Asymmetric activation of racemic ruthenium(II) complexes for enantioselective hydrogenation [9]

Full text of DOI:10.1021/ja972897e

1086
J. Am. Chem. Soc. 1998, 120, 1086-1087
the presence of racemic RuCl2(tolbinap)(dmf)n, (S,S)-1,2-diphe-
nylethylenediamine [(S,S)-DPEN],9 and KOH in a 7:1 mixture
of 2-propanol and toluene ([1] ) 0.6 M, ketone:Ru:diamine:KOH
molar ratio ) 500:1:1:2, 8 atm, 0 °C, 6 h), the allylic alcohol
(S)-2 was produced in 95% ee in 100% yield (eq 1).10,11 The
Asymmetric Activation of Racemic Ruthenium(II)
Complexes for Enantioselective Hydrogenation
Takeshi Ohkuma,† Henri Doucet,† Trang Pham,†
Koichi Mikami,*,‡ Toshinobu Korenaga,‡
Masahiro Terada,‡ and Ryoji Noyori*,†
Department of Chemistry and Molecular Chirality Research
Unit, Nagoya UniVersity, Chikusa, Nagoya 464-8602, Japan
Department of Chemical Technology, Tokyo Institute of
Technology, Meguro, Tokyo 152, Japan
ReceiVed August 18, 1997
The stereoselectivity and turnover frequency (rate) of asym-
metric catalysis with chiral metal complexes are significantly
affected by the nature of the donor compounds present in the
reaction mixture, resulting in various nonlinear phenomena.1-3
Certain racemic metal complexes can catalyze an enantioselective
transformation in the presence of a nonracemic auxiliary, when
one of the catalyst enantiomers is selectively activated4 or
deactivated.5 The recently developed RuCl2(diphosphine)Sn/1,2-
diamine/alkaline base ternary catalyst system effects practical
hydrogenation of a diverse array of nonfunctionalized ketones.6
The reaction with mild conditions (1 to 8 atm) exhibits high CdO/
CdC selectivity and excellent diastereo- and enantioselectivity.
Here if one can use a racemic diphosphine ligand for asymmetric
hydrogenation, the synthetic utility will be further increased. We
now have realized asymmetric activation of racemic diphosphine-
Ru(II) complexes using a nonracemic 1,2-diamine.
enantiomeric purity was very close to the 96% ee attainable with
a combination employing enantiomerically pure (R)-TolBINAP
and (S,S)-DPEN. The (R)-diphosphine/(R,R)-diamine combina-
tion (1:1 molar ratio) catalyzed the reaction slowly to give (S)-2
in only 26% ee. As illustrated in Figure 1, the rate of
hydrogenation with the (()-TolBINAP-Ru complex was en-
hanced with an increase in the amount of (S,S)-DPEN, reaching
a near maximum value with the addition of a 1.0 molar amount
of the diamine. On the other hand, the ee value of the product
was consistently high (>90%) from the beginning (diamine/Ru
> 0.25). Thus, (S,S)-DPEN was shown to more effectively
activate the (R)-TolBINAP-Ru isomer of the racemate under the
hydrogenation conditions employed.
A mixed-ligand catalyst was prepared from equimolar amounts
of the (()-TolBINAP-Ru complex and (S,S)-DPEN, and this
was followed by the addition of an equimolar amount of (R,R)-
DPEN. The system contains equal amounts of enantiomers for
both diphosphine and diamine (diphosphine:diamine ) 1:2).
Nevertheless, this mixture catalyzed hydrogenation of 1 in a
2-propanol-toluene solution containing KOH (8 atm, 14 h)
affording (S)-2 in 91% ee and 100% yield, in which the inherent
stereoselectivity of the (R)-TolBINAP/(S,S)-DPEN combination
was preserved. This result indicates that the interaction of the
RuCl2(diphosphine) complex and DPEN is virtually irreversible.
In fact, a complex prepared from RuCl2[(R)-tolbinap](dmf)n and
(S,S)-DPEN (1:1) in a 1:7 (CD3)2CDOD-C6D5CD3 mixture gave
a single 31P-NMR signal at δ 45.8 ppm (10% H3PO4 as external
standard), while the S/S,S ligand combination gave a signal at δ
46.2 ppm. A 1:0.5 to 1:2 mixture of RuCl2[(()-tolbinap](dmf)n
and (S,S)-DPEN showed these signals with equal intensities.
Hydrogenation of 9-acetylanthracene with the (()-TolBINAP/
(S,S)-DPEN combined system (0.9 M, ketone:Ru:diamine:KOH
) 250:1:1:2, 8 atm, 80 °C, 10 h) gave (R)-1-(9-anthryl)ethanol
RuCl2(tolbinap)(dmf)n,7,8 either racemic or enantio-pure, is a
feeble catalyst for hydrogenation of simple ketones. However,
when 2,4,4-trimethyl-2-cyclohexenone (1) was hydrogenated in
† Nagoya University.
‡ Tokyo Institute of Technology.
