Asymmetric transfer hydrogenation of ketones catalyzed by enantiopure osmium(II) pybox complexes

Article abstract of DOI:10.1021/ic400680r

The complexes trans-[OsCl₂(L){(S,S)-ⁱPr-pybox}] ((S,S)-ⁱPr-pybox = 2,6-bis[4′-(S)-isopropyloxazolin-2′- yl]pyridine, L = P(OMe)₃ (1a), P(OEt)₃ (2a), P(O ⁱPr)₃ (3a), P(OPh)₃ (4a), and cis-[OsCl ₂(L){(S,S)-ⁱPr-pybox}] (L = PPh₃ (5a), P ⁱPr₃ (6a), and PCy₃ (7a)) have been synthesized from the complex trans-[OsCl₂(η²-C₂H ₄){(S,S)-ⁱPr-pybox}] via substitution of ethylene by phosphites and phosphines, respectively, under toluene reflux conditions. On the other hand, the synthesis of the complexes trans-[OsCl₂(L){(R,R)-Ph- pybox}] (L = P(OMe)₃ (1b) and cis-[OsCl₂(L){(R,R)-Ph- pybox}] (L = PPh₃ (5b), PⁱPr₃ (6b), and PCy₃ (7b)) has been achieved from the complex trans-[OsCl ₂(η²-C₂H₄){(R,R)-Ph-pybox}] ((R,R)-Ph-pybox = 2,6-bis[4′-(R)-phenyloxazolin-2′-yl]pyridine under microwave irradiation. Complexes 1a-6a, 1b, 5b, and 6b have been assayed as catalysts for the asymmetric transfer hydrogenation (ATH) of ketones. Among the catalysts tested, the ⁱPr-pybox complexes trans-[OsCl ₂(L){(S,S)-ⁱPr-pybox}] (L = P(OMe)₃ (1a), P(OEt)₃ (2a), P(OⁱPr)₃ (3a), P(OPh)₃ (4a)) have proven to be the most active catalysts for the reduction of a variety of aromatic ketones as nearly complete conversion and high enantioselectivity (up to 94%) are reached.

Full text of DOI:10.1021/ic400680r

Article
pubs.acs.org/IC
Asymmetric Transfer Hydrogenation of Ketones Catalyzed by
Enantiopure Osmium(II) Pybox Complexes
Esmeralda Vega, E. Lastra, and M. Pilar Gamasa*
́ ́ ́
Departamento de Química Organica e Inorganica, Instituto de Química Organometalica “Enrique Moles” (Unidad Asociada al CSIC),
Universidad de Oviedo, 33006 Oviedo, Spain
S
* Supporting Information
ABSTRACT: The complexes trans-[OsCl2(L){(S,S)-iPr-pybox}] ((S,S)-iPr-pybox = 2,6-
bis[4′-(S)-isopropyloxazolin-2′-yl]pyridine, L = P(OMe)3 (1a), P(OEt)3 (2a), P(OiPr)3
(3a), P(OPh)3 (4a), and cis-[OsCl2(L){(S,S)-iPr-pybox}] (L = PPh3 (5a), PiPr3 (6a), and
PCy3 (7a)) have been synthesized from the complex trans-[OsCl2(η2-C2H4){(S,S)-iPr-
pybox}] via substitution of ethylene by phosphites and phosphines, respectively, under
toluene reflux conditions. On the other hand, the synthesis of the complexes trans-
[OsCl2(L){(R,R)-Ph-pybox}] (L = P(OMe)3 (1b) and cis-[OsCl2(L){(R,R)-Ph-pybox}] (L
= PPh3 (5b), PiPr3 (6b), and PCy3 (7b)) has been achieved from the complex trans-
[OsCl2(η2-C2H4){(R,R)-Ph-pybox}] ((R,R)-Ph-pybox = 2,6-bis[4′-(R)-phenyloxazolin-2′-
yl]pyridine under microwave irradiation. Complexes 1a−6a, 1b, 5b, and 6b have been
assayed as catalysts for the asymmetric transfer hydrogenation (ATH) of ketones. Among
i
the catalysts tested, the Pr-pybox complexes trans-[OsCl2(L){(S,S)-iPr-pybox}] (L =
P(OMe)3 (1a), P(OEt)3 (2a), P(OiPr)3 (3a), P(OPh)3 (4a)) have proven to be the most
active catalysts for the reduction of a variety of aromatic ketones as nearly complete conversion and high enantioselectivity (up to
94%) are reached.
On the other hand, the same authors reported that the CN′N
pincer complexes [OsCl(CN′N)(P2)] (P2 = (S,R)-Josiphos or
(S,R)-Josiphos*), obtained from either 2-aminomethylbenzo-
[h]quinoline5 or 1-(6-arylpyridin-2-yl)methanamines6
(HCN′N), also behave very efficiently for transfer hydro-
genation of acetophenone (80−90% ee) and aryl ketones
(74%−97% ee), respectively, with very low catalyst loading.
