A ruthenium catalyst that does not require an N-H ligand to achieve high enantioselectivity for hydrogenation of an alkyl-aryl ketone

Article abstract of DOI:10.1039/b212544g

Ruthenium catalysts of the form trans-RuCl₂((R)-(S)-Josiphos)L₂ where L₂ = pyridine or 1,2-diamine, have been synthesized that display high catalytic activity towards the hydrogenation of 1′-acetonaphthone.

Full text of DOI:10.1039/b212544g

A ruthenium catalyst that does not require an N–H ligand to achieve
high enantioselectivity for hydrogenation of an alkyl-aryl ketone
Carolyn G. Leong,a Okwado M. Akotsi,a Michael J. Fergusonb and Steven H. Bergens*a
a Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
E-mail: steve.bergens@ualberta.ca; Fax: +1 (780) 492-8231; Tel: +1 (780) 492-9703
b X-Ray Crystallography Laboratory, Department of Chemistry, University of Alberta, Edmonton, Alberta
T6G 2G2, Canada. E-mail: michael.ferguson@ualberta.ca
Received (in Cambridge, UK) 20th December 2002, Accepted 12th February 2003
First published as an Advance Article on the web 25th February 2003
Ruthenium catalysts of the form trans-RuCl2((R)-(S)-Josi-
phos)L2 where L2 = pyridine or 1,2-diamine, have been
synthesized that display high catalytic activity towards the
hydrogenation of 1A-acetonaphthone.
piperidine at rt required only 16 h to form trans-RuCl2(NBD)-
(pip)2 (pip = piperidine) (3) in near quantitative yields without
evidence of NBD displacement by piperidine.10 We un-
expectedly found, however, that unlike the pyridine complex 1,
displacement of the NBD ligand in the piperidine complex 3
was difficult. For example, there was no reaction between (R)-
BINAP and 3, even after heating for 18 h in CH2Cl2. We also
attempted to utilize trans-RuCl2(NBD)(dpen) (4) as a catalyst
precursor. Complex 4 was easily prepared by reaction of 1 and
dpen in CH2Cl2, but the NBD ligand in 4 was also difficult to
displace by diphosphine ligands. The origins of the differences
in the rate of NBD displacement between the pyridine (1),
piperidine (3), and dpen (4) complexes are unknown. The amine
ligands in complexes 3 and 4 are more basic than pyridine, and
they do not act as p-acids. As a result, the NBD ligand may be
more strongly bonded to ruthenium in complexes 3 and 4 than
in complex 1. Alternatively, displacement of NBD may occur
by prior dissociation of an amine ligand, and pyridine
dissociates more readily from ruthenium than piperidine or dpen
in these complexes. Regardless, we found that reaction of 3 with
180 equiv. of pyridine at rt for 2 h displaces piperidine to form
1 in 80% yield after recrystallization. Our improved synthesis of
1† thus involves stirring Ru(NBD)Cl2/n in piperidine for 16 h at
rt to form 3 in 90% yield, which is then followed by reaction of
3 with excess pyridine for another 2 h to give 1 in 80% yield.
We recently reported that trans-RuCl2((S,S)-Skewphos)(py)2
((S,S)-Skewphos = (2S,4S)-(2)-2,4-bis(diphenylphosphino)-
pentane) is a hydrogenation catalyst for acetophenone with
useful rates (500 turnovers, 60 °C, 4 atm. H2, 4 equiv. KOtBu/
Ru, 24 h, unoptimized) but with moderate ee (48 % (R)) despite
the absence of a nitrogen ligand bearing a NH bond.7a Fogg et
al. recently reported that [fac-RuH3(CO)(dcypb)]2 (dcypb =
1,4-bis(dicyclohexylphosphino)butane) is a very active catalyst
for the reduction of benzophenone.11 Although the complexes
trans-RuCl2(diphosphine)(py)2 (2) are active for ketone hydro-
genations under our conditions, the N–H groups in the Noyori
catalysts, Ru(diphosphine)(diamine)(dihalide) (e.g. diamine =
dpen), help direct the stereoselectivity of the enantiodetermin-
ing hydride addition to the prochiral ketone.2–4 It thus seemed
unlikely that the complexes trans-RuCl2(diphosphine)(py)2
would obtain high ee for hydrogenation of an alkyl-aryl ketone.
