C-H bond functionalisation with [RuH(codyl)2]BF4 catalyst precursor

Article abstract of DOI:10.1039/c1gc15642j

Direct catalytic diarylation with (hetero)arylhalides of arenes containing an heterocycle (pyridine, oxazoline, pyrazole) has been performed with a ruthenium catalyst assisted by a coordinating base. It constitutes a green process for cross-coupled C-C bo

Full text of DOI:10.1039/c1gc15642j

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C–H bond functionalisation with [RuH(codyl)2]BF4 catalyst precursor†
Wenbo Li, Percia B. Arockiam, Cedric Fischmeister,* Christian Bruneau and Pierre H. Dixneuf*
Received 2nd June 2011, Accepted 23rd June 2011
DOI: 10.1039/c1gc15642j
Direct catalytic diarylation with (hetero)arylhalides of
arenes containing an heterocycle (pyridine, oxazoline,
pyrazole) has been performed with a ruthenium catalyst
assisted by a coordinating base. It constitutes a green
process for cross-coupled C–C bond formation without
any metal salt waste. The new catalytic system is based on
[HRu(codyl)2]BF4/2KY (KY: KOAc, KOPiv, KPI (potas-
sium phtalimide)] in which the assisting ligand Y promotes
the initial cleavage of C–H bonds. It is shown that the
efficiency of the Ru/2KY system strongly depends on the
nature of both substrates.
formal insertion of alkyne8a into ortho C–H bonds and the direct
vinylation of heterocycles.9
It was proposed based on DFT calculations that the initial step
of Ru(II) promoted C–H bond activation involves its cleavage
via deprotonation assisted by the coordinated carbonate base
(eqn (1): M-Y: Ru-O2COH).6 This Ru(II) catalysed mechanism
shows some analogy with Pd catalysed C–H bond activation,
via a Pd(II)-acetate intermediate, by assistance of the acetate10
or concerted metalation deprotonation.11 Moreover, it has
recently been shown that the presence of a carboxylate ligand
(AcO-, PivO-, MesCO2 , AdCO2 , . . . ) linked to a Ru(II)
site tremendously favours the C–H bond activation followed
by functionalisation, and are suitable for arylation5–7 and
even alkylation.12 This C–H bond deprotonation assisted by
carboxylate and Ru(II) centre involves an autocatalytic process
in which the formed RCO2H acid plays a crucial role.13
-
-
Direct catalysed C–H bond functionalisation of aromatic com-
pounds by arylhalides attracts interest as a substitute for
the classical catalytic cross-coupling reaction as it allows the
formation of functional (hetero)aryl-aryl derivatives without
initial formation of a stoichiometric amount of the usual
organometallic intermediates (Li, Mg, Zn, B, Sn . . . ). This
catalytic C–H bond activation/functionalisation offers a greener
process with higher atom economy as the acid HX is the only
by-product (eqn (1)).
Thus the use of stable ruthenium(II) catalysts offers high
potential for C–H bond functionalisation via green catalysis.
The most commonly used ruthenium precursors for C–H bond
cleavage by carboxylate and carbonate include precursors such
as [RuCl2(p-cymene)]2,5–7,12 and RuCl3.5d,5f,8 The development of
C–H bond functionalisation activated by ruthenium(II) catalysts
requires that new accessible ruthenium precursors containing
labile hydrocarbon ligands are explored, which are able to be
assisted by carbonate or carboxylate ligands, and contribute to
the development of greener cross-coupling processes.
(1)
5
We now report that [RuH(codyl)2]BF4 A (codyl = h -
cyclooctadienyl), a precursor for Ru(II) complexes, can be
used for C–H bond functionalisation of arenes with (het-
ero)arylhalides, especially with cheap and available chloride
derivatives under mild conditions. We show that its efficiency
is favoured by carboxylate and phtalimide ligands that can be
used to promote diarylation reactions.
