Aminophosphine ligands R2P(CH2)nNH 2 and ruthenium hydrogenation catalysts RuCl2(R 2P(CH2)nNH2)2

Article abstract of DOI:10.1039/b911459a

The aminophosphine ligands R₂P(CH₂) ₂NH₂ and R₂P(CH₂)₃NH ₂ (R = Ph, ⁱPr, ^tBu) were isolated in good to excellent yields from the reaction of LiPR₂ with Cl(CH ₂)₂N(TMS)₂ and Cl(CH₂) ₃N(TMS)₂, respectively, followed by hydrolysis. This approach allows fine tuning of the ligands' stereoelectronic properties through the variation of the substituents on the phosphine. The aminophosphine ligands were used to prepare the ruthenium complexes RuCl₂(R ₂P(CH₂)₂NH₂)₂ and RuCl₂(R₂P(CH₂)₃NH₂) ₂ by reacting a 2:1 mixture of the respective ligand and [RuCl ₂(cod)]_n in an appropriate solvent. The resulting complexes were found to be excellent catalysts for the hydrogenation of ketones and imines. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b911459a

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www.rsc.org/dalton | Dalton Transactions
Aminophosphine ligands R2P(CH2)nNH2 and ruthenium hydrogenation
catalysts RuCl2(R2P(CH2)nNH2)2†
Wenli Jia,*a Xuanhua Chen,a Rongwei Guo,a Christine Sui-Seng,a Dino Amoroso,a Alan J. Loughb and
Kamaluddin Abdur-Rashid*a
Received 11th June 2009, Accepted 15th July 2009
First published as an Advance Article on the web 12th August 2009
DOI: 10.1039/b911459a
The aminophosphine ligands R2P(CH2)2NH2 and R2P(CH2)3NH2 (R = Ph, iPr, tBu) were isolated in
good to excellent yields from the reaction of LiPR2 with Cl(CH2)2N(TMS)2 and Cl(CH2)3N(TMS)2,
respectively, followed by hydrolysis. This approach allows fine tuning of the ligands’ stereoelectronic
properties through the variation of the substituents on the phosphine. The aminophosphine ligands
were used to prepare the ruthenium complexes RuCl2(R2P(CH2)2NH2)2 and RuCl2(R2P(CH2)3NH2)2 by
reacting a 2:1 mixture of the respective ligand and [RuCl2(cod)]n in an appropriate solvent. The
resulting complexes were found to be excellent catalysts for the hydrogenation of ketones and imines.
ligands R2P(CH2)2NH2 and R2P(CH2)3NH2 can be prepared
and isolated in high yields from the reaction of a metal
Introduction
The hydrogenation of ketones and imines represents one of
phosphide (MPR2, M = Li, Na, K; R = alkyl, aryl) with
Cl(CH2)2N(TMS)2 and Cl(CH2)3N(TMS)2.13 The latter com-
pounds are derived from commercially available chloroalkylam-
monium salts. The preparation of RuCl2(Ph2P(CH2)2NH2)2 was
reported previously.5a,5d Here we report the synthesis of the
the fundamental processes in synthetic organic chemistry and,
as a result, significant effort has been devoted towards the
development of practical protocols for this transformation.1–4
This has led to a variety of notable chiral and achiral catalysts.
The most well-known are the Noyori type RuCl2(diphosphine)-
(diamine) and RuCl2(PR3)2(diamine) complexes.1,3 We have
demonstrated that ruthenium aminophosphine catalysts of
the type RuCl2(aminophosphine)2 and RuCl2(diphosphine)-
(aminophosphine) are also very effective for the hydrogenation of
carbonyl (ketones and aldehydes) and imine substrates.5a–5c Both
the Noyori type and aminophosphine catalysts share a common
mechanistic pathway during ketone hydrogenation: the presence of
a mutually cis Ru-H ◊ ◊ ◊ H-N moiety in the active ruthenium dihy-
dride catalysts which is generated from the dichloride compounds
in the presence of a base and hydrogen gas.5,6
i
t
related compounds RuCl2(R2P(CH2)2NH2)2 (R = Pr, Bu) and
i
t
RuCl2(R2P(CH2)3NH2)2 (R = Ph, Pr, Bu) and their use for the
hydrogenation of a variety of carbonyl and imine substrates.
Results and discussion
A variety of procedures are reported in the literature for the
preparation of aminophosphine ligands.11 The procedure outlined
in Scheme 1 represents a general and efficient procedure for the
synthesis of aminophosphine ligands of the type R2P(CH2)2NH2
and R2P(CH2)3NH2 (R = alkyl, aryl).
Recently, metal complexes containing protic aminophosphine
ligands have been shown to be very versatile in a variety of
other catalytic reductions such as the hydrogenation of esters,7
epoxides,8 imides,8b–8d N-acylcarbamates8a,d,e and N-acylsul-
fonamides.8e Other applications include transfer hydrogen-
ation9 and carbon-carbon10 bond formation, including a variety
of asymmetric processes.5,11,12 One of the drawbacks to the use
of aminophosphines for large scale applications is the lack of
readily available ligands in commercial and industrial quantities.
