Convenient and efficient Suzuki-Miyaura cross-coupling catalyzed by a palladium/diazabutadiene system

Article abstract of DOI:10.1021/ol015676t

(matrix presented) A Pd(OAc)₂/diazabutadiene system has been developed for the catalytic cross-coupling of aryl halides with arylboronic acids. A combination of the diazabutadiene DAB-Cy (1, N,N′-dicyclohexyl-1,4-dizabutadiene) and Pd(OAc)₂ was found to form an excellent catalyst for the Suzuki-Miyaura cross-coupling of various aryl bromides and activated aryl chlorides with arylboronic acids.

Full text of DOI:10.1021/ol015676t

ORGANIC
LETTERS
2
001
Vol. 3, No. 7
077-1080
Convenient and Efficient
Suzuki−Miyaura Cross-Coupling
Catalyzed by a Palladium/Diazabutadiene
System
1
Gabriela A. Grasa, Anna C. Hillier, and Steven P. Nolan*
Department of Chemistry, UniVersity of New Orleans, New Orleans, Louisiana 70148
snolan@uno.edu
Received February 7, 2001
ABSTRACT
A Pd(OAc)
of the diazabutadiene DAB-Cy (1, N,N′-dicyclohexyl-1,4-dizabutadiene) and Pd(OAc)
Miyaura cross-coupling of various aryl bromides and activated aryl chlorides with arylboronic acids.
2
/diazabutadiene system has been developed for the catalytic cross-coupling of aryl halides with arylboronic acids. A combination
2
was found to form an excellent catalyst for the Suzuki−
The Suzuki-Miyaura cross-coupling reaction, involving the
coupling of an arylboronic acid with an organohalide, has
proven to be an extremely useful synthetic tool in organic
a Pd(II) cyclometalated imine catalyst able to mediate both
4
5
Suzuki and Heck reactions has been reported by Milstein.
Unfortunately, this system requires high reaction tempera-
tures and leads to products in modest yields. On the basis of
the Milstein report, we thought a well-known family of
ligands, the diazabutadienes, might possibly mediate the
Suzuki-Miyaura reaction. The chelating nature of these
ligands might also assist in stabilizing catalytic species.
Ligands containing the 1,4-diaza-1,3-butadiene skeleton,
R-diimines, (DAB-R, Scheme 1) have been known for quite
1
synthesis. Although palladium complexes bearing tertiary
phosphine ligands are commonly employed1 in Suzuki-
Miyaura cross-couplings, these catalysts are often sensitive
to air oxidation and therefore require air-free handling in
order to minimize ligand oxidation. Nucleophilic N-hetero-
cyclic carbenes, the imidazol-2-ylidenes, have recently been
used as ancillary ligands for Suzuki-Miyaura cross-coupling
reactions with great success.3
a,2
In the specific area of coupling chemistry, catalytic systems
that contain supporting ligations other than tertiary phosphine
represent a scarcely explored area of investigation. Recently,
Scheme 1. Diazabutadiene Ligands
(
1) (a) For a review, see: Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95,
2
457-2483. (b) Suzuki, A. Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; pp 49-97
and references therein. (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.
6
some time. The coordination versatility of these ligands, a
consequence of the flexibility of the NCCN backbone and
the strong σ-donor and π-acceptor properties, reflects a very
important feature of DAB-R-metal complexes. Few inves-
tigations have focused on the influence of DAB-R as a
(
2) Applications of phosphine ligands in homogeneous catalysis: (a)
Parshall, G. W.; Ittel, S. Homogeneous Catalysis; J. Wiley and Sons: New
York, 1992. (b) Pignolet, L. H., Ed. Homogeneous Catalysis with Metal
Phosphine Complexes; Plenum: New York, 1983.
7
1
0.1021/ol015676t CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/14/2001

