Novel hydrido-ruthenium(II) complexes with histidine derivatives and their application in the hydrogenation of ketones

Article abstract of DOI:10.1039/b702803b

The complexes RuHCl((R)-binap)(L-NH₂) with L-NH₂ = (S)-histidine-Me-ester (1), histamine (3), (S)-histidinol (4) or 1-Me-(S)-histidine-Me-ester (5), and RuHCl((S)-binap)(L-NH₂) with L-NH₂ = (S)-histidine-Me-ester (2) have been prepared in 60-81% overall yields in a one-pot, three-step procedure from the precursor RuCl ₂(PPh₃)₃. Their octahedral structures with hydride trans to chloride were deduced from their NMR spectra and confirmed by the results of a single crystal X-ray diffraction study for complex 3. Under H₂ and in the presence of KOtBu, complexes 1-5 in 2-propanol form moderately active catalyst precursors for the asymmetric hydrogenation of acetophenone to 1-phenylethanol. Complex 5 is more active and enantioselective than complexes 1-4, allowing complete conversion to 1-phenylethanol in 46% e.e. (R) in 72 h at 20 °C under 1 MPa of H₂ with substrate: catalyst: base = 2000: 1: 30. Complex 5, when activated, also catalyzes the hydrogenation of trans-4-phenyl-3-buten-2-one to exclusively the allyl alcohol 4-phenyl-3-buten-2-ol under 2.7 MPa of H₂ at 50°C in 2-propanol. This selectivity for CO versus CC hydrogenation is consistent with a mechanism involving the outer sphere transfer of hydride and proton to the polar bond. Further extensions to complexes with peptides with N-terminal histidine groups appear feasible on the basis of the current work. The Royal Society of Chemistry 2007.

Full text of DOI:10.1039/b702803b

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www.rsc.org/dalton | Dalton Transactions
Novel hydrido-ruthenium(II) complexes with histidine derivatives and their
application in the hydrogenation of ketones
Christine Sui-Seng, Alen Hadzovic, Alan J. Lough and Robert H. Morris*
Received 23rd February 2007, Accepted 4th April 2007
First published as an Advance Article on the web 19th April 2007
DOI: 10.1039/b702803b
The complexes RuHCl((R)-binap)(L-NH2) with L-NH2 = (S)-histidine-Me-ester (1), histamine (3),
(S)-histidinol (4) or 1-Me-(S)-histidine-Me-ester (5), and RuHCl((S)-binap)(L-NH2) with L-NH2 =
(S)-histidine-Me-ester (2) have been prepared in 60–81% overall yields in a one-pot, three-step
procedure from the precursor RuCl2(PPh3)3. Their octahedral structures with hydride trans to chloride
were deduced from their NMR spectra and confirmed by the results of a single crystal X-ray diffraction
study for complex 3. Under H2 and in the presence of KOtBu, complexes 1–5 in 2-propanol form
moderately active catalyst precursors for the asymmetric hydrogenation of acetophenone to
1-phenylethanol. Complex 5 is more active and enantioselective than complexes 1–4, allowing complete
conversion to 1-phenylethanol in 46% e.e. (R) in 72 h at 20 ◦C under 1 MPa of H2 with substrate :
catalyst : base = 2000 : 1 : 30. Complex 5, when activated, also catalyzes the hydrogenation of
trans-4-p◦henyl-3-buten-2-one to exclusively the allyl alcohol 4-phenyl-3-buten-2-ol under 2.7 MPa of
=
=
H2 at 50 C in 2-propanol. This selectivity for C O versus C C hydrogenation is consistent with a
mechanism involving the outer sphere transfer of hydride and proton to the polar bond. Further
extensions to complexes with peptides with N-terminal histidine groups appear feasible on the basis of
the current work.
provides pyridyl and amino donors and thus produce the same
activating effect.
