Chiral pincer ruthenium and osmium complexes for the fast and efficient hydrogen transfer reduction of ketones

Article abstract of DOI:10.1021/om1004918

A series of chiral HCNN ligands ((S)-1b-g) (S)-2-(1-aminoethyl)-6-(aryl) pyridine (aryl = 4-MeO-phenyl, 1b; 4-CF₃-phenyl, 1c; 3,5-di-Me-phenyl, 1d; 3,5-di-CF₃-phenyl, 1e; 1-naphthyl, 1f; 2-naphthyl, 1g) were synthesized starting from commercial 2-acetyl-6- bromopyridine (2), by a chemoenzymatic method involving the dynamic kinetic resolution of the corresponding secondary alcohol (rac-3). The conversion of the resulting (R)-3, obtained in 98% ee, into the homochiral amine ((S)-6), followed by Suzuki coupling with the appropriate arylboronic acids 7b-g, gave access to (S)-1b-g, isolated in 97% ee, with an overall yield up to 50%. The in situ generated pincer complexes [MCl(CNN)(PP)] (M = Ru, Os; PP = Josiphos diphosphine), prepared from [MCl₂(PPh₃)₃], (R,S)-Josiphos diphosphines, and the ligands (S)-1b-g, were found to efficiently catalyze the asymmetric transfer hydrogenation of acetophenone in 2-propanol at 60 °C and in the presence of NaOiPr. On the basis of these data, the 2-naphthyl ruthenium and osmium derivatives [RuCl(CNN)((R,S)-Josiphos*] (8) (HCNN = (S)-1g) and [OsCl(CNN)(PP)] (PP = (R,S)-Josiphos, 9, and (R,S)-Josiphos*, 10) were isolated from [MCl₂(PPh ₃)₃], (R,S)-Josiphos diphosphines, and the ligand (S)-1g. Complexes 8 and 10, displaying the correctly matched chiral PP and CNN ^- ligands, are highly active and productive catalysts for the transfer hydrogenation of alkyl aryl ketones and methyl pyridyl ketones with TOF = 10⁵-10⁶ h^-1, using 0.005 mol % of catalysts and achieving up to 99% ee. The comparison of the catalytic activity of these pincer complexes shows that Ru and Os derivatives display similar rate and enantioselectivity.

Full text of DOI:10.1021/om1004918

Organometallics 2010, 29, 3563–3570 3563
DOI: 10.1021/om1004918
Chiral Pincer Ruthenium and Osmium Complexes for the Fast and
Efficient Hydrogen Transfer Reduction of Ketones
Walter Baratta,*,† Fabio Benedetti,§ Alessandro Del Zotto,† Lidia Fanfoni,§
Fulvia Felluga,§ Santo Magnolia,† Elisabetta Putignano,† and Pierluigi Rigo†
†
ꢀ
Dipartimento di Scienze e Tecnologie Chimiche, Universita di Udine, Via Cotonificio 108, I-33100 Udine,
Italy, and Dipartimento di Scienze Chimiche, Universita di Trieste, Via L. Giorgieri 1, I-34127 Trieste, Italy
§
ꢀ
Received May 19, 2010
A series of chiral HCNN ligands ((S)-1b-g) (S)-2-(1-aminoethyl)-6-(aryl)pyridine (aryl = 4-MeO-
phenyl, 1b; 4-CF3-phenyl, 1c; 3,5-di-Me-phenyl, 1d; 3,5-di-CF3-phenyl, 1e; 1-naphthyl, 1f; 2-naphthyl,
1g) were synthesized starting from commercial 2-acetyl-6-bromopyridine (2), by a chemoenzymatic
method involving the dynamic kinetic resolution of the corresponding secondary alcohol (rac-3). The
conversion of the resulting (R)-3, obtained in 98% ee, into the homochiral amine ((S)-6), followed by
Suzuki coupling with the appropriate arylboronic acids 7b-g, gave access to (S)-1b-g, isolated in 97%
ee, with an overall yield up to 50%. The in situ generated pincer complexes [MCl(CNN)(PP)] (M = Ru,
Os; PP = Josiphos diphosphine), prepared from [MCl2(PPh3)3], (R,S)-Josiphos diphosphines, and the
ligands (S)-1b-g, were found to efficiently catalyze the asymmetric transfer hydrogenation of aceto-
phenone in 2-propanol at 60 °C and in the presence of NaOiPr. On the basis of these data, the 2-naphthyl
ruthenium and osmium derivatives [RuCl(CNN)((R,S)-Josiphos*)] (8) (HCNN = (S)-1g) and [OsCl-
(CNN)(PP)] (PP=(R,S)-Josiphos, 9, and(R,S)-Josiphos*, 10) wereisolatedfrom [MCl2(PPh3)3], (R,S)-
Josiphos diphosphines, and the ligand (S)-1g. Complexes 8 and 10, displaying the correctly matched
chiral PP and CNN- ligands, are highly active and productive catalysts for the transfer hydrogenation of
alkyl aryl ketones and methyl pyridyl ketones with TOF = 105-106 h-1, using 0.005 mol % of catalysts
and achieving up to 99% ee. The comparison of the catalytic activity of these pincer complexes shows that
Ru and Os derivatives display similar rate and enantioselectivity.
Introduction
and [(η6-arene)RuCl(Tsdpen)] for the efficient ketone hydro-
genation and TH reactions, respectively.3 The presence of
the N-H functionality has been shown to be crucial in
enhancing the activity of both systems. Evidence has been
provided that during catalysis the cis-RuH/-NH2 motif plays
a fundamental role through a concerted delivery of a N-H
proton and a Ru-H hydride, via an outer-sphere mechanism
(metal-ligand bifunctional catalysis).4 Inspired by this pio-
neering work, a large number of transition metal complexes
containing N-H ligands have been designed and found to
efficiently catalyze the enantioselective ketone reduction.1,2 It is
worth noting that TH has emerged as a valuable tool to obtain
optically active alcohols, this procedure being a complement/
alternative to the pressure hydrogenation, particularly for
small- to medium-scale production. Recently, we found that
the complexes cis-[RuCl2(PP)(ampy)], containing the mixed
bidentate nitrogen ligand 2-aminomethylpyridine (ampy) in-
stead of a 1,2-diamine, display high catalytic activity for the
TH of ketones in basic 2-propanol.5 A more efficient catalyst
is the pincer complex [RuCl(CNN)(Ph2P(CH2)4PPh2)],6
Asymmetric reduction of ketones to secondary alcohols is
a core reaction for the synthesis of chiral alcohols. A number
of homogeneous catalytic systems based on Ru, Rh, Ir, and
more recently Os complexes have been developed for the
ketone hydrogenation1 and transfer hydrogenation (TH)2
reactions. One of the most significant breakthroughs in this
field was the work of Noyori and co-workers, which led to
the systems trans-[RuCl2(PP)(1,2-diamine)] (PP = diphosphine)
*To whom correspondence should be addressed. E-mail: inorg@
uniud.it.
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J. G., Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2007. (c) Transition
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2010 American Chemical Society
Published on Web 07/23/2010
pubs.acs.org/Organometallics

3564 Organometallics, Vol. 29, No. 16, 2010
Baratta et al.
Figure 1
obtained by orthometalation of the ampy-type ligand 2-(1-amino-
methyl)-6-(4-metylphenyl)pyridine (HCNN), which afforded
extremely high TOF7 and TON values (Figure 1).
