Osmium(II) CNN pincer complexes as efficient catalysts for both asymmetric transfer and H2 hydrogenation of ketones

Article abstract of DOI:10.1002/anie.200800339

Catalysis at a pinch: Osmium CNN pincer complexes [OsCl(CNN)P₂] (see graphic) are extremely active and productive catalysts for both the transfer and asymmetric hydrogenation of ketones (TOF ≈ 10⁶ h ^-1 and TON ≈10⁵). High enantioselectivity is achieved in the presence of only 0.005-0.002 mol% of the chiral osmium derivatives. [OsX(CNN)(dppb)] species with X = H and OR are involved in these catalytic TH and HY reactions. (Chemical Equation Presented)

Full text of DOI:10.1002/anie.200800339

Communications
DOI: 10.1002/anie.200800339
Catalytic Hydrogenation
Osmium(II) CNN Pincer Complexes as Efficient Catalysts for Both
Asymmetric Transfer and H2 Hydrogenation of Ketones**
Walter Baratta,* Maurizio Ballico, Giorgio Chelucci, Katia Siega, and Pierluigi Rigo
Catalytic asymmetric hydrogenation (HY) and transfer
hydrogenation (TH) of carbonyl compounds are usually
performed with Ru, Rh, and Ir complexes,[1] and much less
attention has been devoted to other transition-metal based-
systems. Although osmium complexes have occasionally been
employed in the HY[2] and TH[3] of carbonyl compounds, we
have recently shown that [OsCl2P2(Pyme)][4a] [P2 = diphos-
phane; Pyme = 1-(pyridin-2-yl)methanamine)] complexes are
extremely active catalysts in the TH of ketones, with reaction
rates comparable to those of their Ru analogues.[4b] Owing to
the stronger bonding of Os compared to Ru, robust and
thermally stable chiral complexes can be obtained using a
suitable set of ligands, which is a crucial breakthrough in
achieving catalysts that display high productivity.[5] Since the
CNN pincer complexes [RuCl(CNN)P2][6] obtained from 1-(6-
arylpyridin-2-yl)methanamines (HCNN) are among the most
active catalysts for the TH of carbonyl compounds, we
decided to investigate the chemistry of osmium complexes
with CNN ligands and report herein the isolation of the first
CNN pincer osmium derivatives [OsCl(CNN)P2]. These
Scheme 1. Synthesis of the CNN pincer osmium(II)derivatives 2–6.
complexes are extremely active and productive catalysts for
both the TH and HY of ketones (turnover frequency (TOF)
of up to 1.3 ” 106 hÀ1). Moreover, asymmetric TH[7] and HY[1]
have been achieved (ee values of up to 98%) with a
remarkably low loading (0.005–0.002 mol%) of the chiral
version of these pincer complexes. Finally, the reversible
Complex 3[8] is easily obtained in high yield upon treat-
ment of [OsCl2(PPh3)3] with Ph2P(CH2)4PPh2 (dppb) and then
with 1a in the presence of NEt3 (Scheme 1). The NCH2 group
gives a 13C NMR signal at d = 54.8 ppm (3JC,P = 2.6 Hz),
whereas the orthometalated carbon appears at d =
161.5 ppm (2JC,P = 9.0 and 3.9 Hz). The chiral pincer complex
4 was prepared in a similar manner to 3 but with dppb in
combination with 1b (85% yield), whereas 5 and 6 (55 and
47% yield, respectively) were obtained from (S,R)-Josiphos
with 1a and 1c, respectively (Scheme 1).[8] 31P NMR spectro-
scopic control experiments revealed the formation of differ-
ent isomers in the reaction mixtures; the predominant
stereoisomer was isolated from the reaction mixtures.