Introduction
Certain ruthenium complexes containing both primary or sec-
ondary amine, and phosphine or b-aminophosphine ligands, are
excellent catalysts for the hydrogenation of unsaturated polar
bonds such as ketones1,2 and imines,1,3,4 to give valuable alcohols
or amines. Amine-donor complexes containing the binap ligand or
its analogues are of much current interest in the asymmetric hydro-
genation of ketones.1,2,5–20 Mechanistic studies have demonstrated
that these reactions involved transfer of hydride (from Ru–H) and
a proton (from the amine NH) to the substrate in an outer sphere
mechanism (Scheme 1).21–23 Ruthenium complexes containing the
amino-methylpyridine ligand (ampy)24–28 or its derivatives29 have
proven to be particularly active precatalysts. We wondered whether
derivatives of the amino acid histidine would provide imidazole
and amine donors to ruthenium in the same fashion that ampy
The matching of the chirality of the diphosphine ligand and the
amine donor (L-NH2) in the precatalysts RuXY(diphosphine)(L-
NH2) is key to obtaining high enantioselectivity in the hydrogena-
tion of prochiral ketones.1,6,30–36 Therefore we were interested to
test both enantiomers of binap with L-histidine and its derivatives
in the asymmetric hydrogenation of ketones. Histidine and its
derivatives are known to coordinate to ruthenium (see below) via
the amino and/or imidazole nitrogen and also via the carboxylate
oxygen.37–39 Histidine complexes of copper are of interest for their
use in the treatment of Menke’s disease.40 In this example, the
histidine is bound in a tridentate fashion through the amino,
imidazole and carboxylate groups (Fig. 1). In our case, carboxylate
coordination is predicted to inhibit catalyst activity and so we will
utilize the methyl ester of derivatives of histidine.
Fig. 1 Histidine copper complex used in the treatment of Menke’s
disease.40
Scheme 1 The outer-sphere H−/H+ transfer mechanism of catalyst
action.
Results and discussion
Synthesis and characterization
The hydrido-ruthenium(II) complexes RuHCl(binap)(L-NH2) (L-
NH2 = (S)-histidine-Me-ester (1–2); histamine (3); (S)-histidinol
Department of Chemistry, University of Toronto, 80 St. George Street,
Toronto, Ontario, M5S 3H6, Canada. E-mail: rmorris@chem.utoronto.ca
2536 | Dalton Trans., 2007, 2536–2541
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(4)) have been prepared in a one-pot, three-step procedure from
the precursor RuCl2(PPh3)3 (Scheme 2). The first step involved the
reaction of RuCl2(PPh3)3 with one equiv. of the binap ((R)- or (S)-)
ligand in THF to give the enantiomerically pure intermediate
RuCl2(binap)(PPh3). This was directly followed by a second
reaction under H2 in the presence of an excess of NEt3 to produce
the deep red intermediate RuHCl(binap)(PPh3) that was then
reacted in situ with the histidine derivative to produce the desired
trans-RuHCl(binap)(L-NH2) complexes as yellow solids, in 60–
81% overall yields.
(5) according to Scheme 3. Regioselective methylation at the N-e
position of (S)-histidine was obtained as described by Jain et al.43
after selective protection of the d-N with carbonyldiimidazole.
Alkylation with methyl iodide in refluxing acetonitrile and de-
protection in dilute HCl provide then the 1-Me-(S)-histidine.43
Esterification of the latter using thionyl chloride in methanol gave
the 1-Me-(S)-histidine-Me-ester.44 Its ruthenium complex 5 was
finally prepared in a one-pot reaction from RuCl2(PPh3)2 in the
same way as complexes 1–4 (vide supra).
Complexes 1–4 were isolated in a pure form but the purification
of 5 was not successful because of its greater solubility in common
solvents, including hexanes. The complexes are yellow solids that
are air sensitive both in the solid-state and in solution. Their
structures were deduced from their NMR spectra and confirmed
by the results of elemental analyses and a single crystal X-ray
diffraction study for complex 3. The NMR spectra supported
the trans geometry proposed in Schemes 2–3, with the hydride
1
ligand trans to the chloride, as described below. The 31P{ H} NMR
spectra showed AB doublets at ca. 68 and 73 ppm (JAB ∼ 40 Hz),
and the hydride region of the 1H NMR consists of a triplet centred
at −17 ppm. The magnitude of the 2JH–P coupling constant (26 Hz)
is characteristic of the hydride ligand cis to the two phosphorus
atoms of the binap on ruthenium.9,21,41 The proton resonance of
the N–H on the imidazole ring appears as a sharp singlet at ca.