As we reported previously, 1 reacts with (R)-(S)-Josiphos ((R)-
(2)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohex-
ylphosphine) to generate trans-RuCl2((R)-(S)-Josiphos)(py)2
(5).7a Fig. 1 shows the solid-state structure of 5 as obtained by
X-ray diffraction.‡
We report a Ru(diphosphine)bis(amine)(dichloride) compound
that hydrogenates an alkyl-aryl ketone with high enantiomeric
excess (ee) without the aid of a protic hydrogen bonded to
nitrogen. The most active and generally the most selective
catalyst systems for the enantioselective hydrogenation of
simple ketones are the well-known complexes of the general
form Ru(diphosphine)(diamine)(dihalide) discovered by
Noyori et al.1 A key element of the metal–ligand bifunctional
mechanism for ketone hydrogenation proposed by Noyori is the
presence of a protic hydrogen on nitrogen that hydrogen bonds
to the ketone oxygen, thereby activating the ketone towards
reduction, and directs the face selectivity of hydride addition by
forming a six-membered, pericyclic transition state.1,2 Noyori’s
mechanism is substantiated by mechanistic studies on transfer
hydrogenations catalysed by ruthenium(II) complexes.3 The
mechanism has been investigated by Morris4 and Chen,5 and
Casey has studied related systems.6 We now report a ruthe-
nium(diphosphine) catalyst that hydrogenates 1A-acetona-
phthone with useful rates and high ee in the absence of an N–H
bond in the ligands, and we report an improved, practical
synthesis of the versatile ruthenium(diphosphine) catalyst
synthon trans-RuCl2(NBD)(py)2 (1) (NBD = 2,5-norborna-
diene, and py = pyridine).
We recently reported that 1 is a versatile ruthenium chiral-
diphosphine catalyst synthon, reacting cleanly with a wide
variety of structurally diverse chiral diphosphine ligands to
generate the catalyst precursors trans-RuCl2(diphosphine)(py)2
(2) by displacement of NBD (Scheme 1).7 The James group has
prepared and studied a series of compounds related to 2.8 We
showed that the catalyst precursors 2 react with trace amounts of
aqueous HBF4 (4 eq. HBF4/Ru) in MeOH to generate active
catalysts for low-pressure hydrogenations of b-keto esters, a-
(acylamino)cinnamates, and related substrates.9 The precursors
2 are also active catalysts for hydrogenations of a,b-unsaturated
acids in the presence or absence of Et3N.7a 2 Also reacts with
(1R,2R)- or (1S,2S)-dpen (dpen = diphenylethylenediamine) to
generate the Noyori catalysts trans-RuCl2(P–P*)(N–N*). The
utility of 1 as a general catalyst synthon was limited, however,
by a synthesis involving long reaction times and a tedious
workup.
The original preparation of 1 required stirring a mixture of
Ru(NBD)Cl2/n in pyridine for eight days at room temperature.
Heating the mixture for shorter times resulted in formation of
trans-RuCl2(py)4 as a side product. In accord with the results of
Pannetier, reaction of Ru(NBD)Cl2/n with five equiv. of
We found that 5 catalyzes the hydrogenation of 1A-acetona-
phthone (60 °C, 4 atm. H2, 4 equiv KOtBu/Ru) in 98% ee (S).§
Table 1 summarizes the hydrogenation results we obtained for
this study. Catalyst 5 achieved 2 400 turnovers under our
conditions after 48 h (Table 1, entry 1). 1 000 turnovers were
achieved after the first 24 h, while 1 400 were achieved after the
second 24 h, suggesting there is an activation period for the
reaction.
In
comparison,
trans-RuCl2((R)-(S)-Josi-
phos)((1R,2R)-dpen) (6) (Table 1, entry 2) and trans-
RuCl2((R)-(S)-Josiphos)((1S,2S)-dpen) (7) (Table 1, entry 3)
were at least twice as active as the pyridine catalyst 5. The dpen
Scheme 1
750
CHEM. COMMUN., 2003, 750–751
This journal is © The Royal Society of Chemistry 2003

of 3 from the dark reaction mixture with a yellow precipitate. The
supernatant was filtered, the mustard-yellow solid was washed with
hexanes, and dried in vacuo. Yield: 0.78 g (90%). (Anal. Calc.: C, 47.00; H,
6.96; N, 6.45. Found: C, 46.57; H, 6.76; N, 6.31%). 3 (0.12 g, 0.28 mmol)
was dissolved in 1 mL CH2Cl2 and stirred under N2 at rt for 10 min. Pyridine
(4.0 g, 50 mmol) was added to the yellow solution and stirred for 2 h.
