Self-assembled bidentate ligands for ruthenium-catalyzed hydration of nitriles

Article abstract of DOI:10.1021/om0611047

Novel bis(acetylacetonato)ruthenium(II) complexes bearing the 6-diphenylphosphino-N-pivaloyl-2-aminopyridine and 3- diphenylphosphinoisoquinolone ligands were synthesized. Molecular structures of these complexes were studied in solution and also in the so

Full text of DOI:10.1021/om0611047

Organometallics 2007, 26, 2461-2464
2461
Notes
Self-Assembled Bidentate Ligands for Ruthenium-Catalyzed
Hydration of Nitriles
Toma´sˇ Sˇmejkal and Bernhard Breit*
Institut fu¨r Organische Chemie und Biochemie, Albert-Ludwigs-UniVersita¨t Freiburg, Albertstrasse 21,
79104 Freiburg, Germany
ReceiVed December 4, 2006
Summary: NoVel bis(acetylacetonato)ruthenium(II) complexes
bearing the 6-diphenylphosphino-N-piValoyl-2-aminopyridine
and 3-diphenylphosphinoisoquinolone ligands were synthesized.
Molecular structures of these complexes were studied in solution
and also in the solid state, and unusual hydrogen-bonding
patterns were identified. The prepared compounds constitute
actiVe catalysts for the hydration of nitriles to amides under
neutral conditions.
Introduction
Selective hydration of nitriles to amides represents an example
of an industrially important atom economic reaction.1 A variety
of transition-metal complexes have been investigated as homo-
Figure 1. Molecular structure of complex 3.
geneous catalysts for this transformation.2 Among them, Mu-
rahashi’s ruthenium system3 and Parkins’s platinum complexes4
are especially effective. More recently, Oshiki and co-workers
have described the cis-Ru(acac)2(PPh2py)2 complex (acac )
acatylacetonato, PPh2py ) 2-diphenylphosphinopyridine) as an
excellent catalyst for hydration of nitriles to amides under neutral
conditions.5 The proposed mechanism postulated the activation
of the nitrile by coordination to a vacant site of the metal
(formed by η2 f η1 acac isomerization). Furthermore, it was
suggested that nucleophilic addition of water is promoted via
hydrogen bonding to the PPh2py ligand (Scheme 1). This
mechanism is an example of bifunctional catalysis, which
involves the metal ion acting as a Lewis acid and the ligand
acting as a Lewis base and directing the attack of water.6,7
During the course of our investigations on the formation of
bidentate ligands via self-assembly, we have recently reported
the construction of homodimeric8 and heterodimeric9 bidentate
ligands based on complementary hydrogen bonding between
Scheme 1. Proposed Mechanism of the Catalytic Hydration
of Benzonitrile.
* Corresponding author. E-mail: bernhard.breit@orgmail.chemie.uni-
freiburg.de.
(1) Trost, B. M. Acc. Chem. Res. 2002, 35, 695.
(2) For a recent review on metal-catalyzed nitrile reactions, see:
Kukushkin, V. Y.; Pombeiro, A. J. L. Chem. ReV. 2002, 102, 1771.
(3) (a) Murahashi, S.-I.; Sasao, S.; Saito, E.; Naota, T. J. Org. Chem.
1992, 57, 2521. (b) Murahashi, S.-I.; Naota, T. Bull. Chem. Soc. Jpn. 1996,
69, 1805.
(4) (a) Ghaffar, T.; Parkins, A. W. Tetrahedron Lett. 1995, 36, 8657.
(b) Ghaffar, T.; Parkins, A. W. J. Mol. Catal. A 2000, 160, 249.
(5) Oshiki, T.; Yamashita, H.; Sawada, K.; Utsunomiya, M.; Takahashi,
K.; Takai, K. Organometallics 2005, 24, 6287.
formally monodentate ligands. An adenine/thymine base pair
analogous systemsthe aminopyridine (1)/isoquinolone (2)
platform (Scheme 2)sproved to be particularly useful.
From ligand libraries based on this self-assembly platform,
highly active and regioselective rhodium catalysts for the
hydroformylation of terminal alkenes9 as well as for a highly
enantioselective asymmetric hydrogenation10 were identified.
Furthermore, ruthenium complexes of the general structure
CpRu(MeCN)(1x)(2y) were identified as active catalysts for a
(6) Grotjahn, D. B. Chem.-Eur. J. 2005, 11, 7146.
(7) For an alternative mechanism of Ru-catalyzed hydration of nitriles
see: Murahashi, S.-I.; Takaya, H. Acc. Chem. Res. 2000, 33, 225.
(8) Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608.
(9) Breit, B.; Seiche, W. Angew. Chem. 2005, 117, 1666; Angew. Chem.,
Int. Ed. 2005, 44, 1640.
10.1021/om0611047 CCC: $37.00 © 2007 American Chemical Society
Publication on Web 03/23/2007