As part of our research endeavour to develop practical and
facile large scale processes for the synthesis of aminophos-
phine ligands we discovered that the achiral aminophosphine
Scheme 1 Preparation of R2P(CH2)2NH2 and R2P(CH2)3NH2.
The precursor compounds N,N¢-bis(trimethylsilyl)-2-chloro-
ethanamine and N,N¢-bis(trimethylsilyl)-3-chloropropanamine
were prepared from chloroethylammonium chloride and chloro-
propylammonium chloride, respectively.14 A solution of the pre-
cursor in THF was added dropwise to an ice-cold solution of
lithium phosphide in THF. The mixture was brought to reflux
and after cooling to room temperature, hydrolysis with dilute
sulfuric acid solution and neutralization with sodium hydroxide
aKanata Chemical Technologies Inc., 101 College Street, Office 230, MaRS
Centre, South Tower, Toronto, ON M5G 1L7, Canada. E-mail: kamal@
kctchem.com; http://kctchem.com/
bDepartment of Chemistry, University of Toronto, 80 St. George Street,
Toronto, ON M5S 3H6, Canada
† Electronic supplementary information (ESI) available: NMR spectra
1
(1H, 13C and 31P{ H}) of the 6 aminophosphine ligands. CCDC reference
number 733474. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/b911459a
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solution, the crude aminophosphine was obtained by partitioning
in hexanes and removal of the solvent under vacuum. The pure
ligands were obtained by vacuum distillation and isolated as
colourless to pale yellow viscous oils.
The ruthenium complexes RuCl2(R2P(CH2)2NH2)2 and
RuCl2(R2P(CH2)3NH2)2 were prepared by reacting a mixture of
the respective ligand and [RuCl2(cod)]n in an appropriate solvent
and were isolated as yellow to yellow-brown solids (Scheme 2).
Fig. 1 X-Ray structure of trans-RuCl2(iPr2P(CH2)2NH2)2, (2). Displace-
ment ellipsoids are shown at 30% probability and the hydrogen atoms
Scheme
(CH2)3NH2)2.
2
Preparation of RuCl2(R2P(CH2)2NH2)2 and RuCl2(R2P-
˚
(except for NH2) are omitted for clarity. Selected bond distances (A) and
angles (◦): Ru1-Cl1 = 2.407(1); Ru1-Cl2 = 2.437(1); Ru1-P1 = 2.297(1);
Ru1-P2
=
2.277(1); Ru1-N1
=
2.174(3); Ru1-N2
=
2.179(3);
A range of isomers are obtained depending on the ligand, the
solvent used and the reaction conditions employed. The proce-
dures described in this study focussed on selectively obtaining the
trans-dichloride compounds. Complex 1 was obtained by stirring
a 2:1 mixture of Ph2P(CH2)2NH2 and [RuCl2(cod)]n in methylene
chloride at room temperature. Refluxing in THF or toluene results
in a mixture of the trans-dichloride and cis-dichloride isomers that
are difficult to quantify and characterize because of their insolu-
bility in most common organic solvents. Refluxing a 2:1 mixture
P1-Ru1-N1 = 83.46(9); P2-Ru2-N2 = 83.91(8); P2-Ru1-P1 = 106.39(4);
N2-Ru1-N1 = 86.19(12); Cl1-Ru1-P1 = 86.84(4); Cl2-Ru1-P1 = 92.63(4);
Cl2-Ru1-N1 = 86.55(9); Cl2-Ru1-N2 = 87.22(9); Cl2-Ru1-P2 = 96.61(4);
Cl1-Ru1-Cl2 = 166.31(4).
the results of the hydrogenation of a variety of ketones including
a,b-unsaturated ketones, and imines catalyzed by complexes
1 to 6.
Complexes 1, 2, 4 and 5 are far more active than 3 and
6 (Table 1), hence a more limited range of substrates were
investigated for the latter two. The lower activities of these tert-
butyl complexes indicate that steric inhibitions are more significant
than nucleophilicity of the ligands for this class of catalysts.
Chemoselective hydrogenation of ketones is important for a
variety of industrial applications, and is valuable for the produc-
tion of pharmaceuticals, flavours and fragrances. The catalysts
are excellent for the chemoselective hydrogenation of alkenones
yielding the unsaturated alcohols (entries 22–36, Table 1) as the
only detectable products. The chemoselective hydrogenation of
benzalacetone (entries 29–32, Table 1) and b-ionone (entries 33–
36, Table 1) are important in the flavour and fragrance industry.
The hydrogenation of 4-tert-butylcyclohexanone is also a valu-
able process in the fragrance industry since the alcohol product
4-tert-butyl-cyclohexanol is the precursor for the fragrance 4-tert-
butylcyclohexyl acetate (Woody acetate), which is produced on
a 15 000 ton per year scale (Scheme 3, Table 2). Stoichiometric
reduction of 4-tert-butylcyclohexanone with borohydride reagents
produces an alcohol that contains mainly the trans-alcohol (70%)
relative to the cis-alcohol (30%).15 The acetate fragrance derived
from this alcohol is an inferior product relative to those derived
i
t
of Pr2P(CH2)2NH2 and [RuCl2(cod)]n or Bu2P(CH2)2NH2 and
[RuCl2(cod)]n in toluene results exclusively in the trans-dichloride
complexes 2 and 3, whereas if the reactions are conducted in
THF a mixture of cis- and trans-dichloride isomers resulted.
