Cyclometallation of arylimines and nitrogen-containing heterocycles via room-temperature C-H bond activation with arene ruthenium(ii) acetate complexes

Article abstract of DOI:10.1039/c2dt31401k

The reaction of [RuCl₂(p-cymene)]₂ with arylimines and 4 equiv. of KOAc in methanol at room temperature produces stable (N^C)-cyclometallated ruthenium(ii) complexes via C-H bond activation/ deprotonation. This method can be applied

Full text of DOI:10.1039/c2dt31401k

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Cyclometallation of arylimines and nitrogen-containing heterocycles via
room-temperature C–H bond activation with arene ruthenium(II) acetate
complexes†‡
Bin Li,a Thierry Roisnel,b Christophe Darcel*a and Pierre H. Dixneuf*a
Received 28th June 2012, Accepted 27th July 2012
DOI: 10.1039/c2dt31401k
The reaction of [RuCl2(p-cymene)]2 with arylimines and
4 equiv. of KOAc in methanol at room temperature produces
stable (N^C)-cyclometallated ruthenium(II) complexes via
C–H bond activation/deprotonation. This method can be
applied also to nitrogen-containing molecules: N-phenylpyra-
zole, 2-phenyl-2-oxazoline and benzo[h]quinoline. N-Phenyl-
pyrazole, [RuCl2(p-cymene)]2 and diphenylacetylene directly
lead to alkyne insertion into the metallacycle C–Ru bond.
Surprisingly, whereas arylimines could be functionalized
by catalytic arylation with ruthenium(II) catalysts,15–17 their
cyclometallation with ruthenium(II) complexes is not straightfor-
ward. Previously cationic ruthenium(II) cyclometallated imines
were obtained from benzylideneanilines from RuCl2(PMe3)-
(C6Me6),18 and benzodiazepine offered its arylimine moiety to
generate a ruthenacycle.19 The positive influence of acetate to
promote cyclometallation at room temperature was observed by
Davies13a and two aldimines, containing an N-alkyl group, led
to the (N,C)-cyclometallated product on reaction with RuCl-
(OAc)(p-cymene) but in the presence of benzaldehyde to reach
good yields.13 Whereas arylideneanilines did not lead readily to
the cyclometallated ruthenium(II) complex,13c they easily led to
rhodium or iridium cyclometallated derivatives.13a,14,20 Cyclo-
metallation of arylimines such as oxazolines appears less favor-
able than that of alkylimines and it often failed with ruthenium
and rhodium complexes with respect to iridium promoted
cyclometallation.13c
Aldimine cyclometallation with the ruthenium(II) complex
was previously reported but surprisingly mostly with aldimine
containing an N-alkyl group.13a,18,19 By contrast, catalytic diary-
lation of N-arylimines with arylhalides in the presence of
[RuCl2(p-cymene)]2 1 catalyst activated by KOAc and PPh3 was
recently shown to be successful in both NMP16 and water17 sol-
vents. This reaction is expected to take place via initial formation
of the cyclometallated intermediate that was not observed before
and it motivated our search for imine cyclometallation with the
same complex precursor.
We now report an easy method to directly produce stable
cyclometallated ruthenium(II) complexes of arylimines with a
[RuCl2(p-cymene)]2 precursor, via C–H bond activation/depro-
tonation in the presence of KOAc at room temperature in metha-
nol, a method that can be applied to related nitrogen-containing
heterocyclic molecules. The same reaction in the presence of
alkyne directly leads to alkyne insertion into the cyclometallated
C–Ru bond.