2462 Organometallics, Vol. 26, No. 9, 2007
Notes
Table 3. Hydrogen Bonding in 3, Selected Bond Distances
(Å) and Angles (deg)
Scheme 2. Self-Assembly through Hydrogen Bonding of
Adenine/Thymine and Aminopyridine/Isoquinolone Ligand
Systemsa
N-H‚‚‚O
d(N-H)
d(H‚‚‚O)
d(N‚‚‚O)
(NHO)
N(1)-H(1)‚‚‚O(5)
N(2)-H(2)‚‚‚O(6)
0.88
0.88
1.95
1.98
2.771(4)
2.804(4)
155.6
155.5
Table 4. Selected Bond Distances (Å) and Angles (deg) for 4
O(3)-Ru(1)
O(4)-Ru(1)
O(5)-Ru(1)
O(6)-Ru(1)
P(1)-Ru(1)
P(2)-Ru(1)
2.0654(18)
2.1046(16)
2.0802(18)
2.0600(18)
2.2741(7)
2.2953(7)
O(6)-Ru(1)-O(3)
O(4)-Ru(1)-P(1)
O(5)-Ru(1)-P(2)
P(1)-Ru(1)-P(2)
171.82(7)
175.01(5)
168.64(5)
98.40(2)
a Only the NH‚‚‚O hydrogen bond is observed in the current work.
Table 5. Hydrogen Bonding in 4, Selected Bond Distances
(Å) and Angles (deg)
Table 1. Preparation of Bis-phosphine Ruthenium
Complexes 3-5
N-H‚‚‚O
d(N-H)
d(H‚‚‚O)
d(N‚‚‚O)
(NHO)
N(1)-H(1)‚‚‚O(3)
N(3)-H(3)‚‚‚O(1)
0.88
0.88
1.95
2.08
2.749(3)
2.956(3)
161.6
173.6
spectrum of 3 in CDCl3 at room temperature showed resonances
at δ ) 1.66 (s) and 1.94 (s) for the protons of two nonequivalent
methyl groups. The 31P NMR of 3 in CDCl3 at room temperature
showed a singlet at δ ) 55.2. This is consistent with a
symmetrical octahedral structure having both phosphine ligands
cis-coordinated. The low-field shift of the isoquinolone NH
signal (1H NMR δ ) 11.43 (bs)) suggests that these hydrogen
atoms are involved in hydrogen bonding.
L1
L2
isolated yield (%)
2
2
1
2
1
1
3 (87)
4 (70)
5a/5b (n.d.)
In addition, the molecular structure of complex 3 has been
determined by X-ray diffraction methods. Suitable single crystals
were obtained by slow evaporation of the concentrated CHCl3
solution at room temperature. X-ray crystallographic analysis
confirmed that 3 is a mononuclear complex with distorted
octahedral coordination geometry and the phosphine ligands are
cis-coordinated (Figure 1). The structural parameters for the Ru-
(acac)2(PAr3)2 unit (Table 2) are comparable to those reported
for cis-Ru(acac)2(PPh2py)2.5 Both isoquinolone ligands are
involved in hydrogen bonding with the oxygen atom of the
acetylacetonate ligand (Figure 1, Table 3).
Table 2. Selected Bond Distances (Å) and Angles (deg) for 3
O(3)-Ru(1)
O(4)-Ru(1)
O(5)-Ru(1)
O(6)-Ru(1)
P(1)-Ru(1)
P(2)-Ru(1)
2.047(2)
2.094(2)
2.091(2)
2.072(2)
2.2847(9)
2.2852(9)
O(3)-Ru(1)-O(5)
O(4)-Ru(1)-P(1)
O(5)-Ru(1)-P(2)
P(1)-Ru(1)-P(2)
173.24(10)
168.73(7)
174.45(7)
99.55(3)
highly regioselective anti-Markovnikov hydration of terminal
alkynes to give the corresponding linear aldehydes.11
We assume that during the course of this reaction the
hydrogen-bonding network may serve a dual role: first emula-
tion of a bidentate ligand situation to increase the binding
constant of the phosphine ligands, leading to catalyst stabiliza-
tion, and, second, activation of a water molecule via hydrogen
bonding. Accordingly, we reasoned that metal complexes
derived from our self-assembly ligand system may also serve
as a “hydration” catalyst for other multiple bonds.
When employing a 1:1 mixture of the complementary ligands
1 and 2, the exclusive formation of the heterocomplex 4 was
observed; this was confirmed by mass spectrometry, NMR, and
X-ray crystallography. Thus, the MS ESI+ spectrum showed
the presence of ions at m/z ) 892 ([4 - acac]+, 100%), 1014
([4 + Na]+, 75%). The 31P NMR spectrum of 4 in CDCl3 at
2
room temperature displayed an AB spin system with a JP-P
coupling constant of 33.8 Hz (Figure 2). This confirms the
presence of two nonequivalent phosphine ligands coordinated
Herein we report on the synthesis of new bis(acetylacetonato)-
ruthenium(II) complexes bearing the aminopyridine/isoquinolone
ligands and their application as homogeneous catalysts for the
hydration of nitriles.
Results and Discussion
Treatment of Ru(1,5-COD)(acac)212 with 2 equiv of 6-diphe-
nylphosphino-N-pivaloyl-2-aminopyridine (1), 3-diphenylphos-
phinoisoquinolone (2), or a 1:1 mixture of both in toluene at
150 °C afforded the corresponding bis-phosphine ruthenium
complexes (Table 1).
Complex 3 was isolated by column chromatography as a
yellow microcrystalline solid in good yield. The 1H NMR
(10) Weis, M.; Waloch, C.; Seiche, W.; Breit, B. J. Am. Chem. Soc.
2006, 128, 4188.
(11) Chevallier, F.; Breit, B. Angew. Chem. 2006, 118, 1629; Angew.
Chem., Int. Ed. 2006, 45, 1599.
(12) Powell, P. J. Organomet. Chem. 1974, 65, 89.
Figure 2. 31P NMR spectrum of 4 in CDCl3 solution.