Complexes 4 and 5 were obtained by refluxing a 2:1 mixture
of the ligands Ph2P(CH2)3NH2 and iPr2P(CH2)3NH2, respectively,
and [RuCl2(cod)]n in toluene. The synthesis of complex 6 required
t
refluxing a 2:1 mixture of Bu2P(CH2)3NH2 and [RuCl2(cod)]n in
methylene chloride.
Complex 1 is very sparingly soluble in dichloromethane and
DMSO. It is insoluble in most other solvents including THF,
toluene, ethanol, 2-propanol, ether and hexanes. Complexes 2
and 3 are sparingly soluble in THF and toluene; slightly soluble
in methylene chloride, ethanol and 2-propanol; and insoluble in
diethyl ether and hexanes. Complexes 4–6 are more soluble than
their RuCl2(R2P(CH2)2NH2)2 analogues and dissolve in toluene,
methylene chloride, ethanol and 2-propanol. They are insoluble
in diethyl ether and hexanes. All of the complexes are air stable
as dry solids and can be stored in air for several months. On the
other hand, their solutions are susceptible to slow oxidation in air
and are best stored and handled under inert atmosphere.
The single crystal X-ray structure of 2 is shown in Fig. 1.
The complex crystallizes as a distorted octahedron with trans
chlorides and mutually cis phosphines and NH2 moieties. The
chloride ligands are bent towards the nitrogen atoms (Cl1-Ru-
Cl2 = 166.31(4)◦), possibly due to hydrogen bonding to the NH2
moieties.
Ruthenium aminophosphine complexes of the type
RuCl2(aminophosphine)2 can be used as catalysts for the
hydrogenation of ketones, imines and aldehydes. Table 1 shows
Scheme 3 Hydrogenation of 4-tert-butylcyclohexanone.
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Table 1 Hydrogenation of ketones and imines in the presence of KOtBu
Table 2 Hydrogenation of 4-tert-butylcyclohexanone in the presence of
in 2-propanol (10 atm H2)a
KOtBu in 2-propanol (10 atm H2)a
Entry Substrate
Cat. S:C
T/◦C Time/h
2
Conv. (%)b
Entry
Cat. S:C
T/◦C
Time/h
Conv. (%)b
cis/trans
1
2
3
4
5
6
7
1
2
3
3
4
5
6
5000 25
1800 25
100
100
40
1
2
3
4
5
6
7
1
2
3
3
4
5
6
650
25
25
25
50
25
25
25
2
3
24
2
3
3
100
100
58
100
100
20
86:14
96:4
23:77
22:78
98:2
83:17
60:40
2
24
2
2
2
1000
1000
1000
1000
1000
1000
1000 25
1000 50
5000 25
2000 25
1000 25
78
100
100
90
24
24
90
a A weighed amount of the catalyst was added to a solution of the substrate
in 2-propanol and the mixture was stirred for the allotted time under
hydrogen gas. b Determined by NMR.
8
9
10
11
12
13
14
1
2
3
3
4
5
6
1500 25
1500 25
1000 25
1000 50
1500 25
2000 25
1000 25
2
2
24
2
2
2
100
100
12
96
100
100
33
Table 3 Hydrogenation of norcamphor in the presence of KOtBu in
24
2-propanol (10 atm H2)a
15
16
17
18
19
20
21
1
2
3
3
4
5
6
2000 25
2000 25
1000 25
1000 50
2000 25
2000 25
1000 25
4
4
24
2
4
5
100
100
46
Entry
Cat. S:C
T/◦C
Time/h
Conv. (%)b
endo/exo
1
2
3
4
5
6
7
1
2
3
3
4
5
6
700
25
25
25
50
25
25
25
2
17
24
2
2
2
100
100
17
74
100
10
99:1
95
650
1000
1000
1000
1000
1000
87:13
62:38
56:44
99:1
87:13
46:54
100
100
81
24
22c
23c
24c
25c
26c
27c
28c
1
2
3
3
4
5
6
1000 25
1000 25
1000 25
1000 50
1000 25
1000 25
1000 25
2
4
24
2
2
2
100
100
17
24
90
a A weighed amount of the catalyst was added to a solution of the substrate
in 2-propanol and the mixture was stirred for the allotted time under
hydrogen gas. b Determined by NMR.
58
100
100
34
24
29c
30c
31c
32c
1
2
4
5
1000 25
1000 25
1000 25
1000 25
2
2
2
2
100
100
100
100
Table 4 Hydrogenation of acetophenone using 2/KOtBu as catalyst in
2-propanol (10 atm H2)a
Entry
S:C
T/◦C
Time/h
Conv. (%)b
33c
34c
35c
36c
1
2
4
5
1000 25
500 25
500 25
500 25
2
2
2
2
100
100
100
100
1
2
3
4
10 000
20
50
50
50
4
2
12
24
100
100
100
98
100 000
500 000
1 000 000
37
38
39
40
41
42
43
1
2
3
3
4
5
6
1000 25
500 25
1000 25
1000 50
1000 25
500 25
1000 25
5
4
24
2
5
4
100
100
0
a A weighed amount of the catalyst was added to a solution of the substrate
in 2-propanol and the mixture was stirred for the allotted time under
hydrogen gas. b Determined by GC analysis.
