Ruthenium(II) pincer complexes with oxazoline arms for efficient transfer hydrogenation reactions

Article abstract of DOI:10.1016/j.tetlet.2012.06.041

Well-defined P^NN^CN pincer ruthenium complexes bearing both strong phosphine and weak oxazoline donors were developed. These easily accessible complexes exhibit significantly better catalytic activity in transfer hydrogenation of ketones compared to their PN³P analogs. These reactions proceed under mild and base-free conditions via protonation- deprotonation of the 'NH' group in the aromatization-dearomatization process.

Full text of DOI:10.1016/j.tetlet.2012.06.041

Tetrahedron Letters 53 (2012) 4409–4412
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ruthenium(II) pincer complexes with oxazoline arms for efficient transfer
hydrogenation reactions
⇑
Tao Chen, Li-Peng He, Dirong Gong, Limin Yang, Xiaohe Miao, Jörg Eppinger, Kuo-Wei Huang
KAUST Catalysis Center and Division of Chemicals and Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955 6900, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Well-defined PNNCN pincer ruthenium complexes bearing both strong phosphine and weak oxazoline
donors were developed. These easily accessible complexes exhibit significantly better catalytic activity
in transfer hydrogenation of ketones compared to their PN3P analogs. These reactions proceed under mild
and base-free conditions via protonation–deprotonation of the ‘NH’ group in the aromatization–dearo-
matization process.
Article history:
Received 28 April 2012
Revised 27 May 2012
Accepted 8 June 2012
Available online 15 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Ruthenium
Pincer
Catalysis
Transfer hydrogenation
Transition metal complexes with rigid tridentate pincer ligands
have been studied extensively because their chemical and physical
properties can be tuned by varying the steric and electronic param-
eters of the donor groups to afford interesting and useful reactivi-
ties.1 Many of these complexes have been employed to facilitate a
variety of organic transformations, including carbon dioxide reduc-
tion,2 catalytic dehydrogenation of alkanes,3 catalytic hydrogena-
tion of ketones,4 hydrosilylation of aldehydes and ketones,5
transfer hydrogenation of ketones,6 cross-coupling,7 selective
decarbonylation reactions of alkyl formates and alkynyl aldehydes,8
dehydrogenation of alcohols to ketones,9 dehydrogenative homo-
coupling of primary alcohols to esters,10 direct amidation from
alcohols and amines,11 light-induced water splitting,12 etc. Among
these applications, the concept of cooperative catalysis has received
increasing attention. One of the most remarkable examples is Mil-
stein’s PNN–Ru system.13 The unprecedented reactivities of the
PNN system are believed to be attributed to the introduction of a
hemi-labile donor in the pincer ligand and the ability of the pyri-
dine ring to undergo dearomatization and rearomatization, result-
ing in a ligand that can act cooperatively with the metal center
for substrate activation. Based on a similar concept, analogous
ruthenium complexes using N-heterocyclic carbenes as an alterna-
tive to phosphine donors have also been reported (Fig. 1).14
pincer ligand and offer different reactivities. Pincer ligands with
N–H spacers have been synthesized,16 but their involvement in cat-
alytic reactions has not been studied until our recent work. We have
demonstrated that a dearomatized ruthenium complex based on a
PN3P ligand employing an NH spacer displays good catalytic activ-
ities in transfer hydrogenation of ketones at 82 °C.17 It was envis-
aged that replacement of one of the phosphine groups with a
weaker donor may allow the ligand to dissociate from the metal
center more easily and to facilitate the hydride elimination of a
plausible isopropoxide intermediate,12 and may consequently in-
crease the catalytic activities of this type of pincer catalyst. Oxazo-
lines, derived from amino alcohols, are a sub-class of azole
heterocycles, which commonly act as weak donors. Pincer com-
plexes containing one or two oxazoline groups have received
increasing attention due to their easy accessibility from a wide vari-
ety of commercially available aminoalcohols.18 With this consider-
ation in mind, we combined a phosphine ligand using NH as the
linker and an oxazoline ring as a relatively weaker donor to create
new ligands. Herein, we report the synthesis of novel hemilabile
PNNCN pincer ligands and their Ru(II) complexes, which show sig-
nificantly improved activities in transfer hydrogenation of ketones
compared to those of analogous complexes with the symmetric
PN3P ligand.
Compared to C–H bonds, N–H bonds are in general more
acidic.15 Replacement of the CH2 spacer of the phosphine arm with
an NH may favor the deprotonation/dearomatization of the PNN-
Starting from commercially available 6-bromopicolinic acid
(1), N-(di-tert-butylphosphino)-6-(4,5-dihydrooxazol-2-yl)pyridin
-2-amine (PNNCN 6a) and N-(di-tert-butylphosphino)-6-(4,4-di-
methyl-4,5-dihydrooxazol-2-yl)pyridin-2-amine (PNNCN 6b) were
prepared conveniently in high yields (Scheme 1). Upon treatment
with oxalyl chloride in tetrahydrofuran (THF), acid 1 reacted with
amino alcohols in the presence of triethylamine to afford
⇑
Corresponding author. Tel.: +966 2 808 0328.
E-mail address: hkw@kaust.edu.sa (K. -W. Huang).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.041