The chiral pincer complexes [RuCl(CNN)(PP)], prepared
from chiral Josiphos diphosphines and racemic HCNN
ligands, have proven to catalyze the ketone TH with both
high enantioselectivity and productivity.8 Interestingly, the
analogous osmium complexes [OsCl2(PP)(ampy)] and [OsCl-
(CNN)(PP)] display very high catalytic activity in the enantio-
selective ketone TH (Figure 1).9 In addition, the osmium
pincer compounds9b,10a and the trans-[OsCl2(PP)(1,2-diamine)]10b
derivatives were found to be efficient catalysts in the asym-
metric hydrogenation of ketones. It is worth noting thatonly a
few Os catalysts have been described for the asymmetric reduc-
tion of ketones via TH,11 whereas no example for hydrogena-
tion had been reported before our work on [OsCl(CNN)(PP)].
As a matter of fact, osmium is thought to give more stable
complexes and less active catalysts compared to ruthenium, as a
consequence of the stronger bonding.12 On account of the high
performance of the pincer complexes,13 this class of compounds
appears attractive for obtaining robust catalysts,14 relevant for
industrial applications. The high stability and productivity of
[MCl(CNN)(PP)] complexes arise from the presence of the
σ metal-carbon bond, which prevents ligand dissociation,
retarding catalyst deactivation. In this context, we were inter-
Figure 2. Chiral HCNN ligands (S)-1a-g.
ested in the design of new chiral pincer ligands of the HCNN
type (Figure 2), with different steric and electronic properties
for the development of highly productive catalysts for asym-
metric organic transformations.
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Article
Organometallics, Vol. 29, No. 16, 2010 3565
Scheme 1a
Table 1. Catalytic TH of Acetophenone (0.1 M) with the System
[RuCl2(PPh3)3]/(R,S)-Josiphos*/HCNN ligand (Ru = 0.005 mol %)
and NaOiPr (2 mol %) in 2-Propanol at 60 °C
HCNN ligand
conv (%)a
time (min)
TOF (h-1 b
)
ee (%)a
(S)-1a
(S)-1b
(S)-1c
(S)-1d
(S)-1e
(S)-1f
(S)-1g
98
97
95
27
4
30
30
30
120
60
60
30
1.6 ꢀ 105
1.3 ꢀ 105
6.5 ꢀ 104
92 R
86 R
85 R
84 R
95
98
6.5 ꢀ 104
1.5 ꢀ 105
85 R
92 R
a Conversion and ee were determined by GC analysis. b Turnover
frequency (moles of ketone converted to alcohol per mole of catalyst per
hour) at 50% conversion.
a Reaction conditions: (i) NaBH4, EtOH; (ii) Novozyme 435, p-chloro-
phenylacetate, 2% Shvo’s catalyst, toluene, 70 °C; (iii) K2CO3, MeOH/
H2O, room temperature; (iv) DPPA, DBU, toluene, 0 °C; (v) Ph3P,
THF, H2O, rt; (vi) Pd(OAc)2, PPh3, K2CO3(aq), 1-propanol, reflux.
the corresponding acetate (R)-4 with excellent yield and ee.26a
In order to improve the yield of the kinetic resolution, which is
intrinsically limited to a maximum 50% in its classical version,
we applied to the lipase-catalyzed transesterification of rac-3
alcohols,22 and the origin of this behavior has been fully
explained from the knowledge of the protein structure.23 In this
context, we have recently developed a strategy for the stereo-
selective synthesis24 of enantiomerically pure 2-(1-aminoethyl)-
6-(phenyl)pyridine, based on a well-established biocatalytic
protocol for the stereoselective synthesis of sec-alcohols.20,25
We report herein the synthesis of new chiral pincer HCNN
ligands obtained through a chemoenzymatic approach.
These compounds were used to prepare in situ Ru and Os
pincer [MCl(CNN)(Josiphos)] catalysts for the TH of aceto-
phenone in basic 2-propanol. On account of the high per-
formance of the HCNN ligand containing the 2-naphthyl
moiety, the corresponding Ru and Os complexes [MCl(CNN)-
(Josiphos)], showing the correctly matched chiral ligands,
were isolated. These catalysts have proven to catalyze the
enantioselective TH of alkyl aryl ketones with low loading
(0.005mol%),highrate(TOF≈105-106 h-1), and up to 99% ee.
€
the conditions developed by Backvall for the dynamic kinetic
resolution of sec-alcohols.28 When the acetylation of (()-3,
with p-chlorophenylacetate as the acyl donor, was coupled to
the in situ racemization of the slow reacting S enantiomer with
the Ru-based redox catalyst [Ru2(CO)4(μ-H)(C4Ph4-COHOC-
C4Ph4)] (Shvo’s catalyst), the reaction reached complete con-
version, enantioconverging to the acetate (R)-4, which was iso-
lated in 98% ee and 70% yield after column chromatography
(Scheme 1). Mild basic hydrolysis of the optically active ester (R)-4
gave the corresponding alcohol (R)-3 (98% ee, 70% from (()-3).
To obtain the amine (S)-6, the homochiral alcohol (R)-3
was first converted into the corresponding azide (S)-5 with
diphenylphosphoroazidate (DPPA) in the presence of DBU.29
To avoid epimerization, the reaction was run at 0 °C, leading to
a clean SN2 process, which converted the alcohol (R)-3, having
98% ee, into the inverted azide (S)-5, without significant loss in
the enantiomeric purity (97% ee). Transformation of the azide
into the corresponding amine (S)-6 (97% ee) was carried out by
treatment with Ph3P in refluxing THF/H2O.30 Finally, Suzuki
coupling with the appropriate substituted phenyl and naphthyl
boronic acids 7b-g gave the HCNN ligands (S)-1b-g in
70-95% yield (Scheme 1 and Figure 2).
Results and Discussion
Synthesis of the Chiral Pincer Ligands. The compound (S)-
1a was prepared from 2-(1-hydroxyethyl)-6-phenylpyridine
via dynamic kinetic resolution, as previously described
(Figure 2).24 According to the strategy outlined in Scheme 1,
the HCNN ligands 1b-g in their S configuration and in excellent
enantiomeric excess were obtained starting from the commercial
2-acetyl-6-bromopyridine (2).
On the basis of the high enantioselectivity displayed in the
acetylation of 2-pyridyl alcohols,26 Candida antarctica lipase
B was used for the resolution of racemic 6-bromo-1-(2-pyridyl)-
ethanol, (()-3, obtained by NaBH4 reduction of 2. Exhibiting
the usual enantiospecificity,27 CAL-B, here used in its immo-
bilized form (Novozyme 435), converted (R)-3 selectively into
Asymmetric TH of Acetophenone with in Situ Generated Ru
and Os Complexes. Previous studies with HCNN and the C1-
symmetric (R,S)-Josiphos ligands showed that an increase of
enantioselectivity can be achieved by employment of the (R,S)-
Josiphos* diphosphine containing 4-OMe-3,5-Me2C6H2 in-
stead of Ph. The in situ generated pincer complex [RuCl-
(CNN)((R,S)-Josiphos*)], obtained by refluxing a 2-propanol
solution of [RuCl2(PPh3)3] with (R,S)-Josiphos* (1 h) and
(S)-1a (1 h), promotes the asymmetric transfer hydrogenation
of acetophenone in basic 2-propanol at 60 °C to give quantita-
tively (R)-1-phenylethanolin30min(eq1) withhighrate(TOF=
1.6 ꢀ 105 h-1) and with 92% ee (Table 1).