The osmium derivatives 2–6 were found to be highly
active catalysts for the TH of different ketones 7 (0.1m) in
basic 2-propanol (Scheme 2). Thus, fast reduction of aceto-
phenone (7a) into 1-phenylethanol is achieved in 10 min in
refluxing 2-propanol (TOF = 1.8 ” 105 hÀ1 at 50% conversion)
in the presence of 2 (0.005 mol%) and NaOiPr (2 mol%),
while the reaction with 3 goes to completion in 5 min (TOF =
1.3 ” 106 hÀ1; Table 1).[8] Surprisingly, this rate is slightly higher
than that of the analogous compound [RuCl(CNN)(dppb)]
(TOF = 1.1 ” 106 hÀ1),[6c] which is one of the most active TH
catalysts,[9] and, in contrast to the ruthenium-based catalysts, 3
also displays high activity with only one equivalent of NaOiPr
(TOF = 1.0 ” 106 hÀ1).
À
nature of the ketone insertion into the Os H bond suggests
that Os-hydride and Os-alkoxide species are involved in TH
and HY.
Treatment of [OsCl2(PPh3)3] with 1a (1.2 equiv) in 2-
propanol in the presence of the weak base NEt3 at reflux for
2 h affords the CNN pincer complex 2[8] in 94% yield
(Scheme 1). The 31P NMR spectrum of 2 shows two doublets
2
at d = 7.1and À1.6 ppm with a JP, P coupling constant of
15.7 Hz, which is typical for a cis OsP2 arrangement. The
singlet at d = 7.95 ppm in the 1H NMR spectrum is due to the
CH proton close to the orthometalated carbon.
[*] Prof. W. Baratta, Dr. M. Ballico, Dr. K. Siega, Prof. P. Rigo
Dipartimento di Scienze e Tecnologie Chimiche
Università di Udine, Via Cotonificio 108, 33100 Udine (Italy)
Fax: (+39)0432-558-803
E-mail: inorg@uniud.it
Dr. G. Chelucci
Dipartimento di Chimica, Università di Sassari
Via Vienna 2, 07100 Sassari (Italy)
[**] This work was supported by the Ministero dell’Università e della
Ricerca (MiUR)and the Regione Friuli Venezia Giulia.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
than usually needed for the majority of asymmetric TH
catalysts (1–0.1 mol%) due to the easy deactivation of the
latter.
Interestingly, these pincer osmium complexes are also
active for the HY of ketones (0.5m) in methanol with KOtBu
(0.05 mol%) under 5 atm of H2 pressure at 608C (Scheme 2).
Ketones 7a, 7 f, 7g, and 7h are quantitatively converted into
the corresponding alcohols within 1h in the presence of
0.005 mol% of 3 (TOF of up to 3.3 ” 104 hÀ1; Table 2).[8]
Table 2: Catalytic HY of ketones (0.5m)in the presence of 3, 5, or 6
(0.005 mol% Os)and KO tBu (0.05 mol%)in methanol under 5 atm of
H2 pressure at 608C.
Scheme 2. TH and HY of ketones catalyzed by osmium(II)CNN pincer
complexes (0.005–0.001 mol%).
Complex
Ketone
Conv. [%][a]
t [h]
TOF [hÀ1 [b]
]
ee [%][a]
3
7a
7a
7 f
7g
7h
7a
7a
7e
7 f
>99
97
99
99
>99
98
1
5
1
0.5
1
0.5
2
2
2
1
2.5”104
2.4”104
2.6”104
3.3”104
2.9”104
5.2”104
1.2”104
2.2”104
2.0”104
2.8”104
3.0”104
3[c]
3
Table 1: Catalytic TH of ketones (0.1m)in the presence of 2–6
(0.005 mol% Os)and NaO iPr (2 mol%)in 2-propanol.
Complex Ketone T [8C] Conv. [%][a] t [min] TOF [hÀ1 [b]
]
ee [%][a]
3
3
5
6
6
6
2
3
7a
7a
7a
7c
7g
7i
7a
7a
7a
7b
7c
7e
7 f
7 f
82
82
82
82
82
82
60
60
60
60
60
60
60
70
96
98
97
99
95
96
94
95
97
92
96
95
94
94
10
5
60
5
1.8”105
1.3”106
4.3”105
9.0”105
6.0”105
4.0”105
1.2”105
1.7”105
1.7”105
4.0”104
1.3”105
1.9”105
2.0”105
4.0”105
80 S
86 S
93 S
98 S
98 S
98 S
99
3[c]
3
>99
>99
>99
98
3
3
4
5
6
6
6
6
10
10
120
30
30
60
30
30
10
120
6
7d
7d
6[d]
2
74 S
83 S
93 S
91 S
90 S
97 S
97 S
97 S
[a] The conversion and ee values were determined by GC analysis.
