Application of proline-functionalised 1,2-diphenylethane-1,2-diamine (DPEN) in asymmetric transfer hydrogenation of ketones

Article abstract of DOI:10.1002/ejoc.201101164

A series of enantiomerically pure ligands containing a combination of proline and DPEN groups have been prepared and employed in the asymmetric transfer hydrogenation of ketones. In the case of cyclic ketones, alcohols with ee values of up to 98% were obtained.

Full text of DOI:10.1002/ejoc.201101164

FULL PAPER
DOI: 10.1002/ejoc.201101164
Application of Proline-Functionalised 1,2-Diphenylethane-1,2-diamine (DPEN)
in Asymmetric Transfer Hydrogenation of Ketones
Charles V. Manville,[a] Gordon Docherty,[b] Ranbir Padda,[b] and Martin Wills*[a]
Keywords: Asymmetric catalysis / Hydrogenation / Ruthenium / Iridium / Peptides
A series of enantiomerically pure ligands containing a combi-
nation of proline and DPEN groups have been prepared and
employed in the asymmetric transfer hydrogenation of
ketones. In the case of cyclic ketones, alcohols with ee values
of up to 98% were obtained.
In 1998, Furukawa et al. reported the use of proline and
other amino acids as ligands for the ATH of acetophenone
in iPrOH; enantiomeric excesses of up to 82% were re-
ported.[9] Several other studies have since developed the use
of amino acids[10,11] and their amide derivatives.[12–15]
Chung et al. described the use of complexes of N-aryl-
prolinamides 10 with [RuII(arene)Cl]2.[12] Through variation
of the N-aryl group and the η6-arene, a system capable of
reducing acetophenone derivatives in up to 98.8% ee was
identified. Prolinamide also works effectively as a ligand
with RuII or RhIII in the ATH of ketones with 2-propanol
as the hydrogen source.[14]
Introduction
Asymmetric transfer hydrogenation (ATH) is a mild and
versatile method for the enantioselective reduction of C=O
and C=N bonds.[1] Suitable catalysts for this reaction are
typically complexes of homochiral ligands with Ru, Ir or
Rh, whilst either iPrOH or formic acid/triethylamine
(FA/TEA, 5:2 azeotrope)[2] is normally used as the hydro-
gen donor. The reduction may also be carried out in
aqueous solution using sodium formate as the hydrogen
source.
A number of ligands have been developed for use in or-
ganometallic ATH reactions, which include diamines such
as TsDPEN 1,[3] 2,[4a–4c] 3,[4d] and 4.[5] Complexes of β-
amino alcohols[6–8] such as 5–9 are capable of reducing
ketones with high enantioselectivities when used with
iPrOH as the hydrogen donor. Ligands include 6[7] and the
2-azanorboronyl methanols 8 and 9.[8] In case of ligands 1–
9, an 18-electron complex is formed with a transition-metal
salt, complemented by an η6-arene ring, and this is the
active complex that enters the catalytic cycle.[1]
Adolfsson et al. reported a series of amino-acid-derived
ligands containing proximal alcohol groups, typified by 11
and 12, for ketone ATH.[16] It was found that the configura-
tion of the product was controlled most strongly by the chi-
rality of the stereocentre in the tBoc-protected amino acid
portion of the ligand. The reduction was demonstrated to
involve the participation of Li cations in bridging the
ketone substrate to the Ru-bound alkoxy group.[16g,16h,16i]
Reversal of reduction enantioselectivity could be achieved
[a] Department of Chemistry, The University of Warwick,
Coventry, CV4 7AL, UK
Fax: +44-24-7652 3260
E-mail: m.wills@warwick.ac.uk
[b] New Products and Phosphine Development, Rhodia Consumer
Specialities Ltd.,
P. O. Box 80, Trinity Street, Oldbury, W. Midlands, B69 4LN,
UK
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101164.
Eur. J. Org. Chem. 2011, 6893–6901
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Wills et al.
FULL PAPER
by using thioamide derivatives of the amino acids.[16e,16i,16j]
Compound 21 has been applied to an aldol reaction of
The ATH of ketones in water[17] has been the subject of a ketones with 1,2-diketones,[31] whereas very similar com-
number of studies.[18,19] In 2004, Xiao[20] found that the use pounds (SO2Ph in place of Ts) have been prepared through
of a ruthenium (p-cymene) TsDPEN catalyst [(S,S)-1] in ring opening of a sulfonated aziridine ring and applied to
water gave rise to good catalytic activity when using sodium the organocatalysis of aldol reactions.[32] Several derivatives
formate as the hydrogen donor.[21,22] The pH of the reaction of C2-symmetric DPEN, and of trans-1,2-diaminocyclohex-
had a pivotal effect; at low pH, the nitrogen atom adjacent ane, bearing a combination of prolinamide and carbamate/
to the tosyl group protonates and becomes detached from thiocarbamate,[33–37] or dialkyl substituents,[38] have been
the metal centre, thus reducing activity, whereas at higher reported in organocatalytic asymmetric transformations.
pH values the ligand–metal bond remains intact. Several We first attempted the reduction of acetophenone using 20
water-soluble TsDPEN-derived ligands containing sulfonic and 21 with a 5:2 mixture of FA/TEA as the solvent and
acids[23,24] have been evaluated.
hydrogen donor (Table 1). Unfortunately, under these con-
Prolinamide derivatives were first employed for ketone ditions, as well as by using alternative conditions involving
ATH in water in 2001; reduction products of up to 95.3% iPrOH as the solvent/hydrogen donor, no reduction was
ee were generated[25] and, in some cases, surfactants could achieved. However, the use of sodium formate in water re-
be used to improve activity.[26] Multisubstrate screening sulted in successful reduction, giving 1-phenylethanol in
methods, in which several substrates can be screened simul- 90% ee and 22% conversion after 24 h at 40 °C with 20,
taneously, have been described using prolinamide cata- and complete reduction at 80 °C with either ligand, al-
lysts.[27,28] Dimeric ligands 13–15,[29] when complexed to though amide 20 was marginally more active. The ability to
RuII, were capable of reducing acetophenone in water, using achieve highly enantioselective reduction under such mildly
sodium formate as the hydrogen donor at 40 °C. Increasing basic conditions provides an advantage in some cases, for
the rigidity of the diamine spacer, for example in 14 and 15, example, when base-sensitive substrates are employed.
improved the enantioselectivity of the catalyst, and re-
Table 1. ATH of acetophenone using ligands 20 and 21.[a]
duction products with 56 and 66% ee, respectively, were
formed. Ligands 16 and 17, which were developed by
Mao,[30] are also capable of reducing acetophenone under
the same conditions, with comparable enantioselectivity. Al-
teration of the proline chirality in ligands 16 produced a
reversal in the stereochemistry of reduction.
