Efficient catalysis of the Suzuki-Miyaura reaction under mild conditions with cyclopalladated N,N-dimethylaminomethylferrocene

Article abstract of DOI:10.1007/s11172-010-0322-x

High catalytic activity of N,N-dimethylaminomethylferrocene cyclopalladated derivative was demonstrated in the the Suzuki-Miyaura cross-coupling of aryl bromides with phenylboronic acid, which allowed us to carry out the reaction under extremely mild conditions.

Full text of DOI:10.1007/s11172-010-0322-x

Russian Chemical Bulletin, International Edition, Vol. 59, No. 9, pp. 1840—1842, September, 2010
1840
Efficient catalysis of the Suzuki—Miyaura reaction under mild conditions
with cyclopalladated N,Nꢀdimethylaminomethylferrocene
O. N. Gorunova,a P. A. Zykov,a,b M. V. Livantsov,b K. A. Kochetkov,a Yu. K. Grishin,b and V. V. Duninab
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
bDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119991 Moscow, Russian Federation.
Fax: +7 (495) 932 8846. Eꢀmail: dunina@org.chem.msu.ru
High catalytic activity of N,Nꢀdimethylaminomethylferrocene cyclopalladated derivative
was demonstrated in the the Suzuki—Miyaura crossꢀcoupling of aryl bromides with phenylꢀ
boronic acid, which allowed us to carry out the reaction under extremely mild conditions.
Key words: CNꢀpalladacycle, N,Nꢀdimethylaminomethylferrocene, homogeneous catalyꢀ
sis, the Suzuki—Miyaura reaction, homocoupling, aryl bromides, aryl chlorides.
In the last decades, cyclopalladated complexes (CPC),
der the maximum mild conditions necessary for the furꢀ
ther accomplishment of asymmetric versions of this proꢀ
cess. Preliminary results of this study have been reported
earlier.10
possessing high thermal, oxidative, and hydrolytic stabiliꢀ
ty, showed themselves as excellent highly efficient cataꢀ
lysts of the crossꢀcoupling reactions.1,2 Starting our proꢀ
gram for the testing chiral CPC in enantioselective catalyꢀ
sis, we have chosen the Suzuki—Miyaura reaction for the
following reasons: 1) with the general practice of thermal
(60—160 °C)1,3,4 activation of this type crossꢀcoupling
processes, only several precedents of carrying out such
reactions at room temperature are known;5,6 2) the only
example of moderately successful (up to 49% ee) enantioseꢀ
lective catalysis of crossꢀcoupling with palladacycles deals
with exactly the Suzuki—Miyaura reaction.7
In our search for the complex capable to catalyze reacꢀ
tions of this type under mild conditions, we have chosen
the known8 CNꢀpalladacycle based on N,Nꢀdimethylamiꢀ
nomethylferrocene (1), since the ferrocenyl CPC with
other Nꢀdonor groups have proved especially efficient catꢀ
alysts of achiral Suzuki—Miyaura reactions.5,6 As far as
we know, only one short communication has been pubꢀ
lished on the application of this CPC in catalysis: the
Heck reaction in the highꢀtemperature regime (140—160 °C)
and only involving active aryl iodides.9
Results and Discussion
We used a crossꢀcoupling of phenylboronic acid with
paraꢀtolyl bromide (2) as a model version of the Suzuꢀ
ki—Miyaura reaction. The presence of the Me group in
the starting substrate simplified monitoring the reaction
progress by 1H NMR. In addition, a reduced reactivity of
aryl halides with electronꢀdonating substituents1 in the
crossꢀcoupling processes provides higher correctness of
such model reaction as a method for the evaluation of
a catalyst efficiency.
On catalysis with dimer racꢀ1, in the reaction of aryl
bromide 2 with phenylboronic acid, carried out at room
temperature in air (Scheme 1), the target biaryl 3a is
formed in high yield (94%, Table 1, entry 1) at moderate
loading* of the catalyst in 2.5 mol.%.
Unfortunately, the attempts to decrease amount of the
catalyst have proved not very successful: when the conꢀ
centration of dimer racꢀ1 was decreased to 0.05 mol.%,
the final product 3a in the same temperature regime is
formed only in insignificant yield (7%, entry 2). The yield
is somewhat increased only on heating (20%, entry 3).
A possibility to carry out the model Suzuki—Miyaura
reaction even at negative temperature (–18 °C) upon its
catalysis with CNꢀdimer racꢀ1 is the most important result
The present work deals with evaluation of catalytic
activity of racemic dimer 1 (racꢀ1) in the achiral Suzuꢀ
ki—Miyaura reaction and a possibility to carry out it unꢀ
* Here and further, concentration of the catalyst is given in moꢀ
lar percent of the dimeric complex.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1791—1793, September, 2010.
1066ꢀ5285/10/5909ꢀ1840 © 2010 Springer Science+Business Media, Inc.