11 ppm.
A
single-crystal X-ray diffraction study of RuHCl((R)-
binap)(histamine) (3) confirmed the proposed octahedral trans
geometry (Fig. 2). Various attempts at obtaining X-ray quality
crystals of the other complexes were unsuccessful. However, their
structures are expected to be similar to that of 3 on the basis of
their similar NMR spectra. Crystals of 3, as THF solvate, were
grown from a concentrated THF/hexanes solution. Although no
Scheme 2 One-pot three-step procedure.
This synthetic route constitutes an effective “one-pot” pro-
cedure in high yield for the preparation of trans-RuHCl-
(diphosphine)(diamine) complexes, which are usually obtained
after isolation of the different intermediates in lower combined
yields based on RuCl2(PPh3)3.3,21,41,42
Complexes 1–4 have an acidic N–H proton on the imidazole
ring that will be deprotonated under the basic catalytic conditions.
In order to probe the influence of this deprotonation reaction
on catalytic activity we have also prepared the N-methyl histi-
dine derivative RuHCl((R)-binap)(1-Me-(S)-histidine-Me-ester),
Fig. 2 X-Ray structure of RuHCl((R)-binap)(histamine), (3). Thermal
ellipsoids are shown at 30% probability and the solvent molecule and the
hydrogen atoms of the ((R)-binap) are omitted for clarity. Selected
◦
˚
bond distances (A) and angles ( ): Ru(1A)–H = 1.65(8); Ru(1A)–
Cl(1A) = 2.634(3); Ru(1A)–N(1A) = 2.208(7); Ru(1A)–N(3A) = 2.148(8);
Ru(1A)–P(1A) = 2.236(3); Ru(1A)–P(2A) = 2.245(3); N(1A)–Ru(1A)–
N(3A)
=
81.8(3); P(1A)–Ru(1A)–P(2A)
=
89.6(1); P(2A)–Ru(1A)–
N(1A) = 90.3(2); P(1A)–Ru(1A)–N(3A) = 97.7(2); H–Ru(1A)–N(1A) =
89(3); Cl(1A)–Ru(1A)–N(1A) 81.4(3); Cl(1A)–Ru(1A)–N(3A)
=
=
Scheme 3 Preparation of 1-Me-(S)-histidine-Me-ester and its ruthenium
complex 5.
80.7(2); Cl(1A)–Ru(1A)–P(1A) = 102.81(9); Cl(1A)–Ru(1A)–P(2A) =
105.5(1).
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histamine complexes of ruthenium have been crystallographically
characterized there are structures for four ruthenium histidine
complexes: two with tridentate ligands (chloro(L-histidinato-
2
2
N,Nꢀ,O)(g ,g -norbornadiene)ruthenium(II)37 and chloro(D,L-
histidinato-N,Nꢀ,O)bis(triphenylphosphine)ruthenium(II)),37 one
6
with a bidentate ligand as in complex 3 (chloro(g -benzene)-
(L-histidinato methyl ester-N,Nꢀ)ruthenium(II) chloride) (A),38
and one monodentate through the imidazole ring ((L-histidinato)-
pentaammine-ruthenium(II) trichloride).39 The ruthenium–
˚
nitrogen distances in 3 (Ru–N1 = 2.208(7); Ru–N3 = 2.148(8) A)
are longer than corresponding distances in complex A (Ru–NH2
2.141(3); Ru–N(imidazole) 2.062(3) A), presumably due to the
Scheme 4 Hydrogenation of acetophenone.
