Catalytic cycle for the asymmetric hydrogenation of prochiral ketones to chiral alcohols: Direct hydride and proton transfer from chiral catalysts trans-Ru(H)2(diphosphine)(diamine) to ketones and direct addition of dihydrogen to the resulting

Full text of DOI:10.1021/ja015902u

J. Am. Chem. Soc. 2001, 123, 7473-7474
Catalytic Cycle for the Asymmetric Hydrogenation of
7473
Prochiral Ketones to Chiral Alcohols: Direct
Hydride and Proton Transfer from Chiral Catalysts
trans-Ru(H)2(diphosphine)(diamine) to Ketones and
Direct Addition of Dihydrogen to the Resulting
Hydridoamido Complexes
Kamaluddin Abdur-Rashid, Michael Faatz, Alan J. Lough, and
Robert H. Morris*
Department of Chemistry, UniVersity of Toronto
80 Saint George Street, Toronto
Ontario M5S 3H6, Canada
ReceiVed March 28, 2001
ReVised Manuscript ReceiVed June 13, 2001
The enantioselective hydrogenation of prochiral ketones is a
valuable method of producing a range of chiral alcohols. Noyori
and co-workers have developed excellent ruthenium catalyst
systems in terms of efficiency, enantioselectivity, and flexibility.1
Catalyst precursors are of the form Ru(Cl)2(diphosphine)-
(diamine), where the diphosphine is R- or S-binap or a derivative
of this ligand, and a chiral diamine of correct chirality such as
R,R-NH2CHPhCHPhNH2 (dpen) or R-NH2CHiPrC(C6H4OMe)2NH2
(daipen). An active catalyst mixture consists of the dichloride
complex with alkoxide base, dihydrogen, and ketone in 2-pro-
panol. Noyori and Ohkuma postulated that an unidentified
complex with fac hydride and diamine was responsible for the
hydrogen-transfer reaction.1 Our research showed that the mono-
hydride complexes trans-RuH(Cl)(diphosphine)(diamine) are also
precursors to the active hydride catalytic species by reaction with
alkoxide base and dihydrogen in neat ketones so that prochiral
ketones could be hydrogenated to chiral alcohols under mild
conditions (20 °C, 1-3 atm H2).2
Figure 1. Molecular structure of 1.
Scheme 1
With active catalyst preparations we have observed NMR
resonances consistent with dihydrides trans-RuH2(diphosphine)-
(diamine)3 that form from the chloride precursors by heterolytic
H2 splitting at ruthenium promoted by the alkoxide base.4 The
dihydrides are likely to be the hydrogenation catalysts by analogy
to the extremely active ketone hydrogenation catalyst RuH2-
(PPh3)2(cydn) (cydn ) cyclohexyldiamine) that some of us
previously identified.5 However, they are very reactive and tend,
in the absence of H2, to undergo dehydrogenation of the diamine
as will be described elsewhere.
identified for a monohydride areneruthenium catalyst that transfers
hydrogen to ketones, not from dihydrogen but from 2-propanol.8
Reaction of the precursor RuH(Cl)(R-binap)(tmen) (3)9 in THF
with hydride sources including K[HBsecBu3] or KOiPr/H2 produces
the yellow dihydride trans-Ru(H)2(R-binap)(tmen) (1).10 A single-
crystal X-ray diffraction structure determination reveals an
approximately C2-symmetric, octahedral trans-dihydride complex
(Figure 1).
The tmen ligand is in the δ conformation with two sets of axial
groups N-Hax and C-Meax (C(6) and C(3)) and equatorial groups
N-Heq and C-Meeq (C(4) and C(5)). The Ru-H bond lengths
are 1.64(3) and 1.70(3) Å. The RuH‚‚‚HaxN distances of about
Here we use the diamine NH2CMe2CMe2NH2 (tmen)6 that lacks
hydrogens R to the amino groups to solve this problem and
provide evidence for the catalytic cycle shown in Scheme 1. This
cycle demonstrates the importance of the trans-dihydride 1 with
the bifunctional motif cis-Ru-H‚‚‚H-N to provide nascent,
polarized dihydrogen (Hδ-‚‚‚Hδ+) for the catalytic ionic or
heterolytic hydrogenation of polar bonds7 and of an unprecedented
hydridoamido complex 2 for the rapid heterolytic splitting of H2.