Entry
Ligand Temp. Conditions[a]
[°C]
Conv.
[%][b]
ee
R/S[c]
[%][b]
1
2
3
4
5
6
7
8
20
20
20
20
20
20
21
21
40
40
40
40
60
80
60
80
aq. HCO2Na
FA/TEA
22
0
0
90
–
–
R
–
–
Results and Discussion
2-propanol
FA/TEA[d]
0
–
–
Given the literature precedent, and our ongoing interest
in the development of catalysts for ATH reactions, we inves-
tigated ligands containing a combination of a 1,2-diamine
function and a proline group. The reaction of each enantio-
mer of TsDPEN 1 with a protected S-proline derivative was
achieved by using ethyl chloroformate in the coupling reac-
tion. Removal of the tBoc group from 18 and 19 required
the use of different reagents to obtain products 20 and 21
(Scheme 1).
aq. HCO2Na
aq. HCO2Na
aq. HCO2Na
aq. HCO2Na
100
100
83
100
90
79
83
83
R
R
R
R
[a] Reagents and conditions: With aq. HCO2Na: 20/21 (0.02 mmol,
1 mol-%), [RuCl2(p-cymene)]2 (0.01 mmol, 1 mol-% by Ru),
HCO2Na (10 mmol), H2O (6 mL), acetophenone (2 mmol), 40 °C;
Formic acid/triethylamine: 20 (0.02 mmol, 2 mol-%), [RuCl2(p-
cymene)]2 (0.01 mmol, 2 mol-% by Ru), formic acid/triethylamine
(5:2, 0.5 mL), acetophenone (1 mmol); Isopropanol: 20
(0.02 mmol, 2 mol-%), [RuCl2(p-cymene)]2 (0.01 mmol, 2 mol-% by
Ru), 2-propanol (4 mL), acetophenone (1 mmol). [b] Determined
by GC analysis. [c] Determined by comparison of GC retention
time and optical rotation with literature data. [d] Catalytic species
formed in water and transferred to FA/TEA system.
An attempt was made to form a catalyst in water and
then transfer it to the formic acid system. After stirring li-
gand 20 and [RuCl2(p-cymene)]2 for 1 h in water at 40 °C,
the mixture was extracted with ethyl acetate and the solvent
was removed under reduced pressure to leave an orange so-
lid. Analysis of the mass spectrum of this solid showed the
masses of the expected complexes with ion distributions
that matched the predicted patterns for the 18 electron ([Ru-
(cymene)20·Cl]; m/z 734.18 for the 102Ru35Cl isotope) and
the dechlorinated ([Ru(cymene)20-H]; m/z 698.20 for the
Scheme 1. Synthesis of compounds 20 and 21 from the coupling of
the two enantiomers of 1 and proline.
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Asymmetric Transfer Hydrogenation of Ketones
102Ru isotope) species of the desired complex (see the Sup- Table 3. Transfer hydrogenation of ketones by Ir and Rh complexes
of ligands 20 and 21 in water.[a]
porting Information). This solid was then used under the
5:2 FA/TEA reaction conditions, but once again no reactiv-
ity was observed (Table 1, entry 4).
The reduction of a further series of ketones was investi-
gated (Table 2). When the ligands were tested on the cyclic
ketone 1-tetralone, the enantiomeric selectivity of the two
catalysts proved to be almost the same. Although, once
again, the catalyst containing (S,S)-TsDPEN proved to be
Entry
Metal Ligand R1
R2
Conv.
ee
R/S[c]
more active.
[%][b] [%][b]
1
2
3
4
5
6
7
8
Ir
Ir
Ir
Ir
20
21
20
20
21
20
21
20
21
20
21
20
21
20
21
20
21
Ph
Ph
Me
Me
9
0
5
33
33
13
21
22
28
3
47
–
R
–
Table 2. Transfer hydrogenation of ketones by ruthenium com-
plexes of ligands 20 and 21 in water.[a]
p-(MeO)C6H4 Me
38
29
14
84
67
0
R
R
R
R
S
–
p-(Cl)C6H4
p-(Cl)C6H4
Ph
Ph
c-C6H11
c-C6H11
Me
Me
Me
Me
Me
Me
Ir
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
9
0
–
Entry
Ligand R1
R2
Conv.
[%][b]
ee
R/S[c]
10
11
12
13
14
15
16
17
p-(MeO)C6H4 Me
p-(MeO)C6H4 Me
63
52
83
85
59
50
28
22
R
S
R
S
R
S
R
S
[%][b]
7
p-(Cl)C6H4
p-(Cl)C6H4
o-(Cl)C6H4
o-(Cl)C6H4
Ph
Me
Me
Me
Me
Et
21
68
41
37
10
7
1
2
3
4
5
6
7
8
20
21
20
21
20
21
20
21
20
20
21
20
21
20
21
20
21
20
21
Ph
Ph
c-C6H11
c-C6H11
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
100
100
25
40
76
92
54
95
11
90
100
100
100
66
84
6
90
83
0
R
R
–
0
–
p-(MeO)C6H4
p-(MeO)C6H4
o-(MeO)C6H4
o-(MeO)C6H4
2,4-(MeO)2C6H3
p-(Cl)C6H4
p-(Cl)C6H4
o-(Cl)C6H4
o-(Cl)C6H4
Ph
86
57
74
65
51
88
71
85
64
84
78
32
57
77
78
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
Ph
Et
[a] Reagents and conditions: [IrCl2(Cp*)]2 (0.5 mol-%, equivalent
to 1 mol-% metal centre), proline-TsDPEN (1 mol-%), ketone
(2 mmol), sodium formate (10 mmol), water (6 mL), 60 °C. [b] De-
termined by GC analysis. [c] Determined by comparison of GC
retention time and optical rotation with literature data.
