Homogeneous catalytic hydrogenation of amides to amines

Article abstract of DOI:10.1002/chem.201204270

Hydrogenation of amides in the presence of [Ru(acac)₃] (acacH=2,4-pentanedione), triphos [1,1,1-tris- (diphenylphosphinomethyl)ethane] and methanesulfonic acid (MSA) produces secondary and tertiary amines with selectivities as high as 93 % provided that there is at least one aromatic ring on N. The system is also active for the synthesis of primary amines. In an attempt to probe the role of MSA and the mechanism of the reaction, a range of methanesulfonato complexes has been prepared from prepared from [Ru(acac) ₃], triphos and MSA, or from reactions of [RuX-(OAc)(triphos)] (X=H or OAc) or [RuH₂(CO)(triphos)] with MSA. Crys-tallographically characterised complexes include: [Ru(OAc-κ¹O) ₂(H₂O)-(triphos)], [Ru(OAc-κ²O,O') (CH₃SO₃-κ¹O)(triphos)], [Ru(CH ₃SO₃-κ¹O)₂-(H ₂O)(triphos)] and [Ru₂(μ-CH₃SO ₃)₃-(triphos)₂][CH₃SO₃], whereas other complexes, such as [Ru(OAc-κ¹O)(OAc- κ²O,O')(triphos)],[Ru(CH₃SO₃- κ¹O)(CH₃SO₃-κ²O,O')- (triphos)], H[Ru(CH₃SO₃-κ¹O) ₃-(triphos)], [RuH(CH₃SO₃-κ¹O) (CO)-(triphos)] and [RuH(CH₃SO₃-k²O,O')- (triphos)] have been characterised spectroscopically. The interactions between these various complexes and their relevance to the catalytic reactions are discussed.

Full text of DOI:10.1002/chem.201204270

FULL PAPER
Homogeneous Catalysis
J. Coetzee, D. L. Dodds,
J. Klankermayer, S. Brosinski,
W. Leitner, A. M. Z. Slawin,
D. J. Cole-Hamilton* ........ &&&& — &&&&
triphos be with you: A homogeneous
catalytic system based on complexes
prepared in situ from [RuACTHNUTRGNEN(UG acac)3] and
triphos has been developed for the
(see scheme). This is the first system of
any kind that can catalyse the hydroge-
nation of amides to amines in the pres-
ence of aromatic rings without cleav-
Homogeneous Catalytic Hydrogena-
tion of Amides to Amines
À
hydrogenation of amides to amines
age of the C N bond.
À
with preservation of the C N bond
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DOI: 10.1002/chem.201204270
Homogeneous Catalytic Hydrogenation of Amides to Amines
Jacorien Coetzee,[a] Deborah L. Dodds,[a] Jꢀrgen Klankermayer,[b] Sandra Brosinski,[b]
Walter Leitner,[b, c] Alexandra M. Z. Slawin,[a] and David J. Cole-Hamilton*[a]
Abstract: Hydrogenation of amides in
the presence of [Ru(acac)3] (acacH=
prepared from [Ru
MSA, or from reactions of [RuX-
(OAc)(triphos)] (X=H or OAc) or
[RuH2(CO)(triphos)] with MSA. Crys-
tallographically characterised com-
plexes include: [Ru 2A(H2O)-
(OAc-k1O)
(triphos)], [Ru(OAc-k2O,O’)(CH3SO3-
k1O) [Ru(CH3SO3-k1O)2-
(triphos)],
G
G
G
2ACHTUNGRTNE(NUNG m-CH3SO3)3-
E
ACHTUNGTRENNUNG
2,4-pentanedione), triphos [1,1,1-tris-
(diphenylphosphinomethyl)ethane] and
methanesulfonic acid (MSA) produces
secondary and tertiary amines with se-
lectivities as high as 93% provided that
there is at least one aromatic ring on
N. The system is also active for the syn-
thesis of primary amines. In an attempt
to probe the role of MSA and the
mechanism of the reaction, a range of
methanesulfonato complexes has been
G
E
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
E
G
Keywords: amide hydrogenation ·
amines · catalysis · homogeneous
catalysis · ruthenium
Introduction
the only by-product. Attempted amide hydrogenations using
homogeneous catalysts have been reported by the groups of
À
We report the first successful homogeneous catalysts for the
hydrogenation of amides to amines with preservation of the
Milstein, Saito and Bergens, but they either lead to C N
bond cleavage to give alcohols and amines[1] or to hemiami-
nals by monohydrogenation.[2] Although some heterogene-
ous hydrogenation catalysts have been reported to give
good conversions of amides to amines, they generally re-
quire harsh operating conditions while only displaying moder-
ate to poor selectivity.[3] In addition, their use is mostly limit-
ed to substrates devoid of aromatic ring systems, since un-
wanted ring hydrogenation represents a major side reaction.
More recently, a bimetallic Pt/Re-based catalyst capable of
promoting amide hydrogenations under milder conditions has
been reported by Burch et al.[4] However, we have found the
use of this system to be limited to non-aromatic substrates
owing to the occurrence of unwanted ring hydrogenation.[5]
While this paper was under review, a system using Pd/Re on
graphite was reported. A wide range of amides are hydrogen-
ated to amines under mild conditions, but once again, aro-
matic rings in the substrates are also hydrogenated.[6]
À
C N bond. This is also the first system of any kind that can
catalyse the hydrogenation of amides to amines in the pres-
À
ence of aromatic rings without cleavage of the C N bond.
Many active pharmaceutical compounds contain an amine
functionality, which is often introduced by the formation
and subsequent reduction of an amide using LiAlH4 or
borane reducing agents. These reducing agents, however, are
not only pyrophoric and difficult to handle but also involve
complex work-up procedures while generating large
amounts of waste. These factors make their use on large
scale problematic. Using catalytic hydrogenation would be
an ideal solution to the problem since water is produced as
[a] Dr. J. Coetzee, Dr. D. L. Dodds, Prof. A. M. Z. Slawin,
Prof. D. J. Cole-Hamilton
Catalytic hydrosilylation represents an interesting alterna-
tive for amide reductions and has been shown to proceed
under mild reaction conditions whilst displaying good func-
tional group tolerance.[7] Despite the wider substrate scope,
hydrosilylation reactions still proceed with lower atom effi-
ciency than more classical hydrogenations involving molecu-
lar hydrogen. Thus, selective and environmentally benign
amide hydrogenation reactions are rare and for this reason
the American Chemical Society Green Chemistry Institute
(GCI) and members of the Pharmaceutical Round Table
have identified amide hydrogenation as one of their three
most desirable reactions for development.[8]
EastChem, School of Chemistry
North Haugh, University of St. Andrews
St. Andrews, Fife, KY16 9ST, Scotland (UK)
E-mail: djc@st-andrews.ac.uk
[b] Prof. J. Klankermayer, S. Brosinski, Prof. W. Leitner
Institut fꢁr Technische und Makromolekulare Chemie
RWTH Aachen University, Worringerweg 1
52074 Aachen (Germany)
[c] Prof. W. Leitner
Max-Planck-Institut fꢁr Kohlenforschung, Kaiser-Wilhelm-Platz 1
45470 Mꢁlheim a.d. Ruhr (Germany)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204270.
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Homogeneous Catalytic Hydrogenation of Amides to Amines
Our new amide hydrogenation catalysts, which keep the
FULL PAPER
(Table 1, entry 3), but too much acid is detrimental since the
major products become 6 (R=R’=Ph) and N-phenylpyrro-
lidine (Table 1, entry 4), presumably formed from the acid
catalysed reaction of aniline with the solvent THF. The pres-
sure can be dropped to 5 bar but a longer reaction time is
required and more 6 (R=R’=Ph) is produced (Table 1,
entry 5), presumably because transamidation of 1 (R=R’=
Ph) with the product 3 (R=R’=Ph) competes more effec-
tively with the slower hydrogenation of 1 (R=R’=Ph).
Adding aniline in an attempt to suppress transamidation,
makes little difference to the reaction selectivity (Table 1,
entry 7). The nature of the autoclave is also important. Has-
telloyTM C is ideal whereas stainless steel tends to lead to
products in which the phenyl rings are hydrogenated. This
suggests that metallic ruthenium or nanoparticles, known
catalysts for the hydrogenation of aromatic rings, may form
(Table 1, entry 6), although we have not explored this in
detail. The use of a glass liner in a stainless steel autoclave
alleviates this problem and allows successful reactions.
À
C N bond intact, are based on complexes prepared in situ
from [Ru
N
ethane (triphos), a system which is known to be active for
the hydrogenation of carboxylic acids and esters.[9] We also
describe other precatalysts, the role of acid and discuss the
possible active species present during the reactions. Some of
these results have been communicated in preliminary
form.[10]
Results and Discussion
[Ru
Heating benzanilide (1, R=R’=Ph) in THF in the presence
of [Ru(acac)3] (1 mol%), triphos (2 mol%) and methanesul-
ACHTUNGTRENNUNG(acac)3]/triphos system in catalytic amide reductions:
ACHTUNGTRENNUNG
fonic acid (1 mol%) to 2208C under hydrogen (40 bar at
RT, pressure at the reaction temperature is ca. 70 bar) for
16 h smoothly produces N-benzylaniline (3, R=R’=Ph)
with 88% selectivity. The other products are small amounts
of dibenzylaniline (6, R=R’=Ph), aniline (4) and N-benzy-
lideneaniline (2, R=R’=Ph; Table 1, entry 1). The pro-
posed origin of these products is shown in Scheme 1, which
summarises the reduction and transamination reactions.
