Palladium-imidazolium carbene catalyzed aryl, vinyl, and alkyl Suzuki-Miyaura cross coupling.

Article abstract of DOI:10.1021/ol016724c

[reaction--see text] N,N-Bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride with palladium(II) acetate (2 mol %) was used as catalyst, without added base, to efficiently cross couple aryl, vinyl, and alkyl boronates and boronic acids with aryldiazonium tetrafluoroborate substrates. The reactions were performed at 0 degrees C or rt, giving product in 2 to 4 h with 80 to 90% yields for isolated materials. Diazonium ions, formed in situ, also cross couple under these conditions.

Full text of DOI:10.1021/ol016724c

ORGANIC
LETTERS
2001
Vol. 3, No. 23
3761-3764
Palladium−Imidazolium Carbene
Catalyzed Aryl, Vinyl, and Alkyl
Suzuki−Miyaura Cross Coupling
Merritt B. Andrus* and Chun Song
Department of Chemistry and Biochemistry, Brigham Young UniVersity, C100 BNSN,
ProVo, Utah 84602
mbandrus@chemdept.byu.edu
Received September 7, 2001
ABSTRACT
N,N-Bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride with palladium(II) acetate (2 mol %) was used as catalyst, without added base, to
efficiently cross couple aryl, vinyl, and alkyl boronates and boronic acids with aryldiazonium tetrafluoroborate substrates. The reactions were
performed at 0 °C or rt, giving product in 2 to 4 h with 80 to 90% yields for isolated materials. Diazonium ions, formed in situ, also cross
couple under these conditions.
The Suzuki-Miyaura reaction, the palladium-catalyzed cross
coupling of boranes, boronic esters, and boronic acids with
sp2 halides and pseudohalogens, continues to attract new
methodology, development, and applications.1 Recent de-
velopments by Buchwald and Fu and co-workers include new
palladium catalysts with phosphine ligands that can be used
at rt.2 Copper carboxylate additives, reported by Liebeskind
et al., can also be used at lower temperatures and have the
advantage of being used without added base.3 Nolan and co-
workers have reported imidazolium and diazabutadiene
ligands with Pd2(dba)3 forming catalysts that couple the most
difficult aryl chloride substrates with added cesium carbonate
in refluxing dioxane.4 Couplings have been reported using
aryldiazonium ions, more active substrates, using 10 mol %
of palladium(II) acetate without added base in refluxing
methanol.5 We now report dihydroimidazolium carbene-
palladium acetate catalyzed couplings that are active from 2
to 0.01 mol % of catalyst loading with aryldiazonium ions
and aryl, vinyl, and alkyl boron substrates. These reactions
can be performed at 0 °C or rt without added base. An
efficient one-pot in situ diazonium formation cross coupling
starting with an aniline is also reported using this active
catalyst system.
Arduengo-type imidazolium carbene ligands with pal-
ladium and other transition metals have recently found many
applications as catalysts for palladium cross couplings and
ruthenium-based olefin metathesis.6 The most active bis-2,6-
diisopropylphenyl ligand in the series was selected for this
investigation. A catalytic amount of the imidazolium chloride
(2 mol % based on the substrate), readily prepared according
to literature references,7 was treated with palladium(II)
(1) Suzuki, A. J. Organomet. Chem. 1999, 576, 147. Miyaura, N.; Suzuki,
A. Chem. ReV. 1995, 95, 2457.
(2) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L J. Am. Chem. Soc.
1998, 120, 9722. (b) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald,
S. L J. Am. Chem. Soc. 1999, 121, 9550. (c) Littke, A. F.; Dai, C.; Fu, G.
C. J. Am. Chem. Soc. 2000, 122, 4020.
(3) (a) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260.
Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3, 91. (b) Savarin,
C.; Liebeskind, L. S. Org. Lett. 2001, 3, 2149.
(4) (a) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem.
1999, 64, 3804. (b) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett.
2001, 3, 1077.
(5) Sengupta, S.; Bhattacharyya, S. J. Org. Chem. 1997, 62, 3405.
(6) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953. (b) Lee, H. M.; Nolan, S. P. Org. Lett. 2000, 2, 2053. (c) Yang, C.;
Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511.
10.1021/ol016724c CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/25/2001