Notes
Organometallics, Vol. 26, No. 9, 2007 2463
Figure 5. Catalytic hydration of 4-methylbenzonitrile. Reaction
conditions: 4-methylbenzonitrile (1 mmol); catalyst 3, 4, 5 (10
µmol); H2O (2 mmol); DME (1 mL), 150 °C.
Figure 3. Molecular structure of complex 4.
Figure 6. Hypothetical structures, directing of the nuclephilic attack
of water.
Figure 4. Proposed molecular structure of complexes 5a and 5b.
to the same metal center. The 1H NMR spectrum of 4 in CDCl3
at room temperature showed resonances at δ ) 10.71 (s) and
12.05 (d) for the aminopyridine and isoquinolone NH, respec-
tively. The low-field shift of these signals suggests that these
hydrogen atoms are involved in hydrogen bonding.
described for 2-diphenylphosphinopyridine.5,14 This mixture of
5a and 5b was used as a catalyst without further purification.
Subsequently, the new ruthenium complexes 3-5 were
evaluated as catalysts in the hydration of 4-methylbenzonitrile
(6). The mixture of the substrate 6, water (2 equiv), and the
catalysts 3-5 (1 mol %) was heated in 1,2-dimethoxyethane
(DME) at 150 °C for the given time. After cooling to room
A final confirmation of the molecular structure of 4 could
be gained from X-ray crystallography (Figure 3). Good-quality
crystals for X-ray diffraction were obtained by slow diffusion
of n-hexane into the concentrated CHCl3 solution. Thus, the
two complementary phosphine ligands are cis-coordinated in a
distorted octahedral coordination geometry at the ruthenium
center (Table 4). Hydrogen bonding is observed between the
amide group of the aminopyridine ligand 1 and the isoquinolone
(2) oxygen (N3-H3‚‚‚O1). The isoquinolone N-H is hydrogen
bound to an oxygen atom of the acetylacetonate (N1-H1‚‚‚
O3) (Figure 3, Table 5). The pyridine nitrogen (N2) of the ligand
1 is not involved in the binding to the isoquinolone NH and so
is potentially available for the proposed activation of a water
molecule.
1
temperature the reaction mixture was analyzed with H NMR
spectroscopy. The results of the kinetic measurements are
depicted in Figure 5.
The highest activity was observed for the isoquinolone
complex 3 (100% conversion after 20 h, maxTOF ) 20 (mol
amide)/(mol catalyst)‚h-1), the heterocomplex 4 was less active
(90% conversion, maxTOF ) 5 h-1), and a very low activity
(conversion <5%) was detected for complex 5.
The apparent differences in the activity of the studied catalysts
could stem from several facts. First, in accordance with the
mechanism postulated by Oshiki (Scheme 1) the nitrile is
activated upon coordination to a vacant site of the ruthenium.
Ligand 2 is a weaker donor than ligand 1 due to the electron-
withdrawing character of the isoquinolone substituent. Hence,
the ruthenium complex of 2 should be a stronger Lewis acid
compared to the complex bearing ligand 1 and could more
effectively catalyze the hydrolysis of the coordinated nitrile.
This electronic factor may be responsible for the observed
catalyst activity 3 > 4 > 5. Second, the nucleophilic attack of
water may be facilitated by hydrogen bonding with the ligands.
Two plausible scenarios for catalysts 3 and 4 respectively are
depicted in Figure 6. At this stage of the project, the relative
importance of this effect is difficult to quantify. As a third factor
influencing catalysts activity, the pyridine nitrogen of ligand 1
may compete with the substrate for coordination on the metal.
Thus, additional N-coordination via the pyridine nucleus may
inhibit the formation of the required coordinative unsaturated
ruthenium species that are needed for the activation of the nitrile.
This may be responsible for the low catalytic activity of catalyst
The reaction of 2 equiv of ligand 1 with the complex Ru-
(1,5-COD)(acac)2 afforded a 1:1 mixture of two ruthenium
complexes, 5a and 5b, which could not be separated (Figure
4). The 31P NMR in CDCl3 at room temperature showed signals
at δ ) -0.55 (d, 2JP-P ) 33.4 Hz); 58.96 (s); 64.5 (d, 2JP-P
)
33.4 Hz). MS (ESI+) experiments showed the presence of an
ion at m/z ) 925 (100%, other signals under 10%), for which
the isotopic pattern matches that of ([Ru(1)2(acac)]+; see
Supporting Information). These data are interpreted as 5a/5b
being two isomers and compound 5a (signal at δ ) 58.96) being
a cis-bis-phosphine complex analogous to complexes 3 and 4.
Complex 5b (signals at δ ) -0.55 (d, 2JP-P ) 33.4 Hz);13 64.5
(d, 2JP-P ) 33.4 Hz)) has one aminopyridine ligand coordinated
as a bidentate P,N-ligand, similar to the coordination mode
(13) The high-field shift of the phosphorus is characteristic for the
formation of P,N-coordinated four-membered chelate rings within this class
of ligands; see for example: (a) Olmstead, M. M.; Maisonnat, A.; Farr, J.
P.; Balch, A. L. Inorg. Chem. 1981, 20, 4060. (b) Schutte, R. P.; Retting,
S. J.; Joshi, A. M.; James, B. R. Inorg. Chem. 1997, 36, 5809. (c) See also:
ref 5.
(14) For a review on the coordination of 2-diphenylphosphinopyridine
ligand, see: Zhang, Z.-Z.; Cheng, H. Coord. Chem. ReV. 1996, 147, 1.