Particularly, the complexes [MCl(CN′N){(R,S)-Josiphos*}]
(M = Ru, Os; HCN′N = (S)-2-(1-aminoethyl)-6-(2-naphtyl)-
pyridine) provide the best results, in terms of rate and
enantioselectivity (up to 99% ee), for the conversion of
different alkyl, aryl ketones into the corresponding alcohols.7
All of these results seem to indicate that certain osmium
complexes would be able to catalyze the ATH of ketones with
comparable efficiency to that reported for analogous ruthenium
systems. According to the authors the catalytic activity of these
pincer complexes is ascribed to the Os-NH2 linkage. The
presence of the Os-NH2 linkage favors a hydrogen-bonding
network involving the alkoxyde and the alcohol.5
INTRODUCTION
■
Asymmetric transfer hydrogenation (ATH) of carbonyl
compounds with chiral molecular catalysts is currently
recognized as one of the most powerful and versatile tools to
access enantiopure alcohols. While homogeneous ruthenium,
rhodium, and iridium complexes are usually employed as
catalysts,1 much less attention has been devoted to other
transition-metal-based systems. In particular, osmium catalysts
are usually considered less active than ruthenium analogues
and, thus, have been employed only occasionally.2 An
interesting example has recently been reported by Baratta and
co-workers, who found that osmium complexes, generated in
situ from [OsCl2(PPh3)3], 1-(pyridin-2-yl)methanamine
t
(Pyme), or the racemic ( )-RPyme (R = Me, Bu) and
diphosphine (S,R)-Josiphos or (S,R)-Josiphos* (see Figure 1),
efficiently catalyze the ATH of methyl, aryl ketones (high TOF
values and up to 96% ee).3 These values are close to those
obtained using analogous ruthenium complexes (95%−99%
ee).4
Interestingly, we have recently found that enantiopure
pybox-derived ligands show great efficiency in the case of
ruthenium complexes.8 Thus, the ruthenium complexes trans-
and cis-[RuCl2(L){(R,R)-Ph-pybox}] ((R,R)-Ph-pybox = 2,6-
bis(4′-(R)-phenyloxazolin-2′-yl)pyridine, L = phosphine) cata-
lyze the ATH of aromatic ketones with up to 94% ee and very
high TOF. It should be noted that only a few osmium/pybox
Received: March 19, 2013
Figure 1. Pyme, ( )-RPyme, (S,R)-Josiphos, and (S,R)-Josiphos*.
© XXXX American Chemical Society
A
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complexes have been synthesized as yet9 and no essays have
been reported dealing with their catalytic activity in asymmetric
synthesis.10 Herein, we report the synthesis and catalytic
application of the osmium(II)-pybox complexes bearing
phosphine and phosphite ligands as well as a comparative
study of their catalytic activity in the ATH of ketones. In
particular, the activity of ligands lacking the N−H function
(pybox ligands in this work), relative to that of ligands
containing the N−H function (ancillary ligands in refs 3, 5, 6,
and 7; see above) is studied.
[RuCl2(PPh3){(S,S)-iPr-pybox}], whose structure was con-
firmed by a single-crystal X-ray diffraction (XRD) study.11
Synthesis of Complexes trans-[OsCl2{P(OMe)3}{(R,R)-
Ph-pybox}] (1b) and cis-[OsCl2(L){(R,R)-Ph-pybox}] (L =
PPh3 (5b), PiPr3 (6b), and PCy3 (7b)). The substitution of
ethylene by phosphines and phosphites in the complex trans-
[OsCl2(η2-C2H4){(R,R)-Ph-pybox}] was accomplished in
toluene under microwave irradiation affording trans- (1b, 84%
yield) and cis-complexes (5b−7b, 81%−88% yield), respec-
tively. The process is depcited in Scheme 2 (see the
Experimental Section for further details).
RESULTS AND DISCUSSION
■
Synthesis of Complexes trans-[OsCl2(L){(S,S)-iPr-
pybox}] (L = P(OMe)3 (1a), P(OEt)3 (2a), P(OiPr)3 (3a),
P(OPh)3 (4a)) and cis-[OsCl2(L){(S,S)-iPr-pybox}] (L = PPh3
(5a), PiPr3 (6a), PCy3 (7a)). The reaction of the complex trans-
[OsCl2(η2-C2H4){(S,S)-iPr-pybox}] and phosphites P(OR)3 (R
Scheme 2
i
= Me, Et, Pr, Ph) in refluxing toluene resulted in the
stereoselective formation of the trans complexes 1a−4a, which
were isolated as solids in good yields (80%−88%). On the
other hand, the cis complexes 5a−7a were formed when
i
phosphines PR3 (R = Ph, Pr, Cy), instead of phosphites, were
reacted under similar reaction conditions (84%−92% yield)
(see Scheme 1).
Scheme 1
Catalytic Asymmetric Transfer Hydrogenation of
Ketones. On the basis of comparative purposes, we first
explored the catalytic activity of both (R,R)-Ph-pybox and
(S,S)-iPr-pybox complexes. Regarding the enantioselectivity, the
i
C-4 substituents (Ph and Pr) of the oxazoline rings have been
shown to be crucial.8,12 In a representative run, the osmium
catalyst precursor (0.2 mol %) was added to a solution
containing 5 mmol of acetophenone and 2-propanol (75
mL), and the mixture was stirred for 15 min at 82 °C. NaOH
then was added (ketone/catalyst/NaOH ratio = 500:1:24), and
the resulting mixture was monitored by gas chromatography.
Table 1 summarizes the conversion of acetophenone into 1-
phenylethanol using the catalysts (S,S)-iPr-pybox) (1a, 5a, 6a)
and (R,R)-Ph-pybox (1b, 6b). Interestingly, selective access to
both R- and S-configured secondary alcohols was achieved by
using (S,S)- and (R,R)-pybox ligands, respectively. We also
The complexes thus synthesized were characterized by
infrared (IR) and nuclear magnetic resonance (NMR)
spectroscopy and elemental analysis (see Experimental Section
for details).
i
found that the Pr-pybox osmium derivatives display higher
efficiency than the corresponding Ph-pybox catalysts (Table 1;
see entries: 1 vs 4, 3 vs 5). This result is in sharp contrast with
those reached with analogous ruthenium-pybox complexes for
which the Ph-pybox complexes are the most active catalysts.8
Importantly, the efficiency of the catalyst depends not only on
the chiral ligand but also on the auxiliary nonchiral ligand
(phosphine or phosphite) coordinated to metal. Thus, the
osmium complex containing the phosphite ligand (P(OMe)3)
led to the best results, in terms of reaction rate and
enantiomeric excess (Table 1; see entries 1 vs 2, 3; 4 vs 5).
Unfortunately, the influence of the stereoisomeric arrangement
of the complex (cis-catalysts vs trans-catalysts) could not be
ascertained, because only phosphine-containing cis-isomers and
phosphite-containing trans-isomers are available.
