A versatile catalyst system for Suzuki-Miyaura syntheses of sterically hindered biaryls employing a cyclobutene-1,2-bis(imidazolium) salt

Article abstract of DOI:10.1039/c001362e

The catalyst system consisting of 3,3′-(3,4-bis(dichloro-methylene) cyclobut-1-ene-1,2-diyl)bis(1-methyl-1H-imidazolium) bis(tetrafluoroborate), Pd(OAc)₂ and NaOtBu in toluene proved to be very effective for a broad variety of Suzuki-Miyaura reactions at room temperature. It is also suited for the synthesis of sterically hindered compounds including 2,6-di-tert-butyl-2′-substituted biaryls at elevated temperatures. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/c001362e

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A versatile catalyst system for Suzuki–Miyaura syntheses of sterically
hindered biaryls employing a cyclobutene-1,2-bis(imidazolium) saltw
Andreas Schmidt* and Alireza Rahimi
Received (in Cambridge, UK) 20th January 2010, Accepted 19th February 2010
First published as an Advance Article on the web 5th March 2010
DOI: 10.1039/c001362e
The catalyst system consisting of 3,30-(3,4-bis(dichloro-methylene)-
cyclobut-1-ene-1,2-diyl)bis(1-methyl-1H-imidazolium) bis(tetra-
fluoroborate), Pd(OAc)2 and NaOtBu in toluene proved to be
very effective for a broad variety of Suzuki–Miyaura reactions
at room temperature. It is also suited for the synthesis of
sterically hindered compounds including 2,6-di-tert-butyl-20-
substituted biaryls at elevated temperatures.
when sodium tert-butylate was used as base. Thus, the reaction
of 1.0 mmol of 4-bromotoluene, 1.2 mmol of phenylboronic
acid, 1.7 mmol of NaOtBu, 1.0 mol% of Pd(OAc)2, and 1.0 mol%
of the bis(imidazolium) salt 3 conducted in 5.0 mL of toluene
at room temperature gave 96% of 4-phenyltoluene.
The Suzuki–Miyaura reaction has become an extremely
versatile and successful synthetic tool for carbon–carbon bond
formation.1,2 A broad substrate scope, methods to prepare
sterically hindered biaryls, the ability to operate at low levels
of catalyst for a range of substrates, and the ability to work at
room temperature have been the most important goals of
rational catalyst design,3,4 and remarkable success has been
achieved in the last years.1–4 As the Suzuki–Miyaura reaction
is inter alia influenced by parameters such as palladium source,
ligand, additive, solvent, stoichiometry, and temperature, a
plethora of protocols for accomplishing this transformation
has been published. With respect to this, poly(N-heterocyclic
carbene)s have attracted considerable attention as ligands
because they allow the preparation of organometallic
compounds with a broad variety of geometries.5 In continuation
of our interest in N-heterocyclic carbenes6 we report here a
new cyclobutene-1,2-bis(imidazolium) salt as very efficient
catalyst precursor for a broad variety of Suzuki–Miyaura
reactions at room temperature. The system can also successfully
be employed for the synthesis of sterically hindered tri- and
tetra-ortho-substituted biaryls.
Table 1 summarizes our results starting from (het)aryl
chlorides, iodides, and triflates which all efficiently cross-
coupled with arylboronic acids at room temperature in short
periods of time. As a comparison, 1-(biphenyl-4-yl)ethanone
(entry 2) has been prepared before at rt within 16–40 h in
50–92% yield,8 or in a microreactor on a polymer-bound
Pd–NHC catalyst in 99% yield.9 To the best of our knowledge,
the other transformations presented in Table 1 are new.
Table 1 Suzuki–Miyaura reactions at rt
(het)aryl–
Entry (het)aryl–X B(OH)2
(het)aryl–
(het)aryl
Yield
Time/h (%)
1
2
3
0.5
1
96a
92b
94b
The bis(imidazolium) salt was prepared starting from
perchloropropene
1
which formed 1,2-dichloro-3,4-bis-
(dichloro-methylene)cyclobut-1-ene 2 on treatment with Al/Hg.7
Reaction of cyclobutene 2 with 1-methylimidazole (NMI)
resulted in the formation of (cyclobut-1-ene-1,2-diyl)bis-
(1-methylimidazolium) chloride which was subjected to anion
exchange in a one-pot procedure. Thus, tetrafluoroborate 3
was formed in 73% yield from 2. The salt 3 possesses no water
of crystallization and its purification is simple (ESIw).
1
4
5
3.5
3.5
90a
91a
We selected 4-bromotoluene and phenylboronic acid to
optimize the conditions of Suzuki–Miyaura reactions
(Table 1, entry 1). THF, 2-propanol, and toluene proved to
be suitable solvents (ESIw), but toluene gave the best results,
6
7
3
93b
1.25
93b
88b
Clausthal University of Technology, Institute of Organic Chemistry,
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany.