For benzanilide, full conversion can be achieved in 8 h
and the selectivity towards the desired secondary amine im-
proved by working at lower pressures (Table 1, entry 2). Re-
ducing the [MSA] to 0.5 mol% makes little difference
Very similar chemistry is observed when using N-phenyla-
cetamide as substrate (1, R=Me; R’=Ph) and it was
shown, by working at constant pressure and monitoring gas
uptake from a ballast vessel, that the reaction at 10 bar (RT,
40 bar at the reaction temperature) and 2008C is complete
within 2 h. The effect of added acid is shown in Figure 1,
Table 1. Hydrogenations of benzanilide (1, R=R’=Ph) with [Ru-
ACHTUNGTRENNUNG
(acac)3]/triphos and catalytic amounts of MSA.[a]
Entry PH
MSA
t
2
3
4
6
Conv. Sel.
[%]
2
A
[mol%] [h] [%] [%] [%] [%] [%]
1
2
3
40
10
10
10
5
1
1
0.5
10
0.5
16
8
16
2
3
3
85
93
92
3
0
0
0
5
10
4
5
28
13
100
100
100
100
100
88
93
92
12
82
4[c]
5
16 <1 12
62
16
16
4
78
6[d]
7[e]
10
10
1
1
ring hydrogenation products observed
91 100 91
2
0
7
[a] Conditions: amide (5 mmol), [RuACTHUNGTRENNNUG
Figure 1. Effect of [MSA] on the products of N-phenylacetamide hydro-
genation. N-phenylacetamide (1, R=Me; R’=Ph, 5 mmol), [RuACHTUNGTRENNUNG(acac)3]
AHCTUNGTRENNUNG
lidine, benzylbenzamide and two other impurities are also formed, they
are included as products in the calculation of selectivity. [d] Stainless
steel autoclave. [e] Aniline (1%) added.
(1 mol%), triphos (2 mol%), 2108C, H2 (10 bar), THF, (10 mL), 16 h; for
6 and 3 R=Me and R’=Ph.
with the selectivity towards the desired secondary amine, N-
ethylaniline (3, R=Me; R’=Ph), increasing with added acid
at least to 1.5 mol% (selectivity 92%). In these reactions,
ethanol is the major by-product. This is presumably formed
by hydrogenation of acetic acid, the amide hydrolysis prod-
uct formed from the water generated in the reaction.
Changes in the reaction temperature also greatly affect
the catalytic hydrogenation of N-phenylacetamide, with in-
ternal temperatures below 1208C leading to limited conver-
sion with zero selectivity towards the desired amine
(Figure 2). At temperatures above 1508C, full conversion is
Scheme 1. Origin of the various products observed during the catalytic
hydrogenation of amides.
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D. J. Cole-Hamilton et al.
if there is an aromatic group on N. Finally, the primary
amide butanamide gives mainly secondary and tertiary
amines in the absence of ammonia, as previously found for
reactions carried out in the absence of acid,[9c,10a] but gives
the primary amine butylamine as the major product when
the reaction is carried out in the presence of aqueous am-
monia (Table 2, entry 1).
In order to be sure that the reactions were genuinely re-
producible between laboratories, hydrogenations of N-phe-
nylacetamide were carried out at RWTH Aachen University
using the optimised conditions from the St. Andrews labora-
tory (Table 3). At 10 bar hydrogen pressure, only 51% con-
version was obtained after 16 h due the limited amount of
hydrogen present in the 10 mL autoclave containing a glass
liner (Table 3, entry 1). Increasing the hydrogen pressure
stepwise to 75 bar resulted in full conversion of the N-phe-
nylacetamide (Table 3, entries 2–5). The importance of a
sufficient amount of acidic additive and triphos in the cata-
lytic reaction is demonstrated in the reduced conversion of
87% with only 1 mol% MSA and triphos (Table 3, entry 6).
In most of the reactions the selectivity towards 3 (R=Me;
R’=Ph) is >90%. Small amounts of ethanol and 6 (R=
Me; R’=Ph) represent the major by-products.
Figure 2. Effect of increasing temperatures on the products of hydrogena-
tion of N-phenylacetamide, where “other” refers to ring hydrogenated
products. N-Phenylacetamide (1, R=Me; R’=Ph, 5 mmol), [RuACTHNUTRGNEUNG(acac)3]
(1 mol%), triphos (2 mol%), MSA (1.5 mol%), 120–2358C, H2 (10 bar),
THF (10 mL), 16 h; for 6 and 3 R=Me and R’=Ph.
achieved with the selectivity towards N-ethylaniline (3, R=
Me; R’=Ph) reaching a maximum (92%) at around 2108C.
At even higher temperatures, catalyst decomposition starts
to become important with the metallic Ru generated leading
to the formation of unwanted ring hydrogenated products
(other in Figure 2). A hydrogenation of N-phenylacetamide
carried out at 2008C, under H2 (10 bar) using MSA
(1.5 mol%) gave comparable results in the presence and ab-
sence of added mercury, suggesting that, at least up to
In situ NMR studies: In order to elucidate the formation of
the actual precatalyst from the in situ system, variable tem-
perature high pressure NMR (VT-HP NMR) experiments
were conducted. Solutions of [RuACHTNUTRGNEUNG(acac)3] (10 mol%), tri-
phos (20 mol%) and N-phenylacetamide in degassed
[D8]THF were transferred to a sapphire high pressure NMR
cell under a H2 atmosphere and then pressurised to 10 bar
with H2 in the absence and presence of MSA (1.5 mol%).
Surprisingly, even at the maximum probe temperature of
2008C, the reaction is homogeneous (Table 2, foot
The substrate scope for the catalytic hydrogenation of pri-
mary, secondary and tertiary amides using the [Ru(acac)3]/
ACHTUNGTRENNnUNG ote [e]).
AHCTUNGTRENNUNG
triphos system is summarised in Table 2. It is clear from the
results obtained with secondary and tertiary amides that the
reaction works with high selectivity if there is a phenyl
group on nitrogen. There does not seem to be a correlation
between reaction selectivity and the electron density on the
N-aromatic ring. In some cases, for example, with N-methyl-
benzamide (1, R=Ph; R’=Me; Table 2, entry 2), although
the selectivity to the desired secondary amine is poor, the
major product is dibenzylmethylamine (6, R=Ph; R’=Me).
In the mentioned case, the hydrogenation works, but
slowly compared with the rate of transamidation. Similar ar-
guments apply to the hydrogenation of N-benzylacetamide
(1, R=Me; R’=Bz; Table 2, entry 18). In both cases, minor
products observed have scrambling of the alkyl/aryl groups
on the amine product. The only secondary amide substrates
we have examined with which reactivity is poor are N-(2-
chlorophenyl)acetamide, N-(4-chlorophenyl)acetamide and
N-benzyl-4-methylbenzamide (Table 2, entries 9, 11 and 14)
and N-(4-nitrophenyl)acetamide, with which substantial cat-
alyst decomposition occurs leading to preferential hydroge-
nation of the ring and the nitro group (Table 2, entry 12).
When using tertiary amide substrates, the yields of amine
are generally poor—in some cases because the reaction is
slow, whereas in others because the selectivity is poor. Simi-
lar to the secondary amides, reactions again proceed better
1
1308C, the measured H and 31P{1H} NMR spectra of both
solutions showed very little difference from those of the
starting materials, suggesting that the reduction of RuIII to
RuII with concurrent triphos coordination does not proceed
as readily as was first anticipated. Therefore, a solution of
[RuACTHNUTRGEN(UGN acac)3], triphos (2 equiv) and MSA (1.5 equiv) in THF
was pressurised to 10 bar with H2 in a HastelloyTM autoclave
and heated for 4 h at 2108C. 31P{1H} NMR analysis of the
crude product mixture indicated, in addition to oxidised tri-
phos (resulting from the reduction of Ru), a mixture of flux-
ional species giving rise to a broad resonance around dP =
40 ppm. From low temperature 31P{1H} NMR spectra, it is
evident that the fluxional mixture consists of a number of
new species (Figure 3). As outlined in the next sections, the
majority of these species could be identified and structurally
characterised through the investigation of the reactivity and
catalytic performance of preformed precatalysts in the pres-
ence and absence of MSA.
Preformed precatalysts: Since an RuII–triphos unit seems
likely to be the basis of the active site during the catalytic
cycle, special focus was placed on Ru complexes already
containing this motif (Figure 4). Of the tested precatalysts
7–10, only 9 and 10 displayed catalytic activity towards the
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Homogeneous Catalytic Hydrogenation of Amides to Amines
FULL PAPER
Table 2. Substrate scope for amide hydrogenations with the [RuACTHNUTRGNEUNG
(acac)3]/triphos system.[a]
Entry Substrate
MSA
T
PH
Conv. Sel.
[%]
Entry Substrate
MSA
T
PH
Conv. Sel.