9
10
11
12
13
14
15
16
17
18
19
the catalytic complex formed using ligands 20 and 21 pre-
dominantly coordinate through these two sites to give the
same major product. Arrangement of the ligands with ru-
thenium in this pocket can give a complex (Figure 1, a) that
would form the observed major (R) alcohol in a similar
manner to the established concerted mechanism for arene/
Ru/TsDPEN complexes (Figure 1, b).[1]
Ph
Ph
Ph
Et
cC6H11
cC6H11
6
8
45
α-tetralone
α-tetralone
[a] Reagents and conditions: [RuCl2(p-cymene)]2 (0.5 mol-%, equiv-
alent to 1 mol-% metal centre), proline-TsDPEN (1 mol-%), ketone
(2 mmol), sodium formate (10 mmol), water (6 mL), 60 °C. [b] De-
termined by GC analysis. [c] Determined by comparison of GC
retention time and optical rotation with literature data.
Determination of the configuration of the major prod-
ucts revealed that the proline chirality dominates the
enantioselectivity of the catalyst, with the TsDPEN chiral-
ity having a smaller, but not insignificant, effect. The pro-
line-TsDPEN ligands were also tested in Ir and Ir Cp* com-
plexes (Table 3), however, their reaction rates and selectivi-
ties were reduced compared to the ruthenium metal com-
plexes. Interestingly, with Rh, the TsDPEN chirality domi-
nates the reduction enantioselectivity, which may indicate
Figure 1. Proposed structures of the RuII/arene complexes of (a)
ligand 20, and (b) (R,R)-TsDPEN 1,[1] that would give the R-con-
figured alcohol product following the concerted mechanism for
ATH in water. The position of the substituents on the η6-arene ring
is arbitrary.
Our interest next turned to ligands containing two prolin-
that the metal centre is bound to different sites on the li- amides, i.e., 22 and 23, linked by a DPEN spacer. As was
gand when Rh is used compared to Ru and Ir.
the case for 20 and 21, these have been used previously as
Coordination of ligands 20 and 21 can occur at three catalysts for aldol reactions,[31,39,40] and as ligands for the
sites on the ligand: the secondary amine, the amide, and the addition of cyano groups to ketones.[41] Bisprolinamides
sulfonamide. Ligands 20, 21 and 16/17[21] give the same bridged by 1,2-diamino aryl rings have also been employed
major product enantiomer. As ligands 16 and 17 only con- in aldol reactions.[42] The coupling of two tBoc-protected
tain two of the possible coordination sites, it is likely that prolines to each enantiomer of DPEN was followed by re-
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M. Wills et al.
FULL PAPER
moval of the tBoc groups by using 20% Me2S·CH2Cl2, tri- hexyl methyl ketone to 1-cyclohexylethan-1-ol, which led to
isopropylsilane and trifluoroacetic acid to form ligands 22 a racemic mixture when reduced with 20 and 21. When 22
and 23 (Scheme 2).
and 23 were tested on the bicyclic ketone 1-tetralone, 1-
tetralol was formed with very high ee and at comparable
reaction rates to those with ligands 20 and 21 (Table 5). The
hydrogenation of 1-indanone showed the same pattern with
regards to both enantiomeric selectivity and catalytic ac-
tivity. The more enantioselective ligand 23 was tested with
other bicyclic ketones, varying both the size of the alkyl
cyclic ring and the substituents on both the alkyl and aro-
matic rings (Table 5). These results revealed that the
[RuCl(p-cymene)23] complex is able to catalyse the re-
duction of bicyclic aryl ketones with moderate to good con-
versions and good to excellent enantioselectivity. Reactions
with low conversions could be improved by increasing the
catalyst loading (Table 5, entry 3), or by increasing the reac-
tion time (Table 5, entry 4), with little degradation of
enantioselectivity.
Scheme 2. Synthesis of compounds 22 and 23 through coupling of
the two enantiomers of DPEN and two proline molecules.
Table 5. Transfer hydrogenation of commercially available bicyclic
Initial testing on the use of the diproline/DPEN ligands
were conducted under the previously established conditions,
including the relative equivalents of ruthenium metal to li-
gand (Table 4). Ligands 22 and 23 were found to be less
selective than ligands 20 and 21 for the hydrogenation of
acyclic ketones, although they showed a similar level of ac-
tivity. The exception to this was the hydrogenation of cyclo-
ketones by ruthenium complexes of ligands 22 and 23 in water.[a]
Entry
Ligand
X
n
R
Conv.
[%][b]
ee
R/S[d]
[%][c]
Table 4. Transfer hydrogenation of ketones by ruthenium com-
1
2
3
4
5
6
7
8
22
23
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
O
2
2
2
2
1
1
3
1
2
2
2
2
2
H
H
H
H
H
H
H
7-Me
6-OMe
furyl[h]
H
H
6-Cl
14
48
98
78
99
100
61
43
13
33
75
98
95
98
71
91
89
89
85
R
R
R
R
R
plexes of ligands 22 and 23 in water.[a]
22[e]
23[f]
22
23
23
23
23
23
23
23
23
R
R
R[g]
R
9
Entry
Ligand R1
R2
Conv.
[%][b]
ee
R/S[c]
10
11
12
13
85[i]
96[i]
92
R
R
R
R
[%][b]
100
100
12
S
O
1
2
3
4
5
6
7
8
22
23
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
99
100
11
13
54
22
63
90
66
98
100
98
99
99
82
90
82
90
100
86
83
12
24
68
66
83
77
65
53
87
79
80
66
86
80
86
80
81
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
86
22[d]
23[d]
22
[a] Reagents and conditions: [RuCl2(p-cymene)]2 (0.5 mol-%, equiv-
alent to 1 mol-% metal centre), diproline-DPEN (1 mol-%), ketone
(2 mmol), sodium formate (10 mmol), water (6 mL), 60 °C. [b] De-
termined by GC analysis. [c] Determined by GC analysis unless
shown. [d] Determined by comparison of GC retention time and
optical rotation with literature data. [e] 2 mol-% catalyst used. [f]
Reaction time 48 h. [g] Configuration inferred from results with
other ketones. [h] Furyl in place of phenyl in substrate. [i] Deter-
mined by HPLC analysis.
