Asymmetric deactivation of racemic BINAP-Ru(II) catalysts through complete enantiomer discrimination by dimethylbinaphthylamine: Highly enantioselective hydrogenation of olefin and β-keto ester

Article abstract of DOI:10.1021/ol0256567

Matrix presented 3,3′-Dimethyl-2,2′-diamino-1,1′-binaphthyl (DM-DABN) is designed as a "chiral poison" (deactivator) for complete enantiomer resolution of racemic BINAP-Ru(II) catalysts in a highly enantioselective hydrogenation of β-keto ester and kinetic resolution of racemic 2-cyclohexen-1-ol.

Full text of DOI:10.1021/ol0256567

ORGANIC
LETTERS
2002
Vol. 4, No. 10
1643-1645
Asymmetric Deactivation of Racemic
BINAP-Ru(II) Catalysts through
Complete Enantiomer Discrimination by
Dimethylbinaphthylamine: Highly
Enantioselective Hydrogenation of Olefin
and â-Keto Ester
Koichi Mikami,* Yukinori Yusa, and Toshinobu Korenaga
Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received February 2, 2002
ABSTRACT
3,3′-Dimethyl-2,2′-diamino-1,1′-binaphthyl (DM-DABN) is designed as a “chiral poison” (deactivator) for complete enantiomer resolution of
racemic BINAP-Ru(II) catalysts in a highly enantioselective hydrogenation of â-keto ester and kinetic resolution of racemic 2-cyclohexen-1-ol.
The use of racemic catalysts in catalytic asymmetric synthesis
has been reported in different manners.1 We have reported
the selective activation of one enantiomer of a racemic
catalyst by a “chiral activator” (asymmetric activation).2 In
contrast, the selective deactivation3 or “chiral poisoning”4
of a racemic catalyst has been reported by Brown, Yama-
moto-Maruoka, and Faller. However, the chiral poisoning
approach is useful when a chiral poison completely discrimi-
nates between the two enantiomers of a racemic catalyst,
because asymmetric catalysis is performed by the non-
complexed and remaining catalyst enantiomer (Figure 1a).
Selective complexation of one enantiomer of racemic
catalysts with chiral poisons has been reported to be a
difficult task3c,4 (Figure 1b), using easily available natural
products and their derivatives. In fact, the chiral poisons must
be used in larger amounts5 than the catalyst enantiomers
(1) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe
Asymmetric Catalysis; Springer, Berlin, 1999; Vols. 1-3. (b) Noyori, R.
Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994. (c)
Brunner, H.; Zettlmeier, W. Handbook of EnantioselectiVe Catalysis;
VCH: Weinheim, 1993. (d) Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
VCH: New York, 1993, 2000; Vols. 1 and 2. (e) Kagan, H. B.
ComprehensiVe Organic Chemistry; Pergamon: Oxford, 1992; Vol. 8. (f)
Asymmetric Catalysis; Bosnich, B., Ed.; Martinus Nijhoff Publishers:
Dordrecht, 1986.
(2) (a) Matsukawa, S.; Mikami, K. Enantiomer 1996, 1, 69-73. (b)
Mikami, K.; Matsukawa, S. Nature 1997, 385, 613-615. (c) Ohkuma, T.;
Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.; Terada, M.; Noyori, R.
J. Am. Chem. Soc. 1998, 120, 1086-1087. (d) Mikami, K.; Korenaga, T.;
Terada, M.; Ohkuma, T.; Pham, T.; Noyori, R. Angew. Chem., Int. Ed.
1999, 38, 495-497 and references therein.
(3) (a) Alcock, N. W.; Brown, J. M.; Maddox, P. J. J. Chem. Soc., Chem.
Commun. 1986, 1532-1534. (b) Brown, J. M.; Maddox, P. J. Chirality
1991, 3, 345-354. (c) Maruoka, K.; Yamamoto, H. J. Am. Chem. Soc.
1989, 111, 789-790.
(4) (a) Faller, J. W.; Parr, J. J. Am. Chem. Soc. 1993, 115, 804-805. (b)
Faller, J. W.; Tokunaga, M. Tetrahedron Lett. 1993, 34, 7359-7362. (c)
Faller, J. W.; Liu Sams, X. J. Am. Chem. Soc. 1996, 118, 1217-1218. (d)
Sablong, R.; Osborn, J. A.; Faller, J. W. J. Organomet. Chem. 1997, 527,
65-70.
10.1021/ol0256567 CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/24/2002