2
2
[mol%] [8C]
[bar] [%]
[mol%] [8C]
ACTHNUGRTENUNG[bar] [%] [%]
Primary amide[b]
1
1.5
200
10
100
61
Secondary amides
2
3
4
5
6
1.5
1.5
1.5
1.0
1.5
200
200
200
220
200
10
10
10
10
10
82[c]
<5[c]
92[d]
92[e]
78
11
12
13
14
15
1.5
1.5
1.0
1.5
1.0
200
200
220
200
220
10
10
10
10
10
45
0
92[d]
100[e]
98
100
97
0
78
<5[f]
92
15[f]
100
100
79
7
8
9
1.5
1.0
200
220
10
10
100
99
90
77
16
17
18
1.5
1.5
1.5
200
200
220
10
10
10
100
92[c]
100
94
61[c]
<5
1.5
1.5
200
200
10
10
64
75
28
75
10
Tertiary amides
19
1.5
220
10
92
73
22
1.0
220
40
83
42
20
21
1.5
1.5
220
200
10
10
33[c]
19
7[c]
63
23
24
1.5
1.5
200
200
10
10
19
0
100
0
[a] Conditions: substrate (5 mmol), [RuACTHNUTRGEN(UNG acac)3] (1 mol%), triphos (2 mol%), THF (10 mL), 16 h. Conversion and selectivity were calculated using NMR
integration. [b] Reaction performed in the presence of aq. NH3 (10 mL). [c] Based on uncalibrated GC-FID integration. [d] Ref. [6] reports 87% conv.
and 78% sel. [e] Selectivity for different reactions with N-phenylacetamide under identical conditions varies between 86–92%. In the presence of added
mercury, 100% conversion with 84% selectivity was obtained. [f] Small amounts of mixed tertiary amines formed.
hydrogenation of N-phenylacetamide under the conditions
typically employed for the conventional [RuACTHNURTGNENG(U acac)3]/triphos
system. Under these conditions, 9 gave full conversion of 1
(R=Me, R’=Ph), but with a slightly lower selectivity of
78% towards 3 (R=Me, R’=Ph). The hydrogenation of N-
phenylacetamide in the presence 9 was explored over a
range of temperatures with the results summarised in
Table 4. Catalyst 9 performed rather poorly at lower temper-
atures when compared with [RuACHTNUGRTENUNG(acac)3]/triphos under the
same conditions (Figure 2). It can thus be concluded that
the high temperatures required for these transformations
are not solely associated with initial RuIII reduction and tri-
phos coordination but are also required for the turnover of
the catalytic cycle itself.
Figure 3. Variable temperature 31P{1H} NMR spectra of the complex mix-
ture obtained when [Ru(acac)3] is treated with triphos and MSA
(1.5 equiv) under a H2 pressure of 15 bar at 2108C for 4 h. Markers (thin
arrow, dot in circle, diamond and star) indicate distinct species that will
be identified (vide infra).
AHCTUNGTRENNUNG
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D. J. Cole-Hamilton et al.
Table 3. Catalytic hydrogenation of N-phenylacetamide with [RuACTHNUTRGNEUNG(acac)3]/
triphos in 10 mL autoclave.[a]
Entry
triphos
[mol%]
MSA
[mol%]
PH
A
t
Conv.
[%]
Sel.
[%]
2
G
E
[bar][b]
[h]
1
2
3
4
5
6
2
2
2
2
2
1
1.5
1.5
1.5
1.5
1.5
1
10
30
50
75
75
75
16
16
16
24
16
24
51
90
97
>99
>99
87
91
90
88
92
90
87
[a] Conditions: N-phenylacetamide (1, R=Me; R’=Ph, 0.25 mmol), [Ru-
(acac)3] (1 mol%), 2008C, stainless steel autoclave (10 mL) with a glass
liner. Selectivity is 3/(3+6+[EtOH]); for full product analysis see the
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Supporting Information. [b] Pressure at RT.
Figure 5. Comparison of the 31P{1H} spectra (CD2Cl2, 258C) recorded for
the crude product mixtures obtained after catalytic hydrogenation of N-
phenylacetamide with 9 at various temperatures, displaying mainly reso-
nances corresponding to [Ru(H)2CO
known species (star in circle).
ACHTUNGTRNE(NUNG triphos)] (10; diamond) and an un-
direct routes when N-phenylacetamide is the substrate,
acetic acid and ethanol are produced as side products and
are plausible sources for the carbonyl group. As mentioned,
10 is itself a precatalyst for the hydrogenation of acetanilde.
To add to our understanding of the role of methanesulfon-
ic acid in the catalytic system, a solution of 9 in THF was
treated with either 1 or 2 equiv of MSA at RT and the re-
sulting reaction products were analysed by NMR spectrosco-
py. With the addition of only 1 equiv of MSA, the hydride
ligand in 9 is lost to form hydrogen with the formation of
Figure 4. Preformed precatalysts 7–10 tested for catalytic activity in
amide hydrogenation reactions with N-phenylacetamide.
Table 4. Catalytic hydrogenation of N-phenylacetamide with 9 as preca-
talyst over a range of temperatures.[a]
the mono-substituted complex [Ru
(triphos)] (11) as the only product (Scheme 2 (a)). Interest-
ingly, in the presence of 2 equiv of MSA, a mixture of three
complexes, [Ru2A(m-CH3SO3)3A(triphos)2]CH3SO3 (12),
3A
H[Ru(CH3SO3-k1O) (triphos)] (13) and [Ru(CH3SO3-k1O)
(CH3SO3-k2O,O’)
(triphos)] (14) is initially obtained
(CH3SO3)(OAc-k2O,O’)-
ACHTUNGTRENNUNG
Entry
T
[8C]
3
[%]
6
[%]
EtOH
[%]
Other
[%]
Conv.
[%]
Sel.
[%]
AHCTUNGTRENNUNG
1
2
3
120
150
200
210
210
0
0
75
78
60
0
0
23
11
10
1
1
0.4
0.5
13
26
99
1.6
10.5
0
27
100
100
100
83
0
0
75
78
73
C
CHTUNGTRENNUNG
CTHUNGTRENNUNG
4
AHCTUNGTRENNUNG
5b
(Scheme 2 (b)). An equilibrium, which lies towards the ther-
modynamically more stable monomeric 14, exists between
these compounds (Scheme 2 (c)). The assignment if 12 has
been confirmed by isolation and crystallographic characteri-
sation (Figure S5 in the Supporting Information). The struc-
ture of 13 is tentatively assigned from its low temperature
NMR spectrum, its predominance when excess MSA is pres-
ent and its fluxionality presumably arising from the proton
moving between pairs of methanesulfonato ions. Similarly,
14 is tentatively assigned from its low temperature
31P{1H} NMR spectrum. Attempted crystallisation of 13/14
[a] Conditions: N-phenylacetamide (1, R=Me; R’=Ph, 5 mmol),
[RuH(OAc-k2O,O’)
(triphos)] (9, 1 mol%), MSA (1.5 mol%), THF
(10 mL), H2 (15 bar at RT), 16 h in a HastelloyTM autoclave (250 mL); se-
lectivity is 3/(3+6+[EtOH]); for full product analysis see the Supporting
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
Information. [b] Performed in the absence of added MSA.
31P{1H} NMR analysis of the final product mixture ob-
tained for hydrogenations with 9 at various reaction temper-
atures, indicated the presence of two major species. Interest-
ingly, at lower reaction temperatures an unknown species
giving rise to a triplet at dP =28.4 ppm and a doublet at dP =
45.3 ppm was prevalent, whereas at higher temperatures the
gave [Ru(CH3SO3-k1O)
the Supporting Information).
2ACHUTGTNRENNUG(H2O)ACHTUNGTNER(NUGN triphos)] (19; Figure S6 in
known complex, [Ru(H)2CO
N
In the 31P{1H} NMR spectrum of the mixture run immedi-
ately after it was isolated, 12 is detected as a sharp singlet at
dP =38.5 ppm whereas the fast exchanging 13 and 14, which
could only be assigned tentatively, are only observed by an
averaged broad singlet with a chemical shift dP =40.7 ppm
(Figure S1b in the Supporting Information) in between that
of 13 (dP =48.5 ppm; Figure S1a in the Supporting Informa-
the major species (dP =26.9 ppm (d) and dP =35.2 ppm (t);
Figure 5). The latter has also been reported by some of us
to be present at the end of catalytic hydrogenations using
[RuACHTUNGTRENNUNG(acac)3]/triphos with carboxylic acids as substrate, and
has been shown to be formed by the decarbonylation of al-
dehydes.[9f,g] Although aldehydes cannot be produced by any
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Homogeneous Catalytic Hydrogenation of Amides to Amines
FULL PAPER
period, and the final RT 31P{1H} NMR spectrum was identi-
cal to that measured initially (Figure S2a and f in the Sup-
porting Information). When this 31P{1H} NMR spectra meas-
ured at RT is compared with that of 11 and the initial mix-
ture of 12, 13 and 14, it appears that complexes 11–14 con-
stitute the major species in the mixture (Figure S3 in the
Supporting Information).
At lower temperatures, the fluxionality of these com-
plexes could be slowed down to attain more defined reso-
nances. In the measured 31P{1H} NMR spectra, the major
species were identified as 11 (doublet at dP =40.3 ppm and
triplet at dP =46.8 ppm, Figure 6b–e, thick arrow). In addi-
Scheme 2. Reaction products observed when treating
a) 1 equiv, or b) 2 equiv of MSA.
9 with either:
Figure 6. 31P{1H} VT-HP NMR spectra recorded for a solution of N-phe-
nylacetamide (0.75 mmol), [D8]THF (3 mL), 9 (10 mol%) and MSA
(15 mol%) under H2 (10 bar), where thick arrow, dot in circle and thin
arrow indicate resonances corresponding to 11, 12 and 13, respectively.
tion) and 14 (dP =38.7 ppm; Figure S1c in the Supporting
Information). A 31P{1H} NMR spectrum taken of this mix-
ture after some time in solution, however, shows the change
in the composition to give largely what we propose to be 14
at the expense of 12 and 13 (Figure S1c in the Supporting
Information). Compound 13 can be obtained as the major
species in the presence of a large excess of MSA (>3 equiv)
tion, a weak singlet at dP =38.5 ppm could be assigned to 12
(Figure 6b–e, dot in cicle), whereas a triplet at dP =41.1 ppm
coupled to a doublet at dP =50.0 ppm (2JPP =42.6 Hz; Fig-
ure 6d and e, thin arrow) could be assigned tentatively to
complex 13. No hydride resonances were detected in the
1H NMR spectra. Although unambiguous assignments of all
the observed species could not be made, it seems plausible
that the mixture largely consists of the RuII triphos com-
plexes 11–13 in which one or more of the coordination sites
is occupied by a methanesulfonato group, coordinated in
either a mono- or a bidentate fashion. The nuclearities of
these complexes (i.e., monomeric vs. dimeric) strongly
depend on the conditions, such as the metal precursor em-
ployed, the acid to precursor ratio and the time spent in sol-
ution.