c-C6H11
c-C6H11
p-(MeO)C6H4 Me
p-(MeO)C6H4 Me
o-(MeO)C6H4 Me
o-(MeO)C6H4 Me
p-(Cl)C6H4
p-(Cl)C6H4
o-(Cl)C6H4
o-(Cl)C6H4
Ph
23
22
23
22
23
22
23
22
23
22
23
22
23
23
9
10
11
12
13
14
15
16
17
18
19
Me
Me
Me
Me
Et
Et
c-C6H11
c-C6H11
CH2Cl
Adding an oxygen or sulfur atom to the 4-position of the
tetralone alkyl ring did not reduce the rate of hydrogenation
of the substrate and did little to change the enantio-
selectivity of the catalyst (Table 5, entries 11 and 12). Alter-
ing the aryl ring however, caused a decrease in both reac-
tion rate and enantioselectivity, most significantly when a
substituent was positioned on the 6-position of the tet-
ralone. Ligand 13[29] is similar to ligands 22 and 23, except
that the latter two have two additional chiral centres on the
ethyl linker. The chirality of the major product alcohol (R)
Ph
Ph
Ph
Ph
[a] Reagents and conditions: [RuCl2(p-cymene)]2 (0.5 mol-%, equiv-
alent to 1 mol-% metal centre), diproline-DPEN (1 mol-%), ketone
(2 mmol), sodium formate (10 mmol), water (6 mL), 60 °C. [b] De-
termined by GC analysis. [c] Determined by comparison of GC
retention time and optical rotation with literature data. [d]
[RhCl2(Cp*)]2 used instead of [RuCl2(p-cymene)]2.
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Asymmetric Transfer Hydrogenation of Ketones
formed using all of these ligands is the same, and was deter- mained constant as the reaction proceeded, hence, the cata-
mined by the chirality of the proline portion of the ligand. lytic complex formed in the two reactions appears to be
With the Noyori TsDPEN complex system, the reduction the same. The reduced rate of the 2:1 metal to ligand ratio
of cyclohexyl methyl ketone provides an indication of the indicates that there is less available catalytic complex in this
differences between the reduction of aryl alkyl ketones and reaction and that the catalytic complex contains one metal
dialkyl ketones. In the aryl–alkyl ketone, the stereochemis- centre per ligand. This could be due to steric hindrance
try of the product was directed through a π-face interaction around the coordination sites, which allows only one metal
between the aromatic group on the substrate and the aryl to bind.
group on the complex (Figure 1).[1] With dialkyl ketones,
this interaction cannot occur and the interaction is due to
steric interactions between the largest alkyl group and the Conclusions
η6-arene ring on the complex. For this reason the reduction
Four ligands have been developed for the asymmetric
product of a dialkyl ketone of lower or opposite stereo-
transfer hydrogenation of ketones. These ligands show a
good level of activity when the reaction is performed in
chemistry is often observed. In the reduction of cyclohexyl
methyl ketone by complexes containing ligands 20 or 21, a
water with sodium formate as the hydrogen donor. Ligands
racemic mixture was formed. This indicates that the steric
20 and 21 were the most successful of the four in the re-
interactions between the substrate and both the η6-arene
duction of acyclic ketones, reducing ketones with up to full
ring on the metal centre and the ligand could be similar,
conversion and 90% ee in 24 h. The stereochemistry of the
resulting in no preference between the two possible transi-
tion states. When the reduction was performed with ligand
22 or 23, the product was non-racemic, however, the stereo-
major product was predominantly determined by the ste-
reochemistry of the proline ring, but the 1,2-diphenyl-1,2-
diamine has an effect, possibly due to interactions between
chemistry of the cyclohexyl methyl ketone was the same as
the aryl rings of the ligand and the substrate. For the re-
that for the reduction of aryl alkyl ketones. This suggests
duction of bicyclic ketones, ligands 22 and 23 proved to be
that the cyclohexyl methyl ketone and the aryl alkyl ketones
adopt the same orientation in the reduction step, and indi-
cates that the ligand in the diproline-DPEN (22 and 23)
more effective. Complexes containing ligand 23 proved to
be both more stereoselective than complexes containing li-
gand 22 and also more active. The catalytic complex ap-
pears to contain the metal centre and the ligand in a 1:1
complexes may have a larger effective steric bulk than the
η6-arene ring in the context of the reduction reactions.
ratio.
Ligands 22 and 23 have four coordination sites, therefore
it is possible to coordinate two metal centres to each ligand,
forming a diruthenium complex. To test the effect of alter-
ing the metal/ligand ratio, acetophenone reduction was per-
Experimental Section
formed using half the amount of ligand 22 relative to ruthe-
nium dimer. This creates a 2:1 ratio of metal to dimer, com-
pared to the 1:1 ratio using the original conditions. The
conversions obtained from samples taken from the reaction
at different times indicated that the reaction with a 2:1 ratio
of metal to ligand proceeded at a slower rate than the reac-
tion with a 1:1 ratio (Table 6). The ee of the (R)-phenyl-
ethanol product of the two reactions was the same and re-
General: Unless otherwise stated, all reactions were performed in
oven-dried glassware, under an atmosphere of argon. Room tem-
perature refers to ambient room temperature (20–22 °C), 0 °C re-
fers to an ice slush bath, and –78 °C refers to a dry ice acetone
bath. Heated experiments were conducted by using thermostati-
cally controlled oil baths or Asynt aluminium heating blocks.
NMR spectra were recorded with either a Bruker DPX-300
(300 MHz) or a Bruker DPX-400 (400 MHz) spectrometer. All
NMR δ values are given in ppm and all J values are in Hz. Low-
resolution mass spectrometry was performed with a Bruker Es-
quire2000 electrospray mass spectrometer. High-resolution mass
spectrometry was performed with a Bruker MicrOTOF spectrome-
ter. Melting points were obtained with a Stuart Scientific Melting
Point SMP1 and are uncorrected. Infrared spectroscopy was per-
formed with a PerkinElmer Spectrum 100. Optical rotation values
were obtained with an Optical Activity Ltd. AA-1000 Polarimeter.
GC was performed with either a Hewlett–Packard 5890 gas chro-
matograph linked to a Hewlett–Packard HP3396A integrator, or a
Perkin–Elmer 8500 chromatograph linked to a PC running DataA-
pex Clarity software. HPLC was performed with a chromatograph
consisting of a Gilson 305 Piston Pump, a Gilson 805 Manometric
Module, a Gilson 811B Dynamic Mixer and a Gilson 115 Variable
Wavelength Detector linked to a Hewlett–Packard 3396 Series II
integrator.
Table 6. The effect of altering the ratio between ligand and metal
for the transfer hydrogenation of acetophenone in water.[a]
Time [h] 2:1 Metal/ligand, conv. [%]
1:1 Metal/ligand, conv.
[%][b]
[b]
6
12
24
52
79
92
89
95
99
ee [%][b]
83
83
tert-Butyl (S)-2-{[(1R,2R)-2-(4-Methylphenylsulfonamido)-1,2-di-
phenylethyl]carbamoyl}pyrrolidine-1-carboxylate (18): N-tBoc-(L)-
Proline (1.0 g, 4.7 mmol) and triethylamine (2.1 mL, 14.1 mmol)
were dissolved in anhydrous THF (23.5 mL) and cooled to 0 °C.