6
100
100
53
24
and 4 produce alcohol in an excellent cis/trans ratio (entries 2 and
5, Table 2).
44
45
46
47
1
2
4
5
500 25
500 25
500 25
500 25
12
12
12
12
100
100
100
100
Stereoselective hydrogenation of norcamphor is important in
the pharmaceutical industry since endo-norborneol is used to
prepare a variety of anti-asthmatic and anti-inflammatory drugs
(Scheme 4, Table 3).16 Unfortunately, stoichiometric reduction of
norcamphor with various borohydride reagents only gives good
to moderate yields (60–80%) of the desired endo-norborneol.15
48
49
50
1
2
4
500 25
250 25
500 25
12
24
12
100
73
100
a A weighed amount of the catalyst was added to a solution of the substrate
in 2-propanol and the mixture was stirred for the allotted time under
hydrogen gas. b Determined by GC or HPLC analysis. c Only C O bond
=
reduced.
from alcohols with a high cis-content. Hence, there is a desire
for catalysts that are effective for the stereoselective formation of a
product high in the cis-component. The ruthenium catalysts enable
the hydrogenation of 4-tert-butylcyclohexanone and complexes 2
Scheme 4 Hydrogenation of norcamphor.
Dalton Trans., 2009, 8301–8307 | 8303
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Table 5 Hydrogenation of 4-tert-butylcyclohexanone using 2/KOtBu as
Deuterated solvents were obtained from Cambridge Isotope
Laboratories, and were degassed with argon and dried over
catalyst in 2-propanol (10 atm H2)a
˚
molecular sieves (3 A, beads, 8–12 mesh, Sigma Aldrich). Varian
Entry
S:C
T/◦C
Time/h
Conv. (%)b
cis:trans
Gemini 400 MHz and 300 MHz spectrometers were employed
for recording H (400 MHz and 300 MHz), 13C{ H} (100 MHz
1
1
1
2
3
4
10 000
20
50
50
50
4
2
12
24
100
100
100
80
96:4
95:5
95:5
95:5
and 75 MHz), and 31P{ H} (161 MHz and 121 MHz) NMR
1
100 000
500 000
1 000 000
spectra at ambient temperature. All 31P spectra were recorded with
proton decoupling, and 31P chemical shifts were measured relative
a A weighed amount of the catalyst was added to a solution of the substrate
in 2-propanol and the mixture was stirred for the allotted time under
hydrogen gas. b Determined by NMR.
1
to 85% H3PO4 as an external reference. All H chemical shifts
were measured relative to partially deuterated solvent peaks but
are reported relative to tetramethylsilane. Reaction progress and
products were also analyzed using either an Agilent Technologies
7890A GC system or an Agilent Technologies 1200 Series HPLC.
Unless otherwise stated all chemicals were purchased from
Sigma Aldrich. The ruthenium precursor [RuCl2(cod)]n was
prepared by a literature procedure.17 Ruthenium trichloride
was purchased from Pressure Chemicals. Imines were prepared
from the corresponding ketones and amines using established
literature methods.18 The precursor compounds 2-[N,N-bis-
Hydrogenation of norcamphor using catalysts 1-6 produces endo-
and exo-norborneol in an excellent ratio for complexes 1 and 4
(entries 1 and 5, Table 3). Interestingly, complex 4 is very effective
for producing both cis-tert-butylcyclohexanol (cis:trans = 98:2)
and endo-norborneol (endo:exo = 99:1).
In general, the hydrogenation reactions are very responsive to
temperature and pressure, which allows these reactions to be easily
scaled. The effect of temperature is illustrated in Table 2 and 3
for complex 3, which demonstrates higher reactivity at elevated
temperatures.
(trimethylsilyl)amino]-1-chloroethane
and
3-[N,N-bis-
(trimethylsilyl)amino]-1-chloropropane were prepared according
to reported procedures.14 The ligands 2-(diphenylphosphino)-
ethanamine,19 2-(diisopropylphosphino)ethanamine,19a 2-(di-
tert-butylphosphino)ethanamine,19a
propanamine,19c were previously reported. Argon gas (ultra high
purity grade) and hydrogen gas (grade 4.8) were obtained from
BOC Gases Canada and used without further purification.
Small scale hydrogenation screening reactions were conducted
in a Parr Series 5000 Multireactor apparatus. Larger scale
hydrogenation reactions were conducted in a Parr 100 ml pressure
reactor.
Highly active and efficient hydrogenation catalysts have the
advantage of scalability relative to other reduction protocols.