The stereochemistry of complexes 1a−7a was readily
1
determined based on the H and 13C{1H} NMR spectra. In
accordance with the presence of a C2 symmetry axis for
complexes 1a−4a, single resonance signals were observed for
the C-5 (CH2) and C-4 (CHiPr) carbon atoms of both
oxazoline rings. On the other hand, the 1H and 13C{1H} NMR
spectra of 5a−7a reveal the loss of the C2 symmetry axis. Thus,
their 13C{1H} NMR spectra show double resonance signals for
the nonequivalent carbon nuclei of the oxazoline rings (C-5/C-
5′ and C-4/C-4′) and for the nonequivalent carbon nuclei of
the pyridine ring (C-2/C-6 and C-3/C-5). Moreover, these
data are in accordance with those reported for the complex cis-
B
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optimized reaction conditions (5 mmol of acetophenone and
75 mL of 2-propanol; temp = 82 °C; 0.6 mol % of catalyst;
ketone/catalyst/KOtBu molar ratio = 500:3:60). Table 3
Table 1. Transfer Hydrogenation of Acetophenone
Catalyzed by (S,S)-iPr-pybox)- and (R,R)-Ph-pybox)-
a
Containing Osmium Complexes
time, t
conv
b
b
Table 3. Transfer Hydrogenation of Acetophenone
catalyst
(min)
(%)
ee (%)
Catalyzed by (S,S)-iPr-pybox) Phosphite Osmium
1
2
3
4
5
[OsCl2{P(OMe)3}(iPr-
90
96
75 (R)
a
Complexes under Optimized Conditions
pybox)] (1a)
[OsCl2(PPh3)(iPr-pybox)]
360
26
45 (R)
time, t
(min)
conv
(%)
ee (%)
b
(5a)
catalyst
(R)
[OsCl2(PiPr3)(iPr-pybox)]
360
96
62 (R)
1
2
3
4
5
6
7
8
[OsCl2{P(OMe)3}(iPr-pybox)]
60
60
60
60
75
75
75
75
98
99
99
98
98
97
96
98
94
90
91
92
89
86
89
89
(6a)
(1a)
[OsCl2{P(OMe)3}(Ph-
90 (120)
360
73 (91)
92
64 (62) (S)
26 (S)
[OsCl2{P(OEt)3}(iPr-pybox)]
pybox)] (1b)
(2a)
[OsCl2(PiPr3)(Ph-pybox)]
[OsCl2{P(OiPr)3}(iPr-pybox)]
(6b)
(3a)
a
Reactions were carried out at 82 °C using 5 mmol of acetophenone
and 2-propanol (75 mL), 0.2 mol % catalyst, and NaOH (ketone/
catalyst/NaOH = 500:1:24). As determined by gas chromatography
(GC), using a Supelco β-DEX 120 chiral capillary column.
[OsCl2{P(OPh)3}(iPr-pybox)]
(4a)
b
[OsCl2{P(OMe)3}(iPr-pybox)]
c
(1a)
[OsCl2{P(OEt)3}(iPr-pybox)]
c
(2a)
We then focused on the optimization of the reaction
conditions for the reduction of acetophenone catalyzed by Pr-
pybox complexes 1a, 5a, 6a (Table 2). The following
[OsCl2{P(OiPr)3}(iPr-pybox)]
i
c
(3a)
[OsCl2{P(OPh)3}(iPr-pybox)]
c
(4a)
parameters were explored:
a
Reactions were carried out at 82 °C using 5 mmol of acetophenone
(i) Concentration of the solution: The best results were
obtained using 5 mmol of acetophenone and 2-propanol
(75 mL). Higher concentration of the substrate led to
either similar (compare entries 1 vs 2, 8 vs 9) or poorer
(compare entries 10 vs 11) results, in terms of
conversion and asymmetric induction.
and 2-propanol (75 mL), 0.6 mol % catalyst, and KOtBu
b
(acetophenone/catalyst/KOtBu = 500:3:60). Determined by GC
c
with a Supelco β-DEX 120 chiral capillary column. Reactions were
carried using 0.4 mol % catalyst and KOtBu (acetophenone/catalyst/
KOtBu = 500:2:48).
(ii) Acetophenone/catalyst/base ratio: Increasing the ratio of
catalyst and base, with respect to the ketone, from
500:1:24 to 500:2:48 (ketone:catalyst:base) results in
slightly higher ee values (compare entries 1 vs 3).
summarizes the conversion of acetophenone into 1-phenyl-
ethanol using catalysts 1a−4a. The reactions were almost
complete in 60 min providing very high enantiomeric excess
(entries 1−4, 90%−94%). It then becomes apparent that the
electronic nature and the bulkiness of the phosphite do not
exert much influence in the process in terms of conversion and
enantiomeric excess. For comparative purposes, the results
obtained using a lower catalyst loading (0.4 mol %; ketone/
catalyst/KOtBu molar ratio = 500:2:48) are also collected in
Table 3 (see entries 5−8).
(iii) Base of choice: KOtBu was found to be superior to NaOH
(entries: 1 vs 4; 3 vs 5) and Cs2CO3 (entries: 5 vs 7).
Finally, the optimized acetophenone/catalyst/KOtBu ratio was
found to be 500:3:60 (0.6 mol % of catalyst) (compare entries
6 vs 4, 6 vs 5).