˚
steric crowding imposed by the binap ligand in complex 3. The
N1–Ru–N3 angles are similar (N1–Ru–N3 = 81.8(3)◦ in 3 vs
N–Ru–N = 80.3◦ in A). The histamine ligand forms a similar
twist–boat six membered ring with the metal in each complex so
that one N1–H group can form a hydrogen-bonding interaction
The correct matching of binap chirality with amine chirality
is often crucial in obtaining an elevated e.e. value in such
complexes.10,31 This matching effect is apparent to a limited degree
in comparison of the enantioselectivity of complexes 1 and 2,
diastereomers containing binap in opposite configurations. The
(R)-binap/(S)-histidine isomer 1 gives an alcohol of higher e.e.
than that produced by the (S)-binap/(S)-histidine isomer 2 under
identical conditions (entries 1 and 2).
Moreover, under base-free conditions (entry 4), it appears that
complex 2 can also produce 1-phenylethanol in 15% after 18 h,
with a slight improvement in the e.e. (32%). It was hoped that the
alcohol group of the histidinol ligand in 4 would assist in the H2
splitting reaction in an intramolecular fashion by positioning the
OH group to act as a proton relay from H2 to amido nitrogen
and therefore increase the rate of hydrogenation. Alcohol solvents
are suspected to assist in the splitting of dihydrogen in a variety
of reactions.2,45–47 But in our case there is no observable effect,
possibly because of the large excess of 2-propanol used as the
solvent.
˚
˚
with the adjacent chloride ligand (2.7 A in 3 vs 3.0 A in A). The
˚
RuH–HN distances of 3.1–3.5 A are too long for significant
hydrogen bonding. In other respects the structure of 3 (Ru–Cl =
2.634(3), Ru–P1 = 2.236(3), Ru–P2 = 2.245(3), P1–Ru–P2 =
˚
89.6(1), Ru–NH2 = 2.208(7), RuCl · · · HN 2.7 A) is similar to
those of the other RuHCl(binap)(L–NH2) structures,1,3,10,21,41
particularly RuHCl((R)-binap)(PPh2CH2CH2NH2)1 (Ru–Cl =
2.580(2) Ru–P1(binap) = 2.255(2), Ru–P2(binap) = 2.307(2),
˚
P(1)–Ru–P(2) = 90.67(6), Ru–NH2 2.195(5) RuCl · · · HN 2.6 A).
This latter complex is a very active ketone hydrogenation catalyst
and so the lower catalytic activity of complex 3 (see below) is not
apparent from the geometry.
Hydrogenation of ketones
Complex 5 also hydrogenates trans-4-phenyl-3-buten-2-one to
exclusively the allyl alcohol 4-phenyl-3-buten-2-ol under 2.7 MPa
of H2 at 50 ◦C in 2-propanol (Scheme 5). This selectivity for
Complexes 1–5 were tested as catalyst precursors for the hy-
drogenation of acetophenone to 1-phenylethanol (Scheme 4,
Table 1). Under H2 and in the presence of KOtBu, they constitute
moderately active pre-catalysts with a modest enantioselectivity.
The comparable runs in Table 1 indicate that complex 5 (entry 8)
is significantly more active and enantioselective than complexes 1–
4 (entries 1–2 and 5–6). Using 5, full conversion of acetophenone
in 1-phenylethanol with an e.e. of 46% (R) was achieved in 72 h at
20 ◦C under 1 MPa of H2 with substrate : catalyst : base = 2000 :
1 : 30. Under more severe conditions (2.7 MPa, 50 ◦C), complexes
1–4 showed lower conversions (23–96%) and e.e. values (0–34%
(R)). This suggests that the deprotonation of the imidazole ring
might be deactivating. However the system with catalyst 4 and one
equivalent of base is less active than with 30 equivalents of base
(entry 7), presumably without imidazole deprotonation.
=
=
C O versus C C hydrogenation is consistent with an outer sphere
Scheme 5 Hydrogenation of trans-4-phenyl-3-buten-2-one.
Table 1 The hydrogenation of acetophenone to 1-phenylethanol (R form in excess) catalyzed by complexes 1–5
Entry
Cat.