Tables 4 and 5 illustrate the optimization of the hydrogenation of
acetophenone and 4-tert-butylcyclohexanone, respectively using 2
as the catalyst. These results show that high substrate to catalyst
ratios of up to 1 000 000 to 1 can be achieved under relatively mild
conditions, with retention of product selectivity even at elevated
temperatures.
3-(diphenylphosphino)-
Conclusions
Preparation of aminophosphine ligands
2-(Diphenylphosphino)ethanamine
This work outlines a general and scalable process for the
synthesis of a variety of aminophosphine ligands of the type
R2P(CH2)nNH2. These ligands are easily converted to their respec-
tive ruthenium compounds RuCl2(Ph2P(CH2)nNH2)2 by reacting
a mixture of the ligands and [RuCl2(cod)]n. The ruthenium com-
pounds are excellent catalysts for the hydrogenation of a variety of
ketone and imine substrates. Chemoselective and stereoselective
hydrogenation of a variety of substrates were demonstrated.
The reactions have been optimized and enabled the achievement
of substrate to catalyst ratios of up to 1 000 000 to 1. The
demonstrated activity, chemoselectivity and diastereoselectivity of
these catalysts merit exploration of chiral aminophosphine ligands
and their catalysts as limited studies have been reported to date.
Our studies on the synthesis of a variety of chiral aminophosphine
ligands and their catalysts will be reported in due course.
Butyllithium (155 ml of a 1.6 M solution in hexane) was added
dropwise to a cold (0 ◦C) solution of diphenylphosphine (45 g,
0.24 mol) in THF (200 ml). The mixture was stirred for 2 hours
at room temperature and a solution of N,N¢-bis(trimethylsilyl)-
2-chloroethanamine (54 g, 0.24 mol) added slowly at 0 ◦C. The
mixture was refluxed for 4 hours then cooled to room temperature.
Water (50 ml) was added, followed by 2.0 M H2SO4 solution (200
ml). After stirring for 1 hour at room temperature a solution
of 4.0 M NaOH solution (220 ml) was then added, and the
mixture stirred for 1 hour. Hexane (200 ml) was added and the
aqueous phase was separated and removed. The organic layer
was dried (Na2SO4), filtered through a pad of silica gel, and
evaporated to yield the aminophosphine, which was purified by
vacuum distillation. Yield: 52.3 g, 94%. dH (400 MHz; CDCl3)
1.17 (2 H, s, NH2), 2.23 (2 H, t, J 3.8, CH2), 2.81–2.87 (2 H,
m, CH2), 7.30–7.31 and 7.41–7.43 (10 H, m, Ph); dC (100 MHz;
CDCl3) 33.3, 39.6, 128.7, 132.9 and 138.7; dP (121 MHz, CDCl3)
-20.7 (s).
Experimental
General comments
Unless otherwise stated, all preparations and manipulations
were carried out under purified argon atmosphere with the use
of standard Schlenk, vacuum line, and glovebox techniques in
dry, oxygen-free solvents. Tetrahydrofuran (THF), diethyl ether,
toluene, dichloromethane and hexanes were dried and purified
using an Innovative Technologies solvent purification system.
2-(Diisopropylphosphino)ethanamine
A THF (100 ml) solution of chlorodiisopropylphosphine (30 g,
0.20 mol) was added dropwise at 0 ◦C to a suspension of lithium
granules (5.0 g, 0.72 mol) in THF (100 ml), and the mixture stirred
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for 72 hours at room temperature. The mixture was filtered and the
filtrate cooled to 0 C and a solution of N,N¢-bis(trimethylsilyl)-
Preparation of ruthenium aminophosphine catalysts
◦
Trans-RuCl2(Ph2P(CH2)2NH2)2, 1. A mixture of [RuCl2(cod)]n
(0.60 g, 2.1 mmol) and Ph2P(CH2)2NH2)2 (1.0 g, 4.4 mmol) was
stirred in methylene chloride (5 ml) under argon for 3 hours. The
mixture was concentrated under vacuum and hexane (50 ml) was
added and the resulting suspension stirred for an additional 30
minutes. The product was filtered, washed with hexane (3 ¥ 10 ml)
and dried under vacuum. Yield: 0.50 g, 37%. (Found: C, 53.61;
H, 5.39; N, 4.37%. C28H32Cl2N2P2Ru requires C, 53.34; H, 5.12;
N, 4.44%). The NMR spectra of 1 correspond to those previously
reported.5a
2-chloroethanamine (44.2 g, 0.20 mol) added slowly. The mixture
was refluxed for 4 hours then cooled to room temperature. Water
(50 ml) was added, followed by 2.0 M H2SO4 solution (160 ml).
After stirring for 1 hour at room temperature a solution of 4.0 M
NaOH solution (180 ml) was then added, and the mixture stirred
for 1 hour. Hexane (200 ml) was added and the aqueous phase was
separated and removed. The organic layer was dried (Na2SO4),
filtered through a pad of silica gel, and evaporated to yield the
aminophosphine, which was purified by vacuum distillation. Yield:
28.2 g, 89%. dH (300 MHz; CDCl3) 0.85–0.94 (12 H, m, CH3), 1.07
(2 H, s, NH2), 1.35 (2 H, td, J 8.1 and 3.3, CH2), 1.57 (2 H, septet
of doublet, J 7.1 and 2.4, CH), 2.68 (2H, quartet, J 7.8 Hz, CH2);
dC (75 MHz; CDCl3) 18.7, 20.1, 23.2, 26.6 and 41.4; dP (121 MHz,
CDCl3) -2.0 (s).
