RuHCl(diphosphine)(diamine): Catalyst precursors for the stereoselective hydrogenation of ketones and imines

Article abstract of DOI:10.1021/om001054k

New chiral complexes RuHCl(diphosphine)(diamine) are readily prepared from RuHCl(PPH₃)₃. The diamine complexes, in the presence of alkoxide base, catalyze the hydrogenation of a wide variety of ketones and imines at 3 atm H₂, 20°C, including prochiral imines to chiral amines in good to excellent enantiomeric excess.

Full text of DOI:10.1021/om001054k

Organometallics 2001, 20, 1047-1049
1047
Ru HCl(d ip h osp h in e)(d ia m in e): Ca ta lyst P r ecu r sor s for
th e Ster eoselective Hyd r ogen a tion of Keton es a n d
Im in es1
Kamaluddin Abdur-Rashid,* Alan J . Lough, and Robert H. Morris*
Department of Chemistry, University of Toronto, 80 St. George Street,
Toronto, Ontario M5S 3H6, Canada
Received December 11, 2000
Sch em e 1
Summary: New chiral complexes RuHCl(diphosphine)-
(diamine) are readily prepared from RuHCl(PPh3)3. The
diamine complexes, in the presence of alkoxide base,
catalyze the hydrogenation of a wide variety of ketones
and imines at 3 atm H2, 20 °C, including prochiral
imines to chiral amines in good to excellent enantiomeric
excess.
We have been investigating the ruthenium hydride
species generated in mixtures used by Noyori and co-
workers that generate very active catalytic species for
ketone hydrogenation and asymmetric hydrogenation.
These are obtained by mixing dichlororuthenium species
containing diamines or chiral diamines, phosphines,2 or
chiral diphosphines3-6 with a base in 2-propanol under
H2. Recently, we reported that the active catalytic
species generated in basic media from the RuCl2(PPh3)2-
(cydn)/base system2 (cydn ) R,R-cyclohexyldiamine) is
likely to be the dihydride RuH2(PPh3)2(cydn) that is
readily prepared from the catalytically inactive mono-
hydride complex RuHCl(PPh3)2(cydn).7 The latter is
readily prepared according to Scheme 1. We also re-
ported that the in-situ generation of RuH2(PPh3)2(cydn)
in neat substrates or their solutions in benzene in the
presence of H2 gas could effectively reduce deactivated
and sterically congested ketones and some imines to the
alcohols and amines, respectively. Here, we report a
simple method for the preparation of a series of mono-
hydride complexes, RuHCl(diphosphine)(PPh3), and Ru-
HCl(diphosphine)(diamine) using similar procedures
(Scheme 1); diphosphine ) R-binap and R,R-1,2-bis-
(diphenylphosphinamino)cyclohexane (dppach),8,9 di-
amine ) cydn and R,R-diphenylethylenediamine (dpen).
The patents of Noyori and co-workers mention that a
range of hydride-containing ruthenium species can be
used to generate catalytically active systems for ketone
hydrogenation.10 The present work demonstrates that
certain ruthenium complexes generated by the reaction
of these monohydride complexes with a base in the
presence of hydrogen gas are effective catalysts for the
asymmetric hydrogenation not only of ketones but also,
for the first time, of imines at room temperature under
H2 gas (1-3 atm), especially when the dppach ligand is
employed. The asymmetric hydrogenation of prochiral
imines is an emerging technology for the production of
chiral amines,11-18 and the present work provides a
facile route to a potentially very wide variety of ruthe-
nium-based catalysts for this purpose.
Refluxing a mixture of RuHCl(PPh3)3 and a diphos-
phine in tetrahydrofuran under an argon atmosphere
produces the substituted complex RuHCl(diphosphine)-
(PPh3) (Scheme 1).19 When an equimolar mixture of a
diamine and RuHCl(diphosphine)(PPh3) is stirred in
tetrahydrofuran (THF) at room temperature under a
(1) This was presented at the Canadian Society for Chemistry
Conference, Calgary, May 2000.
(2) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J . Am. Chem. Soc.
1995, 117, 10417-10418.
(3) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.;
Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.; Noyori, R. J . Am.
Chem. Soc. 1998, 120, 13529-13530.
(4) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.;
Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem.,
Int. Ed. 1998, 37, 1703-1707.
(10) Emura, M.; Toyoda, T.; Seido, N.; Noyori, R.; Ikariya, T.;
Ohkuma, T. U.S. Patent 5,856,590, J an 855, 1999, assigned to
Takasago Int. Corp.