It also reveals the origin of the enantioselectivity of the Noyori
catalysts. Cycles related to Scheme 1 have been proposed1,5 and
(7) (a) Chu, H. S.; Lau, C. P.; Wong, K. Y.; Wong, W. T. Organometallics
1998, 17, 2768. (b) Bullock, R. M.; Voges, M. H. J. Am. Chem. Soc. 2000,
122, 12594. (c) Magee, M. P.; Norton, J. R. J. Am. Chem. Soc. 2001, 123,
1778. (d) Nishibayashi, Y.; Takei, I.; Hidai, M. Angew. Chem., Int. Ed. 1999,
38, 3047. (e) Shvo, Y.; Czarkie, D.; Rahamim, Y.; Chodosh, D. F. J. Am.
Chem. Soc. 1986, 108, 7400.
(8) (a) Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew.
Chem., Int. Ed. 1997, 36, 285. (b) Yamakawa, M.; Ito, H.; Noyori, R. J. Am.
Chem. Soc. 2000, 122, 1466. (c) Alonso, D. A.; Brandt, P.; Nordin, S. J. M.;
Andersson, P. G. J. Am. Chem. Soc. 1999, 121, 9580.
(1) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
(2) Abdur-Rashid, K.; Lough, A. J.; Morris, R. H. Organometallics 2001,
20, 1047. The chirality of the product alcohols described in this article is S.
(9) trans-RuH(Cl)(R-binap)(tmen) 3 was prepared in a fashion similar to
that for related RuH(Cl)(diphosphine)(diamine) complexes2 and characterized
by elemental analysis, NMR, IR, and X-ray crystallography.
1
2
(3) trans-RuH2(R, R-dpen)(R-binap). H NMR (C6D6) δ: -4.5 (t, JHP
)
16.6 Hz); 31P{1H}: 89.6 ppm (s). trans-Ru(H1)(H2)(R-daipen)(R-binap). 1H
(10) trans-RuH2(R-binap)(tmen) 1. KHBsecBu3 (0.76 g of a 1.0 M solution
in THF, 0.83 mmol) was added to 3 (0.76 g, 0.87 mmol), and the mixture
was stirred for 30 min under N2. The resulting mixture was filtered, and
hexanes (5 mL) were added, precipitating a bright yellow solid. Yield 0.57 g,
NMR (C6D6) δ: -4.32 (t, JHP ) 17.4 Hz, RuH1, JH < 7 Hz), -4.66 (t,
2
1
2
H
2JHP ) 16.6 Hz, RuH2); 31P{1H}: 90.2 ppm (d), 88.6 (d), JPP ) 47.2 Hz.
2
1
2
trans-RuH2(R-binap)(R-cydn) H NMR(C6D6) δ: -6.1 (t, JHP ) 20.0 Hz);
1
2
min
31P{1H}: 89.4 ppm (s).
70%. H NMR(C6D6) δ: -4.81 (t, JHP 17.2 Hz, 2H, RuH, T1 0.38 s at 20
°C, 500 MHz), 0.21 (s, 6H, Me), 1.06 (s, 6H, Me), 0.95 (d, 2JHH 10.2 Hz, 2H,
NH), 3.13 (d, 2JHH 9.9 Hz, 2H, NH), 6.56-8.60 (m, 32H). 31P{1H}: 89.9 (s).
IR(Nujol): 1774 (νRuH), 3355, 3344, 3292, 3287 cm-1 (νNH). Crystals were
obtained by layering a diethyl ether solution of the complex with hexanes
under 1 atm H2.
(4) Cappellani, E. P.; Maltby, P. A.; Morris, R. H.; Schweitzer, C. T.; Steele,
M. R. Inorg. Chem. 1989, 28, 4437.
(5) Abdur-Rashid, K.; Lough, A. J.; Morris, R. H. Organometallics 2000,
19, 2655.
(6) Chiu, W.-H.; Peng, S.-M.; Che, C.-M. Inorg. Chem. 1996, 35, 3369.