Trans-RuCl2(iPr2P(CH2)2NH2)2,
2.
A
mixture
of
[RuCl2(cod)]n (15.8 g, 56.6 mmol) and iPr2P(CH2)2NH2)2
(18.1 g, 112 mmol) was refluxed in toluene (200 ml) under argon
for 6 hours. The mixture was cooled to room temperature and
ether (300 ml) was added and the suspension stirred for 1 hour.
The product was filtered, washed with ether (3 ¥ 50 ml) and dried
under vacuum. Yield = 20.2 g, 81%. (Found: C, 39.15; H, 8.40; N,
5.63%. C16H40Cl2N2P2Ru requires C, 38.87; H, 8.15; N, 5.67%).
dH (CD2Cl2) 1.17–1.38 (24 H, m, CH3), 2.00 (4 H, m, CH2), 2.52
(4 H, d of septet, JHP 9.3 and JHH 10.5, CH), 3.06–3.19 (4 H, m,
CH2), 3.65 (4 H, br, NH2); dP (CD2Cl2) 64.2 (s).
2-(Di-tert-butylphosphino)ethanamine
A THF (100 ml) solution of chlorodi-tert-butylphosphine (42 g,
0.23 mol) was added dropwise at 0 ◦C to a suspension of lithium
granules (5.0 g, 0.72 mol) in THF (100 ml), and the mixture stirred
for 72 hours at room temperature. The mixture was filtered and the
◦
filtrate cooled to 0 C and a solution of N,N¢-bis(trimethylsilyl)-
2-chloroethanamine (51.7 g, 0.23 mol) added slowly. The mixture
was refluxed for 4 hours then cooled to room temperature. Water
(50 ml) was added, followed by 2.0 M H2SO4 solution (200 ml).
After stirring for 1 hour at room temperature a solution of 4.0 M
NaOH solution (220 ml) was then added, and the mixture stirred
for 1 hour. Hexane (200 ml) was added and the aqueous phase was
separated and removed. The organic layer was dried (Na2SO4),
filtered through a pad of silica gel, and evaporated to yield the
aminophosphine, which was purified by vacuum distillation. Yield:
40.3 g, 91%. dH (300 MHz; CDCl3) 0.94 (18 H, d, J 11.1, CH3),
1.08 (2 H, s, NH2), 1.36 (2 H, td, J 7.5 and 4.5, CH2), 2.67 (2H,
quartet, J 7.5 Hz, CH2); dC (75 MHz; CDCl3) 26.3, 29.6, 31.0 and
42.9; dP (121 MHz, CDCl3) 21.2 (s).
Trans-RuCl2(tBu2P(CH2)2NH2)2,
3.
A
mixture
of
t
[RuCl2(cod)]n (11.5 grams, 41.2 mmol) and Bu2P(CH2)2NH2)2
(15.6 grams, 82.5 mmol) was refluxed in toluene (120 ml) under
argon for 8 hours. The mixture was cooled to room temperature
and ether (250 ml) was added and the suspension stirred for
1 hour. The product was filtered, washed with ether (3 ¥ 50 ml)
and dried under vacuum. Yield: 20.1 g, 88%. (Found: C, 43.66;
H, 9.06; N, 5.08%. C20H48Cl2N2P2Ru requires C, 43.63; H, 8.79;
N, 5.09%). dH (CD2Cl2), 1.35 (36 H, d, JHP 16.2, CH3), 2.11–2.20
(4 H, m, CH2), 3.12–3.23 (4 H, m, CH2), 3.95 (4 H, br, NH2); dP
(CD2Cl2) 66.8 (s).
Trans-RuCl2(Ph2P(CH2)3NH2)2, 4. A mixture of [RuCl2(cod)]n
(1.41 g, 5.04 mmol) and Ph2P(CH2)3NH2 (2.5 g, 10.3 mmol) was
refluxed in toluene (15 ml) for 4 hours. The mixture was cooled to
room temperature and ether (60 ml) was added. After stirring for
another 30 minutes the yellow-brown solid was filtered, washed
with ether and dried under vacuum. Yield = 2.9 g (86%). (Found:
C, 54.92; H, 5.87; N, 4.27%. C30H36Cl2N2P2Ru requires C, 54.71;
H, 5.51; N, 4.25%). dH (CD2Cl2), 1.83–1.87 (2 H, m, CH2), 1.99–
2.04 (2 H, m, CH2), 2.22–2.29 (2 H, m, CH2), 2.64–2.70 (4 H, m,
CH2), 2.97 (4 H, br, NH2), 3.27–3.34 (2 H, m, CH2), 7.06–7.82 (20
H, m, Ph); dP (CD2Cl2) 33.8 (s).