4410
T. Chen et al. / Tetrahedron Letters 53 (2012) 4409–4412
N
N
Ru
CO
N
Ru
CO
Cl
Cl
Cl
R
tBu2
tBu2
P
N
NEt2
P
PtBu2
Ru
Ar = Mes, 2,6-iPr2C6H3
H
H
H
CO
N
Ar
A
B
R = NEt2,
N
C
O
O
O
N
O
HN
P
N
Ru
CO
NH
HN
P
N
Ru
CO
Cl
Cl
PtBu2
N
tBu2
tBu2
Ph2P
M
Br
H
H
R
R
this work
D
E
M = Pd, Pt
Figure 1. Various pincer complexes.
1. (COCl)2, THF
H
N
O
OH
Br
N
Br
N
N
OH
Cl
2. amino alcohol, Et3N
R
R
R
O
1
2a,b
H
H
NH4OH
Cu
SOCl2
CHCl3
N
N
H2N
N
OH
H2N
R
R
R
O
O
3a,b
4a,b
tBu2PCl
Et3N, n-BuLi
NaH
O
O
R
H2N
N
HN
N
tBu2
P
N
N
R
R
R
6a,b
R = H
b R = Me
5a,b
a
Scheme 1. Synthetic route for the preparation of ligands 6a–b.
compounds 2a,b in 76% and 81% overall yields, respectively. Amides
2a,b were then heated with ammonium hydroxide in the presence of
copperina pressuretubeat100 °C for24 h togiveaminocompounds
3a,b as whitesolids in 70% and 72% yields. It was noted that the oxaz-
oline group could undergo ring-opening under the above-men-
tioned conditions, so the amination must be conducted before
constructing the oxazoline. Substitution of the hydroxy group of
3a,b with a chlorine was achieved by reaction with thionyl chloride
in chloroform at reflux to produce compounds 4a,b in 96% and 95%
yields.19 The oxazoline rings were generated by deprotonating
4a,b with sodium hydride followed by intramolecular nucleophilic
substitution to afford 5a,b in 72% and 81% yields. The phosphine do-
nors were introduced according to Benito-Garagorri’s strategy by
treating 5a,b with one equivalent of di-tert-butylchlorophosphine
in the presence of triethylamine and n-butyllithium to give oxazo-
lines 6a,b, which were sufficiently pure to be used without
purification.16a
Reaction of the new pincer ligands 6a,b with Ru(PPh3)3HCl(CO)
in THF at reflux for 16 h resulted in the formation the hydrido chlo-
roruthenium pincer complexes 7a,b as red solids (Scheme 2). The
appearance of a doublet at À16.58 ppm (J = 19.8 Hz) in the 1H
NMR spectrum of 7b indicated the existence of a hydride ligand,
which was further confirmed by the absorptions at 2041 cmÀ1
(Ru-H) in the IR spectrum. The 13C{1H} NMR signal at
206.78 ppm and the absorption at 1926 cmÀ1 in the IR were indic-
O
R
O
R
Ru(PPh3)3HCl(CO)
HN
N
HN
N
Ru
H
tBu2P
N
tBu2P
N
R
R
Cl
CO
7a R = H
7b
6a-b
R = Me
Scheme 2. Synthesis of ruthenium complexes 7a and 7b.
ative of the existence of a CO ligand. 31P{1H} NMR spectroscopy of
7b showed a singlet at 162.6 ppm, 53.9 ppm more downfield com-
pared to the similar ruthenium complex (108.7 ppm) of 2-(di-tert-
butylphosphinomethyl)-6-(diethylaminomethyl) pyridine, mainly
due to the replacement of the CH2 spacer by NH.10 Complex 7a
showed similar spectra to those of 7b. Suitable crystals for sin-
gle-crystal X-ray analysis were obtained by recrystallization of
7b from dichloromethane/n-pentane (Fig. 2). The molecular struc-
ture shows a distorted octahedral geometry around the Ru(II) cen-
ter, with the CO ligand coordinated trans to the pyridine nitrogen
and the hydride trans to the chloride.
Treatment of 7b with one equivalent of KOtBu under an argon
atmosphere in THF resulted in an immediate color change from
bright-red to dark-red and increased solubility (Scheme 3). In the