Mild conditions for Suzuki—Miyaura reaction
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
1841
Scheme 1
Scheme 2
TBAB is the tetrabutylammonium bromide.
R = Me (a), COOMe (b), Ac (c)
of the study. Under these conditions, biaryl 3a is formed
in satisfactory yield (53%, entry 4), however, in this case
the reaction time is significantly longer (to 18 days). To
our knowledge, this is the first example of carrying out the
crossꢀcoupling in so lowꢀtemperature regime.
Attempted involvement of aryl chlorides with either
electronꢀdonating or electronꢀwithdrawing substituents
into the Suzuki—Miyaura reaction failed. In the reactions
of phenylboronic acid with pꢀchlorotoluene (4a) either at
room or elevated temperature (55 °C), the formation of
unsubstituted biphenyl (5) is observed resulting from the
homocoupling, chromatographic isolation yielded 10 and
50% of the product, respectively (Scheme 2). In this case,
the target biaryl 3a is formed only in trace amounts (<1%,
1H NMR data).
Even when more reactive aryl chlorides with electronꢀ
withdrawing substituents (4b and 4c) are used, the homoꢀ
coupling with the formation of biphenyl 5 in 33 and 40%
yield, respectively, remains the main direction of the reacꢀ
tion. The formation of substituted biaryl 3b with the minꢀ
imum yield of 3% was registered spectrally only in the
mixture of reaction products of aryl chloride 4b.
In conclusion, we found unusually mild conditions for
the catalysis of the Suzuki—Miyaura crossꢀcoupling of
aryl bromides, which is based on the use of cyclopallaꢀ
dated N,Nꢀdimethylaminomethylferrocene as the catalyst.
Development of this catalytic system makes promising
further creation of asymmetric versions of the Suzuꢀ
ki—Miyaura reaction with involvement of a wide range of
aryl bromide substrates, particularly because the CNꢀpalꢀ
ladacycle (S)ꢀ1 of high degree of enantiomeric enrichꢀ
ment (96% ee) is easily available.11
Experimental
1
H NMR spectra were recorded on a Bruker Avanceꢀ400
spectrometer (400.1 MHz) in CDCl3 at room temperature;
chemical shifts were measured relatively to Me4Si (internal stanꢀ
dard). Reaction progress and purity of compounds formed were
monitored by TLC on silufol UVꢀ254 with visualization under
the UV light. Flashꢀchromatography on Fluka 60 silica gel was
used for preparative isolation of compounds obtained. Purificaꢀ
tion of solvents was performed using standard methods.12 Dimerꢀ
ic complex racꢀ1 was synthesized using the known procedure.8
Procedure for the Suzuki—Miyaura reaction. A. A mixture of
paraꢀbromotoluene (0.1067 g, 0.6238 mmol), phenylboronic acid
(0.1141 g, 0.9357 mmol), TBAB (0.2011 g, 0.6238 mmol), K2CO3
(0.1724 g, 1.2474 mmol), and catalyst racꢀ1 (0.0120 g, 0.0156 mmol,
2.5 mol.%) was stirred in the methanol—water (3 : 1.5) system at
room temperature for 24 h. The reaction mixture was filtered off
from Pd0, extracted with diethyl ether (3×4 mL) and dichloroꢀ
methane (DCM) (2×4 mL). The organic extracts were washed
with water (2×3 mL), combined, concentrated to dryness, and
purified by column flashꢀchromatography (d = 1 cm, h = 20 cm;
hexane) to obtain 4ꢀmethylꢀ1,1´ꢀbiphenyl (3a) (0.0973 g, 94%)
Table 1. Results of the Suzuki—Miyaura reaction catalysis with
complex racꢀ1
1
as fine colorless crystals. H NMR, δ: 2.45 (s, 3 H, CH3); 7.30
3
(d, 2 H, C(3)H, C(5)H, J = 7.8 Hz); 7.37 (t, 1 H, C(4´)H,
3J = 7.5 Hz); 7.47 (t, 2 H, C(3´)H, C(5´)H, 3J = 7.8 Hz); 7.550
Entry [racꢀ1]
Reaction conditions
Yield* of 3a
3
(mol.%)
(%)
(d, 2 H, C(2)H, C(6)H, J = 7.8 Hz); 7.630 (d, 2 H, C(2´)H,
t/°C
τ
Solvent
C(6´)H, 3J = 7.5 Hz).
The other reactions with pꢀbromotoluene 2 were carried out
similarly with modification of conditions (see Table 1).
B. Catalyst racꢀ1 (0.0120 g, 0.0156 mmol, 2.5 mol.%),
phenylboronic acid (0.1141 g, 0.9357 mmol), TBAB (0.2011 g,
0.6238 mmol), and K2CO3 (0.1724 g, 1.2474 mmol) were added
sequentially to a cooled to –18 °C solution of pꢀbromotoluene 2
(0.1067 g, 0.6238 mmol) in methanol with cooling and the mixꢀ
1
2
3
4
2.5
0.05
0.05
2.5
20
20
55
1 day
4 day
20 h
МеОН/Н2О
MеОН/Н2О
МеОН/Н2О
МеОН
94
7
20
53
–18
18 day
* The yield is given for the chromatographically isolated
4ꢀmethylbiphenyl.