3-(Diphenylphosphino)propanamine. This was prepared as out-
lined above for 2-(diphenylphosphino)ethanamine, by using
N,N¢-bis(trimethylsilyl)-3-chloropropanamine. Yield: 91%. dH
(400 MHz; CDCl3) 1.0 (2 H, s, NH2), 1.53–1.61 (2 H, m, CH2),
2.04–2.08 (2 H, m, CH2), 2.75 (2H, t, J 7.0 Hz, CH2), 7.29–7.41
(10H, m, Ph); dC (75 MHz; CDCl3) 25.5, 30.4, 43.6, 128.6, 132.9
and 139.0; dP (121 MHz, CDCl3) -15.1 (s).
3-(Diisopropylphosphino)propanamine. This was prepared as
outlined above for 2-(diisopropylphosphino)ethanamine, by using
N,N¢-bis(trimethylsilyl)-3-chloro-propanamine. Yield: 85%. dH
(300 MHz; C6D6) 0.59 (2 H, s, NH2), 0.89–0.99 (12 H, m, CH3),
1.16–1.22 (2 H, m, CH2), 1.22–1.55 (4H, m, CH and CH2), 2.51
(2H, t, J 6.8, CH2); dC (75 MHz; CDCl3) 18.1, 20.1, 23.5, 32.6 and
43.7; dP (121 MHz, C6D6) 3.6 (s).
Trans-RuCl2(iPr2P(CH2)3NH2)2,
5.
A
mixture
of
i
[RuCl2(cod)]n (1.88 g, 6.72 mmol) and Pr2P(CH2)3NH2 (2.4 g,
13.7 mmol) was refluxed in toluene (15 ml) for 4 hours. The
mixture was cooled to room temperature and ether (80 ml) was
added. After stirring for another 30 minutes the yellow solid was
filtered, washed with ether and dried under vacuum. Yield = 3.0 g
(86%). (Found: C, 41.60; H, 8.72; N, 5.38%. C18H44Cl2N2P2Ru
requires C, 41.38; H, 8.49; N, 5.36%). dH (CD2Cl2), 1.22–1.28 (24
H, m, CH3), 2.47–2.60 (4 H, m, CH2), 2.59–2.65 (4 H, m, CH2),
2.72–2.90 (4 H, m, CH2), 3.16 (4 H, br, NH2), 3.36–3.45 (2 H, m,
CH), 3.87–3.92 (2 H, m, CH); dP (CD2Cl2) 43.2 (s).
3-(Di-tert-butylphosphino)propanamine. This was prepared as
outlined above for 2-(di-tert-butylphosphino)ethanamine, by us-
ing N,N¢-bis(trimethylsilyl)-3-chloro-propanamine. Yield: 78%.
dH (300 MHz; C6D6) 0.54 (2 H, s, NH2), 1.03 (18 H, d, J 10.5
CH3), 1.23–1.30 and 1.47–1.60 (4 H, m, CH2), 2.57 (2H, t, J
6.8, CH2); dC (75 MHz; C6D6) 18.3, 29.6, 31.0, 34.8 and 43.5; dP
(121 MHz, C6D6) 28.3 (s).
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Trans-RuCl2(tBu2P(CH2)3NH2)2,
6.
A
mixture
of
S:C ratio = 500 000:1. A weighed amount of 2 (5 mg) was dis-
solved in 10.0 ml of 2-propanol. An aliquot of 1.0 ml of this catalyst
solution was further diluted to 10.0 ml with 2-propanol. An aliquot
of 2.0 ml of the dilute catalyst solution (0.1 mg, 0.0002 mmol) and
KOtBu (150 mg) were added to a solution of the substrate (12.15 g,
101 mmol) in 2-propanol in a 100 ml Parr pressure reactor under
a flow of argon. The mixture was degassed with argon and then
with hydrogen. It was finally pressurized to 10 atm of hydrogen
and stirred at 50 ◦C for 12 hours. The NMR and GC spectra
showed complete conversion of the ketone to the alcohol.
[RuCl2(cod)]n (1.47 g, 5.25 mmol) and tBu2P(CH2)3NH2
(2.20 g, 10.8 mmol) in methylene chloride (5 ml) was stirred
for 2 hours at room temperature then refluxed for 3 hours. The
mixture was cooled to room temperature and hexanes (50 ml) was
added. After stirring for an additional hour, the yellow-brown
solid was filtered, washed with hexanes and dried under vacuum.
Yield = 1.0 g (33%). (Found: C, 45.84; H, 9.36; N, 5.10%.
C22H52Cl2N2P2Ru requires C, 45.67; H, 9.06; N, 4.84%). dH
(CD2Cl2), 1.15 (36 H, d, JHP 10.0, CH3), 1.48–1.53 (4H, m, CH2),
1.94 (4 H, d of quintet, JHP 7.8 and JHH 7.9, CH2), 3.10 (4 H, d
of t, J 15.0 and J 7.5, CH2), 3.61 (2 H, br, NH2), 4.20 (2 H, br,
NH2); dP (DMSO) 28.1 (s).
S:C ratio = 1 000 000:1. A weighed amount of 2 (5 mg) was
dissolved in 10.0 ml of 2-propanol. An aliquot of 1.0 ml of this
catalyst solution was further diluted to 10.0 ml with 2-propanol.