E-mail: schmidt@ioc.tu-clausthal.de; Fax: +49-5323-722858;
Tel: +49-5323-723861
w Electronic supplementary information (ESI) available: Experimental
details and characterization data. See DOI: 10.1039/c001362e
8
2
a
b
1.0 mol% Pd(OAc)2, 1.0 mol% 3, 1.7 eq. NaOtBu. 2.0 mol%
Pd(OAc)2, 2.0 mol% 3, 1.7 eq. NaOtBu.
ꢀc
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The synthesis of sterically extremely hindered tri- and
tetra-ortho biaryls under mild conditions remains a challenge
for Suzuki–Miyaura cross-coupling reactions.10,11 We tested
our system starting from bromides and chlorides as shown in
Table 2.
tetra-ortho-substituted biaryls within 24 h.10 Using our
catalytic system, 2,20,4,6,60-pentamethylbiphenyl is formed
starting from 2-bromo-1,3-dimethylbenzene and mesityl boronic
acid in 87% yield after only 3.5 h at 60 1C (Table 2, entry 1).
Literature procedures for the synthesis of this compound give
either considerably lower yields,14 or require temperatures up
to 150 1C,15 or need 24 h of reaction time at 65 1C.10 Starting
from 2-chloro-1,3,5-trimethylbenzene and 2,6-dimethyl-
phenylboronic acid (entry 2) the same biaryl is formed under
comparable conditions as reported.16 The synthesis of 1-(2,6-
dimethylphenyl)-2-methylnaphthalene (entry 3), however, also
proceeds in considerably shorter time (4.5 h vs. 24 h) in
comparison to the usage of Pd-PEPPSI-IPent, although in
Tetra-ortho-substituted biaryls can successfully be formed
from aryl bromides using hindered biarylphosphine ligands
and Pd2(dba)3 at 100 1C–110 1C,4,12 or from aryl chlorides in
the presence of IBiox12ꢁHOTf/Pd(OAc)2 at 110 1C.13 In
addition, ruthenocenylphosphine R-Phos/Pd(dba)3 at 50 1C
to 100 1C proved to be a suitable catalyst system.14 To overcome
the major drawback of significantly elevated temperatures,
Pd-PEPPSI-IPent was employed as catalyst at 65 1C to prepare
Table 2 Suzuki–Miyaura syntheses of tri- and tetra-ortho-substituted biaryls
Entry
1
Aryl–X
Aryl–B(OH)2
Aryl–aryl
Time/h
3.5
Temp./1C
Yield (%)
87a
60
2
3
4
90
70
79a
86a
4.5
4
5
3
3
50
60
91b
89a
6
7
4.5
90
90a
7
90
46b
8
9
10
110
39a
10
10
110
90
37a
79a
10
a
b
2.0 mol% Pd(OAc)2, 2.0 mol% 3, 2 eq. NaOtBu. 2.0 mol% Pd(OAc)2, 2.0 mol% 3, 1.7 eq. of NaOtBu.
ꢀc
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almost identical yields.10 20-Isopropoxy-2,4,6-triisopropyl-
biphenyl (entry 7) was obtained in 46% yield at 90 1C using
our catalytic system. This compound has previously been
prepared in the presence of the aforementioned biphenylene-
substituted ruthenocenylphosphine in 19% yield at 50 1C.14
The title catalyst system was also able to couple 2,6-di-tert-
butyl-6-methylbromobenzene with 2-methylboronic acid and
2-methoxyboronic acid, respectively (Table 2, entries 8 and 9).
Although the conversion of the starting materials is 81% and
54%, respectively, the isolated yields of the biaryls are moderate,
as CH-activation occurred to give a,a-dimethyl-b-aryl hydro-
styrene derivatives as by-products. In a literature-known
procedure, the reaction of 2,4,6-tri-tert-butylbromobenzene
with 2-methylphenylboronic acid using 2-(20,60-dimethoxybi-
phenyl)dicyclohexylphosphine as a ligand yielded an analogous
by-product, but no aryl coupling at all was detectable.4 Thus,
to the best of our knowledge, these reactions presented
here are the first Suzuki–Miyaura syntheses of 20-substituted
2,6-di-tert-butyl-biaryls. The Suzuki–Miyaura synthesis of
9-(2-methylnaphthalen-1-yl)anthracene (entry 10) was finished in
10 h at 90 1C, whereas the usage of 2 mol% of Pd-PEPPSI-IPent
required 24 h at 65 1C to give a yield of 88%.10
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´
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1965; conditions: 0.1–0.2 mol% of Pd(OAc)2, Aphos ligand,
K3PO4, 36–40 h, 81–92%: W.-M. Dai, Y. Li, Y. Zhang, C. Yue
and J. Wu, Chem.–Eur. J., 2008, 14, 5538.
In summary we present a new cyclobutene-1,2-bis(imidazolium)
salt as component of
a versatile catalyst system for
Suzuki–Miyaura reactions at rt and for the preparation of
sterically hindered biaryls.
9 Conditions: imidazol-2-ylidene catalyst on polyvinylpyridine: 1 h,
99%: K. Mennecke and A. Kirschning, Synthesis, 2008, 3267.
10 M. G. Organ, S. C¸ alimsiz, M. Sayah, K. H. Hoi and A. J. Lough,
The Deutsche Forschungsgemeinschaft DFG is gratefully
acknowledged for financial support.
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ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 2995–2997 | 2997