The presence of MSA thus appears to be necessary for
the formation of these hydride-free species containing one
of more weakly coordinated methanesulfonato ligands,
which presumably provide an entry into the catalytic cycle
upon reaction with H2 and substrate. Similar species are ob-
served in the absence of substrate along with a doublet at
dP =41.9 ppm coupled to a triplet at dP =30.0 ppm assigned
to [Ru(CH3SO3-k1O)(CH3SO3-k2O,O’)triphos] (14; Fig-
ure 7d and e, star).
and is also the predominant product if [Ru
(OAc-k1O)(OAc-
ACHTUNGTRENNUNG
k2O,O’)
ACHTUNGTRENNUNG
We thus propose it to be H[Ru(CH3SO3-k1O)3triphos] as the
31P{1H} NMR analysis of 13 frozen out at À808C displayed a
triplet at dP =41.1 ppm and a doublet at dP =50.0 ppm
(2JPP =42.6 Hz). This profile presumably arises because the
acidic proton is hydrogen bonded between only two of the
[CH3SO3]À groups at low temperatures (Scheme 2), whilst
migrating between all three groups at higher temperatures.
The structures of 11 and 12 could be confirmed by single
crystal X-ray diffraction and are discussed in more detail in
the Supporting Information (Figures S4 and S5).
The behaviour of these species in the presence of sub-
strate and hydrogen was assessed by VT-HP NMR spectro-
scopy. Addition of MSA (15 mol%) to a solution of N-phe-
nylacetamide (0.75 mmol) and 9 (10 mol%) in [D8]THF
(3 mL) resulted in the immediate evolution of hydrogen gas.
The RT 31P{1H} NMR spectrum of this solution under a H2
pressure of 10 bar displays a mixture of fluxional species in
the form of a series of broad resonances within the region
dP =48–38 ppm (Figure S2a in the Supporting Information).
At higher temperatures, the rate of exchange is increased
until finally all species are observed as a single averaged
broad singlet at dP =42.1 ppm (Figure S2e in the Supporting
Information), similar to that observed with the in situ
system. No new species were generated during the heating
Given that the hydride ligand in 9 is immediately lost as
H2 in the presence of MSA, the diacetate analogue, [Ru-
ACHUTNGRENNUG CAHTUNGTRENNUNG
(OAc-k1O)(OAc-k2O,O’)
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D. J. Cole-Hamilton et al.
Figure 7. 31P{1H} VT-HP NMR spectra recorded for a solution of 9 and
MSA (1.5 equiv) in [D8]THF under a H2 pressure of 10 bar, where thick
arrow, thin arrow and star indicate resonances corresponding to 11, 13
and 14, respectively.
Figure 8. Effect of increasing [MSA] on the hydrogenation of N-phenyla-
cetamide with [RuACHTUNTRGENNUG ACHUTGNTREN(NUGN triphos)] (15). Conditions:
(OAc-k1O)(OAc-k2O,O’)
iour of 15 in the presence of 1 or 2 equiv of MSA is analo-
gous to that of 9, giving 11 or a mixture of 12–14, respective-
ly. Most significantly, the catalytic reactivity pattern of 15 is
in line with that observed for 9 and the in situ system, re-
ducing the secondary N-phenylacetamide preferentially over
its tertiary congener (Table 5). The catalytic performance
N-phenylacetamide (1, R=Me; R’=Ph, 5 mmol), 15 (1 mol%), 2108C,
H2 (15 bar), THF, 16 h.
and 83% selectivity after 16 h. At the shorter reaction time
of 3.5 h, only 55% conversion was still obtained using 11
with no added MSA, whereas the 15/MSA (1 equiv) system
gave 96% conversion over the same period of time. These
observations clearly indicate that MSA is not essential for
catalysis, but plays an important role in both the formation
of the active species and maintaining efficient catalytic turn-
over.
Table 5. Amide hydrogenations with [Ru
(triphos)] (15) as precatalyst.[a]
(OAc-k1O)(OAc-k2O,O’)-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Entry
Substrate
MSA
[mol%]
PH
A
t
Conv.
[%]
Sel.
[%]
2
G
[bar][b]
[h]
1
2
1.5
1.5
15
15
16
16
100
31
79
57
As mentioned previously, [Ru(H)2COACTHNUTRGNEUNG(triphos)] (10) was
detected as one of the major species present at the end of
successful catalytic hydrogenations with 9 as precatalyst
(Figure 5). Using complex 10 as precatalyst, the catalytic
performance in the hydrogenation of primary, secondary
and tertiary amides again followed the previously observed
trends (Table 6). Full conversion of the primary amide, buta-
[a] Conditions: substrate (5 mmol), 15 (1 mol%), THF (10 mL) at 2108C
in a HastelloyTM autoclave (250 mL). [b] At RT.
for the formation of 3 of 9 (conv. 100%, sel. 78%) and 15
(conv. 100%, sel. 79%) are identical, but deviate slightly
Table 6. Amide hydrogenation with [Ru(H)2CO
talyst.[a]
ACHTUNGERTN(NUNG triphos)] (10) as preca-
from that of the original [RuACHTNUTRGENNG(U acac)3]/triphos system under
the standard conditions (1.5 equiv MSA, conv. 100%, sel.
92%).
Entry
Substrate
MSA
[mol%]
PH
A
t
Conv.
[%]
Sel.
[%]
2
G
[bar][b]
[h]
1[c]
2
1.5
1.5
15
15
16
16
100
100
26
74
Given the strong influence of the MSA/Ru ratio on the
activity of the in situ system, the catalytic performance of 15
was assessed over a range of MSA concentrations using N-
phenylacetamide as the model substrate (Figure 8). It is
noteworthy that even in the absence of added MSA, 15
gives 68% selectivity to the desired N-ethylaniline (6, R=
Me; Figure 8). The optimum performance is obtained at a
slightly lower MSA concentration (1 mol%) when com-
3
1.5
15
16
0
0
[a] Conditions: substrate (5 mmol), 10 (1 mol%), THF (10 mL), 2108C in
a HastelloyTM autoclave (250 mL). [b] At RT. [c] Reaction performed in
the presence of aq. NH3 (5 mL).
pared with the 1.5 mol% required by the [RuACTHNUTRGENUG(N acac)3]/triphos
system, giving full conversion with 86% selectivity towards
the secondary amine. These results compare well with the
original [RuACHTUNGTRENNUNG(acac)3]/triphos system under the same pressure
and heating conditions (conv. 100%, sel. 86%). Almost
identical effects of the acid additive were observed when the
isolated complex 11 was used as the catalyst precursor.
Without added MSA, N-phenylacetamide was hydrogenated
to N-ethylaniline, 3 (R=Me; R’=Ph), with 93% conversion
namide, could be achieved with 10, albeit the selectivity to-
wards the primary amine, n-butylamine (26%) was signifi-
cantly lower than with the in situ system, giving n-butanol,
dibutylamine and tributylamine as the major side products
(Table 6, entry 1). In the case of N-phenylacetamide, the re-
sults were comparable to those previously obtained with
precatalysts 9 and 15 under the same conditions (Table 6,
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Homogeneous Catalytic Hydrogenation of Amides to Amines
FULL PAPER
entry 2). No conversion was observed with the tertiary
amide, 1-methylpyrrolidin-2-one, as substrate (Table 6,
entry 3).
giving rise to three doublets of doublets at dP =2.8, 16.8 and
52.9 ppm (2JPP =28.6, 18.5 and 42.1 Hz; Figure 9a).
Interestingly, a sharp singlet observed at dP =42.9 ppm
To evaluate the stability of 10 under catalytic conditions,
a solution of N-phenylacetamide and 10 in [D8]THF was
treated with MSA (1.5 mol%), pressurised to 10 bar with H2
in a sapphire NMR cell and subjected to VT-HP NMR spec-
troscopy (Scheme 3a; Figure 9). From the initial 31P{1H}
spectrum recorded at RT it is evident that, in the presence
of MSA, one hydride ligand is lost immediately as hydrogen
to give the methanesulfonato monohydride complex [RuH-
could be assigned to the dimeric Ru(I) complex, [{Ru
AHCTUNGTRE(GNUNN triphos)}2] (18), containing two bridging hydride ligands
ACHTUNGTRENNUNG(m-H)-
À
and a formal Ru Ru bond. Serendipitously, this complex
was obtained earlier as the major side-product during the
preparation of 10 and fully characterised. The structure
could be confirmed by X-ray diffraction and its formation
also occurs in other hydrogenation reactions using the Ru/
triphos system.[11] In addition to 18, minor amounts of 12
and 13 were also observed at dP =42.2 ppm (bs).
At higher temperatures (ꢀ
ACHTUNGTRENNUNG ACHTUNGTRENNUNG(triphos)] (16) as the major product,
(CO)(CH3SO3-k1O)
1008C), 16 was gradually con-
verted to the bidentate metha-
nesulfonato
complex
[RuH(CH3SO3-k2O,O’)-
AHCTUNGTERG(NNUN triphos)] (17) with loss of CO.