Thus the ruthenium(II) complex 1 was reacted with 2 equiv. of
aldimine 2a in the presence of 2 equiv. of KOAc as it was also
shown to be profitable for C–H bond activation by deprotonation
on cooperative action of both the Ru(II) centre and the acetate
base.6,13 No reaction occurred in THF, but in methanol after only
5 h at room temperature, 36% of orange complex 3a were iso-
lated. The reaction was then performed in the presence of
Catalytic C–H bond activation and functionalisation of arenes
with ruthenium(II) catalysts is a very fast developing area due to
its success in direct arylation1–3 and alkenylation4 reactions. The
regioselectivity of these catalytic reactions is usually controlled
by a nitrogen-containing directing group such as a heterocycle1–4
that is binding to the ruthenium(II) centre. The mechanism of
ruthenium(II) catalysed sp2C–H bond functionalisation involves
as the initial step the easy formation of an (N,C)-cyclometallated
intermediate via ortho C–H bond deprotonation that is favoured
by a reversibly coordinating base such as carbonate5 and
especially carboxylate.6,7 This C–Ru bond formation key step is
followed by more energetic oxidative addition of arylhalides
leading to arylation6 or by insertion of alkenes en route to C–H
alkenylation after β elimination.8,9
Although (N,C)-cyclometallated ruthenium(II) complexes
were initially made by transmetallation from mercury salts,10
they have been shown, especially by Pfeffer et al.11,12 and
Davies et al.,13,14 to arise from N-containing functional arene
derivatives by C–H bond deprotonation, such as from arylmethyl-
amines,10a,11c,12 1-aminotetraline,11d phenylpyrrolidine,11c phenyl-
pyridine,11a,12,14 oxazolines,13b,c and pyrazole.13c
aInstitut des Sciences Chimiques de Rennes, UMR 6226 CNRS –
Université de Rennes 1, Centre of Catalysis and Green Chemistry,
Campus de Beaulieu, 35042 Rennes, France.
E-mail: pierre.dixneuf@univ-rennes1.fr,
christophe.darcel@univ-rennes1.fr
bInstitut des Sciences Chimiques de Rennes, UMR 6226 CNRS –
Université de Rennes 1, Centre de Diffractométrie X, Campus de
Beaulieu, 35042 Rennes, France
†Dedicated to Professor Cole-Hamilton on the occasion of his retirement
and for his outstanding contribution to transition metal catalysis.
‡Electronic supplementary information (ESI) available. CCDC 891360
and 891361. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2dt31401k
10934 | Dalton Trans., 2012, 41, 10934–10937
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Scheme 1 Ruthenium(II) cyclometallation of arylimines.
Fig. 1 X-ray structure of 3d with 50% probability thermal ellipsoids.
Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and
angles (°): Ru–C11 2.0411(17), Ru–N 2.0916(14), Ru–Cl 2.4149(5),
C11–Ru–N 77.26(6), C11–Ru–Cl 86.87(5), Cl–Ru–N 88.27(4), C17–
N19 1.302(2).
Scheme 2
2 equiv. of KOAc and 3 equiv. of K2CO3 but no product was
obtained. This result is consistent with the observation of Jutand
et al.,6 during the phenylpyridine cyclometallation with Ru-
(OAc)2(arene): on addition of K2CO3 the C–H bond activation
process and the cyclometallation were drastically slowed down,
likely due to competitive coordination of carbonate on the ruthe-
nium(II) centre.21 This reaction of 1 and 2a in methanol with
4 equiv. of KOAc at room temperature for 20 h led to the quanti-
tative formation of 3a that was isolated in 90% yield (Scheme 1).
The reactions of aryl aldimines 2a–c and aryl ketimine 2d
with [RuCl2(p-cymene)]2 in the presence of 4 equiv. of KOAc
per ruthenium dimer complex 1 took place at room temperature
in methanol to generate the ruthenium complexes 3a–d isolated
in 52–90% yields (Scheme 1).