2464 Organometallics, Vol. 26, No. 9, 2007
Notes
5. Interestingly, the presence of the complementary ligand 2
prevents this type of deactivation, and complex 4 is substantially
more active.
Acknowledgment. This work was supported by the Fonds
der Chemischen Industrie, the Alfried Krupp Award for
young university teachers of the Krupp foundation (to B.B.).
T.S. is grateful to the state of Baden-Wu¨rttemberg for a
Landesgraduierten Fellowship. We thank Dr. M. Keller for
X-ray crystal structure analyses of 3 and 4.
Conclusion
Note Added after ASAP Publication. In the version of this
paper published on the Web on March 23, 2007, Scheme 1 con-
tained some extra lines around the structures, due to a production
error. The version of Scheme 1 that now appears is correct.
In summary, novel bis-phosphine ruthenium complexes with
the isoquinolone-aminopyridine self-assembling ligand system
have been prepared. Selective formation of the heterocomplex
4 was observed when a 1:1 mixture of complementary ligands
was used. Two of these complexes proved to be active catalysts
for the hydration of 4-methylbenzonitrile. Although at this stage
the origin of the catalytic activity remains unknown, the
hydrogen-bonding network may play an important role. Ap-
plication of our isoquinolone-aminopyridine ligand libraries8
in order to optimize the catalyst in a combinatorial fashion is
anticipated.
Supporting Information Available: Procedures for the prepa-
ration of catalysts and evaluation of the catalytic activity, charac-
terization data, and crystallographic information files (CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
OM0611047