S : C : B
Solvent
T/◦C
pH2/MPa
Time/h
Conv. (%)
e.e. (%)
1
2
3
4
5
6
7
8
9
1
2
2
2
3
4
4
5
5
2000 : 1 : 30
2000 : 1 : 30
500 : 1 : 2
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
2-PrOH
50
50
50
50
50
50
50
20
20
2.7
2.7
2.7
2.7
2.7
2.7
2.7
1.0
1.0
19
29
16
18
18
18
19
72
48
67
91
99
15
23
96
34
98
99
23
0
0
32
18
34
18
46
7
500 : 1 : 0
500 : 1 : 30
500 : 1 : 30
500 : 1 : 1
2000 : 1 : 30
500 : 1 : 1
2538 | Dalton Trans., 2007, 2536–2541
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mechanism with the transfer of H+/H− only to the polar bond.21–23
This is generally observed for the hydrogenation of polar bonds
by the catalyst system RuHCl(diphosphine)(diamine)/base.21,41,48
1: Yield: 260 mg, 67%. (Found: C, 66.37; H, 5.13; N, 4.79%.
C51H44P2N3Cl1Ru1O2 requires C, 65.91; H, 4.77; N, 4.52%); dH
(300 MHz; C6D6) −17.5 (1 H, t, J 26.1, RuH), 2.19–2.24 (2 H,
m, NH2), 2.63 (1 H, d, J 14.1, CH), 2.71–2.75 (2 H, m, NH2),
3.00 (3 H, s, CO2Me), 3.51–3.63 (2 H, m, CH2) 6.06–8.65 (32
Conclusions
=
H, m, Ph, naphthyl and CH–NH protons), 11.5 (1 H, s, NH);
A variety of potential catalyst precursors RuHCl(binap)(L-
NH2) (L-NH2 = (S)-histidine-Me-ester (1–2); histamine (3); (S)-
histidinol (4); (S)-1-Me-histidine-Me-ester (5)) have been prepared
by an effective one-pot three-step procedure in high yield. Proving
that such complexes are active catalysts for H2-hydrogenation
of ketones opens the door to the coordination chemistry of
polypeptides with N-terminal histidine groups and their use
in asymmetric catalysis. Dipeptides have been used in transfer
hydrogenation catalysis49–52 but not in ketone H2-hydrogenation.
His-his complexes of zinc have been reported as models for zinc
finger proteins53 and his-his complexes of vanadyl are known.54
dC (75 MHz; THF-d8) 33.3 (s, CH2), 53.3 (s, CO2Me), 55.1 (s,
=
CH), 113.24 (s, C–NH), 125.88–142.58 (m, Ph, naphthyl and
=
CH–NH carbons), 175.06 (s, CO); dP (121 MHz; C6D6) 69.8 (d,
JAB 41.5), 73.5 (d, JAB 41.5).
RuHCl[(S)-binap][(S)-histidine-Me-ester], (2). Dry THF
(20 cm3) was added to RuCl2(PPh3)3 (500 mg, 0.52 mmol) and
(S)-binap (325 mg, 0.52 mmol). The dark brown suspension
was stirred under an N2 atmosphere for 5 h. After addition
of triethylamine (218 mm3, 1.6 mmol), the reaction flask was
stirred under an H2 atmosphere overnight. The resulting red
solution was purged with Ar and then (S)-histidine-Me-ester
dihydrochloride (126 mg, 0.52 mmol) was added. After stirring
for 2 h, the resulting orange solution was filtered through a small
pad of Celite, concentrated to a small volume (ca. 5 cm3) and
10 cm3 of Et2O were added. A yellow powder precipitated and
was isolated by filtration, washed with Et2O and vacuum-dried.
2: Yield: 285 mg, 60%. (Found: C, 65.91; H, 4.91; N, 4.30%.