[b] Turnover frequency (moles of ketone converted per mol of catalyst per
hour)at 50% conversion. [c] 0.001 mol% Os; [d] 0.002 mol% Os, T=
708C.
It is worth noting that the reduction of 7a is also possible
at a lower loading of 3 (0.001mol%, 5 h), thereby indicating
that pincer osmium complexes also display a high productivity
in HY. Complex 3 is also active in the HYof 7a using only one
equivalent of base (TOF = 2.4 ” 104 and 1.8 ” 104 hÀ1 with
KOtBu and NaOiPr, respectively), although the rate of this
reaction decreases at higher base/3 ratios (> 20). Interest-
ingly, the asymmetric HY of methyl aryl ketones has been
6
6[d]
[a] The conversion and ee values were determined by GC analysis.
[b] Turnover frequency (moles of ketone converted per mol of catalyst per
hour)at 50% conversion. [c] 0.001 mol% Os; [d] 0.002 mol% Os.
Complex 3 is highly active at even lower loadings
(0.001mol%) and affords complete conversion of 7a in 1h
(TOF = 4.3 ” 105 hÀ1), whereas higher substrate/Os ratios lead
to a turnover number (TON) of 1.4 ” 105. It is noteworthy that
[RuCl(CNN)(dppb)][6c] and [IrH3(iPr2PC2H4)2NH][10] are the
only other systems which allow the TH of ketones at such low
catalyst loadings.
Compound 3 is an efficient catalyst for the reduction of
different types of ketones. Thus, 7c, 7g, and 7i are rapidly and
selectively converted into the corresponding alcohols (TOF of
up to 9.0 ” 105 hÀ1). The asymmetric TH of methyl aryl
ketones also proved possible with the chiral derivatives 4–6
(0.005 mol%) at 608C. Thus, 7a is easily reduced to (S)-1-
phenylethanol (TOF of up to 1.7 ” 105 hÀ1) with 74–93% ee,
with the higher value being obtained for 6 (Table 1). The TH
of 7b, 7c, 7e, and 7 f in the presence of 6 leads to the
corresponding (S)-alcohols with 91, 90, 97, and 97% ee,
respectively (TOF of up to 2.0 ” 105 hÀ1). Importantly, ketone
7 f can also be reduced to (S)-1-(3-methoxyphenyl)ethanol
(97% ee and 94% conversion) in 2 h at 708C with a very low
loading of 6 (0.002 mol%; TOF = 4.0 ” 105 hÀ1). Chiral alco-
hols can therefore be prepared using these new pincer
osmium complexes as catalyst with much lower loadings
achieved with the chiral osmium complexes 5 and
6
(0.005 mol%). Thus, hydrogenation of 7a gives (S)-1-phenyl-
ethanol in 30 min and 2 h with 80 and 86% ee, respectively
(Table 2). Similarly, ketones 7e, 7 f, and 7d are reduced to the
corresponding (S)-alcohols with 93, 98 and 98% ee, respec-
tively, within 2 h (TOF of up to 2.8 ” 104 hÀ1). Ketone 7d is
also quantitatively converted into (S)-1-(2-chlorophenyl)-
ethanol (98% ee) in 2 h at 708C in the presence of a lower
amount of 6 (0.002 mol%).
=
Chemoselective C O hydrogenation of the aliphatic
ketone 7i is possible with 6, but with only low enantioselec-
tivity (10% ee), as is the reduction of 7h (27% ee). Since
reduction does not occur in the absence of H2 (conversion
< 1%), the reaction in methanol has to be regarded as a neat
HY. To the best of our knowledge, this is the first example of
an osmium complex that catalyzes the enantioselective HY of
ketones.