We next assessed the influence of the nature of the phosphite
on the process in the case of (S,S)-iPr-pybox complexes under
i
Table 2. Optimization of Reaction Conditions for Transfer Hydrogenation of Acetophenone Catalyzed by Pr-pybox Osmium
a
Complexes
h
catalyst
catalyst amount (mol %)
time, t (min)
conv (%)
ee (%) (R)
1
2
[OsCl2{P(OMe)3}(iPr-pybox)] (1a)
0.2
0.2
0.4
0.2
0.4
0.6
0.4
0.2
0.2
0.2
0.2
0.2
90
120
96
96
75
73
b
1a
c
3
1a
75
97
81
d
4
1a
75
95
86
e
5
1a
75
98
89
f
6
1a
60
98
94
g
7
1a
240
90
71
8
[OsCl2(PPh3)(iPr-pybox)] (5a)
360 (600)
360 (600)
360
26 (36)
23 (32)
96
45 (38)
41 (36)
62
b
9
5a
10
11
12
[OsCl2(PiPr3)(iPr-pybox)] (6a)
b
6a
480
79
52
d
6a
360 (480)
81 (94)
58 (56)
a
Reactions were carried out at 82 °C using 0.2 mol % catalyst, 5 mmol of acetophenone, 2-propanol (75 mL) and NaOH (ketone/catalyst/NaOH =
b
c
500:1:24). 5 mmol of acetophenone, 2-propanol (50 mL). Reactions carried out using 0.4 mol % catalyst (ketone/catalyst/NaOH 500:2:48).
d
e
Reactions carried out using 0.2 mol % catalyst (ketone/catalyst/KOtBu = 500:1:24) Reactions carried out using 0.4 mol % catalyst (ketone/
f
g
catalyst/KOtBu = 500:2:48). Reactions carried out using 0.6 mol % catalyst (ketone/catalyst/KOtBu = 500:3:60. Reactions carried out using 0.4
mol % catalyst (ketone/catalyst/Cs2CO3 = 500:2:48). Determined by GC with a Supelco β-DEX 120 chiral capillary column.
h
C
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Furthermore, the selected catalysts 1a−4a were screened in
the catalytic reduction of various aryl ketones to the
corresponding secondary alcohols under optimized conditions.
Representative examples are given in Table 4 (additional results
using catalysts 1a−4a are provided in the Supporting
Information). All the reactions went to completion in 60 min
(96%−99% conversion). Most secondary alcohols have the R
configuration, except those derived from o-substituted aryl
ketones and 2′-acetonaphtone, wherein the S enantiomer was
formed as the major isomer. Although the ee values are
influenced by the nature and the position of substituents of the
aryl group of the ketone, a general trend in terms of steric and/
or electronic effects cannot be advanced at this stage. Whereas
o-bromoacetophenone and 2′-acetonaphtone were reduced
with moderate ee values (55%−57% ee, entries 8−9 and 22−
23), excellent enantioselectivity was reached for acetophenone
(92%−94% ee, see entries 1−2), propiophenone (92%−94%
ee, entries 3−5), 3-bromoacetophenone (91%−92% ee, entries
13−14), 4-methoxyacetophenone (93% ee, entries 15−16), and
4-methoxypropiophenone (93.5%−94% ee, entries 19−21).
The ee values for the remaining ketones ranged from 74% to
80% (entries 6−7, 10−12, 17−18). On the other hand, no
appreciable variation in ee was observed when different
phosphite auxiliary ligands were used. This is in contrast to
the trend found in the series of ruthenium pybox complexes,
wherein the complexes containing P(OPh)3 are much less
active than those containing P(OMe)3 ([RuCl2{P(OMe)3}-
{(R,R)-Ph-pybox}], 5 min, 97% conversion, 63% ee; [RuCl2{P-
(OPh)3}{(R,R)-Ph-pybox}], 60 min, 25% conversion, 5% ee).8
Table 4. Selected Examples of Transfer Hydrogenation of
Ketones Catalyzed by (S,S)-iPr-pybox Complexes under
a
Optimized Conditions
SUMMARY
■
We have synthesized the osmium complexes trans-[OsCl2(L)-
(R-pybox)] (L = phosphite) and cis-[OsCl2(L)(R-pybox)] (L =
phosphine) and their catalytic activity toward the asymmetric
transfer hydrogenation (ATH) of aryl ketones has been
compared with that of analogous ruthenium complexes already
reported from our group.8 In particular, the complexes trans-
[OsCl2(L){(S,S)-iPr-pybox}] (L = P(OMe)3 (1a), P(OEt)3
(2a), P(OiPr)3 (3a), P(OPh)3 (4a)) are highly efficient in the
reduction of aryl ketones (nearly quantitative conversion and
90%−94% ee have been reached in the reduction of
acetophenone, propiophenone, 3-bromoacetophenone, 4-me-
thoxyacetophenone, and 4-methoxypropiophenone). Interest-
ingly, the efficiency of these catalysts, as well as that of the
ruthenium analogues, depends not only on the chiral ligand but
also on the nonchiral auxiliary ligand. In the case of osmium
complexes, the best results were reached using the ligand
combination (S,S)-iPr-pybox)/ P(OR)3, whereas the complexes
cis-[RuCl2(L){(R,R)-Ph-pybox}] (L = PPh3, PiPr3) were the
best catalysts for ruthenium catalysts (ee values of up 95%).8
Herein, new examples based on osmium catalysts are presented
that catalyze the ATH of ketones with comparable efficiency as
similar ruthenium systems. On the other hand, it should be
emphasized that osmium complexes based on aprotic nitrogen
ligands are shown for the first time to efficiently catalyze the
ATH of ketones (>90% ee).
EXPERIMENTAL SECTION
■
General Comments. The reactions were performed under an
atmosphere of dry nitrogen using vacuum-line and standard Schlenk
techniques or microwave reaction conditions. The reagents were
obtained from commercial suppliers and used without further
purification. Solvents were dried by standard methods and distilled
under nitrogen before use. The complexes trans-[OsCl2(η2-C2H4)-
{(S,S)-iPr-pybox}] and trans-[OsCl2(η2-C2H4){(R,R)-Ph-pybox}]
were prepared by reported methods.9 IR spectra were recorded on a
Perkin−Elmer Model 1720-XFT spectrometer. The C, H, N analyses
were carried out with a LECO Model CHNS-TruSpec microanalyzer
and a Perkin−Elmer Model 240-B microanalyzer (inconsistent
analyses were found for complexes 7a and 7b, because of incomplete
combustion). A CEM Discover S-Class microwave synthesizer was
used. NMR spectra were recorded on Bruker spectrometers (Model
AV400 operating at 400.13 MHz (1H), 100.61 MHz (13C), and 161.95
a
Reactions were carried out at 82 °C during 60 min, using 5 mmol of
ketone and 75 mL of 2-propanol, 0.6 mol % catalyst, and KOtBu
b
(ketone/catalyst/KOtBu = 500:3:60). Determined by GC with a
Supelco β-DEX 120 chiral capillary column. The absolute config-
uration of the major enantiomer is given in parentheses.