acetate (2 mol %) in THF. Initially it was thought that added
base would be needed to form the active palladium carbene
complex. Others have shown that added base, tert-butoxide,8
carbonate,9 or fluoride, is required.10 Cavell has shown that
palladium carbenes can be formed by treating imidazolium
salts first with silver(I) oxide followed by transfer to
palladium acetate without additional base.11 Couplings were
then performed, but added base was needed for successful
coupling transformations in this case. Initially, base free
conditions were investigated and were found to be successful
for the diazonium Suzuki-Miyaura couplings now reported.
Biaryl compounds were formed from various aryldiazonium
tetrafluoroborates coupled with aryl boronic acids (Table 1).12
After 3 h TLC indicated consumption of the starting materials
and products were isolated in the 80 to 90% range using
silica gel chromatography. In cases performed on a larger
scale (10 mmol), the yields further improved to the high 90%
range. Electron-rich methoxy-substituted substrates allowed
for the use of even lower temperature at 0 °C and the yields
remained high. The electron-deficient benzophenone diazo-
nium ion was equally efficient with the various boronic acids
investigated.
Table 1. Suzuki Coupling with Palladium-Imidazolium
Catalysis
Control experiments included leaving out the imidazolium
salt ligand. Use of either palladium(II) acetate or tetrakis-
(triphenylphosphine) palladium alone as catalysts in THF or
toluene, without added imidazolium chloride, resulted in no
product formation at rt over an extended 36 h time period.
Acetate appears to function as base in this case to generate
the active palladium carbene catalyst under the conditions
investigated. An equimolar CDCl3 solution (0.8 M) of the
imidazolium chloride and palladium acetate monitored by
1H NMR showed complete disappearance of the diagnostic
proton located on the iminium carbon found at 8.15 ppm.13
Homocoupling of phenylboronic acid, when used alone
without added diazonium salt, is not observed at 0 °C. Only
at rt after 16 h was a significant 37% yield of biphenyl
product obtained when the diazonium tetrafluoroborate was
left out.
a Reactions were perfomed on a 0.1 mmol scale at 0.2 M concentration.
b Yields are reported for isolated, chromatographed materials. Numbers in
parentheses are for 10 mmol scale reactions.
Table 2. Effect of Solvent and Substrate/Catalyst Ratio
The biphenyl reaction was explored in various solvents at
a 2 mol % load level, and the isolated yields remained high.
(7) (a) Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R.; Craig, H. A.;
Goerlich, J. R.; Marshall, W. J. Unverzagt, M. Tetrahedron 1999, 55, 14523.
(b) Saba, S.; Brescia, A. M.; Kaloustian, M. K. Tetrahedron Lett. 1991,
32, 5031.
(8) Herrmann, W. A.; Goossen, L. J.; Spiegler, M. Organometallics 1998,
17, 2162.
(9) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889.
(10) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119.
(11) McGuinness, D. S.; Cavell, K. J. Organometallics 2000, 19, 741.
(12) General procedure: To a flask containing magnetically stirred dry
THF (3 mL) under nitrogen at the indicated temperature were added
arenediazonium tetrafluoroborate (0.1 mmol), arylboronic acid (0.11 mmol),
Pd(OAc)2 (2 mol %), and N,N-bis(2,6-diisopropyl)dihydroimidazolium
chloride (2 mol %). Stirring was continued for the indicated time until TLC
analysis revealed consumption of the starting materials. The reaction was
worked up with ether and brine, dried over magnesium sulfate, and purified
by silica gel chromatography. All products, all of which are known, were
a Substrate (0.1 mmol) to catalyst mole ratio. b Yields are reported for
isolated, chromatographed materials.
1
characterized by H NMR and MS.
(13) The imidazolium ligand and palladium acetate were mixed at rt for
2 h to generate a homogeneous, pale yellow solution. A portion was analyzed
by 1H NMR (300 MHz). When sodium tert-butoxide and ligand were mixed
under similar conditions, a black precipitate resulted. Further studies to
establish the structure of the active catalyst in this case will be reported
elsewhere.
Only methanol lowered the yield somewhat to 82% (Table
2). THF was found to be best at 95%. Catalyst loading of
this system was also investigated with various reactions
performed in THF at rt for 3 h (Table 2). The reaction
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Org. Lett., Vol. 3, No. 23, 2001