For C–H bond functionalisation a variety of metal catalysts
have already shown excellent efficiency.1 Among them ruthe-
nium catalysts are tremendously contributing to this field. Initial
results involved Ru(0) catalysts favouring oxidative addition of
the C–H bond and then insertion of an unsaturated substrate
into the resulting C–Ru–H bonds.2,3 Ruthenium(II) catalysts have
now shown their ability to activate functional arene C–H bonds
close to the directing group (DG), allowing the C–C bond cross-
coupling reaction with aryl halides.4–7 They also promote the
Results and discussion
The complex [RuH(codyl)2]BF4 A was selected as it is easily
made from Ru(COD)(COT), and was shown to be a precursor
for a variety of ruthenium(II) complexes on deprotonation and
reactions with hydrocarbon or 2 electron ligands.14 We first
explored the direct arylation with arylchlorides of phenyl-2-
pyridine promoted by potential catalyst A (5 mol%) in the
presence of 2 eq. of several carboxylates (10 mol%) to evaluate
the influence of the carboxylate nature (eqn (2), Table 1). The
Catalyse et Organome´talliques, UMR 6226: CNRS-Universite´ de
Rennes, Institut Sciences Chimiques de Rennes, Campus de Beaulieu,
35042, Rennes, France. E-mail: pierre.dixneuf@univ-rennes1.fr
† Electronic supplementary information (ESI) available: Experi-
mental procedures, spectroscopic and analytical data. See DOI:
10.1039/c1gc15642j
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Table 1 Diarylation of phenylpyridine with RuH(Codyl)2BF4/2
carboxylate is crucial for a given ruthenium(II) catalyst, as with
Ru(O2CR)2(p-cymene) containing pivalate C, in situ generated
from [RuCl2(p-cymene)]2 B, the same reaction was shown to
be more efficiently performed in diethylcarbonate7b than with
Ru(OAc)2(p-cymene). The reaction can be carried out with 10
mol% of PhCO2K, HCO2K or CF3CO2K for 5 mol% of catalyst
A and each of them brings only a slight improvement of activity
with respect to catalyst A alone (entries 1, 6, 7, 8). By contrast
it is noteworthy that a fatty acid and camphoric acid (entries 9–
12) both provide good activity when associated to the ruthenium
precursor A, as diarylation is almost completed after only 2 h.
We then explored the influence, instead of KO2CR ligand on
catalyst A, of 2 eq. of potassium phtalimide (KPI), which led to
a very positive improvement of catalyst activity (entry 13, 14).
Actually it led to the best catalyst system for the arylation by
PhCl of phenylpyridine as it is competitive with the catalyst A
associated to KOAc (entry 2, 3, 13, 14), and after only 1 h the
diarylation was completed.
The reaction of other arylchlorides and heteroarylhalides
with phenylpyridine has then been performed with 5 mol% of
[RuH(codyl)2]BF4 A with 2 eq. of additive (carboxylate or KPI).
The results are displayed in eqn (3) and Table 2. 2-Chlorotoluene
is as expected much less reactive than phenylchloride and at least
12 h at 120 ◦C were necessary to reach complete conversion
of phenylpyridine. The sequence of efficiency for diarylation
was this time KOAc > KOPiv ª KPI (entries 1, 2, 3). With
KOAc the disubstituted product 4 could be isolated in 72%
yield (entry 2). These results show that this catalytic system
(A/2KOAc) displayed the same activity for this reaction as
the catalyst Ru(OPiv)2(p-cymene) C in diethylcarbonate (DEC)
(entry 4).7b
KO2CRa
No.
Ligand
Time (h)
Conv. (%)b
M/Dc
1
2
3
4
5
6
—
KOAc
2
2
1
2
1
2
92
38/62
1/99
6/94
1/99
27/73
16/84
100
100
100
100
100
KOPiv
7
8
2
2
100
100
29/71
22/78
9
10
2
1
100
100
5/95
29/71
11
12
2
1
100
100
3/97
13/89
13
14
2
1
100
100
0/100
2/98
a Reaction conditions: 0.5 mmol of phenylpyridine,
5
mol% of
[RuH(codyl)2]BF4 A, KO2CR or KPI (10 mol%), 3 eq. of K2CO3, 10 mL
of tetradecane as internal standard for GC, 1.25 mmol of chlorobenzene
in 2 mL of NMP. b Conversion determined by gas chromatography using
tetradecane as internal standard. c Ratio Monoarylated/Diarylated
products M/D (2/3) determined by gas chromatography.
diarylation of phenylpyridine was attempted with 2.5 eq. of
phenylchloride and 3 eq. of K2CO3 in NMP at 120 ◦C.
(3)
The diheteroarylation was then attempted with 2-
thienylchloride and the formation of the bis thienyl derivative
5 was better achieved in the presence of KOAc with catalyst A
than KPI (entries 5, 6). Under entry 6 conditions compound 5
was isolated in 72% yield.
(2)
The formation of the tripyridyl-1,2,3-benzene 6 was then
studied in the presence of catalyst A by the reaction of
phenylpyridine with 2-bromo-6-methylpyridine (entries 7–
8). Surprisingly only with this heteroarylhalide, the addi-
tion of KOAc to [RuH(codyl)2]BF4 deactivates the catalyst
system.