D
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(31P) MHz or Model DPX300 operating at 300.13 MHz (1H) and
75.45 MHz (13C)). DEPT experiments were carried out for all of the
compounds. Chemical shifts are reported in parts per million and
referenced to TMS or 85% H3PO4 as standards. Coupling constants
(J) are given in hertz (Hz). The following atom labels have been used
Synthesis of Complexes cis-[OsCl2(L){(S,S)-iPr-pybox}] (L = PPh3
(5a), PiPr3 (6a), and PCy3 (7a)). A solution of complex trans-
[OsCl2(η2-C2H4){(S,S)-iPr-pybox}] (100 mg, 0.169 mmol) and the
corresponding phosphine (0.259 mmol) in toluene (25 mL) was
heated under reflux during 5 h. The solvent was then evaporated under
reduced pressure and the solid residue was purified by chromatog-
raphy over silica gel using dichloromethane/methanol (50:2) as the
eluent.
1
for the H and 13C{1H} spectroscopic data of the pybox ligands.
Complex 5a. Yield: 128 mg, 92%. Garnet solid. Anal. Calcd. for
C35H38Cl2N3O2OsP (824.80 g/mol): C, 50.97; H, 4.64; N, 5.09.
Found: C, 50.88; H, 4.89; N, 5.00. 31P{1H} NMR (161.95 MHz,
1
CD2Cl2, 298 K): δ −29.4 (s). H NMR (300.13 MHz, CD2Cl2, 298
Synthesis of Complexes trans-[OsCl2(L){(S,S)-iPr-pybox}] (L =
P(OMe)3 (1a), P(OEt)3 (2a), P(OiPr)3 (3a), P(OPh)3 (4a). To a solution
of complex trans-[OsCl2(η2-C2H4){(S,S)-iPr-pybox}] (100 mg, 0.173
mmol) in toluene (25 mL), the corresponding phosphite (0.259
mmol) was added and the mixture heated under reflux during 5 h. The
solvent was then evaporated under reduced pressure and the solid
residue was purified by chromatography over silica gel, using
dichloromethane/methanol (50:2) as the eluent.
K): δ 7.68 (m, 3H, PPh3), 7.27−7.23 (m, 12H, PPh3), 6.89 (m, 1H, H4
C5H3N), 6.63 (m, 2H, H3,5 C5H3N), 4.78 (m, 2H, OCH2), 4.70 (m,
1H, OCH2), 4.41 (m, 1H, OCH2), 4.18 (m, 1H, CHiPr), 3.95 (m, 1H,
CHiPr), 2.94 (m, 1H, CHMe2), 2.49 (m, 1H, CHMe2), 1.01 (d, 2JHH
=
2
7.2 Hz, 3H, CHMe2), 0.90 (d, JHH = 8.4 Hz, 6H, CHMe2), 0.01 (d,
JHH = 8.2 Hz, 3H, CHMe2). 13C{1H} NMR (100.61 MHz, CD2Cl2,
298 K): δ = 176.6, 175.7 (2s, OCN), 154.2, 153.8 (2s, C2,6 C5H3N),
133.8−132.3 (6s, PPh3), 128.1−127.9 (6s, PPh3), 125.4, 124.7, 124.1
(3s, C3,4,5 C5H3N), 72.4, 72.0 (2s, OCH2), 71.3, 70.6 (2s, CHiPr), 28.7,
27.9 (2s, CHMe2), 19.9, 19.5, 13.9, 13.3 (4s, CHMe2).
Complex 1a. Yield: 95 mg, 80%. Purple solid. Anal. Calcd. for
C20H32Cl2N3O5OsP (686.59 g/mol): C, 34.99; H, 4.70; N, 6.12.
Found: C, 34.97; H, 4.91; N, 6.15. 31P{1H} NMR (161.95 MHz,
Complex 6a. Yield: 111 mg, 91%. Garnet solid. Anal. Calcd. for
C26H44Cl2N3O2OsP (722.76 g/mol): C, 43.21; H, 6.14; N, 5.81.
Found: C, 43.19; H, 6.10; N, 5.80. 31P{1H} NMR (161.95 MHz,
1
CD2Cl2, 298 K): δ 89.4. H NMR (400.13 MHz, CD2Cl2, 298 K): δ
6.91 (br s, 3H, H3,4,5 C5H3N), 4.95 (m, 4H, OCH2), 4.21 (m, 2H,
CHiPr), 3.85 (br s, 9H, P(OMe)3), 2.74 (br s, 2H, CHMe2), 1.02 (d,
JHH = 8.7 Hz, 6H, CHMe2), 0.82 (d, JHH = 8.7 Hz, 6H, CHMe2).
13C{1H} NMR (100.61 MHz, CD2Cl2, 298 K): δ 171.4 (br s, OCN),
147.3 (s, C2,6 C5H3N), 137.3 (s, C4 C5H3N), 118.7 (s, C3,5 C5H3N),
73.4 (s, CHiPr), 71.6 (s, OCH2), 52.1 (s, P(OMe)3), 28.6 (s, CHMe2),
19.5, 14.9 (2s, CHMe2).
1
CD2Cl2, 298 K): δ 57.4. H NMR (400.13 MHz, CD2Cl2, 298 K): δ
7.11 (m, 2H, H3,5 C5H3N), 6.48 (m, 1H, H4 C5H3N), 4.92 (m, 4H,
OCH2), 4.20 (m, 2H, CHiPr), 2.95 (m, 1H, CHMe2), 2.80 (m, 1H,
CHMe2), 2.12 (m, 3H, P(CHMe2)3), 1.24 (m, 6H, P(CHMe2)3), 1.10
(m, 12H, P(CHMe2)3), 0.99 (d, 2JHH = 7.6 Hz, 6H, CHMe2), 0.89 (d,
2JHH = 6.4 Hz, 6H, CHMe2). 13C{1H} NMR (100.61 MHz, CD2Cl2,
298 K): δ 179.0, 176.9 (2s, OCN), 157.3, 156.9 (2s, C2,6 C5H3N),
124.7, 124.4, 124.1 (3s, C3,4,5 C5H3N), 74.9, 72.8 (2s, CHiPr), 71.4,
71.0 (2s, OCH2), 29.9, 29.0 (2s, CHMe2), 27.5 (br s, P(CHMe2)3),
21.0, 20.3, 19.8, 19.1 (4s CHMe2, P(CHMe2)3), 16.1, 15.5 (2s,
CHMe2).
