CuI/DABCO-catalyzed cross-coupling reactions of aryl halides with arylboronic acids

Article abstract of DOI:10.1002/ejoc.200600026

CuI combined with DABCO (1,4-diaza-bicyclo[2.2.2]octane) was developed as an inexpensive and efficient catalytic system for the Suzuki-Miyaura cross-coupling of aryl halides with arylboronic acids. The couplings between aryl iodides and arylboronic acids catalyzed by catalytic amounts of CuI and DABCO proceeded smoothly in moderate to excellent yields. However, the CuI/DABCO system was less efficient in the reactions of aryl bromides, and a higher reaction temperature was required to improve the yield. For the less activated aryl bromides, a stoichiometric amount of CuI together with TBAB was necessary to obtain satisfactory yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600026

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600026
CuI/DABCO-Catalyzed Cross-Coupling Reactions of Aryl Halides with
Arylboronic Acids
Jin-Heng Li*[a] and De-Ping Wang[a]
Keywords: CuI / DABCO / Suzuki–Miyaura cross-coupling reaction / Aryl halides / Arylboronic acids
CuI combined with DABCO (1,4-diaza-bicyclo[2.2.2]octane)
was developed as an inexpensive and efficient catalytic sys-
tem for the Suzuki–Miyaura cross-coupling of aryl halides
with arylboronic acids. The couplings between aryl iodides
and arylboronic acids catalyzed by catalytic amounts of CuI
and DABCO proceeded smoothly in moderate to excellent
yields. However, the CuI/DABCO system was less efficient
in the reactions of aryl bromides, and a higher reaction tem-
perature was required to improve the yield. For the less acti-
vated aryl bromides, a stoichiometric amount of CuI together
with TBAB was necessary to obtain satisfactory yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
The Suzuki–Miyaura cross-coupling reaction is well-
known as an extremely powerful tool for the formation of
carbon–carbon bonds in organic synthesis.[1–5] A palladium
complex combined with a ligand (usually a phosphane) is
the most commonly used catalytic system for the reac-
tion.[1–3] In view of the economy, however, the recovery as
well as the recycling of the Pd catalyst is mandatory because
of the prices of these catalysts.[3] In addition, the use of a
cheaper metal instead of Pd as catalyst provides another
attractive route.[1,3–5] Among these, copper has been used in
the Suzuki–Miyaura cross-coupling reaction.[1,4] Rothen-
berg and coworkers have reported that the reactions of a
number of aryl halides with phenylboronic acid catalyzed
by copper or copper-based nanocolloids were conducted ef-
ficiently in moderate to excellent yields. Nevertheless, the
couplings of only aryl iodides were investigated when the
catalyst was copper alone.[4] Thus, the development of more
active copper catalytic systems for the Suzuki–Miyaura
cross-coupling reaction to access a wide range of aryl ha-
lides including aryl bromides and aryl chlorides is still a
challenging area. Very recently, we have described that CuI/
DABCO was an effective and inexpensive catalytic system
for the Heck reaction.[5] Herein we wish to report a CuI/
DABCO-catalyzed Suzuki–Miyaura cross-coupling reac-
tion of aryl iodides and bromides with arylboronic acids
[Equation (1)].[6]
(1)
Results and Discussion
As shown in Table 1, the reaction of 1-iodo-4-methoxy-
benzene (1a) with phenylboronic acid (2a) was chosen as a
model to test the catalytic activity of CuI/DABCO. A series
of ligands were first evaluated (entries 1–8). Without the
aid of ligands, the desired product 3 was isolated in a mod-
erate yield after 20 h in the presence of 10 mol-% CuI,
1 mmol Cs2CO3, and 3 mL DMF (entry 1). However, the
yield increased to nearly quantitative when 20 mol-%
DABCO was added (entry 2). Other ligands, such as Et3N,
TMEDA
DMEDA
(N1,N1,N2,N2-tetramethylethane-1,2-diamine),
(N1,N2-dimethylethane-1,2-diamine),
EDA
(ethane-1,2-diamine), PPh3, and PCy3 showed suppressed
effects (entries 3–8). For example, the yield of 3 was reduced
to 31% when DMEDA was used as the ligand (entry 5).
Different copper catalysts were then examined, and CuI
provided the best results (entries 2 and 9–12). It is note-
worthy that no reaction was observed in the absence of cop-
per catalysts (entry 9). Finally, we checked the effects of
both the solvents and the bases on the reaction (entries 2
and 13–18). The results demonstrated that the highest yield
of 3 was obtained when DMF was employed as the medium
together with Cs2CO3 as the base.
[a] Key Laboratory of Chemical Biology & Traditional Chinese
Medicine Research, College of Chemistry and Chemical Engi-
neering (Ministry of Education), Hunan Normal University,
Changsha 410081, China
Subsequently, the CuI/DABCO catalytic system was ex-
tended to various aryl iodides and bromides, and the results
are summarized in Table 2. Treatment of aryl iodides 1b–
e with arylboronic acids 2a–d, CuI (10 mol-%), DABCO
(20 mol-%), and Cs2CO3 (1 mmol) afforded the desired cou-