(22) Orrenius, C.; Ohrner, N.; Rotticci, D.; Mattson, A.; Hult, K.;
Norin, T. Tetrahedron: Asymmetry 1995, 6, 1217.
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Technol. 2005, 36, 70. (b) Uppenberg, J.; Hansen, M. T.; Patkar, S.; Jones,
T. A. Structure 1994, 2, 293. (c) Uppenberg, J.; Ohrner, N.; Norin, M.; Hult,
K.; Kleywegt, G. J.; Patkar, S.; Waagen, V.; Anthonsen, T.; Jones, T. A.
Biochemistry 1995, 34, 16838.
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Benedetti, F. J. Org. Chem. 2009, 74, 3547.
The use of (S,R)-Josiphos* in combination with (S)-1a led
to (S)-1-phenylethanol, but with lower ee (75%), indicating
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Chem. Biol. 2004, 8, 120. (b) Nakamura, K.; Yamanaka, R.; Matsuda, T.;
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K.; Yonemitsu, O.; Tsukube, H. J. Org. Chem. 1998, 63, 2481.
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3566 Organometallics, Vol. 29, No. 16, 2010
Baratta et al.
Table 2. Catalytic TH of Acetophenone (0.1 M) with the System
[OsCl2(PPh3)3]/(R,S)-Josiphos*/HCNN Ligand (Os = 0.005 mol %)
and NaOiPr (2 mol %) in 2-Propanol at 60 °C
RuCl2-(R,S)-Josiphos* system reacts with (S)-1g in toluene
at reflux temperature, affording different species, which con-
vert after 3 h to substantially only one set of resonances, attri-
butable to a single stereoisomer. The isolation of the orange
complex 8 (75% yield) has successfully been achieved by
treatment of [RuCl2(PPh3)3] with 1.2 equiv of (R,S)-Josiphos*
in toluene at 105 °C for 2 h and reaction with 1 equiv of (S)-1g in
the presence of an excess of NEt3 in 2-propanol at reflux
temperature for 3 h (eq 2).
HCNN ligand
conv (%)a
time (min)
TOF (h-1 b
)
ee (%)a
(S)-1a
(S)-1b
(S)-1c
(S)-1d
(S)-1e
(S)-1f
(S)-1g
96
96
76
39
8
30
30
120
120
60
1.5 ꢀ 105
1.2 ꢀ 105
6.0 ꢀ 104
83 R
85 R
83 R
75 R
70
96
120
30
6.6 ꢀ 104
1.5 ꢀ 105
81 R
87 R
a Conversion and ee were determined by GC analysis. b Turnover
frequency (moles of ketone converted to alcohol per mole of catalyst per
hour) at 50% conversion.
that (R,S)-Josiphos* and (S)-1a are the correctly matched
combination of the chiral ligands, in agreement with the results
obtained with the related cis-[RuCl2(Josiphos)(R-ampy)]5b com-
plexes. In order to investigate the stereoelectronic effects of the
substituents of the pincer ligand in the asymmetric TH, we have
prepared in situ ruthenium catalysts with the ligands (S)-1b-g,
containing one or two electron-donating versus electron-with-
drawing groups on the aryl moiety. With (S)-1b and (S)-1c with
OMe and CF3 in the para position, respectively, we observed
complete reduction of acetophenone (30 min) with TOF = 1.3 ꢀ
105 and 6.5 ꢀ 104 h-1 and 86 and 85% ee, suggesting that the
electron-withdrawing CF3 group leads to a decrease of the
activity of the catalyst. Employment of the 3,5-disubstituted
Me and CF3 ligands (S)-1d and (S)-1e, respectively, gave 27%
and 4% conversion, indicating that the presence of two groups
in the 3 and 5 positions affords less active systems, possibly
inhibiting the orthometalation. Interesting results were obtained
with the ligands (S)-1f and (S)-1g, containing the 1-naphthyl and
2-naphthyl moieties bound to the pyridine ring, resulting in the
quantitative conversion of acetophenone with TOF = 6.5 ꢀ 104
and 1.5 ꢀ 105 h-1 and 85 and 92% ee. These data suggest that in
both cases orthometalation occurs, the 2-substituted ligand
affording the best performance in terms of rate and enantio-
selectivity. The effect of the substituents on the ligands (S)-1a-g
was investigated also with the osmium precursor [OsCl2(PPh3)3],
and we observed a trend similar to that found for ruthenium. The
in situ generated complexes, prepared by refluxing a 2-propanol
solution of [OsCl2(PPh3)3] with (R,S)-Josiphos* (1.5 h) in
combination with the pincer ligands (1 h), namely, the phenyl
(S)-1a, the para-methoxyphenyl (S)-1b, and the 1-naphthyl (S)-
The 31P NMR spectrum of 8 shows two doublets at δ 67.1
and 37.6 with 2J(P,P) = 40.5 Hz. In the 1H NMR spectrum
the singlet at δ 8.70 is for one naphthyl proton, whereas the
13C NMR signal at δ 181.2 is for the orthometalated carbon, in
agreement with the proposed naphthyl coordination mode.
Attempts to obtain suitable crystals for X-ray analysis failed.
The stereochemistry for the pincer complexes [RuCl(CNN)-
(Josiphos)] has been proposed on the basis of the structure of
the related Josiphos ruthenium complexes with ampy-type ligand
[RuCl(CNN)(PP)]6b and cis-[RuCl2(Josiphos)(R-ampy)]5b com-
plexes. The orange-red pincer osmium complexes 9 and 10 (77%
and 71% yield) containing (R,S)-Josiphos and (R,S)-Josiphos*,
respectively, were obtained from [OsCl2(PPh3)3], the suitable
diphosphine in combination with (S)-1g, according to the
procedure for 8. The 31P NMR spectrum of 9 shows two
2
1f ligands, gave good values of rate (6.6 ꢀ 104 to 1.5 ꢀ 105 h-1
)
doublets at δ 9.5 and -3.8 with J(P,P) = 22.4 Hz, whereas
the 1H NMR spectrum reveals two singlets at δ 8.67 and 8.29 for
the two protons of the orthometalated naphthyl ring. Similar
spectroscopy data were obtained for the analogous derivative 10,
containing the bulkier (R,S)-Josiphos* diphosphine.
and enantioselectivity (81-85% ee) in the TH of acetophenone
(Table 2).
As for ruthenium, the 2-naphthyl ketone (S)-1g shows the
best performance with TOF = 1.5 ꢀ 105 h-1 and 87% ee. The
ligand (S)-1c, containing the electron-withdrawing group CF3,
led to lower rate and conversion (76%) in 2 h, whereas the
disubstituted methyl and CF3 ligands (S)-1d and (S)-1e gave
incomplete conversion of acetophenone (39% and 8%, res-
pectively) as observed for ruthenium, suggesting that also in
this case the presence of two substituents in the 3,5 positions
may hinder the orthometalated reaction.