Complex 2a. Yield: 103 mg, 82%. Purple solid. Anal. Calcd. for
C23H38Cl2N3O5OsP (728.67 g/mol): C, 37.91; H, 5.26; N, 5.77.
Found: C, 37.67; H, 5.50; N, 5.80. 31P{1H} NMR (161.95 MHz,
1
CD2Cl2, 298 K): δ 76.3. H NMR (400.13 MHz, CD2Cl2, 298 K): δ
7.02 (d, JHH = 7.8 Hz, 2H, H3,5 C5H3N), 6.82 (t, JHH = 7.8 Hz, 1H, H4
C5H3N), 4.42 (m, 2H, OCH2), 4.07 (m, 4H, OCH2 and CHiPr), 3.83
(m, 6H, CH2 P(OEt)3), 2.86 (m, 2H, CHMe2), 1.26 (m, 9H, CH3
P(OEt)3), 1.03 (d, JHH = 6.7 Hz, 6H, CHMe2), 0.93 (d, JHH = 6.7 Hz,
6H, CHMe2). 13C{1H} NMR (75.46 MHz, CD2Cl2, 298 K): δ 172.1
(br s, OCN), 146.7 (s, C2,6 C5H3N), 136.3 (s, C4 C5H3N), 119.2 (s,
Complex 7a. Yield: 124 mg, 84%. Garnet solid. 31P{1H} NMR
(161.95 MHz, CD2Cl2, 298 K): δ 57.3. 1H NMR (300.13 MHz,
CD2Cl2, 298 K): δ 7.88 (br s, 1H, H3,5 of C5H3N), 7.64 (br s, 1H, H3,5
of C5H3N), 7.54 (br s, 1H, H4 C5H3N), 6.07 (br s, 1H, OCH2), 5.88
(br s, 1H, OCH2), 5.78 (br s, 1H, OCH2), 5.45 (br s, 1H, OCH2),
4.78 (br s, 1H, CHiPr), 4.51 (br s, 1H, CHiPr), 3.78 (br s, 1H,
CHMe2), 3.08 (br s, 1H, CHMe2), 1.81−1.31 (m, 33H, PCy3), 0.99
(br s, 6H, CHMe2), 0.89 (br s, 6H, CHMe2). 13C{1H} NMR (100.61
MHz, CD2Cl2, 298 K): δ 175.6 (br s, OCN), 158.8, 156.6 (2s, C2,6
C5H3N), 126.6 (s, C4 C5H3N), 124.1, 123.9 (2s, C3,5 of C5H3N), 72.1,
71.4 (2s, OCH2), 68.4, 68.0 (2s, CHiPr), 37.9 (d, 2JCP = 25 Hz, PCH),
35.1 (d, 2JCP = 50 Hz, PCH), 31.3 (d, 2JCP = 45 Hz, PCH), 29.4, 29.2
(2s, CHMe2), 26.8−23.3 (4s, CH2 PCy3), 22.3, 21.2, 17.4, 16.7 (4s,
CHMe2).
C
3,5 C5H3N), 73.4 (s, CHiPr), 71.0 (s, OCH2), 60.5 (s, CH2 P(OEt)3),
28.0 (s, CHMe2), 19.0 (s, CHMe2), 16.4 (s, CH3 P(OEt)3), 14.7 (s,
CHMe2).
Complex 3a. Yield: 118 mg, 81%. Purple solid. Anal. Calcd. for
C26H44Cl2N3O5OsP (770.75 g/mol): C, 40.52; H, 5.75; N, 5.45.
Found: C, 40.53; H, 5.45; N, 5.20. 31P{1H} NMR (161.95 MHz,
1
CD2Cl2, 298 K): δ 84.2. H NMR (400.13 MHz, CD2Cl2, 298 K): δ
7.00 (d, JHH = 7.8 Hz, 2H, H3,5 C5H3N), 6.34 (t, JHH = 7.2 Hz, 1H, H4
C5H3N), 4.43 (m, 2H, OCH2), 4.33 (m, 3H, CH P(OiPr)3), 3.83 (m,
4H, OCH2 and CHiPr), 1.86 (m, 2H, CHMe2), 1.06 (m, 18H, CH3
P(OiPr)3), 0.83 (d, JHH = 7.7 Hz, 6H, CHMe2), 0.42 (d, JHH = 8.4 Hz,
6H, CHMe2). 13C{1H} NMR (75.45 MHz, CD2Cl2, 298 K): δ 171.0
(br s, OCN), 147.3 (s, C2,6 C5H3N), 136.9 (s, C4 C5H3N), 118.3 (s,
Synthesis of Complex trans-[OsCl2{P(OMe)3}{(R,R)-Ph-pybox}]
(1b). Under a nitrogen atmosphere, a pressure-resistant septum-sealed
glass vial was charged with the complex trans-[OsCl2(η2-C2H4){(R,R)-
Ph-pybox}] (100 mg, 0.161 mmol), P(OMe)3 (30 mg, 0.241 mmol), a
magnetic stirring bar, and toluene (2 mL). The vial was then placed
inside the cavity of the microwave synthesizer, and the power was held
at 300 W until the desired temperature (107 °C) was reached.
Microwave power was automatically regulated for the remainder of the
experiment to maintain the temperature (monitored by a built-in
infrared (IR) sensor). After completion of the reaction (3 h), the vial
was cooled, the solvent was evaporated under reduced pressure, and
the solid residue was purified by chromatography over silica gel using
dichloromethane/methanol (50:2) as the eluent. Yield: 84% (0.101 g).