The latter gives rise to a triplet
and a doublet at dP =6.7 and
18.5 ppm (2JPP =28.1 Hz), re-
spectively, in the 31P NMR spec-
trum (Figure 9d–f). Also, in the
1H NMR spectrum a doublet of
triplets
at
dH =À6.71 ppm
cis
(2JHPtrans =64.6 Hz,
2JHP
=
15.5 Hz) could be assigned to
the hydride ligand. Complex 16
could also be prepared and
characterised independently by
treating a solution of 10 in di-
chloromethane with 1 equiv of
MSA at RT (Scheme 3c). Simi-
larly, complex 17 (~20%) could
Scheme 3. Products observed during reactions of 10 with MSA; *: observed in situ during VT-HP NMR stud-
ies.
be generated by heating isolated 16 and N-phenylacetamide
(0.6 equiv) in THF at 1508C under an atmosphere of H2
(10 bar) for 20 h (Scheme 3d).
As mentioned before, the VT-HP NMR experiments were
performed at significantly lower temperatures than the
standard catalytic conditions (130 vs. 2108C) owing to in-
strumental limitations. It is noteworthy that some minor
conversion (~2.5%) was still achieved during VT-HP NMR
experiments with 10. It is thus plausible that one of the de-
tected hydride complexes represents the most direct entry
into the catalytic cycle.
Interestingly, the optimal MSA concentration (0.5 mol%,
Figure 10) for reactions with 10 was found to be significantly
lower than what was required for successful N-phenylaceta-
mide hydrogenation with either [RuACTHNUTRGEN(UNG acac)3]/triphos
(1.5 mol%, Figure 1) or precatalyst 15 (1.0 mol%, Figure 8).
Moreover, 31P{1H} NMR spectra of the product mixture at
the end of catalytic reactions with 10 at MSA concentrations
of up to 1 mol% still display the presence of significant
amounts of 10. In addition to 10, the earlier observed Ru(I)
dimer 18 is also present with the relative ratio of 18 to 10 in-
creasing with increases in the MSA concentration until final-
ly only 18 is observed at MSA concentrations above
Figure 9. 31P{1H} NMR spectra recorded during a VT HP NMR study on
the in solution behaviour of 10. Conditions: N-phenylacetamide
(0.75 mmol), [D8]THF (3 mL), 10 (10 mol%), MSA (15 mol%) and H2
(10 bar).
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D. J. Cole-Hamilton et al.
2) it provides a balanced pKa in the reaction medium to con-
trol the necessary H-transfer and hydrolytic steps within the
complex reaction sequence. The resulting subtle interplay of
acid and metal catalyst explains the significant variation of
the optimum MSA/precursor ratio with the various precata-
lysts.
Conclusion
A new catalytic system has been developed for the homoge-
neous hydrogenation of amides to the corresponding
amines. It can be conveniently generated in situ from [Ru-
AHCTUNGTERG(NUNN acac)3] and the triphos ligand together with catalytic quan-
Figure 10. Effect of increasing [MSA] on the products of hydrogenation
of N-phenylacetamide with [Ru(H)2CO(triphos)] (10) as precatalyst. N-
Phenylacetamide (1, R=Me; R’=Ph, 5 mmol), 10 (1 mol%), MSA (0–
2.0 mol%), 2108C, H2 (15 bar), THF (10 mL), 16 h.
tities of MSA. Hydrogen pressures as low as 10 bar can be
employed at temperatures around 200–2108C. The system
works very well for N-aromatic secondary amides, such as
N-phenylacetamide. It also provides access to primary
amines from amides, such as butanamide, and allows reduc-
tion of certain tertiary amides. In particular, it allows for the
first-time hydrogenation of aromatic amides to amines with-
AHCTUNGTRENNUNG
1 mol%. Catalytic hydrogenations with isolated 18 as preca-
talyst and 1 mol% MSA per Ru gave no reaction, suggest-
ing that the formation of 18, which cannot be reactivated,
most likely defines a major deactivation pathway.
À
out any competing arene hydrogenation or C N bond cleav-
age.
A detailed high pressure NMR study of the organometal-
lic species present in the reaction solutions arising from the
in situ catalyst, as well as from isolated RuII complexes of
the triphos ligand, revealed the presence of a range of com-
plexes containing coordinated monodentate or chelating
[CH3SO3]À. Several of these species could be isolated and
structurally characterised by single crystal X-ray diffraction.
None of these complexes contain hydrides, and the main
component in solution is proposed to be [Ru(CH3SO3-
Mechanistic proposal: We can now tentatively identify all
the species observed with the in situ catalyst after heating
the [RuACHTUNGTRENNUNG(acac)3]/triphos system with MSA in THF under hy-
drogen (Figure 3). From low temperature 31P{1H} NMR
spectra, it is evident that the mixture largely consists of
complex 14 (Figure 3c, star). Furthermore, the RuII–triphos
complexes containing the MSA anion 12 (dot in circle) and
13 (thin arrow) are observed at À808C. The only hydride
species in solution 18 (diamond) is present in trace amounts.
Since control experiments have shown 18 to be catalytically
inactive, only complexes 12–14 may be regarded as possible
catalytically important species in this mixture. These com-
plexes can be regarded as various isomeric forms of the spe-
k1O)(CH3SO3-k2O,O’)
with its dimeric analogue, [Ru
[CH3SO3]. These species are active in their own right even
ACHTUNGTRENNUNG
C
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
in the absence of added MSA. The only Ru hydride species
that are seen in post-catalytic reaction solutions are the di-
hydrido RuII complex [Ru(H)2CO
ACHTUNGTRENNUNG
cies [Ru
G
G
dimer, [RuACHTNGUTRENNU(G m-H)ACHTUNGTRENNUNG
centration and temperature dependent equilibrium.
alytically active and may thus represent an important deacti-
vation pathway for the catalyst.
Consistent with all experimental results so far, a reasona-
ble scenario involves this “pool” 12–14 as the direct precur-
sor to the active species, reacting with H2 and the substrate
to enter the catalytic cycle. The cationic monohydride com-
plexes 16 and 17 provide plausible candidates for this entry
point based on the experimental results obtained since they
are formed when [Ru(H)2COACTHNUTRGNE(NUG triphos)] (10) is treated with
MSA. Compound 10 is also observed in some post-catalytic
solutions when using the catalyst formed in situ from [Ru-
The obtained data are consistent with the assumption that
the equilibrium mixture of the various MSA complexes act
as a pool or reservoir for the [(triphos)Ru]2+ fragment as
the entry point into the actual cycle upon reaction with H2
and substrate. Formation of hydride complexes or direct het-
erolytic cleavage of the H2 molecule remains equally plausi-
ble at this stage. The function of the acidic additive, MSA,
in these reactions is not only to generate the active catalytic
species, but also to control the protonation–deprotonation
sequences required for efficient catalytic turnover. Although
the exact nature of the individual intermediates in the cata-
lytic cycle remains, as yet, elusive, these data provide impor-
tant guidelines for rational further development of the cata-
lytic system. Therefore, the Ru/triphos system provides a
promising approach towards efficient catalytic reduction of
amides with molecular hydrogen, and can thus have a major
ACHTUNGTRENNUNG(acac)3], triphos and MSA. However, the direct activation of
dihydrogen molecules at the highly Lewis acidic RuII centres
in 12–14 appears equally possible and a final conclusion
cannot be drawn as yet.
In both cases, the acidic additive MSA appears to have a
dual role: 1) it provides a weakly coordinating counterion
that allows sufficient stabilisation of the RuII–triphos frag-
ment without blocking the generation of the active species;
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Homogeneous Catalytic Hydrogenation of Amides to Amines
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clave to the atmosphere in a well-ventilated fume-hood, the content was
sampled under an inert atmosphere prior to transferral of the remaining
content to a sample vial, in air. The crude mixtures were analysed using
GC-MS, GC-FID and NMR spectroscopy. Quantitative calculations were
impact on sustainable production of amines from amides in
the pharmaceutical industry.
1
based on recorded H NMR spectra unless otherwise stated.
[Ru(CH3SO3-k1O)(OAc-k2O,O’)
(5.5 mg, 0.06 mmol, 3.7 mL) was added with a microsyringe to a suspen-
sion of [RuH(OAc-k2O,O’)
(triphos)] (0.05 g, 0.06 mmol) or [Ru(OAc-
k1O)(OAc-k2O,O’)
(triphos)] (0.05 g, 0.06 mmol) in THF (1.5 mL). The
ACHTUNGTRENN(UNG triphos)] (11): Methanesulfonic acid
Experimental Section
U
ACHTUNGTRENNUNG
General materials and methods: All reactions were carried out under an
inert atmosphere of N2 (N2, passed through a column of Cr(II) adsorbed
on silica) unless otherwise stated, using standard Schlenk and vacuum-
AHCTUNGTRENNUNG
resulting mixture was then allowed to stir at RT for 1 h. All volatiles
were subsequently removed under reduced pressure. The crude yellow
residue was washed with hexane (6 mL) and dried in vacuo to give the
pure product as a yellow solid (49.0 mg, 98%). Single crystals of 11 suita-
ble for analysis by X-ray diffraction could be obtained by slow diffusion
of hexane into a solution of 11 in dichloromethane at RT. M.p. 260–
line techniques or in a glovebox when necessary. [RuACTHNURGTNEUNG(acac)3], triphos,
methanesulfonic acid, diphenylamine, acetyl chloride and aniline were
purchased from Aldrich and used as received. N-Phenylacetamide, ben-
zanilide, benzoyl chloride, p-anisoyl chloride and N-(p-tolylacetamide)
were purchased from Acros organics; p-toluoyl chloride, benzylamine, N-
methylbenzamide, N,N-dimethylbenzamide, N-methyl-N-phenylbenza-
mide, 1-methylpyrrolidin-2-one, 1-phenylpyrrolidin-2-one were from Alfa
Aesar and butanamide from Fluka. Aqueous ammonia (35%) and tetra-
hydrofuran were purchased from Fisher Scientific; N-(4-methoxypheny-
l)acetamide and N,N-diphenylacetamide were purchased from TCI
Europe. N-(4-Fluorophenyl)acetamide was purchased from Apollo Scien-
tific. Amide substrates not listed here were prepared using standard liter-
ature procedures; more details can be found in the Supporting Informa-
tion. Gases were supplied by BOC.