Table 3. Suzuki Coupling with Styryl Boric Acid
Table 4. Alkyl Catecol Borane Coupling
Table 5. In Situ Aniline Suzuki Coupling
remained highly efficient even when performed at 0.1 mol
%, with a 1000:1 substrate-to-catalyst ratio, giving product
with a yield of 86%. Only at 0.01 mol % did the yield fall
off to a moderate 68% yield after 3 h. Longer reaction times
may further extend the load level to even higher substrate
to catalyst levels with this active ligand system.
Vinyl cross coupling was explored using this catalyst
system with â-styryl boronic acid (Table 3). In all cases good
yields in the 80% range were obtained. Again, the more
electron rich methoxy substrates allowed for efficient
reactivity at 0 °C. Only the more hindered o-methyldiazo-
nium tetrafluoroborate substrate gave product with lower
yield at 68% in this case.
a Substrate (0.1 mmol) to catalyst mole ratio. b Yields are reported for
isolated, chromatographed materials.
Suzuki-Miyaura coupling is unique in that alkyl boron
compounds, both alkylboranes and boronic esters, are known
to participate in coupling reactions to produce alkyl-sp2
linked products. Usually this transformation requires a more
active catalyst, excess substrate, and higher temperatures.14
Using this palladium acetate-imidazolium carbene catalyst
(2 mol %), 4-bromo-1-catecolboranylbutane coupled with
aryldiazonium tetrafluoroborates at rt to give arylalkanes in
good yields. Phenyl coupling gave 61% yield while the more
electron rich substrates generated product in 80% yield after
4 h (Table 4).
indicated were treated with tert-butyl nitrite followed by
boron trifluoride etherate at 0 °C in THF for 30 min
according to the procedure of Doyle (Table 5).16 To this
mixture were added the imidazolium chloride and palladium-
(II) acetate (2 mol %) followed by addition of the aryl
boronic acid. The reaction was warmed to rt and TLC was
again used to monitor consumption of the starting materials.
(15) Doyle, M. P.; Siegfreid, B.; Elliot, R. C.; Dellaria, J. F. J. Org.
Chem. 1977, 42, 2431.
(16) General in situ procedure: To a flask containing stirred, dry THF
at 0 °C (2 mL) was added the aniline compound (0.2 mmol) followed by
BF3‚OEt2 (22.7 mg, 0.2 mmol), diluted with THF (2 mL). Following stirring
for 15 min, to the solution was added tert-butyl nitrite (23 mg, 0.22 mmol)
diluted in THF (2 mL) and stirring was continued for 30 min. To the mixture
were added arylboronic acid (0.2 mmol), Pd(OAc)2 (0.9 mg, 0.004 mmol),
and N,N-bis(2,6-diisopropyl)dihydroimidazolium chloride (1.2 mg, 0.004
mmol) diluted in THF (5 mL). Stirring continued and the reaction was
worked up at the indicated time. The product was isolated and characterized
as before.
The utility of this system is further illustrated by the
flexibility of being able to start with an aniline substrate and
employ an in situ diazonium formation step.15 The anilines
(14) (a) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.;
Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314. (b) Chemler, S. R.;
Danishefsky, S. J. Org. Lett. 2000, 2, 2695. (c) Furstner, A.; Seidel, G.
SynLett 1998, 161.
Org. Lett., Vol. 3, No. 23, 2001
3763

Somewhat longer reaction times were needed. Yet, in all
cases the products were isolated in good yield, in the 60 to
70% range. Only the o-methoxy substrate was lower yielding
at 53%.
plicable to the development of asymmetric versions17 due
the high reaction rates now demonstrated at lower temper-
atures.
Acknowledgment. We are grateful for the support
provided by Brigham Young University and the National
Institutes of Health (GM57275). We also thank Bruce
Jackson for MS analyses.
With ease and flexibility, this new active palladium
acetate-imidazolium catalyst system readily cross couples
aryl, vinyl, and alkyl boron reagents with aryldiazonium ions
in high yield at rt. Added base is not needed, and a two-
step, single flask operation is productive using simple aniline
starting materials. Acetate appears to function as base in this
case, producing the active palladium catalyst. When the
ligand is removed, the reaction does not occur. Very high
turnover numbers are possible in some cases, giving high
yields with as little as 0.01 mol % of catalyst. The system
should find applications with more complex targets that
contain base-sensitive functionality. It should also be ap-
Supporting Information Available: Analytical data for
the known product compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL016724C
(17) (a) Herrmann, W. A.; Goossen, L. J.; Kocher, C.; Artus, G. R. J.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2805. (b) Herrmann, W. G.; Goossen,
L. J.; Spiegler, M. Organomet. 1998, 17, 2162.
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