Purple solid. Anal. Calcd. for C26H28Cl2N3O5OsP (754.63 g/mol): C,
41.38; H, 3.74; N, 5.57. Found: C, 41.28; H, 3.61; N, 5.23. 31P{1H}
C
3,5 C5H3N), 73.5 (s, CHiPr), 71.0 (s, OCH2), 61.2 (s, CH P(OiPr)3),
28.1 (s, CHMe2), 19.7 (s, CHMe2), 16.7 (s, CH3 P(OiPr)3), 15.0 (s,
CHMe2).
Complex 4a. Yield: 131 mg, 88%. Purple solid. Anal. Calcd. for
C35H38Cl2N3O5OsP (872.80 g/mol): C, 48.16; H, 4.39; N, 4.81.
Found: C, 48.31; H, 4.41; N, 4.85. 31P{1H} NMR (161.95 MHz,
1
CD2Cl2, 298 K): δ 84.0. H NMR (300.13 MHz, CD2Cl2, 298 K): δ
7.40 (m, 6H, P(OPh)3), 7.24 (m, 9H, P(OPh)3), 7.02 (d, JHH = 7.8
Hz, 2H, H3,5 C5H3N), 6.82 (t, JHH = 7.8 Hz, 1H, H4 C5H3N), 4.92 (m,
4H, OCH2), 3.82 (m, 2H, CHiPr), 2.73 (m, 2H, CHMe2), 0.83 (d, JHH
= 6.6 Hz, 6H, CHMe2), 0.64 (d, JHH = 5.7 Hz, 6H, CHMe2). 13C{1H}
NMR (100.61 MHz, CD2Cl2, 298 K): δ 172.0 (s, OCN), 156.5, 152.7
(2s, C2,6 C5H3N), 130.0−121.7 (5s, C4 C5H3N, P(OPh)3), 120.9 (s,
1
NMR (161.95 MHz, CDCl3, 298 K): δ 88.9. H NMR (400.13 MHz,
CD2Cl2, 298 K): δ 7.46 (m, 4H, Ph), 7.25 (m, 6H, Ph), 6.91 (br s, 3H,
H
3,4,5 C5H3N), 5.05 (m, 4H, OCH2), 4.71 (m, 2H, CHPh), 3.74 (br s,
C
3,5 C5H3N), 73.2 (s, OCH2), 71.3 (s, CHiPr), 32.8 (s, CHMe2), 19.3,
9H, P(OMe)3). 13C{1H} NMR (100.61 MHz, CD2Cl2, 298 K): δ
14.4 (2s, CHMe2).
172.8 (br s, OCN), 147.8 (s, C2,6 C5H3N), 139.6 (s, Cipso Ph), 137.0
E
dx.doi.org/10.1021/ic400680r | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(s, C4 C5H3N), 128.3−127.7 (6s, Ph), 118.5 (s, C3,5 C5H3N), 79.6 (s,
OCH2), 72.7 (s, CHPh), 51.2 (s, P(OMe)3).
AUTHOR INFORMATION
Corresponding Author
*E-mail address: pgb@uniovi.es.
Notes
■
Synthesis of Complexes cis-[OsCl2(L){(R,R)-Ph-pybox}] (L = PPh3
(5b), PiPr3 (6b), and PCy3 (7b). Under nitrogen atmosphere, a
pressure-resistant septum-sealed glass vial was charged with the
complex trans-[OsCl2(η2-C2H4){(R,R)-Ph-pybox}] (100 mg, 0.161
mmol), the phosphine (0.241 mmol), a magnetic stirring bar, and
toluene (2 mL). The vial was then placed inside the cavity of the
microwave synthesizer, and the power was held at 300 W until the
desired temperature (107−112 °C) was reached. Microwave power
was automatically regulated for the remainder of the experiment to
maintain the temperature (monitored by a built-in IR sensor). After
completion of the reaction (2 h), the vial was cooled, the solvent was
evaporated under reduced pressure, and the solid residue was purified
by chromatography over silica gel, using dichloromethane/methanol
(50:2) as the eluent.
Complex 5b. Yield: 126 mg, 88%. Garnet solid. Anal. Calcd. for
C41H34Cl2N3O2OsP (892.84 g/mol): C, 55.15; H, 3.84; N, 4.71.
Found: C, 55.18; H, 3.88; N, 4.78. 31P{1H} NMR (161.95 MHz,
CD2Cl2, 298 K): δ −26.3. 1H NMR (400.13 MHz, CD2Cl2, 298 K): δ
7.55 (m, 2H), 7.34 (m, 8H), 7.27−7.14 (m, 12H), 7.02 (m, 3H, Ph
and PPh3), 6.96 (m, 2H, H3,5 C5H3N), 6.70 (m, 1H, H4 C5H3N), 5.32
(m, 1H, OCH2), 5.14 (m, 1H, OCH2), 4.74 (m, 1H, OCH2), 4.61−
4.57 (m, 3H, CHPh, OCH2). 13C{1H} NMR (100.61 MHz, CD2Cl2,
298 K): δ 179.2, 177.7 (2s, OCN), 154.8, 154.7 (2s, C2,6 C5H3N),
138.9, 137.6 (2s, Cipso Ph), 133.7−127.6 (10s, Ph, PPh3), 125.5, 125.4,
125.2 (3s, C3,4,5 C5H3N), 81.2, 78.3 (2s, OCH2), 70.8, 70.7 (2s,
CHPh).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the MICINN of Spain (Nos.
CTQ-2010-17005 and CTQ2011-26481 and CONSOLIDER
INGENIO CSD2007-00006). E.V. thanks MICINN for the
award of a Ph.D. fellowship.
REFERENCES
■
(1) (a) For selected representative reviews, see: Noyori, R.;
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Complex 6b. Yield: 106 mg, 84%. Garnet solid. Anal. Calcd. for
C32H40Cl2N3O2OsP (790.79 g/mol): C, 48.60; H, 5.10; N, 5.31.