Synthesis and Characterization of [MCl(CNN)(PP)] (M =
Ru, Os) Complexes. On account of the high activity and
enantioselectivity achieved with the in situ prepared metal
catalysts obtained from (R,S)-Josiphos* in combination
with the 2-naphthyl ligand (S)-1g, the corresponding ruthe-
nium and osmium complexes were isolated. A control 31PNMR
experiment for ruthenium reveals that the in situ prepared
Asymmetric TH of Ketones with the Pincer Ru and Os Com-
plexes. The ruthenium compound 8 and the osmium com-
plexes 9 and 10 were found to efficiently catalyze the enantio-
selective reduction of alkyl aryl ketones with high rate and ee,
using a low amount of catalyst. Thus, acetophenone 11 is
rapidly and quantitatively converted into (R)-1-phenyl-
ethanol in 2-propanol at 60 °C using 8, 9, and 10 (0.005% mol)
and in the presence of NaOiPr (2 mol %) (Scheme 2), achiev-
ing ee = 92%, 89%, and 91% and TOF = 1.2 ꢀ 105 to 3.2 ꢀ
105 h-1 (Table 3).
These data show that under these catalytic conditions the
osmium complexes 9 and 10 are faster compared to the ruthe-
nium complex 8, indicating that the formation of the catalytically
active osmium species is a rapid process. In addition, complex 10,

Article
Organometallics, Vol. 29, No. 16, 2010 3567
Scheme 2
Table 4. Catalytic TH of Ketones (0.1 M) with the Ru System 8
(0.005 mol %) and NaOiPr (2 mol %) in 2-Propanol
ketone
conv (%)a
T (°C)
time (min)
TOF (h-1 b
)
ee (%)a
12
13
14
15
16
16
17
18
19
19
20
21
22
23
24
25
26
90
60
60
60
60
60
82
60
60
60
82
60
60
60
60
60
60
60
120
30
30
60
30
5
30
60
30
2
60
60
30
10
30
120
60
7.7 ꢀ 104
4.7 ꢀ 104
1.6 ꢀ 105
2.5 ꢀ 104
1.3 ꢀ 105
8.4 ꢀ 105
2.6 ꢀ 105
9.0 ꢀ 104
2.1 ꢀ 105
1.8 ꢀ 106
1.9 ꢀ 104
3.9 ꢀ 104
6.6 ꢀ 104
1.2 ꢀ 105
99 R
96 R
93 R
96 R
99 R
99 R
96 R
94 R
95 R
91 R
98 R
86 R
92 R
97 R
98c
96
80c
99
99
99
96
97
97
99c,d
93
99d
99c,d
4
10
20
a Conversion and ee were determined by GC analysis. b Turnover
frequency (moles of ketone converted to alcohol per mole of catalyst per
hour) at 50% conversion. c Substrate/8/NaOiPr = 10 000/1/200. d In situ
reaction.
Table 5. Catalytic TH of Ketones (0.1 M) with the Os System 10
(0.005 mol %) and NaOiPr (2 mol %) in 2-Propanol
Table 3. Catalytic TH of Acetophenone (0.1 M) with the
Complexes 8-10 (0.005 mol %) and NaOiPr
(2 mol %) in 2-Propanol at 60 °C
ketone
conv (%)a
T (°C)
time (min)
TOF (h-1 b
)
ee (%)a
12
13
14
15
16
17
18
19
20
21
22
23
93
60
60
60
60
82
60
60
82
60
60
60
60
30
30
10
60
5
20
30
10
30
30
30
10
1.4 ꢀ 105
5.9 ꢀ 104
3.4 ꢀ 105
5.9 ꢀ 104
4.8 ꢀ 105
1.8 ꢀ 105
2.0 ꢀ 105
9.0 ꢀ 105
5.1 ꢀ 104
1.2 ꢀ 105
7.6 ꢀ 104
8.3 ꢀ 104
99 R
96 R
99 R
94 R
99 R
94 R
99 R
97 R
98 R
91 R
90 R
97 R
complex
conv (%)a
time (min)
TOF (h-1 b
)
ee (%)a
98c
97
8
95
96
97
30
30
30
1.2 ꢀ 105
2.5 ꢀ 105
3.2 ꢀ 105
92 R
89 R
91 R
93c
97
9
10
99
97
a Conversion and ee were determined by GC analysis. b Turnover fre-
quency (moles of ketone converted to alcohol per mole of catalyst per
hour) at 50% conversion.
97d
99c,e
99
99e
99c,e
with the bulkier (R,S)-Josiphos* with respect to complex 9,
shows both higher ee and rate. With 8 a number of ketones
have quickly been reduced using 0.005 mol % of catalyst.
Propiophenone 12 has been reduced to (R)-1-phenylpropan-
1-ol with 99% ee and TOF = 7.7 ꢀ 104 h-1, whereas the
1-acetonaphthone 13 and 2-acetonaphthone 14 are con-
verted into the corresponding R-alcohols with 96% and
93% ee and TOF = 4.7 ꢀ 104 and 1.6 ꢀ 105 h-1, respectively
(Table 4).
a Conversion and ee were determined by GC analysis. b Turnover fre-
quency (moles of ketone converted to alcohol per mole of catalyst per hour)
at 50% conversion. c Substrate/10/NaOiPr = 10 000/1/200. d Substrate/10/
NaOiPr = 50 000/1/1000. e In situ reaction.
osmium derivative 10 catalyzes the asymmetric TH of 12 with
the same enantioselectivity (99% ee) observed for 8 and higher
rate (TOF = 1.4 ꢀ 105 h-1) (Table 5).
The naphthyl substrates 13 and 14 were efficiently con-
verted with 10 into the R-alcohols with higher rate (TOF up
to 3.4 ꢀ 105 h-1) with respect to 8 and up to 99% ee. The
monosubstituted acetophenone substrates 15-18 were re-
duced with TOF = 5.9 ꢀ 104 to 4.8 ꢀ 105 h-1 and 94-99% ee.
It is worth noting that 16 is reduced with 10 with 99% ee
at 82 °C, without erosion of enantioselectivity. While the
disubstituted ketone 20 is converted with the osmium 10 with
the same ee but with higher rate with respect to ruthenium 8,
the substrate 19 is reduced with 10 with higher ee (97%) even
at 82 °C and with a lower catalyst loading (0.002 mol %),
compared to 8. These data agree with those found for other
Os catalysts for asymmetric TH9 and hydrogenation10 of
ketones and suggest that osmium is a valid complement to
ruthenium for asymmetric synthesis, especially at high tem-
perature on account of the stronger bonding. Finally, the
pyridyl ketones 21-23 are efficiently reduced with the
osmium complex with much the same performance of ruthe-
nium, with TOF values being up to 1.2 ꢀ 105 h-1 and
The ortho methyl acetophenone 15 and the meta-substituted
Cl, CF3, and OMe derivatives 16, 17, and 18 are promptly
reduced to R-alcohols with both high TOF (2.5 ꢀ 104 to 2.6 ꢀ
105 h-1) and enantioselectivity (94-99% ee). The reduction of
the ketone 16 at 82 °C occurs in 5 min with a remarkably high
rate (TOF = 8.4 ꢀ 105 h-1) and without erosion of ee (99%).