10.1021/ja015902u CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/07/2001

7474 J. Am. Chem. Soc., Vol. 123, No. 30, 2001
Communications to the Editor
2.4 Å are at the outer limit of protonic-hydridic or dihydrogen
bonding.11 A characteristically low wavenumber Ru-H vibration
at 1774 cm-1 due to the high trans influence of hydride also
provides evidence for the uncommon trans stereochemistry in the
solid state.12 This weakening of the Ru-H bond helps explain
the reactivity of this hydridic hydride toward ketones. The
Ru(1)-N(1) and Ru(1)-N(2) bond lengths of 2.202(2) and
2.193(2) Å are shorter than those reported for cis-RuH2(PPh3)2-
(cydn) but are comparable to those of trans-RuHCl(R-binap)-
(dpen)2 and trans-RuHCl(R-binap)(tmen).9 The temperature-
Chart 1
1
independent dihydride triplet at -4.8 ppm in the H NMR and
singlet or triplet at 89.9 ppm in the 31P{1H} or 31P NMR spectra,
respectively, of 1 in solution are unambiguous for a trans structure.
The rigid stereochemistry of the ligands dictates that there are
two axial (Hax) and two equatorial (Heq) N-H hydrogens. Their
chemical shifts are 3.13 and 0.95 ppm, respectively according to
nOe and T1 experiments. The T1 of Hax is about 20% lower that
that of Heq over the temperature range 215-313 K. These data
When one equivalent of acetophenone is added to 1 in C6D6,
the yellow color immediately changes to deep red, and 1H
resonances associated with the complex 2 appear. When this
solution is placed under H2, 1 is regenerated along with phenyl-
ethanol. Complex 1 in acetophenone under H2 catalytically
produces S-phenylethanol in about 14% ee. In contrast the RuH2-
(R,R-dpen)(R-binap) and RuH2(R-daipen)(R-binap) systems are
more active and produce alcohols in the S configuration in very
high ee as observed also starting from dichloride or hydrido-
chloride precursors.1,2 These observations are nicely explained
by the structures in Chart 1.
The prochiral ketone with a big substitutent (Rbig, e.g., Ph) and
small substituent (Rsmall, e.g., Me) is shown approaching the trans-
dihydride so that the oxygen forms a hydrogen bond with an axial
NH and the carbon starts accepting the hydride. To complexes
with the diamine locked into the λ configuration with equatorial
aryl groups and axial hydrogens C-Hax such as R,R-dpen or
R-daipen (Chart 1, A), the ketone will approach with Rbig away
from the binap backbone and axial phenyl. Direct transfer of
polarized dihydrogen to the polar CdO bond provides the
observed S-alcohol. In C2-symmetric dihydrides, the asymmetric
induction will be identical for dihydrogen transfer from the
HRuNHax unit on either face of the complex. It is clear that a
change in substitution of C-Hax in A with C-Meax in B and a
flipping of the five-membered ring into the δ configuration as
observed for the tmen ligand will result in more steric interference
of the H2 transfer process and result in a less active and
enantioselective catalyst. This is observed experimentally for 1.
10
along with T1min(RuH) indicate the presence of a RuH‚‚‚Hax
interaction with an H‚‚‚Hax distance of 2.2 Å. The complex RuH-
(tsdpen)(cymene) has a 2.2 Å RuH‚‚‚HN bond.8a
Complex 1 is yellow under H2 but under Ar, N2 or vacuum
slowly loses H2 in the solid state to produce a dark-red ruthenium
hydridoamido complex, Ru(H)(NHCMe2CMe2NH2)(R-binap) (2).