C51H44P2N3Cl1Ru1O2 requires C, 65.91; H, 4.77; N, 4.52%); dH
(300 MHz; C6D6) −17.50 (1 H, t, J 26.1, RuH), 2.63–2.79 (3 H,
m, CH and NH2), 2.82 (2 H, m, NH2), 2.93 (3 H, s, CO2Me),
3.11–3.27 (2 H, m, CH2) 5.98–8.64 (32 H, m, Ph, naphthyl and
Experimental
General comments
All preparations and manipulations were carried out under an
argon, nitrogen, or hydrogen atmosphere using standard Schlenk,
vacuum-line, and glove-box techniques. Dry, oxygen-free solvents
were prepared by distillation from appropriate drying agents and
employed throughout. The synthesis of 1-methyl-(S)-histidine
dihydrochloride has been reported previously.43 The 1-methyl-
(S)-histidine methyl ester dihydrochloride has been prepared by
esterification of 1-methyl-(S)-histidine dihydrochloride according
to the general procedure described by Mancilla et al. for esterifi-
cation of a-amino acid.44 RuCl2(PPh3)3 was prepared by a slight
modification of the published procedure.55 All other reagents used
in the experiments were obtained from commercial sources and
used as received. The elemental analyses were performed at the
University of Toronto, on samples handled under argon. Varian
Gemini 400 MHz and 300 MHz spectrometers were employed
=
CH–NH protons), 11.2 (1 H, s, NH); dP (121 MHz; C6D6) 68.9
(d, JAB 41.1), 72.5 (d, JAB 41.1).
RuHCl[(R)-binap][histamine], (3). Dry THF (60 cm3) was
added to RuCl2(PPh3)3 (1.2 g, 1.25 mmol) and (R)-binap (780 mg,
1.25 mmol). The dark brown suspension was stirred under an
Ar atmosphere for 3 h. After addition of triethylamine (522 mm3,
3.75 mmol), the reaction flask was stirred under an H2 atmosphere
overnight. The resulting red solution was purged with Ar and
then histamine (138 mg, 1.25 mmol) was added. After stirring
for 1 h, the resulting orange solution was filtered through a
small pad of Celite, concentrated to a small volume (ca. 5 cm3)
and 20 cm3 of Et2O were added. A yellow powder precipitated
and was isolated by filtration, washed with Et2O and vacuum-
dried. 3: Yield: 880 mg, 81%. (Found: C, 67.18; H, 5.34; N,
4.52%. C49H42P2N3Cl1Ru1 requires C, 67.54; H, 4.86; N, 4.82%);
dH (400 MHz; C6D6) −17.59 (1 H, t, J 26.8, RuH), 1.71–1.98,
2.41–2.43, 3.02–3.05 (6 H, m, CH2 and NH2), 5.87–8.57 (32 H,
1
1
for recording H (400 MHz and 300 MHz), 13C{ H} (100 MHz
and 75 MHz), and 31P{ H} (161 MHz and 121 MHz) NMR
1
spectra at ambient temperature. The 1H and 13C NMR spectra were
referenced to solvent resonances, as follows: 7.26 and 77.16 ppm
for CHCl3 and CDCl3, 7.16 and 128.06 ppm for C6D5H and
C6D6, 1.85 and 25.62 ppm for THF-d8. The 31P NMR spectra
were referenced to 85% H3PO4 (0 ppm). Gas chromatography was
carried out on a Perkin Elmer Autosystem XL.
=
m, Ph, naphthyl and CH–NH protons), 11.5 (1 H, s, NH);
dC (75 MHz; THF-d8) 33.3 (s, CH2), 53.3 (s, CO2Me), 55.1 (s,
Preparations
RuHCl[(R)-binap][(S)-histidine-Me-ester] (1). Dry THF
(20 cm3) was added to RuCl2(PPh3)3 (400 mg, 0.42 mmol) and
(R)-binap (260 mg, 0.42 mmol). The dark brown suspension
was stirred under an Ar atmosphere for 7 h. After addition of
triethylamine (174 mm3, 1.2 mmol), the reaction flask was stirred
under a H2 atmosphere overnight. The resulting red solution was
purged with Ar and then (S)-histidine-Me-ester dihydrochloride
(101 mg, 0.42 mmol) was added. After stirring for 2.5 h, the
resulting orange solution was filtered through a small pad of
Celite, concentrated to a small volume (ca. 2 cm3) and 10 cm3
of Et2O were added. A yellow powder precipitated and was
isolated by filtration, washed with Et2O and vacuum-dried.