At 60 °C, also the 3,5-disubstituted ketones 19 and 20 have
quickly been converted into R-alcohols with TOF up to 2.1 ꢀ
105 h-1 and 95% and 98% ee. At 82 °C the derivative 19
undergoes a rapid reduction (2 min) with very high TOF (1.8 ꢀ
106 h-1) and a decrease of ee (91%). Heterocyclic ketones, such
as 2-, 3-, and 4-pyridyl methyl ketones 21-23, have been
converted quantitatively at 60 °C into the (R)-pyridyl alcohols
with TOF in the range 3.9 ꢀ 104 to 1.2 ꢀ 105 h-1 and 86%,
92%, and 97% ee, respectively. Attempts to reduce more
sterically demanding ketones such as 2-methyl-1-phenylpro-
pan-1-one (24) or dialkyl ketones, namely, 2-decanone 25 or
5-hexen-2-one 26, resulted in low alcohol conversion (<20%).
Under identical catalytic condition to those used for 8, the

3568 Organometallics, Vol. 29, No. 16, 2010
Baratta et al.
enantioselectivity up to 97%. On the basis of our previous
catalytic studies on the TH with the complexes [RuCl-
(CNN)(diphosphine)]31 it is likely that the new system [MCl-
(CNN)(diphosphine)] (M = Ru, Os) reacts with NaOiPr,
affording the Ru (Os) isopropoxide, which equilibrates with
the corresponding hydride species via β-hydrogen elimina-
tion, involving the NH2 moiety. The M-H complex reacts
with the ketone substrate, leading to the metal alkoxide,
which is protonated by the 2-propanol media, affording the
alcohol product and closing the cycle. On the basis of the
similar results obtained for Ru and Os in terms of ee, rate,
and productivity, it is reasonable that the asymmetric reduc-
tion takes place on the same metal-hydride complex [MH-
(CNN)(Josiphos)] (M = Ru, Os) and that no M-C cleavage
occurs in the basic media.
a Perkin-Elmer model 241 polarimeter at 25 °C, and CD spectra
were recorded on a JASCO J-710 spectropolarimeter at 25 °C. ESI-
MS were run on a Bruker Esquire 4000 instrument. Enzymatic
reactions were monitored by high-resolution GLC (HRGC) ana-
lyses, run on a Carlo Erba GC 8000 instrument, the capillary
column being OV 1701 (25 m ꢀ 0.32 mm), carrier gas He, 40 kPa,
split 1:50. Enantiomeric excesses were measured by chiral high-
resolution GLC (HRCGC), run on a Shimadzu GC-14B instru-
ment, the capillary columns being Chiraldex type G-TA, γ-cyclo-
dextrin (40 m ꢀ 0.25 mm) (carrier gas helium, 180 kPa, split 1:100),
or DiMePe β-cyclodextrin (25 m ꢀ 0.25 mm) (carrier gas He,
110 kPa, split 1:50). GC analyses of the catalytic reactions were
performed with a Varian GP-3380 gas chromatograph equipped
with a MEGADEX-ETTBDMS-β chiral column. TLCs were per-
formed on silica gel, using light petroleum/ethyl acetate mixtures
as the eluent. Flash chromatography was run on silica gel, 230-
400 mesh. Elemental analyses (C, H, N) were carried out with a
Carlo Erba 1106 elemental analyzer.
(()-2-(1-Hydroxyethyl)-6-bromopyridine (3). NaBH4 (1.9 g,
50 mmol) was added portionwise, at room temperature, to an
ethanol solution of 2-acetyl-6-bromopyridine (2) (10.0 g, 50 mmol).
The mixture was stirred for 2 h (TLC); then the solvent was
evaporated under reduced pressure, and the residue was washed
with brine and extracted with CH2Cl2. The organic phase was dried
on anhydrous Na2SO4 and evaporated to give alcohol 3(99%yield),
which was used without further purification. Spectroscopic and
analytical data are in full agreement with the literature.26b
Dynamic Kinetic Resolution of Racemic 3. (R)-(þ)-2-(1-Acetoxy-
ethyl)-6-bromopyridine ((R)-4). Catalyst [Ru2(CO)4(μ-H)(C4Ph4-
COHOCC4Ph4)] (21 mg, 0.04 mmol) and Novozyme 435 (60 mg)
were suspended in toluene, under argon. A degassed solution of
the racemic alcohol 3 (0.400 g, 2 mmol) and 4-chlorophenylacetate
(1.02 g, 6 mmol) in toluene (5 mL) was transferred to this suspen-
sion, and the mixture was stirred under argon, at 70 °C, until
complete conversion (GC). The enzyme was filtered off, and the
reaction mixture was separated by flash chromatography (eluent:
petroleum ether/EtOAc, 9:1), to yield (R)-4, 78% yield at 88% conv,
99% ee (by chiral HRGC), [R]D þ70.1 (c 0.5, CHCl3) [lit.26b [R]D
þ72.0 (c 2.09, CHCl3). Spectroscopic data are in full agreement with
the literature.26b
(R)-(þ)-2-(1-Hydroxyethyl)-6-bromopyridine ((R)-3). The acetate
(R)-4(1.4 mmol) was hydrolyzed with K2CO3 (193mg,1.4mmol) in
methanol/water (1:1) solution at room temperature following the
reaction with TLC. Methanol was evaporated under reduced
pressure, and the aqueous phase was extracted with CH2Cl2 (3 ꢀ
20 mL). The combined organic phases were washed with brine, dried
over Na2SO4, and concentrated under reduced pressure. Purifica-
tion by flash chromatography (petroleum ether/ethyl acetate, 9:1)
gave the pure alcohol (R)-3 quantitatively, 99% ee (by chiral
HRGC), [R]D þ12.0 (c 0.5, CHCl3). [lit.35 [R]D þ10.8 (c 2.75,
CHCl3), 92% ee].
Concluding Remarks
In summary, we have prepared a series of chiral pincer
ligands of formula (S)-2-(1-aminoethyl)-6-(aryl)pyridine
(HCNN) (aryl = substituted phenyl, naphthyl), via dynamic
kinetic resolution of 2-(1-hydroxyethyl)-6-bromopyridine,
followed by Suzuki coupling reaction with a series of aryl-
boronic acids. These ligands were employed in the in situ
formation of highly efficient ruthenium and osmium cata-
lysts [MCl(CNN)(PP)] (M = Ru, Os; PP = Josiphos diphos-
phine) for the rapid asymmetric transfer hydrogenation of
ketones in 2-propanol and in the presence of base. The pincer
ligand containing the 2-naphthyl group in combination with
the (R,S)-Josiphos* gave the best results in terms of rate and
enantioselectivity, for both ruthenium and osmium com-
plexes. Thus, different alkyl aryl ketones have been con-
verted into alcohol using 0.005 mol % of complex with a
TOF of 104-105 h-1 and up to 99% ee. Interestingly, the
osmium complex displays much the same catalytic activity as
ruthenium, leading to a better performance for some sub-
strates. Similar enantioselectivity is also observed for the two
metals, osmium being a valid complement to ruthenium,
particularly at high temperature, where deactivation is re-
tarded. Work is in progress to extend the use of these ligands
for the synthesis of robust and efficient pincer complexes for
catalytic asymmetric reactions.