Hexanes (100 mL) were added to precipitate the product (1), then filtered,
washed with hexanes and dried in vacuo. Yield: 0.094 g (80%). The NMR
data of 1 matches that reported in ref. 7a. We found that some batches of
Ru(NBD)Cl2/n produced 1 containing small amounts ( ~ 3%) of trans-
RuCl2(pip)4. If required, this impurity is easily removed by recrystallization
from CH2Cl2–hexanes. The impurity is substantially less soluble than 1 in
this solvent mixture.
‡
Crystal data for 5: C46H54Cl2FeN2P2Ru·0.5C2H4Cl2, M = 974.15,
orthorhombic, a = 22.663(3), b = 13.3050(15), c = 14.5132(16) Å, V =
4376.2(8) Å3, T = 193 K, space group P21212 (no. 18), Z = 4, m (Mo Ka)
= 0.969 mm21, 24 602 reflections measured, 9 008 unique (Rint = 0.0985),
2
R1 (F) = 0.0565 for 6545 observed data [Fo 4 2s(Fo2)], wR2 (F2) =
0.1107 for all unique data, Flack parameter x = 20.02(3).
CCDC 199753. See http://www.rsc.org/suppdata/cc/b2/b212544g/ for
crystallographic data in .cif or other electronic format.
§ The ee’s were determined as described in ref. 7a.
Fig. 1 Crystal structure of trans-RuCl2((R)-(S)-Josiphos)(py)2 (5) as
determined by X-ray diffraction. Hydrogen atoms on C(1) and C(2) are
shown with arbitrarily small thermal parameters in idealized positions. All
other hydrogen atoms have been omitted. Only the ipso carbons of the
phenyl and cyclohexyl groups are shown. Selected bond distances [Å] and
bond angles [°] are as follows. Ru–Cl(1) 2.4310(16), Ru–Cl(2) 2.4170(15),
Ru–P(1) 2.2878(18), Ru–P(2) 2.3309(18), Ru–N(1) 2.233(5), Ru–N(2)
2.224(5), Cl(1)–Ru–Cl(2) 173.51(6), P(1)–Ru–P(2) 88.56(6), N(1)–Ru–
N(2) 83.87(19).
1 (a) R. Noyori and T. Ohkuma, Angew. Chem., Int. Ed., 2001, 40, 40; (b)
T. Ohkuma, M. Koizumi, K. Muñiz, G. Hilt, C. Kabuto and R. Noyori,
J. Am. Chem. Soc., 2002, 124, 6508; (c) R. Noyori, Angew. Chem., Int.
Ed., 2002, 41, 2008.
2 R. Noyori, M. Koizumi, D. Ishii and T. Ohkuma, Pure Appl. Chem.,
2001, 73, 227.
3 (a) K.-J. Haack, S. Hashiguchi, A. Fujii, T. Ikariya and R. Noyori,
Angew. Chem., Int. Ed., 1997, 36, 285; (b) D. A. Alonso, P. Brandt, S.
J. M. Nordin and P. G. Andersson, J. Am. Chem. Soc., 1999, 121, 9580;
(c) M. Yamakawa, H. Ito and R. Noyori, J. Am. Chem. Soc., 2000, 122,
1466; (d) N. Bernard, F. Delbecq, P. Sautet, F. Fache and M. Lemaire,
Organometallics, 2000, 19, 5715; (e) D. G. I. Petra, J. N. H. Reek, J.-W.
Handgraaf, E. J. Meijer, P. Dierkes, P. C. J. Kamer, J. Brussee, H. E.
Schoemaker and P. W. M. van Leeuwen, Chem. Eur. J., 2000, 6, 2818;
(f) R. Noyori, M. Yamakawa and S. Hashguchi, J. Org. Chem., 2001, 66,
7931.
4 (a) K. Abdur-Rashid, A. J. Lough and R. H. Morris, Organometallics,
2000, 19, 2655; (b) K. Abdur-Rashid, A. J. Lough and R. H. Morris,
Organometallics, 2001, 20, 1047; (c) K. Abdur-Rashid, M. Faatz, A. J.
Lough and R. H. Morris, J. Am. Chem. Soc., 2001, 123, 7473; (d) K.
Abdur-Rashid, S. E. Clapham, A. Hadzovic, J. N. Harvey, A. J. Lough
and R. H. Morris, J. Am. Chem. Soc., 2002, 124, 15104.
