl bromides and iodides.

Full text of DOI:10.1021/ol990987d

ORGANIC
LETTERS
1
999
Vol. 1, No. 8
307-1309
General and Efficient Catalytic
Amination of Aryl Chlorides Using a
Palladium/Bulky Nucleophilic Carbene
System
1
Jinkun Huang, Gabriella Grasa, and Steven P. Nolan*
Department of Chemistry, UniVersity of New Orleans, New Orleans, Louisiana 70148
snolan@uno.edu
Received August 27, 1999
ABSTRACT
A combination of palladium and an imidazolium chloride has been used as catalyst precursor in the amination of aryl chlorides. The imidazolium
salt IPrHCl (4, IPr ) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) was found to provide the most efficient transformation rates in this
catalytic system. This new system proves general and efficient for aryl chlorides as well as aryl bromides and iodides.
Palladium-catalyzed cross-coupling reactions of aryl halides
or halide equivalents with various nucleophiles have been
shown to be highly effective and practical methods for the
in homogeneous catalysis.7,8 The primary advantage of these
ligands appears to be that they do not easily dissociate from
the metal center, and as a result an excess of the ligand is
not required in order to prevent aggregation of the catalyst
1
formation of C-C bonds. In a closely related area, pal-
9
ladium- or nickel-mediated coupling of aryl halides with
amines has attracted significant interest because of the use
of this methodology in organic synthesis and material
usually affording the bulk metal. The use of some of these
ligands in palladium-catalyzed Heck and Suzuki reac-
10,11
12
tions,
rhodium-assisted hydrosilylation, and ruthenium-
2
science. The pioneering studies of Hartwig and Bulchwald
(3) For representative examples dealing with the amination of aryl
on catalytic amination have shown that the supporting ligands
on the metal center play a crucial role in dictating the
chlorides, see: (a) Wolfe, J. P.; Buckwald, S. L. Angew. Chem., Int. Ed.
Engl. 1999, 38, 2413-2416. (b) Bei, X.; Uno, T.; Norris, J.; Turner, H.
W.; Weinburg, W. H.; Guram, A. S.; Petersen, J. L. Organometallics 1999,
2
efficiency of the catalytic system. To this end, bulky
18, 1840-1853. (c) Bei, X.; Guram, A. S.; Turner, H. W.; Weinburg, W.
monodentate phosphine or bidentate PX (X ) P, N, O)
H. Tetrahedron Lett. 1999, 40, 1237-1240. (d) Old, D. W.; Wolfe, J. P.;
Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722-9723. (e) Hamann,
B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369-7370. (f) Brenner,
E.; Fort, Y. Tetrahedron Lett. 1998, 39, 5359-5362. (g) Yamamoto, T.;
Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367-2370. (h) Wolfe,
J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054-6058. (i)
Riermeier, T. H.; Zapf, A.; Beller, M. Top. Catal. 1997, 4, 301-309. (j)
Reddy, N. P.; Tanaka, M. Tetrahedron Lett. 1997, 38, 4807-4810.
3,4
ligands are usually employed. Most recent examples deal
with Suzuki3 and Stille coupling reactions.
a
4a
5
Nucleophilic N-heterocyclic carbenes, or so-called “phos-
phine mimics”, have attracted considerable attention as
6
possible alternatives for the widely used phosphine ligands
(4) For more examples dealing with couplings involving aryl chlorides,
(
1) (a) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe Organometallic
see: (a) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. Engl. 1999, 38,
2411-2413. (b) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. Engl. 1998,
37, 3387-3388. (c) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew.
Chem. Int. Ed. Engl. 1998, 37, 481-483. (d) Littke, A. F.; Fu, G. C. J.
Org. Chem. 1999, 64, 10-11. (e) Bei, X.; Guram, A. S.; Turner, H. W.;
Weinburg, W. H. Tetrahedron Lett. 1999, 40, 3855-3858. (f) Indolese, A.
F. Tetrahedron Lett 1997, 38, 3513-3516. (g) Saito, S.; Oh-tani, S.;
Miyaura, N. J. Org. Chem. 1997, 62, 8024-8030. (h) Saito, S.; Sakai, M.;
Miyaura, N. Tetrahedron Lett. 1996, 37, 2993-2996.
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) For important recent review of palladium- and nickel-mediated aryl
aminations, see: (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald,
S. L. Acc. Chem. Res. 1998, 31, 805-818. (b) Hartwig, J. F. Acc. Chem.
Res. 1998, 31, 852-860. (c) Hartwig, J. F. Angew. Chem., Int. Ed. Engl.
(5) (a) Regitz, M. Angew. Chem. Int. Ed. Engl. 1996, 35, 725-728. (b)
Arduengo, A. J. III; Krafczyk, R. Chem. Zeit. 1998, 32, 6-14. (c) Herrmann,
W. A.; K o¨ cher, C. Angew. Chem. Int. Ed. Engl. 1997, 36, 2163-2187.
1
998, 37, 2046-2067. (d) Hartwig, J. F. Synlett 1997, 329-340. (e) Yang,
B. H.; Buckwald, S. L. J. Organomet. Chem. 1999, 576, 125-146.
1
0.1021/ol990987d CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/23/1999

mediated olefin metathesis7,8 has opened new opportunities
in catalysis.