Experimental Section
The syntheses of the complexes were carried out under an
argon atmosphere using standard Schlenk techniques. The sol-
vents and the ketones were carefully dried by standard methods
and distilled under Ar before use. The Josiphos diphosphines,
Shvo’s catalyst, and the arylboronic acids were purchased from
Sigma-Aldrich, whereas CAL-B (Novozyme 345) was purchased
from Novo Nordisk A/S, 7000 u/g. The ligand (S)-1a24,32 and the
complexes [RuCl2(PPh3)3]33 and [OsCl2(PPh3)3]34 were prepared
according to literature procedures. 1H NMR spectra were recorded
on JEOL EX 400 and Bruker AC 200 spectrometers, and the
chemical shifts, in ppm, are relative to TMS for 1H and 13C{1H}
and 85% H3PO4 for 31P{1H}. Optical rotations were measured on
Transformation of the Alcohol (R)-3 into the Amine (S)-6.
(S)-(-)-2-(1-Azidoethyl)-6-bromopyridine ((S)-5). Diphenylphos-
horoazidate (2.2 mL, 10 mmol) was added dropwise, at 0 °C, under
an argon atmosphere, to a solution of alcohol (R)-3having a 98% ee
(1.4 g, 7.0 mmol) and DBU (1.5 mL, 10 mmol) in dry toluene, and
the reaction mixture was stirred for 2 h at 0 °C, then at room
temperature overnight. The resulting two-phase mixture was ex-
tracted with brine and then with 5% HCl. The organic phase was
dried over Na2SO4, and the solvent was evaporated under reduced
pressure. The crude reaction mixture was purified by flash chroma-
tography (eluent: petroleum ether/ethyl acetate, 8:2), giving pure
(S)-5; 70% yield, 97% ee (HRGC), [R]D -15.5 (c 0.25, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 7.6, 8.0 Hz, 1H), 7.41
(d, J = 8.0 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 4.66 (q, J = 6.8 Hz,
1H, CH3CH), 1.59 (d, J = 6.8 Hz, 3H, CH3CH); 13C NMR (100.1
MHz, CDCl3) δ161.7, 141.7, 139.4, 127.3, 119.3, 61.1, 20.3; ESI-MS
(31) (a) Baratta, W.; Ballico, M.; Esposito, G.; Rigo, P. Chem. Eur.
;
J. 2008, 14, 5588. (b) Baratta, W.; Siega, K.; Rigo, P. Chem. Eur. J. 2007,
;
13, 7479.
(32) Chelucci, G.; Cabras, M. A.; Saba, A. Tetrahedron: Asymmetry
1994, 5, 1973.
(33) Stephenson, T. A.; Wilkinson, G. J. Inorg. Nucl. Chem. 1966, 28,
945.
(34) Elliott, G. P.; McAuley, N. M.; Roper, W. R. Inorg. Synth. 1989,
26, 184.
(35) Bolm, C.; Ewald, M.; Felden, M.; Schlingloff, G. Chem. Ber.
1992, 125, 1169.

Article
Organometallics, Vol. 29, No. 16, 2010 3569
250 (M þ Naþ); HRMS, m/z, Mþ calcd for C7H7BrN4 225.9854,
found 225.9840.
(S)-(þ)-2-(1-Aminoethyl)-6-(1-naphthyl)pyridine ((S)-1f). Yield:
1
73%, 98% ee, [R]D þ1.5 (c 0.65, CHCl3); H NMR (400 MHz,
(S)-(-)-2-(1-Aminoethyl)-6-bromopyridine ((S)-6). H2O (0.16 g,
9 mmol) and PPh3 (1.4 g, 5.4 mmol) were added to a solution of (S)-
5 (1.0 g, 4.5 mmol) in THF (10 mL). The mixture was refluxed until
the starting material had disappeared (TLC) and then concentrated
under reduced pressure. The residue was partitioned between water
and dichloromethane, and the organic phase was dried over anhy-
drous Na2SO4. The solvent was evaporated under reduced pressure
to give the crude amine, which was purified by flash chromato-
graphy (eluent: CHCl3, then EtOAc/MeOH, 8:2); 96% yield, 97%
CDCl3) δ 7.90 (d, J = 8 Hz, 2H), 7.78 (dt, J = 0.8, 8 Hz, 1H),
7.42-7.61 (m, 4H), 7.33 (d, J= 8 Hz, 1H), 4.28 (q, J= 6.8 Hz, 1H,
CHCH3), 2.37 (bs, 2H), 1.52 (d, J = 6.8 Hz, 3H, CHCH3); 13C
NMR (100.1 MHz, CDCl3) δ 165.0, 158.5, 137.0, 134.0, 131.2,
128.8, 128.3, 127.5, 126.3, 125.8, 125.7, 125.3, 123.2, 128.3, 52.5,
24.4; ESI-MS 249 (M þ Hþ), 232 (M - NH2); HRMS (EI) calcd
for C17H16N2 (Mþ•) 248.1313; found 248.1302.
(S)-(þ)-2-(1-Aminoethyl)-6-(2-naphthyl)pyridine ((S)-1g). Yield:
1
95%, 98% ee, [R]D þ1.4 (c 0.6, CHCl3); H NMR (400 MHz,
1
CDCl3) δ 8.50 (s, 1H), 8.21 (dd, J = 1.6, 8.4 Hz, 1H), 7.95 (m, J =
6.8, 8.8 Hz, 2H), 7.87 (m, 1H), 7.75 (m, J = 4.4 Hz, 2H), 7.51 (m,
J = 0.8, 4.0, 4.4 Hz, 2H), 7.25 (d, J = 4.4 Hz, 1H), 4.25 (q, J = 6.4,
ee (HRGC), [R]D -15.5 (c 0.25, CH3OH); H NMR (400 MHz,
CDCl3) δ 7.50 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.28 (d,
J = 7.2 Hz, 1H), 4.13 (q, J = 6.8 Hz, 1H, CHCH3), 1.79 (bs, 2H),
1.42 (d, J =6.8 Hz, 3H CHCH3);13C NMR (100.1 MHz, CDCl3) δ
179.6, 141.7, 139.0, 126.2, 118.8, 52.2, 24.2; ESI-MS 184, 186 (M -
NH2), 201, 203 (M þ Hþ), 223, 225 (M þ Naþ); HRMS, m/z, Mþ
calcd for C7H9BrN2 199.9949, found 199.9961.
1H, CHCH3), 1.94 (bs, 2H), 1.53 (d, J = 6.4 Hz, 3H, CHCH3); 13
C
NMR (100.1 MHz, CDCl3) δ 165.4, 156.3, 137.3, 136.8, 133.6,
133.5, 128.7, 128.3, 127.6, 126.4, 126.2, 124.7, 118.7, 118.5, 52.6,
24.6; ESI-MS 249 (M þ Hþ), 271 (M þ Naþ), 232 (M-NH2);
HRMS (EI) calcd for C17H16N2 (Mþ•) 248.1313; found 248.1299.