[a] Reagents and conditions: [RuCl2(p-cymene)]2 (0.5 mol-%, equiv-
alent to 1 mol-% metal centre), 22 [1 mol-% (1:1) or 0.5 mol-%
(2:1)], acetophenone (2 mmol), sodium formate (10 mmol), water
(6 mL), 60 °C. [b] Determined by GC analysis.
Eur. J. Org. Chem. 2011, 6893–6901
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6897

M. Wills et al.
FULL PAPER
Ethyl chloroformate (0.47 mL, 5.0 mmol) was added and the mix-
roformate (0.24 mL, 2.5 mmol) was added and the mixture was
ture was stirred at 0 °C for 30 min. (R,R)-1,2-Diphenylethylene-1,2- stirred at 0 °C for 30 min. (R,R)-1,2-Diphenylethylene-1,2-diamine
diamine (1; 1.7 g, 4.7 mmol) was added and the reaction was stirred
at room temperature overnight. THF was removed under reduced
pressure and ethyl acetate and water were added. The organic layer
was washed with water and brine and dried with magnesium sul-
fate. The solvent was removed under reduced pressure to leave the
product 18 as a white solid. (1.8 g, 3.2 mmol, 68%); m.p. 187–
(1; 850 mg, 2.32 mmol) was added and the reaction was stirred at
room temperature overnight. THF was removed under reduced
pressure and ethyl acetate and water were added. The organic layer
was washed with water and brine and dried with magnesium sul-
fate. The solvent was removed under reduced pressure to leave the
product 19 as a white solid. (743 mg, 1.32 mmol, 57%); m.p. 102–
192 °C. [α]3D1 = –34.0 (c = 1.0, in CHCl ). IR: νmax = 2975 (w), 1652
106 °C. [α]3D2 = –17.1 (c = 1.0, in CHCl ). IR: νmax = 3351 (w), 3196
˜
˜
3
3
(s), 1521 (m), 1496 (m), 1456 (m), 1385 (s), 1366 (s), 1324 (s), 1253 (w), 2975 (w), 1695 (s), 1666 (s), 1600 (w), 1543 (m), 1496 (m), 1478
(w), 1154 (s), 1120 (s), 1089 (s), 1028 (w), 919 (m), 853 (w), 810 (w), 1456 (m), 1393 (s), 1366 (s), 1324 (m), 1289 (m), 1245 (m),
(m), 771 (m), 730 (m) and 697 (s) cm–1
CDCl3, Me4Si): δ = 1.14 [br. s, 3 H, –C(CH3)3 rotamer], 1.54 [br.
s, 6 H, –C(CH3)3 rotamer], 1.89–1.96 (m, 1 H, –CHH–), 2.12–2.14
(m, 1 H, –CHH–), 2.25 (s, 3 H, –CH3), 2.33–2.46 (m, 1 H, –CHH–
), 3.35–3.59 (m, 1 H, –CHH–), 3.66 [dd, JH,H = 2.3, JH,H
7.8 Hz, 1 H, –C(O)CH–], 4.20–4.37 (m, 2 H, –NCH2–), 5.28 [br. s, 1 H, –C(O)CH–], 4.25 [d, JH,H = 8.8 Hz, 1 H, –C(O)NHCH–],
.
1H NMR (300 MHz,
1209 (w), 1155 (s), 1121 (s), 1089 (s), 1070 (m), 1029 (w), 927 (m),
887 (w), 853 (w), 812 (m), 770 (m), 759 (m), 697 (s), 667 (s) cm–1.
1H NMR (400 MHz, CDCl3, Me4Si): δ = 1.32 [s, 9 H, –C(CH3)3],
1.84–1.89 (m, 3 H, –CH2– and –CHH–), 2.30 (s, 3 H, –CH3), 2.46
3
3
=
[br. s, 1 H, –S(O)2NH–], 3.22–3.33 (m, 2 H, –CH2–), 3.42–3.48 [m,
3
3
1 H, –C(O)NHCH–], 6.54 [br. s, 1 H, –S(O)2NHCH–], 6.81 (d, 4.62 [d, JH,H = 8.8 Hz, 1 H, –S(O)2NHCH–], 5.03–5.20 (m, 1 H,
3JH,H = 7.5 Hz, 2 H, Ar-H), 6.88–7.01 (m, 7 H, Ar-H), 7.12–7.15
–NCHH–), 6.31 (br. s, 1 H, –NCHH–), 6.82 (d, JH,H = 7.2 Hz, 2
3
3
(m, 3 H, Ar-H), 7.37 (d, JH,H = 7.5 Hz, 2 H, Ar-H) ppm. 13C
H, Ar-H), 6.95–7.03 (m, 7 H, Ar-H), 7.12 (br. m, 3 H, Ar-H), 7.44
3
NMR (75 MHz, CDCl3): δ = 20.7, 23.8, 27.4, 30.7, 46.7, 57.5, 59.8, (d, JH,H = 7.2 Hz, 2 H, Ar-H), 8.23 [br. s, 1 H, –C(O)NHCH–]
61.4, 62.2, 79.8, 126.1, 126.6, 126.9, 127.1, 127.3, 127.8, 128.3,
137.1, 137.5, 137.7, 141.8, 154.6, 172.9 ppm. MS (ESI+): m/z (%)
= 586 (100) [M + Na]. HRMS: calcd. for C31H37N3NaO5S
586.2346; found 586.2348 (0.3 ppm error).
ppm. MS (ESI+): m/z (%) = 586 (100) [M + Na]. HRMS: calcd.
for C31H37N3NaO5S 586.2346; found 586.2353 (1.1 ppm error).
(S)-N-[(1S,2S)-2-(4-Methylphenylsulfonamido)-1,2-diphenylethyl]-
pyrrolidine-2-carboxamide (21):[30] To compound 19 (150 mg,
0.266 mmol) was added formic acid (1.1 mL) dropwise at 0 °C. The
resulting solution was stirred at 0 °C for 12 h. The formic acid was
then removed under reduced pressure to leave a white solid, which
was neutralised by the addition of aqueous ammonia. The product
was extracted with CH2Cl2 and the combined organic extracts were
dried with magnesium sulfate and the solvent removed under re-
duced pressure to leave the product 21 as a white solid (61 mg,
0.132 mmol, 50%); m.p. 97–100 °C. [α]3D2 = –0.7 (c = 0.5, in CHCl3).