Scheme 1. Imidazolium Salts
Recently, we examined the thermochemistry of transition
metal-centered ligand substitution involving nucleophilic
8
N-heterocyclic carbenes. This allowed us to quantify the
considerable stabilizing effect brought by this class of ligands
to organometallic systems. An understanding of ligand
stereoelectronic effects provided by the thermochemical
investigations has led to the use of this ligand class in a ring-
8a
opening/closing metathesis system.
We have most recently focused our efforts on palladium-
mediated processes which appear to benefit from the use of
sterically demanding, electron-donating ligands. We have
recently reported on the Suzuki and Kumada cross-coupling
2 3 2
reactions of aryl chlorides employing Pd (dba) or Pd(OAc)
and an imidazolium salt as catalyst systems.1 The use of
aryl chlorides in coupling chemistry has proven difficult but
would economically benefit a number of industrial pro-
cesses.1
3,14
Table 1. Amination of 4-Chlorotoluene Using Different
Imidazolium Chlorides
5,16
Considering the major effect of the use of bulky carbene
ligands in the related C-C bond formation processes
discussed above, we wondered if catalytic amination could
be performed with the help of a judiciously selected bulky
imidazolium salt. We now wish to report the palladium-
mediated C-N bond coupling of normally less reactive aryl
chlorides with various amines using a bulky nucleophilic
yields (%)a
entry
ligand L
time (h)
1
2
3
4
5
none
ITol
IXy
IMes
IPr
3
3
3
3
3
0
<5
11
22
98
17
carbene as supporting ligand.
18
a
On the basis of our recent success with IMesHCl (3, IMes
Isolated yields represent the average of two runs.
)
1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) and IP-
1
9
rHCl (4, IPr ) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidene) as ancillary ligand precursors in Suzuki and
Kumada14 couplings involving aryl chlorides, a similar
protocol was used to perform the amination of aryl chlorides.
In an effort to select the most effective imidazolium salt, a
number of 1,3-aryl-substituted imidazolium chlorides (Scheme
1
3
(
6) Applications of phosphine ligands in homogeneous catalysis: (a)
Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles
andApplications 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.
1
, 1-4) were used in a model reaction (Table 1).
The bulky (vide infra) IPrHCl (4) was found to be the
most effective imidazolium salt examined, leading to isola-
tion of the coupled product in a 98% isolated yield (Table
1, entry 5).
(7) (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. T.; Grubbs, R. H. Tetrahedron Lett. 1999, 40,
2
247-2250.
8) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am.
A survey of catalytic cross-coupling of aryl halides with
primary and secondary cyclic or acyclic amines using IPrHCl
(4) as the supporting ligand is provided in Table 2. The role
(
Chem. Soc. 1999, 121, 2674-2678. (b) Huang, J.; Schanz, H.-J.; Stevens,
E. D.; Nolan, S. P. Organometallics 1999, 18, 2370-2375.
(9) Voges, M. H.; Rømming, C.; Tilset, M. Organometallics 1999, 18,
t
of the added base KO Bu is 2-fold: it initially deprotonates
5
29-533.
10) Herrmann, W. A.; Reisinger, C.-P.; Spiegler, M. J. Organomet.
Chem. 1998, 557, 93-96.
11) (a) Herrmann, W. A.; Elison, M.; Fisher, J.; K o¨ cher, C.; Autus, G.
the imidazolium chloride to form the free carbene ligand in
situ which then coordinates to Pd(0). It also serves as a strong
base to neutralize the HX formed in the course of the
coupling reaction. This catalytic system proved to be general
and efficient as shown by results presented in Table 2.
The less reactive unactivated aryl chlorides reacted with
various amines including primary (Table 2, entries 6, 7, and
9) and secondary cyclic (Table 2, entries 1-3 and 10) or
acyclic (Table 2, entries 4, 5, and 11) amines in high yields.
Ortho-substitued aryl chlorides reacted with amine without
difficulty. The reaction of 4-chlorotoluene with highly
hindered amines (Table 2, entry 7) leads to lower yields.
(
(
R. Angew. Chem. Int. Ed. Engl. 1995, 34, 2371-2373. (b) Herrmann, W.
A.; Fischer, J.; Elison, M.; K o¨ 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.; K o¨ cher, C.; Autus, G. R. J.
Angew. Chem. Int. Ed. Eng. 1996, 35, 2805-2807.
13) (a) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem.
999, 64, 3804-3805. (b) Huang, J.; Grasa, G.; Zhang, C.; Trudell, M. L.;
Nolan, S. P. Manuscript in preparation.
(
(
1
(
14) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. In press.
(15) (a) Grushin, V. V.; Alper, H. Chem. ReV. 1994, 94, 1047-1062.
(
b) Cornils, B., Herrmann, W. A., Eds. Applied Homogeneous Catalysis
with Organometallic Compounds; VCH: Weinheim, 1996.