(5) Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.;
Terada, M.; Noyori, R. J . Am. Chem. Soc. 1998, 120, 1086-1087.
(6) Ohkuma, T.; Ishii, D.; Takeno, H.; Noyori, R. J . Am. Chem. Soc.
2000, 122, 6510-6511.
(11) Blaser, H.-U.; Studer, M. Chirality 1999, 11, 459-464.
(12) J ames, B. R. Catal. Today 1997, 37, 209-221.
(13) Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A. J . Am. Chem.
Soc. 1999, 121, 6421-6429.
(7) Abdur-Rashid, K.; Lough, A. J .; Morris, R. H. Organometallics
2000, 19, 2655-2657.
(14) Mao, J . M.; Baker, D. C. Org. Lett. 1999, 1, 841-843.
(15) Tani, K.; Onouchi, J .-I.; Yamagata, T.; Kataoka, Y. Chem. Lett.
1995, 955-956.
(8) Onuma, K.-I.; Ito, T.; Nakamura, A. Bull. Chem. Soc. J pn. 1980,
53, 2012-2015.
(9) The Supporting Information describes an improvement on the
synthesis8 of R,R-dppach. The solvent for all NMR experiments here
and in ref 7 is C6D6. Yield: 4.13 g, 98%. 1H NMR: 0.82-2.76 ppm (m,
12 H), 7.03-7.45 ppm (m, 20 H). 31P{1H} NMR: 34.4 ppm (s).
(16) Tararov, V. I.; Kadyrov, R.; Riermeier, T. H.; Holz, J .; Borner,
A. Tetrahedron Asymmetry 1999, 10, 4009-4015.
(17) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R.
J . Am. Chem. Soc. 1996, 118, 4916-4917.
(18) Zhang, X. M. Enantiomer 1999, 4, 541-555.
10.1021/om001054k CCC: $20.00 © 2001 American Chemical Society
Publication on Web 02/21/2001

1048 Organometallics, Vol. 20, No. 6, 2001
Communications
F igu r e 2. Structure and atomic numbering of 4.
1
The H, 31P, and 31P{1H} spectra of RuHCl(R-binap)-
F igu r e 1. Structure and atomic numbering of 2.
(cydn), 3, RuHCl(R-binap)(dpen), 4, RuHCl(R,R-
dppach)(cydn), 5, and RuHCl(R,R-dppach)(dpen), 6, are
consistent with an octahedral coordination geometry for
these complexes, with the hydride ligand trans to the
chloride. This is confirmed by the single-crystal X-ray
structure of 4 (Figure 2). The complex crystallizes as
RuHCl(R-binap)(dpen)‚THF. The Ru-H bond length is
1.55(3) Å. The Ru(1)-N(1) and Ru(1)-N(2) bond lengths
are 2.164(2) and 2.198(2) Å, respectively, which are
comparable to those previously reported for RuCl2-
(binap)(dpen).4
nitrogen atmosphere, the substituted amino complex
RuHCl(diphosphine)(diamine) is formed quantitatively.20
In addition, RuHCl(R-binap)(cydn) can also be gener-
ated by refluxing RuHCl(PPh3)2(cydn) with 1 equiv of
R-binap in toluene under argon. The doublet of triplets
and the ABX patterns in the 1H and 31P{1H} NMR
spectra, respectively, of RuHCl(R-binap)(PPh3), 1, and
RuHCl(R,R-dppach)(PPh3), 2, are consistent with dis-
torted square pyramidal geometries for these complexes.
The X-ray structure of 2 is shown in Figure 1. The
phosphine ligands are meridional, with the triphen-
ylphosphine ligand, P(3), being approximately trans to
one of the phosphorus atom, P(1), of the dppach ligand,
while the other, P(2), occupies the apical position of the
square pyramid. The hydride ligand is trans to the
chloride (H(1Ru)-Ru-Cl(1) ) 158.7(12)°), which in turn
is weakly hydrogen bonded (H‚‚‚Cl ) 2.74(3) Å) to
hydrogen, H(1N), of the dppach ligand. Various at-
tempts at obtaining X-ray quality crystals of 1 were
unsuccessful. However, its structure is expected to be
similar to that of 2 on the basis of their similar infrared
The solid state infrared spectra of 3, 4, 5, and 6 show
ν(RuH) bands at 1968, 1974, 1989, and 1969 cm-1
,
respectively. There are also ν(NH) bands between 3340
and 3140 cm-1
.