(S)-N-[(1R,2R)-2-(4-Methylphenylsulfonamido)-1,2-diphenylethyl]-
pyrrolidine-2-carboxamide (20): Compound 18 (355 mg, 0.63 mmol)
was dissolved in 20% Me2S·CH2Cl2 complex (9.3 mL). Triisopro-
pylsilane (0.18 mL, 0.78 mmol) was added and the mixture cooled
to 0 °C. Trifluoroacetic acid (8.7 mL, 113.6 mmol) was added drop-
wise at 0 °C and the mixture was allowed to slowly warm to room
temperature and stirred overnight. The reaction was quenched at
0 °C with the addition of saturated aqueous potassium carbonate
and the majority of the dimethyl sulfide was removed under re-
duced pressure. Water was added and the product was extracted
with CH2Cl2 (2ϫ30 mL). The organic extracts were combined,
dried with magnesium sulfate and the organic solvent was removed
under reduced pressure to leave the crude product as a pale-yellow
solid. The crude product was dissolved in hot ethyl acetate and
hexane was added until the product precipitated out of solution.
The pure product 20 was filtered off as a white solid (251 mg,
0.54 mmol, 86%); m.p. 100–102 °C. [α]3D1 = –17.6 (c = 1.0, in
IR: ν
= 3063 (w), 3031 (w), 2873 (w), 1647 (s), 1600 (w), 1511
˜
max
(s), 1495 (m), 1455 (m), 1322 (s), 1203 (w), 1184 (w), 1153 (s), 1089
(s), 1071 (m), 1029 (m), 934 (m), 811 (m), 756 (m), 697 (s), 666
1
(s) cm–1. H NMR (400 MHz, CDCl3, Me4Si): δ = 1.52–1.65 (m, 2
H, –CH2–), 1.73–1.80 (m, 1 H, –CHH–), 2.06–2.13 [m, 2 H, –CHH-
and C(O)CH–], 2.18 (s, 3 H, –CH3), 2.82–2.88 (m, 1 H, –NHCHH–),
3
3
2.91–2.97 (m, 1 H, –NHCHH–), 3.85 [dd, JH,H = 8.2, JH,H
=
3
9.7 Hz, 1 H, –C(O)NHCH(Ph)CH–], 4.53 [d, JH,H = 9.7 Hz, 1
3
3
H, –S(O)2NHCH–], 5.12 [dd, JH,H = 9.7, JH,H = 9.7 Hz, 1 H,
CHCl ). IR: ν
= 3299 (w), 2870 (w), 1643 (s), 1600 (w), 1497 –S(O)2NHCH(Ph)CH–], 6.78–6.92 (m, 10 H, Ar-H), 7.07 (m, 2 H,
˜
3
max
(s), 1456 (m), 1325 (s), 1203 (m), 1156 (s), 1089 (s), 1029 (w), 921 Ar-H), 7.33 (d, 3JH,H = 7.9 Hz, 2 H, Ar-H), 8.58 [d, 3JH,H = 8.2 Hz,
(m), 807 (s), 772 (m), 756 (m), 698 (s) and 668 (s) cm–1. H NMR 1 H, –C(O)NH–] ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3, 26.0,
1
(300 MHz, CDCl3, Me4Si): δ = 1.69–1.82 (m, –CH2–, 2 H), 1.89– 30.5, 47.1, 58.7, 60.5, 63.9, 126.7, 127.2, 127.5, 127.6, 127.7, 127.9,
2.02 (m, 1 H, –CHH–), 2.09–2.22 [m, 3 H, –CHH–, –CH2NHCH– 128.4, 129.0, 138.1, 138.4, 138.5, 142.3, 176.0 ppm. MS (ESI+): m/z
3
3
and –C(O)CH–], 2.26 (s, 3 H, CH3), 3.07 (ddd, JH,H = 2.3, JH,H (%) = 464.2 (100) [M + H]. HRMS: calcd. for C26H30N3O3S
= 6.6, 3JH,H = 6.6 Hz, 2 H, –NHCH2–), 3.79 [dd, 3JH,H = 5.6, 3JH,H
464.2002; found 464.2000 (0.5 ppm error).
3
= 8.9 Hz, 1 H, –C(O)NHCH(Ph)CH–], 4.66 [d, JH,H = 10.1 Hz, 1
(S)-tert-Butyl 2-({(1R,2R)-2-[(S)-1-(tert-Butoxycarbonyl)pyrrol-
idine-5-carboxamido]-1,2-diphenylethyl}carbamoyl)pyrrolidine-1-
carboxylate: N-tBoc-(L)-proline (2.0 g, 9.3 mmol) and triethyl-
amine (2 mL) were dissolved in anhydrous THF (23.6 mL) and
cooled to 0 °C. Ethyl chloroformate (0.96 mL, 10.0 mmol) was
added and the mixture was stirred at 0 °C for 30 min. (R,R)-1,2-
Diphenylethylene-1,2-diamine (1.2 g, 5.6 mmol) was added and the
reaction was stirred at room temperature overnight. THF was re-
moved under reduced pressure and ethyl acetate and water were
added. The organic layer was washed with water and brine and
3
3
H, –S(O)2NHCH–], 5.12 [dd, JH,H = 8.9, JH,H = 10.1 Hz, 1 H,
–S(O)2NHCH(Ph)CH–], 6.79 (d, 3JH,H = 8.3 Hz, 2 H, Ar-H), 6.89–
6.98 (m, 5 H, Ar-H), 7.00–7.03 (m, 2 H, Ar-H), 7.16–7.18 (m, 3 H,
Ar-H), 7.34 (d, 3JH,H = 8.3 Hz, 2 H, Ar-H), 8.62 [d, 3JH,H = 5.6 Hz,
1 H, –C(O)NH–] ppm. 13C NMR (75 MHz, CDCl3): δ = 20.7, 25.6,
30.1, 46.7, 57.7, 59.8, 63.5, 126.1, 126.6, 126.9, 127.2, 127.9, 128.3,
128.6, 130.4, 137.2, 137.4, 137.5, 141.8, 175.6 ppm. MS (ESI+): m/z
(%) = 464 (100) [M + H]. HRMS: calcd. for C26H30N3O3S
464.2002; found 464.2011 (1.8 ppm error).
tert-Butyl (S)-2-{[(1S,2S)-2-(4-Methylphenylsulfonamido)-1,2-di- dried with magnesium sulfate. The solvent was removed under
phenylethyl]carbamoyl}pyrrolidine-1-carboxylate (19): N-tBoc-(l)-
Proline (500 mg, 2.33 mmol) and triethylamine (1.1 mL) were dis-
solved in anhydrous THF (11.7 mL) and cooled to 0 °C. Ethyl chlo-
reduced pressure to leave the product as a white solid (2.5 g,
4.1 mmol, 89%); m.p. 104–108 °C. [α]3D2 = –98.7 (c = 0.5, in CHCl3).