2658C (decompose). 1H NMR (400 MHz, CD2Cl2, 258C): dH =1.57 (q,
4
À
À
À
À
3H, JHP =2.7 Hz; CH3), 1.98 (s, 3H, C(O)CH3), 2.27 (bs, 6H, CH2 ),
2.46 (bs, 3H, SCH3), 6.88–7.79 ppm (m, 30H, Ph); 13C{1H} NMR
(100 MHz, CD2Cl2, 258C): dC =26.1 (s, C(O)CH3), 32.6 (m, CH2 ),
À
À
À
À
3
2
À
À
37.8 (q, JCP =11.1 Hz, CH3), 38.4 (q, JCP =2.8 Hz,
CACHTGNUTERNNU(G CH2PPh2)3), 41.3
(s, SO3CH3), 128.1 (m, Phmeta), 129.5 (s, Phpara), 132.5 (m, Phortho), signal
À
too weak (Phipso), 190.3 ppm (s, C(O)CH3); 31P{1H} NMR (161 MHz,
À
À
CD2Cl2, 258C): dP =39.4 (bd, 2P, JPP =43.2 Hz, PPh), 45.3 ppm (bt, 1P,
J
PP =43.2 Hz, PPh); 31P{1H} NMR (121 MHz, [D8]THF, À408C): dP =
À
G
E
(triphos)2]Cl,[12]
[Ru(H)
G
(triphos)],[13]
[Ru(H)2CO-
À
À
40.3 (d, 2P, JPP =43.2 Hz, PPh), 46.8 ppm (t, 1P, JPP =43.2 Hz, PPh); IR
(KBr): v˜ =3054 [w, sp2
n
G
nACTHUNGTERNNU(G C H)], 1461 [st,
3
R
ACHTUNGTRENNUNG
À
À
n(k2-OCOsym)], 1434 [st, n
(P Ph)], 1247–1156 cm [st, n(SO)]; elemental
À1
ACHTUNGTRENNUNG
À
amide substrates were purified by recrystallisation (typically from tol-
uene) prior to use. Toluene and tetrahydrofuran were dried using a
Braun solvent purification system and used without any further degassing
steps.
analysis (%): found: C 57.98, H 5.15; C44H45O5P3RuS requires: C 60.06,
H 5.15; for C44H45O5P3RuS·H2O: C 58.86, H 5.28.
Mixture of [Ru
3A
k1O) (triphos)] (13) and [Ru(CH3SO3-k1O)(CH3SO3-k2O,O’)
(14): Methanesulfonic acid (9.5 mg, 0.10 mmol, 6.4 mL) was added with a
microsyringe to a suspension of [RuH(OAc-k2O,O’)
(triphos)] (0.04 g,
0.05 mmol) or [Ru (triphos)] (0.04 g, 0.05 mmol)
(OAc-k1O)(OAc-k2O,O’)
2ACHUTGTRENNGU(m-CH3SO3)3ACTHNUTGR(EUNNNG triphos)2]CH3SO3 (12), H[Ru(CH3SO3-
C
ACHTUNGTRENNUNG
NMR spectra were recorded on a Bruker Avance 300 FT or Bruker
Avance II 400 MHz spectrometer (1H NMR at 300/400 MHz and
13C{1H} NMR at 75/100 MHz) with chemical shifts reported relative to
tetramethylsilane (TMS). 1H and 13C{1H} NMR spectra were referenced
internally to deuterated solvent resonances, which were referenced rela-
tive to TMS. In situ VT-HP NMR studies were performed using a sap-
phire NMR cell purchased from Hydraulik und Industrie-Technik
GmbH.
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
in THF (1.5 mL). The resulting mixture was then allowed to stir at RT
for 1 h. All volatiles were subsequently removed under reduced pressure.
The crude yellow residue was washed with hexane (6 mL) and dried in
vacuo to give a mixture initially (0.50 g) of 13+14 (57%) and 12 (43%)
as a bright yellow solid. This mixture, if left standing in solution, equili-
brates over a time to give largely 14 after a period of 5–6 days. Single
crystals of 12 suitable for analysis by X-ray diffraction could be obtained
by slow diffusion of hexane into a solution of the mixture in dichlorome-
À
Solid state IR spectra were recorded using pressed KBr pellets on a
Perkin–Elmer Spectrum GX IR spectrometer. Elemental analysis was
performed by London Metropolitan University. Melting points were de-
termined on a Gallenkamp apparatus and are uncorrected. GC-MS chro-
matograms were recorded on a Hewlett–Packard 6890 series GC system
equipped with an Agilent J&W HP-1 general purpose column (fused
silica capillary) and an HP 5973 Mass selective detector for both qualita-
tive (MS) and quantitative (FID) analysis. A Hewlett–Packard Chemsta-
tion allowed for the computerised integration of peak areas. Method:
flow rate 1 mLminÀ1 (He carrier gas), split ratio 100:1, starting tempera-
ture 508C (4 min) ramp rate 208CminÀ1 to 1308C (2 min), ramp rate
208CminÀ1 to 2208C (15.5 min).
thane at RT. IR (KBr) for the mixture: v˜ =3049 [m, sp2
nAHCUTNGERNUN(G C H)], 2955–
À1
2871 [m, sp3
For [Ru2A(m-CH3SO3)
CD2Cl2, 258C): dH =1.55 (m, 6H, CH3), 1.99 (s, 3H, SCH3), 2.17 (s,
n
G
ACHTUGTNRENN(GU P Ph)], 1235–1051 cm [st, nACHTUNGTRENNUNG( SO3)].
À
À
À
G
À
À
À
À
À
À
À
9H, SCH3), 2.22 (m, 6H, CH2 ), 2.43 (m, 6H, CH2 ), 6.97–7.64 ppm
(m, 60H, Ph); 31P{1H} NMR (161 MHz, CD2Cl2, 258C): dP =38.5 ppm (bs,
À
6P,
PPh); elemental analysis (%): found:
C
56.20,
H
5.08;
C86H90O12P6Ru2S4 requires: C 56.39, H 4.95.
For H[Ru(CH3SO3-k1O)
pared independently by the addition of methanesulfonic acid (79.0 mg,
0.82 mmol, 0.05 mL) with a microsyringe to a solution of [Ru(OAc-
k1O)(OAc-k2O,O’)
(triphos)] (0.14 g, 0.16 mmol) in dichloromethane
(2.0 mL) at RT. The resulting orange mixture was then allowed to stir at
RT for 1 h after which the crude mixture was analysed by NMR spectro-
scopy. This complex appears only to exist in the presence of an excess of
MSA as all attempts to isolate this complex resulted in the isolation of a
mixture of 12 and 14 instead. 1H NMR (300 MHz, CD2Cl2, 258C): dH =
3ACHTUNGTRENUN(NG triphos)] (13): This complex could also be pre-
Catalysis, synthesis and VT-HP NMR spectroscopy
General procedure for catalytic batch reactions with [Ru
ACHTUNGTERN(NGNU acac)3]/triphos
ACHTUNGTRENNUNG
or precatalysts 9–15: [Ru(acac)3] (0.02 g, 0.05 mmol, 1 mol%) and triphos
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(0.062 g, 0.10 mmol, 2 mol%) or one of the precatalysts 9–15 (0.05 mmol,
1 mol%) were added to a HastelloyTM autoclave fitted with a stirrer bar,
in air. An amide substrate (5 mmol) was added and the autoclave was
subsequently sealed and purged by three vacuum/N2 cycles using
a
Schlenk line. A septum was fitted and dry, degassed THF (10 mL) was in-
troduced by using a syringe. In the case of addition of acid, a solution of
methanesulfonic acid (3–4.87 mL, 0.05–0.075 mmol, 1–1.5 mol%) in THF
(10 mL) was added to the autoclave instead. For primary amides aqueous
ammonia (5 mL) was also added to the autoclave. The autoclave was
sealed again, purged (~10 bar H2, six times), pressure tested (40–50 bar
of H2) and then pressurised with H2 (10–40 bar). The autoclave was then
heated with stirring to an internal temperature of 200–2208C using an ex-
ternal heating jacket for 4–16 h. At the end of the reaction, the autoclave
was cooled rapidly by immersing it in cold water. After venting the auto-
À
À
À
À
1.80 (bs, 3H, CH3), 2.50 (s, 6H, CH2 ), 3.10 (bs, 9H, SCH3), 7.12 (t,
12H, 3JHP =7.9 Hz, Ph), 7.30 ppm (t, 18H, 3JHP =7.9 Hz, Ph);
13
1
À
C{ H} NMR (75 MHz, CD2Cl2, 258C): dC =22.7 (s,
CACHTGNUTERNNU(G CH2PPh2)3), 32.1
(m, CH2 ), 36.1 (q, 3JCP =11.6 Hz, CH3), 39.3 (s, SO3CH3), 128.8 (m,
À
À
À
À
Phmeta), 130.9 (s, Phpara), 131.8 (m, Phortho), 132.4 ppm (m, Phipso);
31P{1H} NMR (121 MHz, CD2Cl2, 258C): dP =48.5 ppm (bs, 3P, PPh);
À
31P{1H} NMR (121 MHz, [D8]THF, À808C): dP =41.1 (t, 1P, JPP =42.6 Hz,
2
2
À
À
PPh), 50.0 ppm (d, 2P, JPP =42.6 Hz, PPh).