In the presence of catalytic amounts of potassium
isopropoxide under H2 gas (3 atm) at 20 °C, complexes
3 and 4 efficiently catalyze the hydrogenation of various
ketones (neat or dissolved in benzene) to the alcohols
(Table 1).21 In the absence of a base, no hydrogenation
was observed, indicating that an in-situ-generated spe-
cies that has lost chloride, possibly a dihydride similar
to RuH2(PPh3)2(cydn)7 or a related compound, is likely
to be the true catalyst. The high activity of the catalyst
generated from 3 is illustrated by the hydrogenation of
the various dialkyl ketones listed in Table 1, including
deactivated and sterically congested pinacolone (entry
4). The enantiometric excess (ee) for the dialkyl alcohol
products range from 40 to 50%. The phenethyl alcohol
and 4-phenyl-3-buten-2-ol, derived from acetophenone
and benzalacetone (Table 1; entries 5 and 6), were
obtained in ee of 88 and 64%, respectively, by use of 3,
numbers similar to those reported by Noyori et al., using
the RuCl2(R-binap)(diamine)/KOtBu system in 2-pro-
panol.4 The reduction of benzalacetone using 3 and 4
1
and H and 31P{1H} NMR spectra.
(19) 1. Identified in solution by K. S. Macfarlane and B. R. J ames
(personal communication). Yield: 1.48 g, 89%. 1H NMR: -21.69 ppm
(dt, 1H, RuH, 2J HP ) 36.1, 22.5 Hz), 6.22-8.38 ppm (m, 47H). 31P(1H}:
2
2
34.3 ppm (dd, J PP ) 307, 20.0 Hz), 43.8 ppm (dd, J PP ) 307, 38.0
Hz), 90.0 ppm (dd, 2J PP ) 38.0, 20.0 Hz). IR (Nujol): 2067 cm-1 (RuH).
2. Yield: 1.34 g, 93%. 1H NMR: -16.40 ppm (dt, 1H, RuH, 2J HP ) 34.2,
22.1 Hz), 0.61-4.26 ppm (m, 12H), 6.80-7.92 ppm (m, 35H). 31P(1H}:
2
2
35.5 ppm (dd, J PP ) 253, 33.0 Hz), 99.4 ppm (dd, J PP ) 253, 47.2
Hz), 122.5 ppm (dd, 2J PP ) 33.0, 47.2 Hz). IR (Nujol): 2025 cm-1 (RuH),
3369 cm-1 (NH). Anal. Calcd: C, 65.34; H, 5.48; N, 3.17. Found: C,
65.69; H, 5.71; N, 3.19.
(20) 3. Yield: 236 mg, 93%. 1H NMR: -17.1 ppm (vt, 1H, RuH, 2J HP
) 25.4 Hz), 0.26-3.85 ppm (m, 14H), 6.29-8.63 ppm (m, 32H). 31P-
{1H}: 73.0 ppm (d), 65.1 ppm (d), 2J PP ) 45 Hz. IR (Nujol): 1968 cm-1
(RuH), 3339, 3276, 3238, 3139 cm-1 (NH). 4. Yield: 261 mg, 92%. 1H
2
NMR: -16.9 ppm (vt, 1H, RuH, J HP ) 25.2 Hz), 0.08-4.24 ppm (m,
6H), 6.34-8.72 ppm (m, 42H). 31P{1H}: 73.0 ppm (d), 65.1 ppm (d),
2J PP ) 45 Hz. IR (Nujol): 1974 cm-1 (RuH), 3339, 3281, 3239, 3139
cm-1 (NH). Anal. Calcd: C, 71.63; H, 5.08; N, 2.88. Found: C, 71.24; H,
5.51; N, 2.73. 5. Yield: 236 mg, 95%. 1H NMR: -17.6 ppm (vt, 1H,
(21) Ca ta lysis P r oced u r e. A typical catalytic run using 5 for the
hydrogenation of phenyl(1-phenylethylidene)amine is described here.
Phenyl(1-phenyl-ethylidene)amine (2.0 g) was added under a flow of
hydrogen gas to a Schlenk flask containing 5 (5 mg) and KOiPr (5 mg)
in benzene (1.0 mL). The flask was cooled to liquid nitrogen temper-
ature, filled with H2 gas, closed, and allowed to gradually warm to
2
RuH, J HP ) 28.8 Hz), 0.11-4.98 ppm (m, 26H), 6.98-8.09 ppm (m,
20H). 31P{1H}: 104.3 ppm (d), 106.0 ppm (d), J PP ) 59.4 Hz. IR
2
(Nujol): 1989 cm-1 (RuH), 3381, 3362, 3348, 3341, 3330, 3282, 3251,
3215, and 3137 cm-1 (NH). Anal. Calcd: C, 58.89; H, 6.45; N, 7.63.