16) (a) Chem. Eng. News 1998, June 1, 24. (b) Chem. Eng. News 1998,
July 13, 71.
(
(18) (a) Arduengo, A. J., III; Dias, H. V. R.; Harlow, R. L.; Kline, M.
J. Am. Chem. Soc. 1992, 114, 5530-5534. (b) Arduengo, A. J., III; Dias,
H. V. R.; Calabrese, J. C.; Davidson, F. J. J. Am. Chem. Soc. 1992, 114,
4391-4393.
(17) A recent report by Hartwig shows that a bulky monodentate tertiary
phosphine can be used as ancillary ligand in aryl amination: Hartwig, J.
F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L.
M. J. Org. Chem. 1999, 64, 5575-5580.
(19) Jafarpour, L.; Stevens, E. D.; Nolan, S. P. Manuscript in preparation.
1308
Org. Lett., Vol. 1, No. 8, 1999

Table 2. Amination of Aryl Chlorides with Various Aminesa
Table 3. Amination of Aryl Bromides and Iodides
a
Reaction conditions: 1.0 mmol of aryl halides, 1.2 mmol of amine,
t
1
.5 mmol of KO Bu. 1.0 mol % of Pd2(dba)3, 4.0% IPrHCl (2 L/Pd), 3 mL
of dioxane, room temperature. Reactions were complete in 3-30 h, and
reaction times were not minimized. b Average isolated yields of two runs.
Results of structural studies in related platinum complexes
of general formulation L PtMe (L) nucleophilic carbene)
2 2
indicate that these ortho positions are oriented directly toward
the groups involved in the reductive elimination step. Steric
hindrance imparted by the ligands may therefore favor this
reductive elimination step. We believe a combination of
effects are at play: once the electron donor carbene imparts
enough electron density to the metal to enable it to perform
the oxidative addition, the ligand sterics may subsequently
facilitate the reductive elimination. The steric effects provided
by ortho substituents on the carbene aryl groups influence
the efficiency of the catalytic transformation in a dramatic
fashion (Table 1). Our thermochemistry studies on ruthenium
a
Reaction conditions: 1.0 mmol of aryl chloride, 1.2 mmol of amine,
t
1
.5 mmol of KO Bu. 1.0 mol % of Pd2(dba)3, 4.0% IPrHCl (2 L/Pd), 3 mL
of dioxane, 100 °C. Reactions were complete in 3-30 h, and reaction times
were not minimized. Average isolated yields of two runs. Dialkylaniline
was isolated as a byproduct in 5% yield.
b
c
8
b,19
systems involving these carbenes
show that ITol is the
best electron donor (ITol > IMes ≈ IXy > IPr) while IPr is
the most bulky ligand (IPr > IMes ≈ IXy > ITol). Up to
now the catalytic activity of systems involving these various
imidazolium salts follows the steric trend.
The generality of the method is illustrated by the efficient
coupling of unhindered aryl chlorides with both acyclic
primary and secondary alkylamines. To the best of our
knowledge, no reported catalyst allows this transformation.
Generally, aminations involving aryl bromides and iodides
proceed under milder conditions than those involving aryl
chlorides. To examine the halide substituent effect, the
efficiency and selectivity of the present catalytic system for
amination of aryl bromides and iodides was examined. Both
aryl bromides and iodides (Table 3) reacted with amines
smoothly at room temperature. Most interesting in these
studies involving an aryl bearing both chloro and iodo (or
bromo) substituents is the observation that bromo and iodo
functionalities can be converted at room temperature (Table
In summary, a general and efficient methodology for the
amination of aryl chlorides (and bromides and iodides) has
been developed. The simple methodology makes use of a
combination of a palladium(0) complex and an imidazolium
chloride forming the catalytic precursor which proves ef-
fective for unactivated aryl chlorides as well as aryl bromides
and iodides in high isolated yields. This methodology
provides the first report of aryl amination involving aryl
chlorides with both acyclic primary and secondary alkyl-
amines. Application of similar and improved protocols20 to
related coupling reactions using nucleophilic carbene as
supporting ligand is ongoing.
3, entries 3 and 4) and the remaining chloro functionality
can subsequently be converted at more elevated temperatures.
This could prove to be a significant advantage in process
chemistry.
Acknowledgment. The National Science Foundation is
gratefully acknowledged for partial support of this research.
While the detailed mechanism remains to be elucidated,
it seems apparent that arylamidopalladium intermediates are
involved in this reaction as previously observed.2,3 It appears
to us that both steric and electronic effects combine to
mediate the coupling process. Initially, the electron donor
properties of the carbene facilitate the activation of aryl
chlorides. A secondary effect may be provided by the bulk
located at the ortho positions of the carbene aryl group.
Supporting Information Available: Experimental pro-
cedures and references to known compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL990987D
(
20) We have recently determined that 1 equiv of the IPr‚HCl salt could
be used instead of two, leading to similar isolated yields in approximately
half the time. A full report of this improvement is forthcoming.
Org. Lett., Vol. 1, No. 8, 1999
1309