However, the catalyst A only in the presence of coordinating
carbonate at 150 ◦C allows the mono and diarylation (entry
8). Catalyst Ru(OPiv)2(p-cymene) C appears to be the best
catalyst to reach the trispyridine derivative 6 (entry 9). The
action of KPI as additive slows down the reaction but especially
After 2 h the diarylation was completed with KY = KOAc
and KOPiv (KO2CCMe3) but not in the carboxylate absence
(Table 1, entries 1, 2, 4). K2CO3 was selected as the added
base because using the conditions in entry 4, the following
sequence was established after 2 h at 120 ◦C: (conversion:
mono 2/diarylated 3): K2CO3 (100%: 1/99) > KHCO3 (100%:
27/73) > K3PO4 (100%: 33/67). The same reaction performed
at 120 ◦C for 1 h (entries 3, 5) showed the highest efficiency of
acetate ligand with respect to pivalate. Thus the nature of the
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Table 2 Arylation of phenylpyridine with heterocyclic halides and aryl halidesa
Entry
Het-X
Ligand Additive
T (h)
Conv. (%)
Product
M/D (IY)b
1
2
3
4
KPI
KOAc
KOPiv
Catalyst C
12
12
12
12
100
100
100
100
30/70 (42)
6/94 (72)
27/73 (48)
8/92c
5
6
KPI
KOAc
16
16
72
100
30/70
1/99 (72)
7
8
9
KPI
No ligand
Catalyst C
24 (120 ◦C)
24 (150 ◦C)
16 (120 ◦C)
100
92
100
60/40
25/75
8/92
10
11
KOAc
KPI
1
100
76
0/100 (94)
24
(71)
a Reaction conditions and conversion as in Table 1. b Isolated yields. c In diethylcarbonate7b
the diarylation with respect to monoarylation (entry 7) and
suggests that this system might be selected later to produce
more selectively monoarylated products under appropriate
conditions.
The diarylation with an electron withdrawing aryl bromide
NC–C6H4–Br was very succesful. Catalyst A with 2 KOAc very
quickly gives the diarylated product 7 (entry 10) whereas KPI
deactivates the system to generate only 28% conversion (75/25).
The diarylation with 4-bromomethyl benzoate was selectively
performed by A/2 KPI and after 24 h the pure derivative 8 was
isolated in 71% yield (entry 11).
(4)
The arylation with phenylchloride of two arenes containing
a heterocycle as the directing group, phenylpyrazole 9 and
phenyloxazoline 10, have been performed (eqn 4, 5). The
phenylpyrazole was completely diarylated, to give derivative 12,
in the presence of the catalyst system [RuH(codyl)2]BF4/2KOPiv
in only 3 h at 120 ◦C. The [RuH(codyl)2]BF4/2KOAc system
leads to slightly lower activity. By contrast KPI as additive shows
a much lower activity affording this time a mixture of mono and
diarylated products (eqn 4).
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The complete diphenylation of phenyloxazoline 10 into
derivative 13 requires only 4 h at 120 ◦C in the presence
of the catalyst system [RuH(codyl)2]BF4/2KOPiv (eqn (5)),
whereas the related KOAc system affords 97% conversion (8
monoarylation/92 diarylation 13) after 3 h and KPI leads to
lower conversion of 10. It is noteworthy that the derivatives 12
and 13 were previously obtained in the presence of R◦u(OPiv)2(p-
cymene) catalyst in more drastic conditions at 120 C for 10 h
and 16 h respectively.7b Thus the catalyst A /2 KO2CR appears
an efficient catalyst for production of diarylated heterocycles 12
and 13, but with the best assistance of KOAc or KOPiv. Thus
for each heterocycle the best assisting ligand has to be found for
a given ruthenium catalyst precursor and substrate.
Conclusion
The above results show that catalyst [RuH(codyl)2]BF4
A
appears to be an excellent catalyst precursor to perform direct
arylation with aryl- and heterohalides of arenes with a N-
containing heterocycle as the directing group, via a greener
process rather than via classical organometallic cross coupling
reactions. However, this catalyst is very sensitive to the nature
of the assisting ligand, carboxylate or potassium phtalimide
(KPI) and the efficiency strongly depends on the nature of the
used (hetero)aryl halides for a given functionalized arene. The
comparison of catalyst A/2KY, for which the structure of active
species has to be elucidated, with the previous in situ prepared
Ru(O2CR)2(arene) catalysts shows that they are complementary
as, at this point for a suitable substrate, the nature of both the
ruthenium precursor and the assisting ligand has to be selected
to find the best catalyst system. This selection will become
a key for the success of ruthenium(II) promoted C–H bond
functionalisation.
(5)
Acknowledgements
The authors are grateful to CNRS, the French Ministry for
Research, the Institut Universitaire de France (P.H.D.), the
ANR program 09-Blanc-0101-01 for support and PhD grant
to P. A.
The diarylation with 1,4-dihalobenzene has then been inves-
tigated in order to study the selectivity of the arylhalide reaction
and to form dihalide containing pyridines for the profit of further
cross-coupling reactions and as bifunctional monomers (eqn
(6)).
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