Found: C, 59.03; H, 6.53; N, 7.35. 6. Yield: 274 mg, 97%. 1H NMR:
room temperature. The mixture was vigorously stirred for 24 h. A 1
H
NMR spectrum of the reaction mixture indicated complete conversion
of the imine to the amine. Hexanes (10 mL) were added to the mixture,
which was then eluted (hexanes) through a short column (10 cm) of
silica gel in order to remove the spent catalyst and KOiPr. Evaporation
of the hexanes under reduced pressure resulted in pure phenyl(1-
phenyl-ethyl)amine. Yield: 1.98 g, 98%.
2
-17.4 ppm (vt, 1H, RuH, J HP ) 28.9 Hz), 0.81-4.98 ppm (m, 20H),
6.30-8.18 ppm (m, 30H). 31P{1H}: 102.3 ppm (d), 106.1 ppm (d), J PP
2
) 59.5 Hz. IR (Nujol): 1969 cm-1 (RuH), 3339, 3281, and 3243 cm-1
(NH).

Communications
Organometallics, Vol. 20, No. 6, 2001 1049
Ta ble 1. Ca ta lytic Hyd r ogen a tion of Nea t Keton es
a n d Im in es Usin g 3/KOiP r a n d 4/KOiP r a n d H2 Ga s
(3 a tm ), 20 °C (solid su bstr a tes w er e d issolved in
ben zen e)a
Sch em e 2
various activated acyclic imines (neat or in benzene),
producing the amines in fairly good yields and moderate
ee (Table 1). The high activity and turnovers using these
comparatively mild conditions (20 °C and 3 atm H2 gas)
for imine hydrogenation are unprecedented. The hydro-
genation of the imines using the dppach complexes 5
and 6 (Table 2) was even more facile than for the binap
analogues. A comparison of the results in Tables 1 and
2 indicates that the turnover rate increases by almost
an order of magnitude for the phosphinamino com-
plexes, relative to the binap analogues. An ee of 92%
was obtained for N-butyl-1-phenylethylamine that was
produced from the hydrogenation of neat N-(1-phenyl-
ethylidene)butylamine using complex 5 and KOiPr
under hydrogen (Table 2, entry 5). Current research
toward the optimization of this process is underway,
since this is a simple procedure for the facile production
of chiral secondary amines.
Initial experiments indicate that the dppach complex
6 appears to be more selective for the hydrogenation of
the CdN over the CdC bond of the R,â-unsaturated
imine I (Scheme 2) compared to the binap analogue 4.
Thus, the hydrogenation of I using 4/KOiPr (S:C )
500:1) resulted in 20% of both the allyl (II) and
saturated (IV) amines and 60% of III after 24 h at 20
°C, with no further change in the composition of the
mixture after 48 h. On the other hand, hydrogenation
of I using 6/KOiPr under similar conditions resulted in
only the allyl (48%) and saturated (52%) amines after
2 h. Thus, our on-going work to optimize this process
could lead to a simple and mild procedure for the
production of valuable chiral allylamines.
a
nd ) not determined; S:C ) substrate to catalyst.
Ta ble 2. Ca ta lytic Hyd r ogen a tion of Nea t Im in es
Usin g 5/KOiP r a n d 6/KOiP r a n d H2 Ga s (3 a tm ), 20
°C (solid su bstr a tes w er e d issolved in ben zen e)
The coordinated diamine ligands are necessary for
complexes 3-6 to function as hydrogenation catalysts
in the presence of KOiPr. For example, with a S:C ratio
of 2000:1, only 5% conversion of neat acetophenone was
obtained after 24 h using 1/KOiPr (20 °C and 3 atm H2).
Complexes 1 and 2 were totally ineffective for the
hydrogenation of ketimines under similar conditions.
Ack n ow led gm en t. This work was supported by a
grant to R.H.M. from the NSERC of Canada. R-binap
was donated by Digital Specialty Chemicals.
Su p p or tin g In for m a tion Ava ila ble: Text giving syn-
thetic methods and complete X-ray crystallographic tables.
This material is available free of charge via the Internet at
http://pubs.acs.org.
in the presence of potassium isopropoxide under hydro-
gen results in 100 and 96% of the allyl alcohol, respec-
tively, which is also consistent with the reported CdO
versus CdC bond selectivities using the Noyori system.3
This hydrogenation process is also very effective for
OM001054K