Table 1. Influence of DAB-R Ligands on the
Table 2. Effect of Base on Pd(OAc)
Cross-Coupling of 4-Bromotoluene with Phenylboronic Acid
2
/DAB-Cy (1)-Catalyzed
a
Palladium-Catalyzed Cross-Coupling Reaction of
a
4
-Bromotoluene with Phenylboronic Acid
entry
base
none
yieldb,d
1
2
3
4
5
6
7
8
9
nr
nr
nr
nr
10c
11c
14c
44
63
78
87
99
Na2CO3
Ca(OH)2
NaOMe
t
K(O Bu)
TBAF
KOMe
Ba(OH)2
K2CO3
KF
1
1
1
0
1
2
CsF
Cs2CO3
a
Reaction conditions: 1.0 mmol of aryl bromide, 1.5 mmol of phenyl-
boronic acid, 2 mmol of base, 3.0 mol % Pd(OAc)2, 3.0 mol % DAB-Cy,
mL of dioxane, 80 °C. b Isolated yields. c GC yields. d All reactions were
monitored by GC. Yields are average of two runs.
3
3
e
salt catalyzed Suzuki-Miyaura reaction, we observed that
the coupling of 4-bromotoluene and phenylboronic acid in
the presence of 3 mol % of Pd(OAc)
4), and Cs CO in dioxane, at 80° C, proceeded to give
-methylbiphenyl in 85% isolated yield (Table 1, entry 5).
2
, 3 mol % DAB-Mes
(
2
3
4
Investigation of other diazabutadiene ligands led to the
observation that alkyl-diazabutadienes (Table 1, entries 2 and
3
) are superior supporting ligands for the Pd-catalyzed Suzuki
reaction compared to aryl-diazabutadienes (Table 1, entries
-8). This reactivity trend is in agreement with the stronger
4
donating ability of alkyl substituents, making the ligand more
electron-rich. Other bis(nitrogen donor) ligands were inves-
(
3) (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725-728. (b)
Arduengo, A. J., III; Krafczyc, R. Chem. Zeit. 1998, 32, 6-14. (c) Herrmann,
W. A.; Kocher, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2163-2187. (d)
Herrmann, W. A.; Reisinger, C. P.; Spiegler, M J. Organomet. Chem. 1998,
5
57, 93-96. (e) Zhang, C.; Huang, J.; Trudell, M. T.; Nolan, S. P. J. Org.
Chem. 1999, 64, 3804-3805. (f) B o¨ hm, V. P. W.; Gst o¨ mayr, C. W. K.;
a
Weskamp. T.; Herrmann, W. A. J. Orgamomet. Chem. 2000, 595, 186-
Reaction conditions: 1.0 mmol of 4-bromotoluene, 1.5 mmol of
190.
phenylboronic acid, 2 mmol of Cs2CO3, 3.0 mol % Pd(OAc)2, 3.0 mol %
b
c
(4) Weissman, H.; Milstein, D. Chem. Commun. 1999, 1901-1902.
(5) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun. 1999, 357-358.
6) van Koten, G.; Vrieze, K. AdV. Organomet. Chem. 1982, 21, 151-
39 and references cited.
7) (a) Mathur, P.; Ghosh, S.; Sarkar, A.; Rheingold, A. L.; Guzei, I. A.
ligand, 3 mL odioxane, 80 °C, 3 h. Isolated yields. All reactions were
d
monitored by GC. Yields are average of two runs.
(
2
(
J. Organomet. Chem. 1998, 566, 159-164. (b) Lehmann, J. F.; Urquhart,
S. G.; Ennis, L. E.; Hitchcock, A. P.; Hatano, K.; Gupta, S.; Denk, M. K.
Organometallics 1999, 18, 1862-1872. (c) Greulich, S.; Kaim, W.; Stange,
A.; Stoll, H.; Fiedler, J.; Zalis, S. Inorg. Chem. 1996, 35, 3998-4002. (d)
Breuer, J.; Fruhauf, H.-W.; Smeets, W. J. J.; Spek, A. L. Inorg. Chim. Acta
1999, 291, 438-447.
supporting ligand in catalytic processes. The most notable
exceptions have been the use of metal-diimine complexes
8
to mediate olefin polymerization and alkyne cyclotrimer-
9
ization processes.
(
8) (a) Johnson, L. K.; Killian, C. M.; Brookhart, M. S. J. Am. Chem.
We now wish to report an additional use of these ligands
in the efficient catalytic cross-coupling of aryl halides with
Soc. 1995, 117, 6414-6416. (b) Killian, C. M.; Tempel, D. J.; Johnson, L.
K.; Brookhart, M. S. J. Am. Chem. Soc. 1996, 118, 11664-11665. (c)
Tempel, D. J.; Johnson, L. K.; Huff, R. L.; White, P. S.; Brookhart, M. S.
J. Am. Chem. Soc. 2000, 122, 6686-6700 and references cited.
arylboronic acids using a combination of Pd(OAc)
2
/diaza-
butadiene (DAB-R) as the catalytic system.
(9) van der Poel, H.; van Koten, G.; Kokkes, M.; Stam, C. H. Inorg.
On the basis of our previous experience in Pd/imidazolium
Chem. 1981, 20, 2941-2950.
1078
Org. Lett., Vol. 3, No. 7, 2001