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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11
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D. J. Cole-Hamilton et al.
For [Ru(CH3SO3-k1O)(CH3SO3-k2O,O’)
(300 MHz, CD2Cl2, 258C): dH =1.55 (m, 3H,
N
CO); 31P{1H} NMR (121 MHz, CD2Cl2, 258C); see Scheme 3 for P atom
2
2
labels: dP =2.8 (dd, 1P, JPAPB =28.6 Hz, JPAPC =18.5 Hz, PA), 16.8 (dd, 1P,
CH2 ), 2.68 (s, 6H, SCH3), 7.06–7.64 ppm (m, 30H, Ph); 13C{1H} NMR
2JPBPA =28.6 Hz, 2JPBPC =42.1 Hz; PB), 52.9 ppm (dd, 1P, 2JPCPA =18.5 Hz,
À
À
(100 MHz, CD2Cl2, 258C): dC =33.0 (m, CH2 ), 37.7 (m, CH3), 38.0 (s,
2JPCPB =42.1 Hz; PC); ATR-IR: v˜ =3053 [w, sp2
n
G
À
À
C
(CH2PPh2)3), 40.5 (s, SO3CH3), 128.6 (m, Phmeta), 130.1 (s, Phpara),
sp3
n
N
E
À
À
À
À
132.9 (m, Phortho), 135.2 ppm (d, 1JCP =45.4 Hz, Phipso); 31P{1H} NMR
1246, 1151, 1030 cmÀ1 [st, n(k1-SO3CH3)]; elemental analysis (%): found:
(121 MHz, CD2Cl2, 258C): dP =38.7 ppm (bs, 3P, PPh); 31P{1H} NMR
C 60.88, H 5.17; C43H43O4P3RuS requires: C 60.77, H 5.10.
(121 MHz, CD2Cl2, À808C): dP =29.1 (t, 1P, 2JPP =48.8 Hz, PPh),
A
2ACHUTGTNREN(NUG m-H)2ACHTNUGTRENNNUG
(triphos)2] (18): Following a published procedure for the syn-
2
42.9 ppm (d, 2P, JPP =48.8 Hz, PPh); 31P{1H} NMR (121 MHz, [D8]THF,
À
G
(acac)3] (0.40 g, 1.0 mmol) and tri-
À808C): dP =30.0 (t, 1P, 2JPP =48.8 Hz, PPh), 41.9 ppm (d, 2P, JPP
phos (0.69 g, 1.1 mmol) was added to a high pressure HastelloyTM auto-
clave equipped with a magnetic stirrer bar. The autoclave was sealed and
purged by three vacuum/N2 cycles. Degassed propanal (10 mL) was
added to the autoclave under a flow of nitrogen. The autoclave was then
sealed, purged with H2 (3ꢂ20 bar) and finally pressurised with H2 to
90 bar. After stirring at 1508C for 20 h, the autoclave was cooled to 08C,
and vented to the atmosphere in a well-ventilated fume-hood. The
orange product mixture was transferred to a Schlenk flask and ethanol
(20 mL) added to the mixture to precipitate the formed by-product
À
À
48.8 Hz, PPh). During an attempt to isolate 14 by crystallisation, crys-
tals of the water coordinated analogue [Ru
(19) were isolated instead.
2ACTHNUTRGENN(UG H2O)ACHTUNGTRENNGUN
For [Ru(CH3SO3-k1O) (triphos)] (19): 1H NMR (300 MHz,
À
[D8]THF, 258C): dH =1.54 (m, 3H, CH3), 2.39 (m, 6H, CH2 ), 2.57 (s,
6H, SCH3), 7.05–7.58 ppm (m, 30H, Ph); 31P{1H} NMR (121 MHz,
À
[D8]THF, 258C): dP =38.4 ppm (bs, 3P, PPh); 31P{1H} NMR (121 MHz,
[D8]THF, À808C): dP =37.3 (d, 2P, JPP =47.0 Hz, PPh), 40.2 ppm (t, 1P,
À
À
J
PP =47.0 Hz, PPh).
(OAc-k1O)(OAc-k2O,O’)
[Ru(H)2CO
ACHTUNGTRENUN(NG triphos)] as a white solid. Removal of the [Ru(H)2CO-
AHCTUNGTRENNUNG
[Ru
(PPh3)3]:
A
product could be precipitated by addition of hexane (70 mL). The orange
solid was collected, washed with hexane (2ꢂ10 mL) and recrystallised
from dichloromethane layered with hexane as bright orange crystals
(1.0 g, 70%). Single crystals of 18 suitable for X-ray diffraction could be
obtained as orange platelets by the same method of crystallisation. M.p.
210–2158C (decompose); 1H NMR (400 MHz, CD2Cl2, 258C): dH =À8.84
(7.2 g, 7.5 mmol) in methanol (250 mL) was treated with a solution of
NaOAc·3H2O (10.6 g, 106.3 mmol) in methanol (5 mL). The resulting
mixture was then refluxed at 758C for 75 min with stirring. The mixture
was subsequently slowly cooled to 08C and the orange solid, which pre-
cipitated from solution, was collected in air, washed with ethanol (2ꢂ
25 mL) and dried, overnight, in vacuo to obtain the pure product as an
orange microcrystalline solid (5.8 g, 78%). 1H NMR (300 MHz, CD2Cl2,
À
À
À
À
(vt, 2H, RuH), 1.52 (bs, 6H, CH3), 2.26 ppm (bs, 12H, CH2 );
13
1
À
À
C{ H} NMR (100 MHz, CD2Cl2, 258C): dC =34.4 (m, CH2 ), 37.4 (m,
À
258C): dH =1.48 (s, 6H, C(O)CH3), 6.90–7.32 ppm (m, 45H, Ph);
CACTHNGUTERNNUG
(CH2PPh2)3), 127.6 (s, Phmeta), 129.2 (s, Phpara), 132.5 (s,
31P{1H} NMR (121 MHz, CD2Cl2, 258C): dP =63.8 ppm (s). These data
À
À
CH3), 37.8 (s,
Phortho), 138.3 ppm (bm, Phipso); 31P{1H} NMR (161 MHz, CD2Cl2, 258C):
are consistent with those from the literature.[17]
2
À
À
dP =42.9 ppm (s, 6P, PPh); ATR-IR: v˜ =3053 [w, sp
nACTHNGUTERNNU(G C H)], 2916–
[Ru
G
ACHUTGTNRENNUG(triphos)] (15): A suspension of [RuACHUTNGTREN(NUGN OAc-
2870 [w, sp3
n
(C H)], 1433 cm [st, n
(P Ph)]; elemental analysis (%):
À1
À
À
k1O)(OAc-k2O,O’)
ACHTUNGTRENNUNG
found C 62.23, H 5.34; C82H80P6Ru2 requires: C 67.76, H 5.55; for
treated with triphos (3.9 g, 6.2 mmol). The resulting mixture was then re-
fluxed at 1138C for 3 h with stirring. The mixture was subsequently
slowly cooled to 08C and the orange solid, which precipitated from solu-
tion, was collected under an inert atmosphere of N2, washed with toluene
(2ꢂ10 mL), diethyl ether (2ꢂ10 mL) and dried in vacuo to obtain the
pure product as an orange microcrystalline solid (3.6 g, 70%). Single
C82H80P6Ru2·2CH2Cl2 (crystallisation solvent) C 62.15, H 5.22.
VT-HP NMR experiment with [RuACHTNUGTRENNUNG
phenylacetamide, MSA and H2:
A
ACHTUNGTRENNUNG
0.15 mmol), triphos (0.30 g, 0.19 mmol) and N-phenylacetamide (0.06 g,
0.45 mmol) was dissolved in [D8]THF (3 mL) in a 20 mL Schlenk flask
under an inert atmosphere of N2. Methanesulfonic acid (14.6 mL,
0.23 mmol) was added to the solution, with stirring. The resulting red sol-
ution was then transferred to a sapphire HP NMR cell under an inert at-
mosphere of H2. The solution and HP NMR cell were purged by H2 bub-
bling before being sealed and pressurised to 10 bar with H2. The reaction
mixture was then analysed by HP NMR spectroscopy at temperatures 25,
60 and 1308C. No significant change in composition of the reaction mix-
ture was observed.