clarify whether the remaining BINAP-Ru enantiomer shows
a high level of enantioselectivity in olefin hydrogenation.
XylBINAP-RuCl29,10 (BINAP-Ru(II), 1) with DM-DABN (2)
gave the stable trans-RuCl2[(S)-xylbinap][(S)-dmdabn]
(1/2) complex as expected by the CAChe molecular modeling
study (Figure 2).7 Indeed, (S)-2 in (S)-1/(S)-2 did not
exchange at all with another diamine such as DPEN even
after 24 h at ambient temperature.
Complete resolution and asymmetric deactivation of the
racemic XylBINAP-Ru(II) (1) by DM-DABN (2) was found
to be effective for kinetic resolution6 of racemic 2-cyclo-
hexen-1-ol (3) through olefin hydrogenation4b (Table 1). To
Table 1. Kinetic Resolution of Racemic 2-Cyclohexen-1-ol (3)
by Racemic XylBINAP-Ru(II) Catalyst through Asymmetric
Deactivation
Figure 1. Chiral poisoning of racemic catalysts.
because of ineffective discrimination thereof, and high
enantioselectivities equal to those by enantiopure catalysts
have not been attained (Figure 1b). Herein, we report
asymmetric deactivation of racemic BINAP-Ru(II) catalysts
through complete enantiomer discrimination by a designed
deactivator (Figure 1a), 3,3′-dimethyl-2,2′-diamino-1,1′-
binaphthyl (DM-DABN) in a highly enantioselective hydro-
genation of â-keto ester and kinetic resolution6 of racemic
2-cyclohexen-1-ol, using just 1.0 molar amount with respect
to the BINAP-Ru(II) catalyst enantiomer.
c
run
cat.
(S)-2
none
0.5 equiv
none
% conva
% ee of 3b
kf/ks
1d
(()
(()
(R)
(()
100
53
53
2d
100 (S)
100 (S)
88 (S)
3e
4d,f
0.5 equiv
48
102
The highly effective resolving agent DM-DABN7 with
sterically demanding methyl substituents at 3,3′-positions
in diaminobinaphthyl (DABN)8 was thus employed to
a Determined by GC analysis (TC-1701). b Determined by chiral GC
analysis (CP-Chirasil-Dex CB). c Relative rate is calculated by the following
equation: ln[(1- conv.)(1 - eesub)]/ln[(1 - conv.) (1 + eesub)] (conv. )
0.482, eesub ) 0.879). d S/C (substrate to catalyst molar ratio) ) 250. e S/C
) 500. f H2 ) 1 atm.
the mixture of RuCl2[(()-xylbinap](dmf)n complex (1) and
(S)-DM-DABN (2) (0.5 equiv) in an autoclave was added
CH2Cl2 under argon atmosphere. After stirring for 1 h at
room temperature, CH2Cl2 was removed under reduced
pressure. Racemic 2-cyclohexen-1-ol (3), MeOH, and H2
were subsequently introduced. Hydrogenation of (()-2-
cyclohexen-1-ol (3) by (()-1 was done in MeOH at room
temperature for 5 min under H2 (2 atm). The racemic
XylBINAP-Ru(II) (1) without DM-DABN (2) led to cyclo-
hexanol (4) quantitatively with no remaining cyclohexenol
(5) Amounts of chiral poisons: 2.0 equiv for Al (ref 3c); 1.4 equiv for
Rh (ref 4a); 20 equiv for Ru (ref 4b); 3.0 equiv for Ti (ref 4c); 2.0 equiv
for Ir (ref 4d).
(6) Reviews on kinetic resolutions: Kagan, H. B.; Fiaud, J. C. Top.
Stereochem. 1988, 18, 249-330. (b) Brown, J. M. Chem. Ind. (London),
1988, 612-617.
(7) Mikami, K.; Korenaga, T.; Ohkuma, T.; Noyori, R. Angew. Chem.,
Int. Ed. 2000, 39, 3707-3710.
(8) Commercially available from Aldrich Co., no. 38,242-6. Brown, K.
J.; Berry, M. S.; Murdoch, J. R. J. Org. Chem. 1985, 50, 4345-4349.
(9) Kitamura, M.; Tokunaga, T.; Ohkuma, T.; Noyori, R. Org. Synth.
1993, 71, 1-13.
(10) 2,2′-Bis(di-3,5-xylylphosphino)-1,1′-binaphthyl: (a) Mashima, K.;
Matsumura, Y.; Kusano, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki,
T.; Akutagawa, S.; Takaya, H. J. Chem. Soc., Chem. Commun. 1991, 609-
610. (b) Mashima, K.; Kusano, K.; Sato, N.; Matsumura, Y.; Nozaki, K.;
Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya,
H. J. Org. Chem. 1994, 59, 3064-3076.
Figure 2. CAChe modeling study of a chiral deactivator for
enantiomer discrimination of racemic BINAP-Ru(II) complexes.
1644
Org. Lett., Vol. 4, No. 10, 2002