This process is accelerated by refluxing a THF solution of 1 under
Ar to produce a pure sample of the very air-sensitive complex
2.13 Complex 2 can also be produced by the reaction of 3 with a
strong base such as KOiPr under Ar. The complex is fluxional in
1
solution and produces a broad hydride triplet in the H NMR
spectrum at -19.2 ppm at room temperature. The related amido
complex [Ru(bipy)(NHCMe2CMe2NH2)2](ZnBr4) has been re-
ported.6
Complex 2 in toluene-d8 reacts instantaneously with 1 atm H2
at 293 K and reacts even at 213 K, to produce 1. Complex 1 in
C6D6 reacts with D2 to produce H2 and HD gas and isotopomers
deuterated at the Ru-D and N-Dax and N-Deq positions as
expected if dihydrogen loss and addition is reversible as shown
in Scheme 1. The reversible intramolecular heterolytic splitting
of dihydrogen is rare and may proceed by an η2-dihydrogen14
intermediate. Attempts are underway to try and detect such an
intermediate. The irreversible reaction of the related 16-electron,
silyl-stabilized amido complex Ru(Cl){N(SiMe2CH2PPh2)2}(PPh3)
with dihydrogen gives an amino hydride complex,15 possibly
In conclusion the use of a diamine without R-hydrogens allows
the isolation of a trans-dihydride and the amido complex with
which it is in equilibrium by loss of H2. Such species are proposed
to form in the Noyori mixture used for the enantioselective
hydrogenation of ketones by the reaction of the precursor chloro
complexes with dihydrogen and alkoxide base. A model of
Hδ+‚‚‚Hδ- transfer from such a trans-dihydridediamine complex
to a prochiral ketone is proposed that explains, and allows the
prediction of, the stereochemistry of the chiral alcohols produced
in these reactions.
1
via a dihydrogen complex.14b The H NMR resonance of the
RuH(D) isotopomer appears at -4.75 ppm, showing a downfield
isotope shift of 0.06 ppm that is also observed for other trans-
RuH2(diamine)(diphosphine) species.3 The NHD resonances at
1.45 and 3.55 ppm experience even larger downfield shifts of
about 0.5 ppm from the NH2 chemical shifts and large increases
in T1 values.
(11) (a) Stevens, R. C.; Bau, R.; Milstein, D.; Blum, O.; Koetzle, T. F. J.
Chem. Soc., Dalton Trans. 1990, 1429. (b) Lough, A. J.; Park, S.; Ramachan-
dran, R.; Morris, R. H. J. Am. Chem. Soc. 1994, 116, 8356. (c) Crabtree, R.
H.; Siegbahn, P. E. M.; Eisenstein, O.; Rheingold, A. L. Acc. Chem. Res.
1996, 29, 348.
Acknowledgment. This work was supported by grants to R.H.M. from
NSERC Canada and PRF, as administered by the American Chemical
Society, and by a donation of R-binap from Digital Chemical Co. and a
loan of RuCl3 from Johnson-Matthey. M. Faatz thanks the DAAD for
support.
(12) (a) Rahmouni, N.; Osborn, J. A.; Decian, A.; Fischer, J.; Ezzamarty,
A. Organometallics 1998, 17, 2470. (b) Yandulov, D. V.; Huang, D. J.;
Huffman, J. C.; Caulton, K. G. Inorg. Chem. 2000, 39, 1919. (c) Bautista, M.
T.; Earl, K. A.; Maltby, P. A.; Morris, R. H.; Schweitzer, C. T. Can. J. Chem.
1994, 72, 547. (d) Ayllon, J. A.; Gervaux, C.; Sabo-Etienne, S.; Chaudret, B.
Organometallics 1997, 16, 2000.
(13) RuH(R-binap)(NHCMe2CMe2NH2) 2. 1H NMR(C6D6) δ: -19.23
2
(t, JHP ) 33 Hz, 1H RuH), 0.86-0.94 (m, br, 12H, CH3), 1.22 (s, br, 1H,
Supporting Information Available: Preparation and properties of
the complexes 1, 2, and 3 (PDF). The X-ray structure data for complexes
1 and 3 (CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
NH), 2.80 (s, br, 1H, NH), 3.39 (s, br, 1H, NH), 6.53-8.65 (m, 32H). 31P-
{1H}: 79.2 ppm (br) 78.7 (br). IR (Nujol): 2000, 1953 cm-1 (νRuH), 3332,
3276 cm-1 (νNH).
(14) (a) Jessop, P. G.; Morris, R. H. Coord. Chem. ReV. 1992, 121, 155.
(b) Morris, R. H. Inorg. Chem. 1992, 31, 1471.
(15) Fryzuk, M. D.; Montgomery, C. D.; Rettig, S. J. Organometallics 1991,
10, 467.
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