Synthesis of Complex 8. [RuCl2(PPh3)3] (100 mg, 0.104 mmol)
and (R,S)-Josiphos* (89 mg, 0.125 mmol) were treated with
toluene (2 mL), the suspension was stirred at 105 °C for 2 h, and
the solvent was evaporated. The ligand (S)-1g (31 mg, 0.125
mmol) and triethylamine (145 μL, 1.04 mmol) were added to the
solid suspended in 2-propanol (2 mL), and the mixture was
refluxed for 3 h. The solution was concentrated to 0.5 mL, and
diethyl ether (2 mL) was added, allowing the precipitation
of NHEt3Cl, which was eliminated by filtration. Diethyl ether
(3 ꢀ 2 mL) and toluene (1 ꢀ 2 mL) were added, and the filtrate
was concentrated. Addition of pentane gave an orange precipi-
tate, which was filtered and dried under reduced pressure. Yield:
85 mg (75%); 1H NMR (200.1 MHz, C6D6, 20 °C) δ 8.70 (s, 1H;
aromatic proton), 8.30-8.20 (m, 2H; aromatic protons), 8.00-
6.44 (m, 10H; aromatic proton), 4.99 (m, 1H; C5H3), 4.76 (m,
1H; PCH), 4.43 (bs, 1H; NCH), 4.34 (t, 3J(H,H) = 15.4 Hz, 1H;
C5H3), 4.28 (bs, 1H; C5H3), 3.95 (s, 5H; C5H5), 3.70 (m, 1H;
NH2), 3.28 (s, 3H; OMe), 3.26 (s, 3H; OMe), 2.22 (s, 6H; Me),
2.07 (s, 6H; Me), 1.70-0.69 (m, 29H; CH3, Cy, NH2); 13C{1H}
NMR (50.3 MHz, C6D6, 20 °C) δ 181.2 (m; CRu), 165.8-117.2
(m; aromatic carbons), 75.0 (s; FeC5H3), 70.9 (s; FeC5H5), 69.8
(s; FeC5H3), 68.0 (d, J(C,P) = 4.2 Hz; FeC5H3), 59.0 (s; OMe),
57.9 (s; CHN), 40.9 (d, J(C,P) = 15.6 Hz; CH of Cy), 38.0
(d, J(C,P) = 17.8 Hz; CH of Cy), 32.2 (s; CH2 of Cy), 30.8
(s; CH2 of Cy), 30.2 (s; CH2 of Cy), 29.2-26.9 (m; CH2 of Cy),
25.5 (s; PCMe), 22.7 (s; NCMe), 16.6 (s; Me), 16.3 (s; Me), 15.6
(d, J(C,P) = 6.9 Hz; PCMe); 31P{1H} NMR (81.0 MHz, C6D6,
20 °C) δ 67.1 (d, 2J(P,P) = 40.5 Hz), 37.6 (d, 2J(P,P) = 40.5 Hz).
Anal. Calcd (%) for C59H71ClFeN2O2P2Ru: C 64.74, H 6.54, N
2.56. Found: C 64.68, H 6.69, N 2.49.
Synthesis of Complex 9. The preparation of 9 was carried out in
a way similar to that described for 8, using [OsCl2(PPh3)3] (100 mg,
0.095 mmol) and (R,S)-Josiphos (80 mg, 0.125 mmol), instead
of [RuCl2(PPh3)3] and (R,S)-Josiphos*, respectively, and (S)-1g
(31 mg, 0.125 mmol). Orange-red complex: yield 78 mg (77%); 1H
NMR (200.1 MHz, C6D6, 20 °C) δ 8.67 (s, 1H; aromatic proton),
8.29 (d, 3J(H,H) = 8.5 Hz, 1H; aromatic proton), 8.24 (s, 1H; aro-
matic proton), 8.00-6.80 (m, 15H; aromatic protons), 6.40 (d,
3J(H,H) = 7.9 Hz, 1H; aromatic proton), 5.06 (m, 1H; PCH), 4.60
(bs, 1H; C5H3), 4.21 (m, 2H; C5H3), 3.94 (m, 6H; C5H5 and NCH),
3.72 (m, 1H; NH2), 2.17-0.90 (m, 29H; CH3, Cy, NH2); 13C{1H}
NMR (50.3 MHz, C6D6, 20 °C) δ 167.9-117.4 (m; aromatic
carbons), 97.7 (d, J(C,P) = 22.7 Hz; ipso-FeC5H3), 74.6 (s;
FeC5H3), 70.8 (s; FeC5H5), 69.7 (s; FeC5H3), 67.6 (m; FeC5H3),
57.9 (d; J(C,P) = 6.2 Hz; CHN), 41.3 (d, J(C,P) = 21.4 Hz; CH of
Cy), 38.4 (d, J(C,P) = 23.1 Hz; CH of Cy), 32.2 (s; CH2 of Cy),
31.2 (s; CH2 of Cy), 30.2 (s; CH2 of Cy), 29.5-27.0 (m; CHP, CH2
of Cy), 22.1 (s; MeCN), 16.5 (d, J(C,P) = 6.9 Hz; PCMe); 31P{1H}
NMR (81.0 MHz, C6D6, 20 °C) δ 9.5 (d, 2J(P,P) = 22.4 Hz), -3.8
(d, 2J(P,P) = 22.4 Hz). Anal. Calcd (%) for C53H59ClFeN2OsP2:
C 59.63, H 5.57, N 2.62. Found: C 60.03, H 5.62, N 2.69.
General Procedure for the Synthesis of Pincer Ligands (S)-
1b-g. Palladium(II) acetate (2.2 mg, 0.01 mmol), triphenylpho-
sphine (8 mg, 0.03 mmol), 2.0 M aqueous K2CO3 (5 mL, mmol),
and distilled water (4 mL) were added to a degassed solution of
(S)-6 (0.520 g, 2.58 mmol) and the appropriate arylboronic acid
(3.26 mmol) in 1-propanol (16.5 mL), and the mixture was
refluxed overnight. After cooling at room temperature and
solvent evaporation, saturated NaHCO3 solution (10.0 mL)
was added and the mixture was extracted with ethyl acetate
(4 ꢀ 15 mL). The organic layer was dried over anhydrous Na2SO4,
and the solvent was evaporated to give the crude amine, which was
purified on a SiO2 column (eluent: petroleum ether/ethyl acetate
from 8:2 to 1:1, then EtOAc/MeOH/NH3, 90:10:0.1).
(S)-(-)-2-(1-Aminoethyl)-6-(4-methoxyphenyl)pyridine ((S)-1b).
1
Yield: 70%, 95% ee, [R]D -3.3 (c 0.35, CHCl3); H NMR (400
MHz, CDCl3) δ7.99 (dm, J= 8.8 Hz, 2H), 7.66 (dd, J =7.6, 8 Hz,
1H), 7.52 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 6.99 (dm,
J = 8.8 Hz, 2H), 4.19 (q, J = 6.8 Hz, 1H, CHCH3), 2.47 (bs, 2H),
3.86 (s, 3H, OCH3), 1.48 (d, J = 6.8 Hz, 3H, CHCH3); 13C NMR
(100.1 MHz, CDCl3) δ 164.7, 160.4, 156.1, 137.2, 132.1, 128.1,
117.8, 117.7, 114.0, 55.3, 52.4, 24.3; ESI-MS 229 (M þ Hþ), 212
(M - NH2); HRMS (EI) calcd for C14H16N2O (Mþ•) 228.1263;
found 228.1271.
(S)-(þ)-2-(1-Aminoethyl)-6-(4-(trifluoromethyl)phenyl)pyridine
((S)-1c). Yield: 75%, 95% ee, [R]D þ3.6 (c 0.6, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 8.16 (dm, J = 8.4 z, 2H), 7.75 (dd, J = 7.6,
8 Hz, 1H), 7.72 (d, J = 8 Hz, 2H), 7.63 (d, J = 7.2, 1H), 7.29 (d,
J = 7.6 Hz, 1H), 4.24 (q, J = 6.4 Hz, 1H, CHCH3), 1.99 (bs, 2H),
1.50 (d, J = 6.4 Hz, 3H, CHCH3); 13C NMR (100.1 MHz,
CDCl3) δ 165.3, 155.0, 142.7, 137.6, 130.9 (q, CF3), 127.3, 125.7,
125.6, 119.6, 119.0, 52.5, 24.5; SI-MS 267 (M þ Hþ), 250 (M -
NH2); HRMS (EI) calcd for C14H13F3N2 (Mþ•) 266.1031; found
266.1045.