IR: ν
= 3338 (w), 2974 (w), 1695 (s), 1652 (s), 1520 (s), 1478
˜
max
6898
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6893–6901

Asymmetric Transfer Hydrogenation of Ketones
(m), 1454 (m), 1390 (s), 1365 (s), 1252 (m), 1159 (s), 1120 (m), 1087 Ar-H), 8.05 [br. s, 1 H, –C(O)NH–], 8.44 [br. s, 1 H, –C(O)NH–]
(m), 1029 (w), 979 (w), 952 (w), 925 (w), 858 (w), 772 (m), 698
(s) cm–1. 1H NMR (300 MHz, CDCl3, Me4Si): δ = 1.17 [br. s, 9
H, –C(CH3)3], 1.45 [br. s, 9 H, –C(CH3)3], 1.83 (br. s, 6 H, alkyl-
H), 3.25–3.56 (br. m, 4 H, alkyl-H), 4.05–4.31 (br. m, 4 H, alkyl-
H), 5.20–5.30 (br. m, 2 H, –CHCH–), 7.07–7.10 (m, 4 H, Ar-H),
7.15–7.20 (m, 6 H, Ar-H), 7.61–7.86 [m, 2 H, 2ϫ –C(O)NH–] ppm.
MS (ESI–): m/z (%) = 605 (24) [M – H], 531 (93), 457 (100). HRMS:
calcd. for C34H45N4O6 605.3345; found 605.3314 (5.1 ppm error).
ppm. MS (ESI–): m/z (%) = 605 (47) [M – H], 531 (100), 457 (57).
HRMS: calcd. for C34H45N4O6 605.3345; found 605.3322 (3.7 ppm
error).
(S)-N-{(1S,2S)-1,2-Diphenyl-2-[(S)-pyrrolidine-5-carboxamido]-
ethyl}pyrrolidine-2-carboxamide (23):[39,40] (S)-tert-Butyl 2-
({(1S,2S)-2-[(S)-1-(tert-butoxycarbonyl)pyrrolidine-5-carbox-
amido]-1,2-diphenylethyl}carbamoyl)pyrrolidine-1-carboxylate
(500 mg, 0.83 mmol) was dissolved in 20% Me2S·CH2Cl2 complex
(10.6 mL). Triisopropylsilane (0.4 mL, 1.7 mmol) was added and
the mixture was cooled to 0 °C. Trifloroacetic acid (10 mL,
131 mmol) was added dropwise at 0 °C and the mixture was al-
lowed to slowly warm to room temperature and stirred overnight.
The reaction was quenched at 0 °C with the addition of saturated
aqueous potassium carbonate and the majority of the dimethyl sul-
fide was removed under reduced pressure. Water was added and
the product was extracted with CH2Cl2 (2ϫ30 mL). The organic
extracts were combined, dried with magnesium sulfate and the or-
ganic solvent was removed under reduced pressure to leave the
crude product as a pale-yellow solid. The crude product was dis-
solved in hot ethyl acetate and hexane was added until the product
precipitated out of solution. The pure product 23 was filtered off
as a white solid (104 mg, 0.26 mmol, 31%); m.p. 114–118 °C. [α]2D6
(S)-N-{(1R,2R)-1,2-Diphenyl-2-[(S)-pyrrolidine-5-carboxamido]-
ethyl}pyrrolidine-2-carboxamide (22):[31,39] tert-Butyl (S)-2-
({(1R,2R)-2-[(S)-1-(tert-butoxycarbonyl)pyrrolidine-5-carbox-
amido]-1,2-diphenylethyl}carbamoyl)pyrrolidine-1-carboxylate
(1.0 g, 1.7 mmol) was dissolved in 20% Me2S-CH2Cl2 complex
(21.3 mL). Triisopropylsilane (0.8 mL, 3.5 mmol) was added and
the mixture was cooled to 0 °C. Trifloroacetic acid (20 mL,
261 mmol) was added dropwise at 0 °C and the mixture was al-
lowed to slowly warm to room temperature and stirred overnight.
The reaction was quenched at 0 °C with the addition of saturated
aqueous potassium carbonate and the majority of the dimethyl sul-
fide was removed under reduced pressure. Water was added and
the product was extracted with CH2Cl2 (2ϫ30 mL). The organic
extracts were combined, dried with magnesium sulfate and the or-
ganic solvent was removed under reduced pressure to leave the
crude product 22 as a pale-yellow solid. The crude product was
dissolved in hot ethyl acetate and hexane was added until the prod-
uct precipitated out of solution. The pure product was filtered off
as a white solid (384 mg, 0.94 mmol, 56%); m.p. 140–144 °C. [α]3D2
= +7.3 (c = 1.0, in CHCl ). IR: ν
= 3296 (m), 3033 (w), 2951
˜
3
max
(w), 2870 (w), 1645 (s), 1513 (s), 1455 (m), 1255 (m), 1201 (m),
1103 (m), 1030 (m), 915 (m), 841 (m), 755 (m), 697 (s) cm–1. 1H
NMR (300 MHz, CDCl3, Me4Si): δ = 1.52–1.68 (4 H, m 2 ϫ
–CH2–), 1.68–1.81 (m, 2 H, 2ϫ –CHH–), 2.01–2.13 (m, 2 H, 2ϫ
–CHH–), 2.55 [br. s, 2 H, –NHCH(Ph)CH(Ph)NH–], 2.81–2.89 (m,
2 H, 2ϫ –NHCHH–), 2.94–3.02 (m, 2 H, 2ϫ –NHCHH–), 3.74
(dd, 3JH,H = 6.3, 3JH,H = 8.8 Hz, 2 H, 2ϫ –CH2NHCH–), 5.19 [dd,
= –39.8 (c = 0.4, in CHCl ). IR: ν
= 3290 (m), 3062 (w), 2948
˜
3
max
(w), 2874 (w), 1646 (s), 1516 (s), 1495 (s), 1455 (m), 1418 (m), 1290
(m), 1253 (m), 1201 (s), 1131 (m), 1030 (m), 1002 (w), 915 (w), 834
1
(m), 800 (m), 755 (m), 697 (s) cm–1. H NMR (300 MHz, CDCl3,
3
3JH,H = 2.3, JH,H = 6.3 Hz, 2 H, 2ϫ –C(O)CH–], 7.05–7.08 (m, 4
Me4Si): δ = 1.66–1.77 (m, 4 H, alkyl-H), 1.79–1.90 (m, 2 H, alkyl-
H), 2.08–2.20 (m, 2 H, alkyl-H), 2.38 [br. s, 2 H, –NHCH(Ph)-
H, Ar-H), 7.15–7.18 (m, 6 H, Ar-H), 8.51 [br. s, 2 H, 2ϫ –C(O)-
NH–] ppm. 13C NMR (75 MHz, CDCl3): δ = 25.9, 30.5, 47.1, 58.7,
61.5, 127.4, 127.7, 128.5, 138.8, 175.0 ppm. MS (ESI+): m/z (%) =
407.3 (100) [M + H], 429.2 (69) [M + Na]. HRMS (ESI+): calcd.