=
CH), 113.24 (s, C–NH), 125.88–142.58 (m, Ph, naphthyl and
=
CH–NH carbons), 175.06 (s, CO); dC (100 MHz; C6D6) 28.7 (s,
=
CH2CH2), 40.3 (s, CH2NH2), 109.97 (s, C–NH), 124.59–142.73
(m, Ph, naphthyl and CH–NH carbons); dP (121 MHz; C6D6)
68.5 (d, JAB 39.4), 72.9 (d, JAB 39.4).
=
RuHCl[(R)-binap][(S)-histidinol], (4). Dry THF (25 cm3) was
added to RuCl2(PPh3)3 (700 mg, 0.73 mmol) and (R)-binap
(455 mg, 0.73 mmol). The dark brown suspension was stirred
under an Ar atmosphere for 5 h. After addition of triethylamine
(300 mm3, 2.2 mmol), the reaction flask was stirred under an H2
atmosphere overnight. The resulting red solution was purged with
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Table 2 Summary of crystal data, details of intensity collection and least-
squares refinement parameters for 3
Ar and then (S)-histidinol dihydrochloride (157 mg, 0.73 mmol)
was added. After stirring overnight, the resulting orange solution
was filtered through a small pad of Celite, concentrated to a small
volume (ca. 5 cm3) and 15 cm3 of Et2O were added. A yellow
powder precipitated and was isolated by filtration, washed with
Et2O and vacuum-dried. 4: Yield: 450 mg, 68%. (Found: C, 66.57;
H, 4.66; N, 4.55%. C50H44P2N3Cl1Ru1O1 requires C, 66.62; H, 4.92;
N, 4.66%); dH (300 MHz; C6D6) −17.89 (1 H, t, J 26.4, RuH),
2.17–2.21, 2.34–2.36, 2.70–2.79, 3.06–3.21 (5 H, m, CH, CH2 and
3
Empirical Formula
Formula weight
Crystal size/mm
Crystal class
Space group
T/K
C49H42N3P2ClRu·C4H8O
943.42
0.12 × 0.14 × 0.16
Orthorhombic
P 212121
150.0
˚
a/A
19.3194(9)
20.3567(9)
22.6289(8)
90
90
90
8899.5(7)
8
1.408
0.528
3904
2.69 to 25.07
38283
15602
0.0694
0.1681
0.971
=
NH2), 6.11–8.52 (32 H, m, Ph, naphthyl and CH–NH protons),
˚
b/A
11.1 (1 H, s, NH); dC (100 MHz; CDCl3) 29.7 (s, CH2), 50.6 (s,
˚
c/A
=
CH), 63.7 (s, CH2OH), 111.7 (s, C–NH), 124.4–141.7 (m, Ph,
a/◦
b/◦
c /◦
=
naphthyl and CH–NH carbons); dP (121 MHz; C6D6) 67.9 (d,
JAB 39.0), 72.7 (d, JAB 39.0).
3
˚
V/A
Z
RuHCl[(R)-binap][1-Me-(S)-histidine-Me-ester],
(5). Dry
qcalc/Mg m−3
THF (25 cm3) was added to RuCl2(PPh3)3 (520 mg, 0.54 mmol)
and (R)-binap (338 mg, 0.54 mmol). The dark brown suspension
was stirred under an N2 atmosphere for 5 h. After addition of
triethylamine (250 mm3, 1.6 mmol), the reaction flask was stirred
under an H2 atmosphere overnight. The resulting red solution
was purged with N2 and then 1-Me-(S)-histidine-Me-ester
dihydrochloride (140 mg, 0.54 mmol) was added. After stirring
for 5 h, the resulting orange solution was filtered through a small
pad of Celite, concentrated to a small volume (ca. 5 cm3) and
15 cm3 of Et2O were added. A yellow powder precipitated and
was isolated by filtration, washed with Et2O and vacuum-dried.