T. Chen et al. / Tetrahedron Letters 53 (2012) 4409–4412
4411
Table 1
Transfer hydrogenation of ketones with Ru complexes 7a,b and 8ba
O
OH
R2
OH
O
Catalyst
iPrOH
+
+
R1
R2
R1
Entry
Catalyst
Substrate
Time (h)
Yieldb (%)
1
7a
7a
7b
7b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
2-Hexanone
2-Heptanone
3-Hexanone
4-Heptanone
4-tert-Butylacetophenone
Acetophenone
16
16
16
16
16
16
16
16
16
16
16
16
10
5
0
96
0
98
99
91
94
91
99
99
61
74 (70)
87 (85)
93 (92)
2c
3
4c
5
6
7
8
9d
10d
11
12
13
14d
4-Bromoacetophenone
1-Acetonaphthone
a
Reaction conditions: 0.5 mmol of ketone, 1.0 mol % of Ru complex in 1 mL of
iPrOH at 40 °C.
Figure 2. ORTEP representation of complex 7b with thermal ellipsoids drawn at the
30% probability level. Hydrogen atoms (except hydride) are omitted for clarity.
b
Determined by GC–MS or 1H NMR spectroscopy, isolated yield in parenthesis.
c
1.0 mol % of KOtBu was added.
d
Reactions were conducted at 82 °C.
a lower reaction temperature and in a shorter reaction time com-
pared to the results of similar complexes with the PN3P ligand.17
To explore the scope of the reaction catalyzed by ruthenium
complex 8b, a variety of ketones were examined (Table 1, entries
5–14). In general, the PNNCN-Ru complex 8b showed significantly
improved catalytic activity compared to the complex with the
symmetric PN3P ligand. Excellent yields (91 to >99%) were
achieved for cycloketones and 2-alkylketones (entries 5–8) at
40 °C. For 3-hexanone and 4-heptanone, the reactions were a little
slow, but more than 99% yields were obtained in 16 h at elevated
temperature (entries 9 and 10). Aromatic ketones can be hydroge-
nated to the corresponding alcohols in moderate to good yields
(61–93%, entries 11–14). An aromatic ketone with an electron-
withdrawing substituent at the para position gave better results
than those with electron-donating substituents.
In summary, we have reported the design, synthesis, and char-
acterization of novel PNNCN pincer ligands with oxazoline arms
and their corresponding ruthenium complexes. By introducing an
oxazoline arm, the dearomatized ruthenium complexes exhibited
much increased catalytic activities for the transfer hydrogenation
of ketones compared to similar ruthenium complexes with a
PN3P ligand. Further modification of the ligand to tune the steric
environment and hemi-lability, and the exploration of their appli-
cations are ongoing in our laboratories.
O
KOtBu
THF
N
tBu2P
N
Ru
H
7b
N
CO
8b
Scheme 3. Synthesis of ruthenium complex 8b.
1H NMR spectrum of 8b, the disappearance of the broad NH signal
at 8.10 ppm indicated that the N–H bond was deprotonated and
the signals at 7.05, 6.61, and 6.25 ppm confirmed the dearomatiza-
tion of the pyridine ring in the complex. The deprotonated and
dearomatized complex 8b was isolated as a brown-red solid in
97% yield. The hydride of 8b appeared as
a doublet at
À26.83 ppm (J = 19.5 Hz), an upfield shift of 10.25 ppm, suggesting
that the trans chloride ligand had been removed. The IR spectrum
showed a CO absorption at 1897 cmÀ1 (Ru-CO), in good agreement
with a more electron-rich ruthenium center.
The reduction of ketones employing catalytic hydrogenation
transfer conditions with 2-propanol as the hydrogen source has
been extensively investigated, and several ruthenium complexes
have been proven to be efficient catalysts/catalyst precursors in
transfer hydrogenation reactions.20 In this regard, a number of pin-
cer ruthenium complexes have also been employed as catalysts in
the transfer hydrogenation of ketones. Selected recent examples
include ruthenium CNN pincer complexes,21 pincer-type pyri-
dine-based (NHC)NN–Ru(II) complexes,14a and ruthenium(II) com-
plexes bearing an unsymmetrical NNN ligand.22 The activities of
our new PNNCN–Ru complexes 7a,b toward transfer hydrogenation
were examined (Table 1). Initial experiments were conducted
using cyclohexanone as the substrate with 2-propanol as the
hydrogen source. Ruthenium complexes 7a,b were found to be effi-
cient catalysts in the presence of a base at 40 °C: 96% and 98%
yields were achieved respectively in 16 h (entries 2 and 4). How-
ever, in the absence of a base, the reaction failed to proceed under
similar reaction conditions (entries 1 and 3), suggesting that
deprotonation of ruthenium complexes 7a,b was necessary for
the transfer hydrogenation reactions. Consistent with these obser-
vations, the deprotonated ruthenium complex 8b displayed excel-
lent catalytic activity under base-free conditions: 99% yield at
40 °C in 16 h (entry 5), a clearly improved result was achieved at
Acknowledgement
We are grateful for the generous financial support from the King
Abdullah University of Science and Technology.
Supplementary data
Supplementary data associated with this article can be found, in
theonlineversion, at http://dx.doi.org/10.1016/j.tetlet.2012.06.041.
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