As regards the species involved in TH and HY, it is
reasonable to assume that complex 3 forms the corresponding
osmium hydride complex in basic alcohol.[3a,11] Thus, treat-
ment of 3 with one equivalent of NaOiPr in 2-propanol/C6D6
(1:1 v/v) at room temperature affords a red solution contain-
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ing a mixture of the osmium alkoxide 8[8] stabilized by the
Since our investigations show that chloride 3 forms an
equilibrium mixture of hydride and alkoxide complexes in
basic alcohol, it is probable that these species are involved in
both TH[7b,15] and HY. Thus, [OsH(CNN)P2] is likely to be a
key species in both catalytic reactions and leads to the
alkoxide [Os(OR)(CNN)P2] upon reaction with the ketone
substrate. Protonation of [Os(OR)(CNN)P2] with 2-propanol
or methanol gives [Os(OR’)(CNN)P2] (R’ = iPr, Me) and the
alcohol product with much the same ee value in both TH and
HY. However, while in TH the Os-OiPr species equilibrates
to acetone and [OsH(CNN)P2], thereby closing the catalytic
cycle, the osmium hydride is regenerated in HY by heterolytic
H2 splitting promoted by the Os-OMe species. The high
catalytic activity and productivity of this robust osmium
system can be ascribed to the formation of Os-X (X = H, OR)
species with X trans to a phosphorus atom and cis to the CNN
ligand. As the Os-NH2 linkage is involved in hydrogen-bond
interactions with the ketone and alcohol, the flat pyridine
system may favor the access of the substrate.
alcohol and hydride 9 in a 4:1molar ratio (Scheme 3). The
31P NMR spectrum of 8 in 2-propanol shows two doublets at
In conclusion, we have described the isolation of the first
CNN pincer osmium complexes [OsX(CNN)P2] to display
high catalytic activity and productivity in the reduction of
ketones by either TH or HY (TOF and TON up to 106 hÀ1 and
105, respectively). A high enantioselectivity (up to 98% ee) is
possible in both reactions with a remarkably low catalyst
loading (0.005–0.002 mol%). To the best of our knowledge,
this is the first example of an osmium complex that catalyzes
the asymmetric HY of ketones. Evidence for an Os-OR vs.
Os-H equilibrium suggests that both these species are
involved in the catalytic pathways. Mechanistic studies as
well as the preparation of new CNN pincer osmium catalysts
are currently underway.
Scheme 3. Formation of osmium(II)alkoxide and hydride complexes.
d = 3.8 and À0.3 ppm (2JP, P = 9.7 Hz). This species is in rapid
equilibrium[12] with the hydride 9, as inferred from variable-
temperature 31P NMR measurements.[13]
Received: January 22, 2008
Revised: March 7, 2008
Published online: April 28, 2008
Hydride 9 was isolated in 88% yield upon evaporation of
the solvent from a 2-propanol/toluene solution of the 8/9
Keywords: asymmetric catalysis · hydrides · hydrogen transfer ·
hydrogenation · osmium
.
1
mixture by elimination of acetone.[8] The H NMR signal for
the Os-bound hydride appears as a doublet of doublets at d =
À5.32 ppm (2JH,P = 73.0 and 23.7 Hz), which is consistent with
the presence of trans and cis phosphorus atoms. The mixture
8/9 reacts with ketones, and alkoxide 10 was obtained in 74%
yield upon treatment of this mixture with (4-C6H4F)2CO
(Scheme 3).[8] The broad signal at d = 5.08 ppm in the
1H NMR spectrum of this compound can be assigned to one
NH proton and is consistent with an intramolecular NH···O
hydrogen-bonding interaction. The singlets at d = À119.3 and
À119.8 ppm in the 19F NMR spectrum are for the two
nonequivalent C6H4F groups and disappear upon addition
of 4,4’-difluorobenzhydrol, which leads to a signal close to
that of the free alcohol. The 31P NMR spectrum of 10 in the
presence of this alcohol shows two doublets at d = 2.5 and
0.6 ppm (2JP, P = 9.0 Hz) in addition to those of 10, which is
consistent with the formation of the alcohol adduct
10·(ROH). It should be pointed out that the synthesis of 10
is accomplished without isolation of the hydride and by
exploiting the higher redox potential of the diaryl ketone
compared to Me2CO.[14]
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