5 R. Hartmann and P. Chen, Angew. Chem., Int. Ed., 2001, 40, 3581.
6 C. P. Casey, S. W. Singer, D. R. Powell, R. K. Hayashi and M. Kavana,
J. Am. Chem. Soc., 2001, 123, 1090.
Table
1 Hydrogenation of 1A-acetonaphthone catalyzed by trans-
a
RuCl2((R)-(S)-Josiphos)L2
Catalyst
S/C
Time/h
% Conversion
% ee
5
2 500
24
48
24
24
40
96
100
90
98 (S)
98 (S)
98 (S)
99 (S)
6
7
2 500
2 500
a Hydrogenations done in 2-propanol at 60 °C under 4 atm. dihydrogen, in
the presence of 4 equiv. of KOtBu per Ru, where [ketone] = 1 M.
catalysts 6 and 7, containing the opposite enantiomers of dpen,
both produced 1-(1-naphthyl)ethanol in nearly the same ee as 5,
showing that the asymmetric induction of the Josiphos ligand
dominates the enantioselectivity of this catalytic hydrogenation.
Only 5% conversion was obtained after 24 h using 5 as catalyst
in the absence of hydrogen.
7 (a) O. M. Akotsi, K. Metera, R. D. Reid, R. McDonald and S. H.
Bergens, Chirality, 2000, 12, 514; (b) O. M. Akotsi, R. McDonald and
S. H. Bergens, Can. J. Chem., 2002, 80, 1555.
Noyori et al.’s discovery and development of Ru(diphosphi-
ne)(diamine) catalysts incorporating amine ligands with N–H
bonds has revolutionized the field of enantioselective catalytic
hydrogenation of ketones. The catalysts incorporating ligands
with N–H groups are more active and are generally more
selective than trans-RuCl2(diphosphine)(py)2. The results pre-
sented in this paper do show, however, that useful rates and high
enantioselectivities can be obtained in the absence of ligands
with N–H groups.12 As such, they add flexibility to the design
of catalyst precursors for such hydrogenations. Consistent with
this premise is our direct observation that addition of hydrogen
and ruthenium across the ketone double bond is quite rapid in
the absence of N–H groups for certain catalyst–ketone combina-
tions.13 Finally, the new synthesis of 1 facilitates its use as a
general synthon for ruthenium-diphosphine catalysts.
8 (a) S. L. Quieroz, A. A. Batista, G. Oliva, M. T. D. P. Gambardell, R.
H. A. Santos, K. S. MacFarlane, S. J. Rettig and B. R. James, Inorg.
Chim. Acta, 1998, 267, 208; (b) P. W. Cyr, S. J. Rettig, B. O. Patrick and
B. R. James, Chem. Commun., 2001, 17, 1570; (c) P. W. Cyr, B. O.
Patrick and B. R. James, Organometallics, 2002, 21, 4672.
9 For comprehensive reviews on asymmetric hydrogenations see ref 1a
and: (a) R. Noyori, in Asymmetric Catalysis in Organic Synthesis,
Wiley-Interscience, New York, 1994, p. 16; (b) Reductions in Organic
Chemistry, Ed. A. F. Abdel-Magid, Adv. Chem. Ser. No. 641, American
Chemical Society, Washington, DC, 1996; (c) D. J. Ager and S. A.
Laneman, Tetrahedron: Asymmetry, 1997, 8, 3327; (d) Comprehensive
Asymmetric Catalyses, Eds. E. N. Jacobsen, A. Pfaltz and H.
Yamamoto, Springer, Berlin, 1999; (e) T. Ohkuma, M. Kitamura and R.
Noyori, in Catalytic Asymmetric Synthesis, Ed. I. Ojima, Wiley-VCH,
New York, 2000, Chap. 1; (f) J. P. Genêt, Pure Appl. Chem., 2002, 74,
77.
10 C. Potvin, J. M. Manoli, G. Pannetier, R. Chevalier and N. Platzer, J.
Organomet. Chem., 1976, 113, 273.
11 S. D. Drouin, D. Amoroso, G. P. A. Yap and D. E. Fogg,
Organometallics, 2002, 21, 1042.
Notes and references
† Preparation of trans-RuCl2(NBD)(py)2 (1) via trans-RuCl2(NBD)(pip)2
(3): Ru(NBD)Cl2/n (0.51 g, 1.9 mmol) and piperidine (0.81 g, 9.6 mmol)
were suspended in 2.3 mL of acetone and the mixture stirred rapidly under
N2 at rt for 16 h. Hexanes (30 mL) was added to complete the precipitation
12 We point out that numerous derivatives of Josiphos are now available
commercially (e.g. Strem Chemicals, Inc.).
13 C. J. A. Daley and S. H. Bergens, J. Am. Chem. Soc., 2002, 124,
3680.
CHEM. COMMUN., 2003, 750–751
751