5: Crude yield: 270 mg, 53% (the product contains free PPh3 and
(R)-binap). dH (300 MHz; C6D6) −16.47 (1 H, t, J 26.9, RuH),
1.94 (3 H, s, NMe) 2.10–2.40, 2.8–3.8 (m, 5H, CH, CH2 and
NH2), 3.06 (3 H, s, CO2Me), 6.53–8.8 (32 H, m, Ph, naphthyl and
l(Mo-Ka)/mm−1
F(000)
Range h collected/◦
No. of reflections
Independent reflections
R1(I > 2r(I))
wR2 (all data)
Goodness of fit
Parameters refined
Maximum peak in final DF map/e A
1105
0.721
−3
˚
2
Definition of R indices: R1 = R(Fo − Fc)/R(Fo) wR2 = [R[w(Fo
Fc2)2]/R[w(Fo2)2]]1/2
−
by1H NMR spectroscopy and the data obtained matched literature
values.56
=
CH–NH protons); dP (121 MHz; C6D6) 69.8 (d, JAB 41.5), 73.5
(d, JAB 41.5).
X-Ray crystal structure determination of complex 3
General procedure for the hydrogenation of acetophenone
X-Ray crystallographic data for 3 were collected on a Bruker-
Nonius Kappa-CCD diffractometer using monochromated Mo-
Ka radiation and were measured using a combination of φ
scans and x scans with j offsets, to fill the Ewald sphere. The
data were processed using the Denzo-SMN package. Absorption
corrections were carried out using SORTAV. The structure was
solved and refined using SHELXTL V6.1 for full-matrix least-
squares refinement that was based on F2. The hydride position
was refined. All other H atoms were included in calculated
positions and allowed to refine in riding-motion approximation
with Uiso tied to the carrier atom. Crystallographic data for the
compounds is given in Table 2. The structural parameters for the
two independent molecules in the unit cell of 3 were quite similar
and only details for one of them have been reported (Fig. 2).
CCDC reference number 633747.
In the Ar glovebox, the ruthenium complex (5.0 × 10−3 mmol)
and acetophenone (500–2000 equiv.) were dissolved in 2 cm3 of
the 2-propanol and stirred for 2 min. The solution of base was
prepared by dissolution of potassium tert-butoxide (1–30 equiv)
in 3 cm3 of 2-propanol. The solution containing the substrate and
the precatalyst, followed by the solution of base were injected into
a 50 cm3 Parr hydrogenator reactor at the desired pressure and
temperature, maintained by use of a Fischer Scientific Isotemp
1016D water bath. The conversion and enantiomeric excess of the
products were determined with GC analysis using a chiral column
(CP Chirasil-Dex CB 25 m × 2.5 mm) utilizing an H2 carrier gas
at a column pressure of 5 psi, an oven temperature of 130 ◦C,
an injector temperature of 250 ◦C, and a FID of 275 ◦C. The
retention times were acetophenone 5.0 min, (R)-1-phenylethanol
8.5 min, (S)-1-phenylethanol 9.1 min.
For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b702803b
Hydrogenation of trans-4-phenyl-3-buten-2-one
The hydrogenation reactions and the GC analysis were conducted
as above, except that for the GC conditions the oven temperature
was 140 ◦C. The retention times were trans-4-phenyl-3-buten-2-
one 13.4 min, trans-(R)-4-phenyl-3-buten-2-ol 15.9 min, trans-(S)-
4-phenyl-3-buten-2-ol 16.2 min. The product was also identified
Acknowledgements
We thank NSERC for a discovery grant to R. H. M. and Johnson-
Matthey for a loan of RuCl3. Le Fond Que´be´cois de la Recherche
sur la Nature et les Technologies provided funding to C. S. S.
2540 | Dalton Trans., 2007, 2536–2541
This journal is
The Royal Society of Chemistry 2007
©

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28 W. Baratta, E. Herdtweck, K. Siega, M. Toniutti and P. Rigo,
Organometallics, 2005, 1660–1669.
29 A. Hadzovic, C. M. MacLaughlin, D. Song, and R. H. Morris, in
preparation.
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