1842
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
Gorunova et al.
ture was kept in refrigerator (–18 °C) for 18 days. The workꢀup
of the reaction mixture was performed at –5 °C: Pd0 was removed
by filtration, extraction was made by diethyl ether (3×4 mL) and
DCM (2×4 mL). The organic layers were washed with water
(2×3 mL), combined, and concentrated to dryness. Purification
of the product was performed by chromatography (see above) to
obtain 4ꢀmethylbiphenyl 3a (0.0293 g, 53%).
4. E. Alacid, D. A. Alonso, L. Botella, C. Nájera, C. Pachero,
Chem. Record, 2006, 6, 117.
5. B. Mu, T. Li, J. Li, Y. Wu, J. Organomet. Chem., 2008,
693, 1243.
6. J. Ma, X. Cui, B. Zhang, M. Song, Y. Wu, Tetrahedron,
2007, 63, 5529.
7. T. Takemoto, S. Iwasa, H. Hamada, K. Shibatomi, M. Kaꢀ
meyama, Y. Motoyama, H. Nishiyama, Tetrahedron Lett.,
2007, 48, 3397.
The Suzuki—Miyaura reactions with aryl chlorides were perꢀ
formed using general procedure A; modifications of conditions
are given in the text. The biphenyl 5 isolated was characterized
8. J. C. Gaunt, B. L. Shaw, J. Organomet. Chem., 1975, 102, 511.
9. F. Yang, Y. Zhang, R. Zheng, J. Tang, M. He, J. Organomet.
Chem., 2002, 651, 146.
1
3
spectrally. H NMR, δ: 7.38 (t, 2 H, pꢀH, J = 7.5 Hz); 7.47
(t, 4 H, mꢀH, 3J = 7.5 Hz); 7.63 (d, 4 H, oꢀH, 3J = 7.5 Hz).
10. O. N. Gorunova, P. A. Zykov, M. V. Livantsov, K. A.
Kochetkov, Yu. K. Grishin, V. V. Dunina, Tez. dokl. Vserosꢀ
siiskoi molodezhnoi konferentsiiꢀshkoly «Idei i nasledie A. E.
Favorskogo v organicheskoi i metalloorganicheskoi khimii
XXI veka» [Abstrs of AllꢀRussian Young Scientists Conferenceꢀ
School "A. E. Favorsky Ideas and Legacy in Organic and Orgaꢀ
nometallic Chemistry of XXI Century" (StꢀPetersburg, March
23—26, 2010), StꢀPetersburg, 2010, p. 224 (in Russian).
11. M. E. Günay, C. J. Richards, Organometallics, 2009, 28, 5833.
12. V. V. Dunina, O. N. Gorunova, E. B. Averina, Yu. K. Grishꢀ
in, L. G. Kuz´mina, J. A. K. Howard, J. Organomet. Chem.,
2000, 603, 138.
This work was partially financially supported by the
Division of Chemistry and Materials Science of the
Russian Academy of Sciences (Grant OKhNMꢀ1) and
the Russian Foundation for Basic Research (Project
No. 08ꢀ03ꢀ92209 GFENa).
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Received April 2, 2010;
in revised form June 30, 2010