It is noteworthy that when complex 1 was reacted with
2 equiv. of KOAc per ruthenium atom, in the absence of aldi-
mine but in methanol at r.t., the quantitative formation of Ru-
(OAc)2(p-cymene)3a,b took place easily (Scheme 2). Thus in the
presence of aldimine in methanol the quantitative metallacycle
formation was fast, with respect to that of Ru(OAc)2(p-cymene),
and one chloride was retained in complex 3a. Actually when this
isolated complex Ru(OAc)2(p-cymene) was formed in methanol,
the addition of aldimine 2a to the methanol solution did not give
the metallacycle 3a. However the reaction of isolated Ru-
(OAc)2(p-cymene) with 2a in the presence of 1 equiv. of KCl in
methanol led to the formation of complex 3a with 66% isolated
yield (Scheme 2). This is consistent with a fast exchange of
OAc−/Cl− in methanol to give the more stable complex 3a con-
taining chloride than acetate, and with Davies’ observation of
the crucial role of the RuCl(OAc)(arene) intermediate for
cyclometallation.13a
Scheme 3 Ruthenium(II) cyclometallation of 1-phenylpyrazole and 2-
phenylpyridine.
1
The H NMR spectrum of 3a shows that the cyclometallated
phenyl H6 and H3 protons are observed as two inequivalent
doublets at δ = 8.19 ppm and δ = 7.54 ppm, respectively. The
1
CHvN proton gives a singlet at δ = 8.10 ppm. The H NMR
data of p-cymene are consistent with a chiral metal centre. The
ν(CvN) free imine absorption at 1621 cm−1 decreases to
1579 cm−1 as expected by coordination of the aryl aldimine
nitrogen. In the 13C NMR spectra, notably the phenylmetallated
carbon atoms of ruthenium complexes 3a–3d are observed at
δ 188–192 ppm, respectively.22
The molecular structure of the new complex 3d was
confirmed by X-ray crystallography. ORTEP drawings with the
corresponding atom labelling are shown in Fig. 1. The structure
shows a typical piano-stool type geometry.13a,22
This easy cyclometallation synthetic method for imines led us
to apply this method in the synthesis of known cyclometallated
Ru(II) complexes. The reaction of 2-phenylpyridine 4 with
[RuCl2(p-cymene)]2 in the presence of 4 equiv. of KOAc led to
the formation of ruthenium cyclometallated complex 5 in 94%
yield after 20 h at room temperature (Scheme 3).6,23 The reaction
of 1-phenylpyrazole 6 with [RuCl2(p-cymene)]2 in the presence
of 4 equiv. of KOAc gave after 20 h at room temperature
complex 713c that was isolated in 79% yield.
2-Phenyloxazoline 8, that was not previously cyclometallated
with the (arene)–ruthenium(II) complex, was reacted with
[RuCl2(p-cymene)]2 in the presence of KOAc in methanol and
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2-phenyl-2-oxazoline and benzo[h]quinoline. The mild reaction
conditions in methanol at room temperature and the action of
4 equiv. of KOAc per ruthenium dimer appear crucial, and are
consistent with C–H bond activation/deprotonation by external
acetate. It is shown that the imine cyclometallated complex is
isolated in the presence of chloride, rather than with only acetate,
and that N-phenylpyrazole and diphenylacetylene and the
complex resulting from alkyne insertion into the metallocycle
C–Ru bond can be obtained directly.
Scheme 4 Ruthenium(II) cyclometallation of 2-phenyloxazoline.
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, and the Chinese Scholarship
Council for a PhD grant to B.L.
Notes and references
Scheme 5 Ruthenium(II) cyclometallation of benzo[h]quinoline.
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Scheme 6 Ruthenium(II) cyclometallation of phenylpyrazole.
led to the formation of complex 9 isolated in 40% yield
(Scheme 4). This low yield may be due to the weak coordinating
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4KOAc in methanol show the crucial role of at least one chloride
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1 equiv. of diphenylacetylene led directly to the formation of
complex 12 that was isolated in 67% yield after 20 h
(Scheme 6). Complex 12 corresponds to the insertion product of
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carbon atomvC(Ph)–Ru moiety a singlet at δ = 183.3 ppm,
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24 This complex 12 was previously obtained by Davies by insertion of
diphenylacetylene into complex 7 (42%).13
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 10934–10937 | 10937