Table 3. Pd(OAc)
2
/DAB-Cy (1)-Catalyzed Cross-Coupling of
2
Table 4. Pd(OAc) /DAB-Cy (1)-Catalyzed Cross-Coupling of
4-Bromotoluene with Various Arylboronic Acidsa
Aryl Halides with Phenylboronic Acida
a
Reaction conditions: 1.0 mmol of 4-bromotoluene, 1.5 mmol of
arylboronic acid, 2 mmol of Cs2CO3, 3.0 mol % Pd(OAc)2, 3.0 mol %
DAB-Cy, 3 mL of dioxane, 80 °C. b Isolated yields. c All reactions were
monitored by GC. Yields are average of two runs.
and Ba(OH)
2
proved to be ineffective for the cross-coupling
of 4-bromotoluene with phenylboronic acid (Table 2, entries
2
-5, 7, 8). Moreover, KF, a very effective additive for
t
10
2 3
Pd(dba) /( Bu) P-catalyzed Suzuki-Miyaura reaction, also
proved to be less effective in the present system.
As illustrated in Table 3, the palladium-catalyzed Suzuki-
Miyaura reaction with the DAB-Cy (1) ancillary ligand
proved exceptionally active. Not surprisingly the nonactivated
aryl bromides (Table 3, entry 3) were easily converted. This
reaction could be performed in the air as well but requires
longer reaction times (Table 3, entry 2). Moreover, ortho-
substituted substrates also led to excellent yields (Table 3,
entries 6 and 7). The catalytic effect was confirmed by
running the standard reaction on 4-bromoacetophenone
without ligand. The reaction proceeds, but it requires much
a
Reaction conditions: 1.0 mmol of aryl halide, 1.5 mmol of phenylbo-
ronic acid, 2 mmol of Cs2CO3, 3.0 mol % Pd(OAc)2, 3.0 mol % DAB-Cy,
mL of dioxane, 80 °C. Isolated yields. The reaction was performed in
the air. The reaction was performed using Pd(OAc)2 only. The reaction
was performed at 100 °C. GC yield. All reactions were monitored by
b
c
3
d
e
f
g
GC. Yields are average of two runs.
2
longer reaction times compared to the Pd(OAc) /DAB-R
system (Table 3, entries 4 and 5). Activated aryl chlorides
led to moderate to high yields when this catalytic system
was employed (Table 3, entries 11 and 12). Attempts to
couple the electron-neutral 4-chlorotoluene and the electron-
rich 4-chloroanisole were not successful. Investigations
regarding the steric and electronic properties of diazabuta-
diene ligands able to activate the aryl chlorides are presently
underway.
tigated, but considering the electronic argument presented
above, it was not surprising to observe a poorer performance
of the commercially available ligands 2,2′-bipyridyl (Table
1, entry 9) and 1,10-phenanthroline (Table 1, entry 10).
An investigation of the influence of the base suggested
that Cs CO was the reagent of choice. In turn, K CO , an
2 3 2 3
effective base for the cyclopalladated-imine catalyst for the
4
Suzuki-Miyaura reaction, proved to be less effective,
leading to a 63% isolated yield (Table 2, entry 9). Other
(
10) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-
t
bases such as Na
2 3
CO , Ca(OH)
2
, NaOMe, K(O Bu), KOMe,
4028.
Org. Lett., Vol. 3, No. 7, 2001
1079

The effect of varying the aryl boronic acids in the Suzuki-
Miyaura cross-coupling reactions was also investigated using
-bromotoluene as the substrate (Table 4). para-Substituted
aryl boronic acids led to excellent yields of the desired
products (Table 4, entries 3 and 4), while the sterically
hindered 2-methylphenylboronic acid required longer reac-
tion time before affording very good yields of the product
DAB-R system is very efficient in the Suzuki-Miyaura
cross-coupling reaction of aryl bromides with aryl boronic
acids in terms of reactivity, reaction temperature, reaction
time, and air-stability. This system represents unprecedented
reactivity for a bis(nitrogen) ligand system with regard to
reactivity with unactivated and sterically encumbered sub-
strates, as well as activated aryl chlorides. Investigations
4
(Table 4, entry 2). Attempts to couple 4-bromotoluene with
2
regarding the utility of Pd(OAc) /DAB-R systems toward
meta-substituted aryl boronic acids such as 3-cyanophenyl-
boronic acid or 3-methoxyphenylboronic acid resulted in low
yields. The lower reaction rate may be explained in terms
of the different electronic properties of meta-substituted
boronic acids.11
In summary, an unprecedented, general, and efficient
2
methodology based on the Pd(OAc) /DAB-R system has
been developed. The use of DAB-R as supporting ligands
for the Suzuki-Miyaura cross-coupling reaction represents
an interesting alternative to existing catalytic systems based
the activation of electron-rich and electron-neutral aryl
chlorides, as well as the influence of the steric and electronic
factors of DAB-R ligands are ongoing.
Acknowledgment. The National Science Foundation, the
Albermarle Corporation, and the Petroleum Research Fund
administered by the American Chemical Society are grate-
fully acknowledged for support of this research.
Supporting Information Available: Experimental pro-
cedure and references to known compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
2
on the use of tertiary phosphine ligands. The Pd(OAc) /
(
11) March, J. AdVanced Organic Chemistry; J. Wiley and Sons: New
York, 1992; pp 278-286.
OL015676T
1080
Org. Lett., Vol. 3, No. 7, 2001