(OAc-k1O)
crystals of the analogous complex [RuACHTGNURTENNNUG 2ACHTUNTRGENN(GUN H2O)ACHTUNGTREN(NUGN triphos)] (20)
suitable for analysis by X-ray diffraction could be obtained by slow diffu-
sion of hexane into a solution of 15 in dichloromethane at RT. For com-
pound 15: M.p. 249–2528C (decomp); 1H NMR (400 MHz, CD2Cl2,
258C): dH =1.57 (q, 3H, 4JHP =2.7 Hz, CH3), 1.89 (s, 6H, C(O)CH3),
À
À
2.20 (m, 6H, CH2 ), 6.99 (t, 12H, 3JHH =7.5 Hz, Phmeta), 7.14 (t, 6H,
3JHH =7.5 Hz, Phpara), 7.40 ppm (m, 12H, Phortho); 13C{1H} NMR
À
À
À
À
À
(100 MHz, CD2Cl2, 258C): dC =25.5 (s, C(O)CH3), 34.3 (m, CH2 ),
3
2
À
À
C
37.8 (q, JCP =10.6 Hz, CH3), 38.6 (t, JCP =3.4 Hz,
N
VT-HP NMR experiment with [RuH(OAc-k2O,O’)
catalyst in the presence of N-phenylacetamide, MSA and H2:
[RuH(OAc-k2O,O’)
(triphos)] (0.06 g, 0.08 mmol) was suspended in a sol-
ACHTUNGTREN(NUNG triphos)] (9) as pre-
(m, Phmeta), 129.2 (bs, Phpara), 132.7 (m, Phortho), 137.2 (m, Phipso),
181.6 ppm (s, C(O) ); 31P{1H} NMR (161 MHz, CD2Cl2, 258C): dP =40.3
AHCTUNGTRENNUNG
À
À
3
(s); IR (KBr): v˜ =3049 [m, sp2
n
(C H)], 2921–2857 [m, sp
n
N
ution of N-phenylacetamide (0.10 g, 0.75 mmol) in [D8]THF (3 mL) in a
20 mL Schlenk flask under an inert atmosphere of N2. Methanesulfonic
acid (7.3 mL, 0.11 mmol) was added to the mixture, with stirring. The re-
sulting orange solution was then transferred to a sapphire HP NMR cell
under an inert atmosphere of H2. The solution and HP NMR cell were
purged by H2 bubbling before being sealed and pressurised to 10 bar with
H2. The reaction mixture was then analysed by HP NMR spectroscopy—
first at the higher end (25 to 1308C) and then at the lower end of the
temperature range (25 to À808C). Species observed included compounds
11, 12, 13, 14 and 18.
À
À
1609 [st, n(k1-OCOassym)], 1456 [st, n(k2-OCOsym)], 1370 cmÀ1 [m, n(k1-
OCOsym)]; elemental analysis (%): found C 64.10, H 5.47; C45H45O4P3Ru
requires: C 64.05, H 5.38.
A
ACHTUNGTREN(NUNG triphos)] (16): Methanesulfonic acid (12.0 mg,
ACHTUNGTRENNUNG
The resulting mixture was then allowed to stir at RT for 1 h. All volatiles
were subsequently removed under reduced pressure and the product was
dried in vacuo to give 16 as a yellow solid (0.09 mg, 81%). M.p. 185–
1888C (decomp); 1H NMR (300 MHz, CD2Cl2, 258C): dH =À5.56 (ddd,
VT-HP NMR experiment with [RuH(OAc-k2O,O’)
catalyst in the presence MSA and H2 (no substrate): [RuH(OAc-k2O,O’)-
(triphos)] (0.06 g, 0.08 mmol) was suspended in [D8]THF (3 mL) in a
ACHTUNGTREN(NUNG triphos)] (9) as pre-
1H, JHPtrans =95.5 Hz, JHPcis =19.8 Hz, JHPcis =14.3 Hz, Ru-H), 1.60 (bs,
2
2
2
À
À
À
À
À
À
3H, CH3), 2.18 (m, 2H, CH2 ), 2.31 (m, 2H, CH2 ), 2.53 (m, 2H,
ACHTUNGTRENNUNG
CH2 ), 2.55 (m, 3H, SCH3), 6.62–7.90 ppm (m, 30H, Ph); 13C{1H} NMR
20 mL Schlenk flask under an inert atmosphere of N2. Methanesulfonic
acid (7.3 mL, 0.11 mmol) was added to the mixture, with stirring. The re-
sulting orange solution was then transferred to a sapphire HP NMR cell
under an inert atmosphere of H2. The solution and HP NMR cell were
purged by H2 bubbling before being sealed and pressurised to 10 bar with
H2. The reaction mixture was then analysed by HP NMR spectroscopy—
À
À
(75 MHz, CD2Cl2, 258C): dC =33.0 (dt, 1JCP =23.4 Hz, 3JCP =5.8 Hz,
À
CH2 ), 33.9 (dt, 1JCP =20.2 Hz, 3JCP =3.6 Hz, CH2 ), 35.7 (dt, JCP
=
=
1
À
À
À
28.3 Hz, 3JCP =5.4 Hz, CH2 ), 38.3 (s,
(CH2PPh2)3), 38.6 (t, JCP
3
À
À
À
C
9.4 Hz, CH3), 38.8 (s, SO3CH3), 128.3 (m, Phmeta), 129.5 (m, Phpara),
À
À
131.5 (m, Phortho), 132.8 (m, Phortho), 133.9–139.8 (m, Phipso), 203.3 ppm (s,
&
12
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www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Homogeneous Catalytic Hydrogenation of Amides to Amines
FULL PAPER
first at the higher end (25 to 1308C) and then at the lower end of the
temperature range (25 to À808C). Species observed included compounds
11, 12, 13, 14 and 18.
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Commun. 2007, 3154–3156; b) D. L. Dodds, J. Coetzee, J. Klanker-
mayer, S. Brosinski, W. Leitner, D. J. Cole-Hamilton, Chem.
Commun. 2012, 48, 12249–12262 (published additions and correc-
tions to Ref [10a]).
[11] T. vom Stein, J. Klankermayer, W. Leitner, private correspondence,
2012.
[12] L. F. Rhodes, C. Sorato, L. M. Venanzi, F. Bachechi, Inorg. Chem.
1988, 27, 604–610.
tion of [RuH(SO3CH3-k1O)
ꢀ1008C.
ACHTUNGTRENNUNG
For [RuH(SO3CH3-k2O,O’)
ACHTUNGTRENNUNG
based on 31P{1H} integrals) could also be generated by heating a solution
of 16 (0.16 g, 0.18 mmol) and N-phenylacetamide (0.04 g, 0.10 mmol) in
THF (10 mL) in a hastelloy autoclave under an atmosphere of H2
(10 bar) at 1508C for 20 h. After 20 h, the autoclave was cooled to RT,
vented to the atmosphere and the orange product mixture transferred to
a Schlenk flask under an atmosphere of N2. All volatiles were removed
under reduced pressure to give the crude product mixture as an orange
solid. All attempts to isolate 17 from the resulting mixture were unsuc-
1
2
trans
cessful. H NMR (300 MHz, CH2Cl2, 258C): dH =À6.71 (dt, 1H, JHP
=
À
2
cis
À
À
64.6 Hz, JHP =15.5 Hz, Ru H), 1.82 (m, 3H, CH3), 2.55 (bs, 3H,
À
À
SO3CH3), 2.66 (m, 6H,
CH2 ), 6.60–7.66 ppm (m, 30H, Ph);
31P{1H} NMR (121 MHz, [D8]THF, 258C): dP =6.7 (t, 1P, 2JPP =28.1 Hz,
2
PPh), 18.5 ppm (d, 2P, JPP =28.1 Hz, PPh).
X-ray crystal structure determinations: The molecular structures and
tables containing a summary of the crystal data collection and refinement
parameters of compounds 11, 12, 19 and 20 can be found in the Support-
ing Information. Data sets were collected on a Rigaku Mo MM007 (dual
port) high brilliance diffractometer with graphite-monochromated MoKa
radiation (l=0.71075 ꢃ). The diffractometer was fitted with Saturn 70
and Mercury CCD detectors and two XStream LT accessories. Data re-
duction was carried out with standard methods using Rigaku Crystal-
Clear. All the structures were solved using direct methods and conven-
tional difference Fourier methods. All non-hydrogen atoms were refined
anisotropically by full-matrix least squares calculations on F2 using
SHELXTL or SHELX-97[18] within an X-seed[19] environment. In most
cases, the hydrogen atoms were fixed in calculated positions. Figure were
generated with X-seed and POV Ray for Windows, with the displacement
ellipsoids at 50% probability level unless stated otherwise.
[13] L. F. Rhodes, L. M. Venanzi, Inorg. Chem. 1987, 26, 2692–2695.
[14] R. W. Mitchell, A. Spencer, G. Wilkinson, J. Chem. Soc. Dalton
Trans. 1973, 846–854.
[15] A. B. Chaplin, P. J. Dyson, Inorg. Chem. 2008, 47, 381–390.
[16] All the complexes have second order spin systems for Cipso and for
CCDC-944784, CCDC-944785, CCDC-944786, and CCDC-944787 con-
tain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
PCH2. For complexes of the form [Ru
CH2 C atoms are chemically equivalent but all are magnetically in-
equivalent. For [Ru(triphos)X2Y]; Cipso on P trans to X form an
ACHTUNGTRNENUN(G triphos)X3]; all the Cipso or
AHCTUNGTRENNUNG
ABPP’A’B’ spin system, while those on P trans to Y form an AA’P
spin system. There may be additional coupling between the two spin
systems.
Acknowledgements
We thank the American Chemical Society, Pharmaceutical Round Table
for a Postdoctoral Fellowship (D.L.D) and other support, and the Euro-
pean Commission for a Fellowship to J.C. The research leading to these
results has received funding from the European Communityꢄs Seventh
Framework Programme (FP7/2007-2013) for SYNFLOW under grant
agreement no: NMP2-LA-2010-246461. Additional support from the
Cluster of Excellence EC 236 “Tailor-made Fuels from Biomass” at
RWTH Aachen University is also acknowledged.[5]
[17] E. Lindner, R. Fawzi, W. Hiller, A. Carvill, M. McCann, Chem. Ber.
1991, 124, 2691–2695.
[18] SHELXL program package (version 5.1), Bruker APX Inc., Madi-
son, WI, USA.
[19] a) L. J. Barbour, J. Supramol. Chem. 2001, 1, 189–191; b) J. L.
Atwood, L. J. Barbour, Cryst. Growth Des. 2003, 3, 3–8.
Received: November 30, 2012
Revised: May 3, 2013
Published online: && &&, 0000
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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