for C24H31N4O2 407.2442; found 407.2444 (0.5 ppm error).[39,40]
3
CH(Ph)NH–], 2.90–3.05 (m, 4 H, 2؋ –CH2NH–), 3.69 (dd, JH,H
3
3
= 5.5, JH,H = 9.0 Hz, 2 H, 2ϫ –CH2NHCH–), 5.21 [dd, JH,H
=
3
2.5, JH,H = 5.5 Hz, 2 H, 2؋ –C(O)CH–], 7.06–7.09 (m, 4 H, Ar-
H), 7.14–7.21 (m, 6 H, Ar-H), 8.40 [br. s, 2 H, 2؋ –C(O)NH–]
ppm. 13C NMR (75 MHz, CDCl3): δ = 25.4, 31.0, 46.5, 57.7, 58.3,
General Procedure for the Racemic Reduction of Ketones: Ketone
126.8, 126.9, 127.9, 138.3, 173.7 ppm. MS (ESI+): m/z (%) = 407.2 (2 mmol) was dissolved in methanol (1 mL) and CH2Cl2 (1 mL),
(100) [M + H]. HRMS (ESI+): calcd. for C24H31N4O2 407.2442;
found 407.2449 (1.8 ppm error).[39]
and sodium borohydride (49 mg, 1.3 mmol) was added in portions.
The reaction was stirred at room temperature for 1 h, then the sol-
vents were removed under reduced pressure and water was added.
The product was extracted with CH2Cl2 and the organic extracts
were combined, dried with magnesium sulfate and the solvent re-
moved under reduced pressure to leave the racemic alcohol, which
was purified by column chromatography if necessary.
tert-Butyl (S)-2-({(1S,2S)-2-[(S)-1-(tert-Butoxycarbonyl)pyrrolidine-
5-carboxamido]-1,2-diphenylethyl}carbamoyl)pyrrolidine-1-carb-
oxylate: N-tBoc-(l)-Proline (2 g, 9.4 mmol) and triethylamine
(2 mL) were dissolved in anhydrous THF (23.6 mL) and cooled to
0 °C. Ethyl chloroformate (0.96 mL, 10.0 mmol) was added and the
mixture was stirred at 0 °C for 30 min. (R,R)-1,2-Diphenylethylene-
1,2-diamine (1.2 g, 5.6 mmol) was added and the reaction was
stirred at room temperature overnight. THF was removed under
reduced pressure and ethyl acetate and water were added. The or-
ganic layer was washed with water and brine and dried with magne-
sium sulfate. The solvent was removed under reduced pressure to
leave the product as a white solid (2.5 g, 4.1 mmol, 89%); m.p. 118–
General Procedure for Asymmetric Transfer Hydrogenation: Ligand
(0.02 mmol) and (dichloro-p-cymene)ruthenium dimer (6.1 mg,
0.01 mmol) were dissolved in water (6 mL) and the mixture was
stirred at 60 °C for 1 h. Ketone (2 mmol) and sodium formate
(1.04 g, 10 mmol) were added and the mixture was stirred at 60 °C
for 24 h. The reaction was then allowed to cool to room tempera-
ture and the product was extracted with ethyl acetate. The organic
layer was filtered through a plug of silica and the solvent was re-
moved under reduced pressure to leave the product, which was
purified by column chromatography if necessary. Characterisation
data and ee determination methods for the reduction products[43–50]
are given in the Supporting Information.
123 °C. [α]2D8 = –28.7 (c = 0.2, in CHCl ). IR: νmax = 3320 (w), 2977
˜
3
(w), 2879 (w), 1689 (s), 1661 (s), 1526 (m), 1496 (m), 1479 (w), 1455
(w), 1398 (s), 1365 (s), 1283 (w), 1240 (m), 1208 (w), 1160 (s), 1121
(m), 1089 (w), 1030 (w), 984 (w), 924 (w), 887 (w), 860 (w), 771
(m), 698 (s) cm–1. 1H NMR (300 MHz, CDCl3, Me4Si): δ = 1.34
[br. s, 18 H, 2ϫ –C(CH3)3], 1.77–1.90 (m, 6 H, 3ϫ alkyl-H), 2.27–
2.53 (m, 2 H, alkyl-H), 3.16–3.35 (br. m, 2 H, alkyl-H), 3.35–3.61
Supporting Information (see footnote on the first page of this arti-
(m, 2 H, alkyl-H), 4.28–4.41 (br. m, 2 H, alkyl-H), 5.11–5.14 (m, 2 cle): Characterisation data for the ketone reduction products and
H, –CHCH–), 6.98–7.09 (br. m, 4 H, Ar-H), 7.09–7.18 (br. m, 6 H, copies of NMR, GC and HPLC data.
Eur. J. Org. Chem. 2011, 6893–6901
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6899

M. Wills et al.
FULL PAPER
[16]
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Acknowledgments
The authors thank the Engineering and Physical Sciences Research
Council (EPSRC) and Rhodia Consumer Specialities Ltd. for fund-
ing of C. V. M. through the Collaborative Training Account (CTA)
grant. We thank Johnson Matthey for loans of the Ru and Rh
complexes that were used in this project.
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Received: August 8, 2011
Published Online: August 10, 2011
Eur. J. Org. Chem. 2011, 6893–6901
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