pled products 3–9 in moderate to excellent yields (entries
Fax: + 86-731-8865-515
E-mail: jhli@hunnu.edu.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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J.-H. Li, D.-P. Wang
SHORT COMMUNICATION
Table 1. Copper-catalyzed cross-coupling reaction of 1-iodo-4-methoxybenzene (1a) and phenylboronic acid (2a).[a]
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), catalyst (10 mol-%), ligand (20 mol-%), and base (1 mmol) in solvent (3 mL) at
125–130 °C for 20 h. [b] Isolated yield.
1–7). However, the activity of the CuI/DABCO catalytic to 68% when 0.5 mmol TBAB was added (entry 15). In-
system was reduced in the couplings of aryl bromides. Low creasing the amount of TBAB to 1 mmol resulted in
yields were obtained even from the reaction of the activated 77% yield of 3 (entry 16). Other bromides 1i–k worked
bromides 1f and 1g with 2a, performed at 125–130 °C (en- well under these conditions (entries 17–20). An attempt to
tries 8 and 10). We were pleased to find that good yields couple the activated chloride 1l was unsuccessful
were achieved when the reaction temperature was increased (entry 21).
to 150 °C (entries 9 and 11). However, the coupling of the
deactivated aryl bromide 1h was not successful under the
same reaction conditions. In many of the earlier reports on
Cu-mediated transformations,[7] the addition of a stoichio-
metric amount of CuI often results in satisfactory yields of
the expected products. Accordingly, we decided to increase
Conclusion
the amount of CuI to improve the reaction yields. To our
In summary, we have developed an inexpensive and ef-
delight, the corresponding product 3 was isolated in a mod- ficient protocol for the Suzuki–Miyaura cross-coupling re-
erate yield when the loading of Cu was increased to action catalyzed by the CuI/DABCO system. A variety of
100 mol-% (entries 12–14). It is interesting to find that aryl halides including iodides and bromides, whether elec-
TBAB (Bu4NBr) has a beneficial effect on the reaction (en- tron-rich or electron-deficient, all coupled with arylboronic
tries 14–16). In the presence of CuI (100 mol-%) and acids to give moderate to excellent yields. Further investi-
DABCO (200 mol-%), the coupling of 4-bromo-1-methoxy- gations to extend the application of the system in other
benezene (1h) with 2a gave the corresponding product 3 in coupling transformations and overcome the drawbacks of
45% yield (entry 14), whereas the yield of 3 was enhanced the less activated aryl bromides are in progress.
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CuI/DABCO-Catalyzed Cross-Coupling of Aryl Halides with Arylboronic Acids
SHORT COMMUNICATION
Table 2. CuI/DABCO-catalyzed cross-coupling reactions of aryl halides (1) with arylboronic acids (2).[a]
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), CuI (10 mol-%), DABCO (20 mol-%), and Cs2CO3 (1 mmol) in DMF (3 mL) at
125–130 °C. [b] Isolated yield. [c] At 150 °C. [d] CuI (50 mol-%) and DABCO (100 mol-%). [e] CuI (100 mol-%) and DABCO (200 mol-
%). [f] TBAB (0.5 mmol). [g] TBAB (1 mmol).
Typical Experimental Procedure for the CuI/DABCO-Catalyzed
Experimental Section
Suzuki–Miyaura Cross-Coupling Reactions:
A mixture of 1
General Remarks: 1H- and 13C NMR spectra were recorded with
an INOVA-400 (Varian) spectrometer and a Bruker AMX-300
spectrometer with the use of CDCl3 as solvent. All reagents were
directly used as obtained commercially. All products 3–12 are
known, and their analytical data and spectra (1H- and 13C NMR)
are available in the Supporting Information.[2–5]
(0.50 mmol), 2 (0.60 mmol), CuI (the indicated amount in Table 1
and Table 2), DABCO (the indicated amount in Table 1 and
Table 2), Cs2CO3 (2 equiv.), and DMF (3 mL) was stirred under
nitrogen at 125–150 °C until the starting material was consumed
completely, as determined by TLC. The mixture was then filtered,
washed with H2O, extracted with diethyl ether, and the solvent was
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J.-H. Li, D.-P. Wang
SHORT COMMUNICATION
15195–15201; g) T. E. Barder, S. D. Walker, J. R. Martinelli,
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evaporated. The residue was purified by flash column chromatog-
raphy (hexane or hexane/ethyl acetate) to afford the desired cou-
pled products.
Supporting Information (see footnote on the first page of this arti-
cle): Analytical data and spectra (1H- and 13C NMR) of com-
pounds 3–12.
Acknowledgments
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We thank the National Natural Science Foundation of China (Nos.
20202002 and 20572020), the Hunan Provincial Natural Science
Foundation of China (No. 05JJ1002), and the Scientific Research
Fund of the Hunan Provincial Education Department (No.
05B038) for financial support.
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Received: January 15, 2006
Published Online: March 13, 2006
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