An aliquot of 1.0 ml of the dilute catalyst solution (0.05 mg,
0.0001 mmol) and KOtBu (150 mg) were added to a solution of
the substrate (12.15 g, 101 mmol) in 2-propanol in a 100 ml Parr
pressure reactor under a flow of argon. The mixture was degassed
with argon and then with hydrogen. It was finally pressurized
to 10 atm of hydrogen and stirred at 50 ◦C for 24 hours. The
NMR and GC spectra showed 98% conversion of the ketone to the
alcohol.
General procedure for the hydrogenation of ketones and imines
In a typical hydrogenation procedure weighed amounts of the
respective catalyst and KOtBu were added to a solution of the
substrate in the desired solvent under hydrogen gas. The pressure
and temperature were adjusted to the desired values and the
reaction progress was monitored by the change in pressure or
by withdrawing a sample of the reaction mixture and assaying
the conversion by NMR, GC or HPLC. After completion of
the reaction, the solvent was removed from the crude product by
evaporation under reduced pressure. The products were purified
by filtering a hexane solution of the crude product through a pad
of silica gel, then removing the hexane under reduced pressure. The
conversion and purity of the products were assessed using NMR.
X-Ray structure determination of complex 2
Crystals suitable for single crystal X-ray diffraction studies were
obtained by slowly cooling a hot solution of the compound in
toluene to room temperature. The X-ray diffraction data were
collected using a Nonius Kappa-CCD diffractometer with MoKa
Example: hydrogenation of acetophenone. A weighed amount
of 2 (5.0 mg, 0.01 mmol) and KOtBu (10 mg) were added to a
solution of acetophenone (2.0 g, 16.6 mmol) in 2-propanol in a
100 ml Parr pressure reactor under a flow of argon. The mixture
was degassed with argon and then with hydrogen. It was finally
pressurized to 10 atm of hydrogen and stirred at room temperature.
After completion of the reaction, the solvent was removed from
the crude product by evaporation under reduced pressure. Hexanes
(5 ml) was added and the solution was filtered through a pad of
silica gel. The solvent was then removed under reduced pressure to
yield the pure product. The NMR and GC spectra of the product
showed 100 percent conversion of the ketone to phenylethanol.
Yield = 1.98 g, 97%.
S:C ratio = 10 000:1. A weighed amount of 2 (3.2 mg,
0.0065 mmol) and KOtBu (100 mg) were added to a solution
of the substrate (7.80 g, 65 mmol) in 2-propanol in a 100 ml Parr
pressure reactor under a flow of argon. The mixture was de-gassed
with argon and then with hydrogen. It was finally pressurized to
10 atm of hydrogen and stirred at room temperature for 4 hours.
The NMR and GC spectra showed complete conversion of the
ketone to the alcohol.
˚
radiation (l = 0.71073 A). The CCD data were integrated and
scaled using the Denzo-SMN package. The structures were solved
and refined using SHELXTL V5.1. Refinement was by full-matrix
Table 6 Summary of crystal data, details of intensity collection and least-
squares refinement parameters for 2
Empirical formula
C16H40Cl2N2P2Ru
Formula weight
Crystal size/mm
Crystal class
Space group
T/K
494.41
0.12 ¥ 0.17 ¥ 0.37
Monoclinic
P 21/c
150.0
˚
a/A
11.4627(3)
13.1649(6)
15.2297(5)
90
104.992(2)
90
2220.0(1)
1.479
1.093
1032
2.77 to 27.51
13589
5063
0.0466
˚
b/A
˚
c/A
a/◦
b/◦
g /◦
3
˚
V/A
r
calc/Mg m-3
m (Mo Ka)/mm-1
F(000)
Range q collected/◦
No. of reflections
Independent reflections
R1 (I > 2 s(I))a
wR2 (all data)a
S:C ratio = 100 000:1. A weighed amount of 2 (5 mg) was
dissolved in 10.0 ml of 2-propanol. An aliquot of 1.0 ml of
the diluted catalyst solution (0.5 mg of catalyst, 0.001 mmol)
and KOtBu (150 mg) were added to a solution of the substrate
(12.15 g, 101 mmol) in 2-propanol in a 100 ml Parr pressure
reactor under a flow of argon. The mixture was degassed with
argon and then with hydrogen. It was finally pressurized to 10 atm
of hydrogen and stirred at 50 ◦C for 2 hours. The NMR and GC
spectra showed complete conversion of the ketone to the alcohol.
0.1022
1.079
216
1.617
Goodness of fit
Parameters refined
Maximum peak in final DF map/e A
-3
˚
ꢀ
ꢀ
ꢀ
2
a Definition of R indices: R1
=
(Fo - Fc)/ (Fo); wR2 = [ [w(Fo
-
ꢀ
Fc2)2]/ [w(Fo2)2]]1/2
.
8306 | Dalton Trans., 2009, 8301–8307
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least-squares on F2 using all data (negative intensities included).20
Crystallographic data for compound 2 is given in Table 6.
CCDC reference number 733474.†
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This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 8301–8307 | 8307
©