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(10) A mixture of RuCl2[(()-tolbinap](dmf)n8 (9.4 mg, 0.01 mmol), (S,S)-
DPEN9 (2.1 mg, 0.01 mmol), 2-propanol (3 mL), toluene (1 mL), and a 0.5
M KOH solution in 2-propanol (40 µL, 0.02 mmol) placed in a glass autoclave
was degassed and sonicated for 15 min. 2-Propanol (4 mL) and 1 (691 mg,
5.0 mmol) were added to the autoclave and hydrogen was introduced to a
pressure of 8 atm. The reaction mixture was vigorously stirred for 6 h at 0
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95% ee (684 mg, 98% yield), [R]24 -88.3° (c 1.03, CH3OH).
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S0002-7863(97)02897-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/22/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 1087
Scheme 1. Mechanism of Asymmetric Activation
Figure 1. Asymmetric activation of a racemic TolBINAP-Ru complex
with (S,S)-DPEN in the hydrogenation of 1 (1:Ru:KOH ) 500:1:10, 8
atm, 28 °C).
in 80% ee in 99% yield. The ee value was comparable with the
82% accessible with the pure R/S,S combination.
When o-methylacetophenone (3) was used as substrate, (S,S)-
DPEN enhanced the activity of the (S)-TolBINAP-Ru complex
more than that of the (R)-TolBINAP-based isomer. The hydro-
genation in the presence of RuCl2[(()-tolbinap](dmf)n, (S,S)-
DPEN, and KOC(CH3)3 in a 7:1 mixture of 2-propanol and
toluene (0.6 M, ketone:Ru:diamine:base ) 500:1:1:2, 4 atm, 0
°C, 10 h) gave (R)-4 quantitatively and in 90% ee (eq 2). Separate
diphosphine/diamine complex.14 This equilibrium lies far to the
mixed-ligand complex regardless of the chirality of the ligands.
The real hydrogenation catalyst is probably the chiral Ru mono-
or dihydride formed from the dichloride, alkaline base, and
2-propanol and/or hydrogen.15,16 The rate and stereoselectivity
including the sense of asymmetric induction achieved with these
diastereomeric catalysts are highly dependent on the structures
of ketonic substrates. During hydrogenation of the cyclohexenone
1 (eq 1), the R/S,S cycle with an S:R enantioselectivity of 98:2
occurs 121 times faster than the S/S,S cycle which has an S:R
ratio of 37:63. On the other hand, with the aromatic ketone 3 as
substrate (eq 2), the S/S,S cycle, which displays an S:R enanti-
oselectivity of 1.3:98.7, turns over 13 times faster than does the
diastereomeric R/S,S cycle with an S:R ratio of 54:46.
experiments revealed that an enantiomerically pure complex,
RuCl2[(S)-tolbinap](dmf)n, coupled with (S,S)-DPEN, catalyzes
hydrogenation of 3 giving (R)-4 in 97.5% ee and that the reaction
with (R,R)-DPEN affords (R)-4 in only 8% ee. Hydrogenation
of 1′-acetonaphthone with the (()-TolBINAP/(S,S)-DPEN system
(0.6 M, ketone:Ru:diamine:KOH ) 500:1:1:2, 4 atm, 0 °C, 6 h)
gave (R)-1-(1-naphthyl)ethanol with 76% ee in 100% yield. The
R alcohol is obtainable in 97% ee with the (S)-diphosphine/(S,S)-
diamine combination.6a
Scheme 1 provides the simplest explanation for the observed
asymmetric activation of the racemic Ru complex with (S,S)-
DPEN. The enantioselectivity of hydrogenation reflects the
relative turnover numbers of the competing R/S,S and S/S,S
catalytic cycles, and the ratio is determined by the relative
concentrations and reactivities of the coexisting diastereomeric
diphosphine/diamine Ru catalysts.1,12,13 The TolBINAP-Ru
dichloride existing as aggregates8 is feeble for hydrogenation of
simple ketones. Under the reaction conditions, the labile ligands
(S) are readily displaced by (S,S)-DPEN to form a monomeric
Acknowledgment. A discussion between Professor Carsten Bolm and
R.N. at Bad Nauheim, on September 20, 1996, stimulated the examination
of this subject. The encouragement of Professor Bolm is deeply
appreciated. This work was aided by the Ministry of Education, Science,
Sports and Culture of Japan (Nos. 07CE2004 and 09238209).
Supporting Information Available: Experimental procedures for
hydrogenation and GC, HPLC, and 1H-NMR data of the products (5
pages). See any current masthead page for ordering and Internet access
instructions.
JA972897E
(14) Cenini, S.; Porta, F.; Pizzotti, M. J. Mol. Catal. 1982, 15, 297-308.
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(16) The geometry of the Ru complexes may be cis or trans or a mixture
of both. The sensitivity of the catalytic complexes did not allow for structural
elucidation.
(12) Review of double stereodifferentiation, see: Masamune, S.; Choy, W.;
Petersen, J. S.; Sita, L. R. Angew. Chem., Int. Ed. Engl. 1985, 24, 1-30.
(13) Molecular association of the catalyst or its precursors may lead to
2
further complicated nonlinear effects.1,