(S)-(-)-2-(1-Aminoethyl)-6-((3,5-dimethyl)phenyl)pyridine ((S)-1d).
1
Yield: 70%, 95% ee, [R]D -1.1 (c 0.45, CHCl3); H NMR (400
MHz, CDCl3) δ 7.68 (dd, J = 7.6, 8 Hz, 1H), 7.62 (s, 2H), 7.56 (d,
J = 7.6 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 7.05 (s, 1H), 4.23 (q, J =
6.4 Hz, 1H, CHCH3), 2.56 (bs, 2H), 2.40 (s, 6H, 3,5-CH3-Ar), 1.50
(d, J = 6.4 Hz, 3H, CHCH3); 13C NMR (100.1 MHz, CDCl3) δ
164.6, 156.9, 139.4, 138.2, 137.2, 130.6, 124.8, 118.8, 118.3, 52.4,
24.2, 21.4; ESI-MS 227 (M þ Hþ), 210 (M - NH2); HRMS (EI)
calcd for C15H18N2 (Mþ•) 226.1470; found 226.1463.
(S)-(-)-2-(1-Aminoethyl)-6-((3,5-bis(trifluoromethyl)phenyl)-
pyridine ((S)-1e). Yield: 90%, 95% ee, [R]D -1.2 (c 0.9, CHCl3);
1H NMR (400 MHz, CDCl3) δ 8.49 (s, 2H), 7.91 (s, 1H), 7.80 (dd,
J = 7.6, 8 Hz, 1H), 7.68 (dd, J = 0.8, 7.6 Hz, 1H), 7.36 (d, J =
8 Hz, 1H), 4.27 (q, J = 6.8 Hz, 1H, CHCH3), 1.91 (bs, 2H), 1.51
(d, J = 6.8 Hz, 3H, CHCH3); 13C NMR (100.1 MHz, CDCl3)
δ 165.9, 153.3, 141.4, 138.0, 132.0 (q, CF3), 127.0, 124.8, 122.4,
122.3, 120.3, 118.8, 52.5, 24.6; ESI-MS 335 (M þ Hþ), 318 (M -
NH2); HRMS (EI) calcd for C15H12F6N2 (Mþ•) 334.0905; found
334.0915.

3570 Organometallics, Vol. 29, No. 16, 2010
Baratta et al.
Synthesis of Complex 10. The preparation of 10 was carried
out in a way similar to that described for 8, using [OsCl2(PPh3)3]
(100 mg, 0.095 mmol), instead of [RuCl2(PPh3)3], (R,S)-Josi-
phos* (89 mg, 0.125 mmol), and (S)-1g (31 mg, 0.125 mmol).
Orange-red complex: yield 80 mg (71%); 1H NMR (200.1 MHz,
C6D6, 20 °C) δ 8.61 (s, 1H; aromatic proton), 8.24 (s, 1H;
aromatic proton), 7.98-6.85 (m, 10H; aromatic protons), 6.37
(d, 3J(H,H) = 7.6 Hz, 1H; aromatic proton), 5.06-4.93 (m, 2H;
C5H3 and PCH), 4.30 (m, 2H; C5H3), 3.97 (m, 6H; C5H5 and
NCH), 3.78 (m, 1H; NH2), 3.28 (s, 3H; OMe), 3.26 (s, 3H; OMe),
2.22 (s, 6H; Me), 2.09 (s, 6H; Me), 2.00-0.70 (m, 29H; CH3, Cy,
NH2); 13C{1H} NMR (50.3 MHz, C6D6, 20 °C) 167.8-117.4 (m;
aromatic carbons), 97.6 (d, J(C,P) = 21.5 Hz; ipso-FeC5H3),
74.6 (s; FeC5H3), 70.8 (s; FeC5H5), 67.7-67.6 (m; FeC5H3), 60.3
(s; CHN), 59.1 (s; OMe), 59.0 (s; OMe), 41.3 (d; J(C,P) = 21.5
Hz; CH of Cy), 38.4 (d, J(C,P) = 23.2 Hz; CH of Cy), 32.2
(s; CH2 of Cy), 31.2 (s; CH2 of Cy), 30.1 (s; CH2 of Cy), 29.5
(s; PCHMe), 29.1-27.0 (m; CH2 of Cy), 22.1 (s; MeCN), 16.6
(s; Me), 16.3 (s; Me), 16.1 (d, J(C,P) = 6.7 Hz; PCMe); 31P{1H}
were dissolved in 3 mL of 2-propanol and refluxed for 1 h for Ru
and 1.5 h for Os. The chiral pincer ligand 1a-g (2.08 μmol for Ru
and 1.90 μmol for Os) was added, and the solution was refluxed
for another 1 h. The ketone (2 mmol) was dissolved in 2-propanol
(18 mL), and the solution was heated at 60 °C under argon. By
addition of NaOiPr (0.1 M, 400 μL, 40 μmol) in 2-propanol, the
appropriate volume of the solution of catalyst (0.1 μmol), and
2-propanol (final volume of the solution = 20 mL) the reduction
of the ketone starts immediately, and the yield was determined by
GC (Ru or Os 0.005 mol %, NaOiPr 2 mol %, ketone 0.1 M).
Procedure for the Catalytic Asymmetric TH of Ketones with
Complexes 8-10. The ruthenium or osmium complex (1.0 mg)
was dissolved in 3 mL of 2-propanol. The ketone (2 mmol) was
dissolved in 2-propanol (18 mL), and the solution was heated
at 60 °C under argon. By addition of NaOiPr (0.1 M, 400 μL,
40 μmol) in 2-propanol, the appropriate volume of the solution
of catalyst (0.1 μmol), and 2-propanol (final volume of the solu-
tion = 20 mL) the reduction of the ketone starts immediately,
and the yield was determined by GC (Ru or Os 0.005 mol %,
NaOiPr 2 mol %, ketone 0.1 M).
2
NMR (81.0 MHz, C6D6, 20 °C) δ 9.6 (d, J(P,P) = 22.4 Hz),
-7.3 (d, 2J(P,P) = 22.4 Hz). Anal. Calcd (%) for C59H71ClFe-
N2O2OsP2: C 59.87, H 6.05, N 2.37. Found: C 60.01, H 6.14,
N 2.34.
Acknowledgment. This work was supported by the Minis-
ꢀ
tero dell’Universita e della Ricerca (MIUR) and the Regione
Procedure for the Catalytic Asymmetric TH of Ketones with
the in Situ Prepared Catalyst. [RuCl2(PPh3)3] (1.0 mg, 1.04 μmol)
and (R,S)-Josiphos* (1.1 mg, 1.55 μmol) or [OsCl2(PPh3)3]
(1.0 mg, 0.95 μmol) and (R,S)-Josiphos* (1.0 mg, 0.141 μmol)
Friuli Venezia Giulia. We thank Johnson-Matthey/Alfa Aesar
for a generous loan of ruthenium and osmium and
Mr. P. Polese for carrying out the elemental analyses.