Found: C, 48.68; H, 4.53; N, 5.32. 31P{1H} NMR (161.95 MHz,
Organometallics 2012, 31, 3333−3345. (c) Highly enantioselective
reduction of ketones (conv. 37−87%; ee 91−98%) was obtained with
the system that was generated in situ from [OsCl2(cymene)]2 and β-
amino alcohols: Faller, J. W.; Lavoie, A. R. Org. Lett. 2001, 3, 3703−
3706.
1
CD2Cl2, 298 K): δ 59.9. H NMR (300.13 MHz, CD2Cl2, 298 K): δ
7.69 (m, 2H, Ph), 7.60 (m, 2H, Ph), 7.35−7.15 (m, 8H, H3,5 C5H3N,
Ph), 6.47 (m, 1H, H4 C5H3N), 5.37 (m, 2H, OCH2), 5.23 (m, 2H,
OCH2), 4.73 (m, 2H, CHPh), 2.15 (m, 3H, P(CHMe2)3), 1.32−1.12
(m, 18H, P(CHMe2)3). 13C{1H} NMR (100.61 MHz, CD2Cl2, 298
K): δ 170.4 (br s, OCN), 159.9, 158.7 (2s, C2,6 C5H3N), 147.3 (s, Cipso
Ph), 135.4 (s, C4 C5H3N), 132.1 (s, Cipso Ph), 128.4−127.5 (6s, Ph),
118.8, 117.9 (2s, C3,5 C5H3N), 79.7, 78.5 (2s, CHPh), 72.4, 72.0 (2s,
OCH2), 28.1 (s, P(CHMe2)3), 21.7, 20.1 (2s, P(CHMe2)3).
(3) Baratta, W.; Ballico, M.; del Zotto, A.; Siega, K.; Magnolia, S.;
Rigo, P. Chem.Eur. J. 2008, 14, 2557−2563.
(4) Baratta, W.; Chelucci, G.; Herdtweck, E.; Magnolia, S.; Siega, K.;
Rigo, P. Angew. Chem., Int. Ed. 2007, 46, 7651−7654.
(5) Baratta, W.; Ballico, M.; Baldino, S.; Chelucci, G.; Herdtweck, E.;
Siega, K.; Magnolia, S.; Rigo, P. Chem.Eur. J. 2008, 14, 9148−9160
and references therein.
Complex 7b. Yield: 128 mg, 81%. Garnet solid. 31P{1H} NMR
(161.95 MHz, CD2Cl2, 298 K): δ 59.1. 1H NMR (400.13 MHz,
CD2Cl2, 298 K): δ 7.57 (m, 2H, Ph), 7.46 (m, 2H, Ph), 7.37−7.20 (m,
8H, H3,5 C5H3N, Ph), 6.73 (m, 1H, H4 C5H3N), 5.09 (m, 4H, OCH2),
4.67−4.39 (m, 2H, CHPh), 1.80−1.62 (2m, 33H, PCy3). 13C{1H}
NMR (100.61 MHz, CD2Cl2, 298 K): δ 170.4 (br s, OCN), 159.2,
158.7 (2s, C2,6 C5H3N), 135.8 (s, Cipso Ph), 134.3 (s, C4 C5H3N),
132.0 (s, Cipso Ph), 128.7−127.3 (4s, Ph), 122.9 (s, C3,5 C5H3N), 79.8
(s, OCH2), 70.9 (s, CHPh), 36.3 (d, 2JCP = 48 Hz, PCH), 35.3 (d, 2JCP
(6) Baratta, W.; Ballico, M.; Chelucci, G.; Siega, K.; Rigo, P. Angew.
Chem., Int. Ed. 2008, 47, 4362−4365.
(7) Baratta, W.; Benedetti, F.; del Zotto, A.; Fanfoni, L.; Felluga, F.;
Magnolia, S.; Putignano, E.; Rigo, P. Organometallics 2010, 29, 3563−
3570.
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425−432.
(9) Nishiyama, H.; Aoki, K.; Itoh, H.; Iwamura, T.; Sakata, N.;
Kurihara, O.; Motoyama, Y. Chem. Lett. 1996, 1071−1072.
(10) Complex trans-[RuCl2(η2-C2H4)){(S,S)-(CH3OCO)-pybox}] is
active in H/D exchange of benzene in the presence of Zn: Young, K.
J.; H. Lokare, K. S.; Leung, C. H.; Cheng, M.-J.; Nielsen, R. J.; Petasis,
N. A.; Goddard, W. A., III; Periana, R. A. J. Mol. Catal. A: Chem. 2011,
339, 17−23.
2
= 54 Hz, PCH), 32.8 (d, JCP = 43 Hz, PCH), 27.9−26.2 (5s, CH2
PCy3).
General Procedure for Hydrogen Transfer Reactions. The ketone
(5 mmol) and the catalyst (0.01−0.03 mmol) were placed in a three-
bottomed Schlenk flask under a dry nitrogen atmosphere and 2-
propanol (75 mL) was added. The solution was heated at 82 °C, and
the corresponding amount of base (0.08 M solution in 2-propanol)
was added after 15 min. The reaction was monitored by gas
chromatography using Agilent Model HP-6890 equipment. The
corresponding alcohol and acetone were the only products detected
in all cases. The conversions and ee values were determined by gas
chromatography (GC) with a Supelco β-DEX 120 chiral capillary
column.
(11) Cadierno, V.; Gamasa, M. P.; Gimeno, J.; Iglesias, L.; García-
Granda, S. Inorg. Chem. 1999, 38, 2874−2879.
(12) Paredes, P.; Díez, J.; Gamasa, M. P. Organometallics 2008, 27,
2597−2607.
ASSOCIATED CONTENT
■
S
* Supporting Information
Additional catalytic results using catalysts 1a−4a. This material
is available free of charge via the Internet at http://pubs.acs.org.
F
dx.doi.org/10.1021/ic400680r | Inorg. Chem. XXXX, XXX, XXX−XXX