(run 1). However, the use of 0.5 equiv of (S)-2 to (()-1 gave
enantiopure (S)-3 (run 2). Racemic 2-cyclohexen-1-ol (3) was
kinetically resolved in the same (53%) conversion as
enantiopure (R)-1 (run 2 vs 3). Indeed, the relative rate of
hydrogenation of (R)- vs (S)-3 in the presence of just a 0.5
molar amount of (S)-2 to (()-1 was found to be large (kf/ks
) 102).11
Table 2. Hydrogenation of Methyl 3-Oxobutanoate (5) by
Racemic Catalyst XylBINAP-Ru(II) through Asymmetric
Deactivation
Racemic BINAP-Ru(II) (1) was also effective for the
enantioselective hydrogenation of â-keto esters12 using
enantiopure DM-DABN (2) (Table 2). Methyl 3-oxo-
butanoate (5), MeOH, and H2 were introduced after removal
of CH2Cl2 (vide supra). Methyl (R)-3-hydroxybutanoate (6)
was thus obtained in virtually enantiopure (99.3% ee) form
in quantitative yield (run 1). The enantioselectivity (99.3%
run
cat.
(S)-2
% ee of 6a
% yield of 6b
1c
2d
(()
(R)
0.5 equiv
none
99.3 (R)
99.9 (R)
quant
quant
a Determined by chiral HPLC analysis (CHIRALCEL OB-H) after
conversion to methyl 3-benzoyloxybutanoate. b Determined by GC analysis
(TC-1701). c S/C (substrate to catalyst molar ratio) ) 750. d S/C ) 1500.
e See ref 11a.
(11) Typical Experimental Procedure. Kinetic Resolution of Racemic
2-Cyclohexen-1-ol by Racemic XylBINAP-Ru(II) catalyst (1) with DM-
DABN (2). To the mixture of RuCl2[(()-xylbinap](dmf)n catalyst (1) (5.2
mg, 0.005 mmol) and (S)-DM-DABN (2) (0.8 mg, 0.0025 mmol) in a 100-
mL autoclave was added dichloromethane (2.0 mL) under argon atmosphere.
After 1 h of stirring at room temperature, dichloromethane was removed
under reduced pressure. After replacement with argon, methanol (1.0 mL)
and racemic 2-cyclohexen-1-ol (1.23 mL, 1.25 mmol) was added to the
autoclave under a stream of argon. Hydrogen was introduced at a pressure
of 2 atm. The solution was stirred for 5 min at room temperature. After
concentration under reduced pressure, the residue was filtered through a
short column on silica gel to give the mixture of 100% ee of (S)-2-
cyclohexen-1-ol and cyclohexanol. Conversion and % ee of (S)-2-cyclo-
hexen-1-ol was calculated by GC analysis. GC analysis for conversion to
cyclohexanol: column, OV-1701; i.d. 0.25 mm × 25 m; carrier gas, nitrogen
(75 kPa); column temp, 60 °C; injection temp, 90 °C; split ratio, 100:1, tR
of cyclohexanol, 15.8 min (53.4%); tR of 2-cyclohexen-1-ol 16.9 min
(46.6%). GC analysis for % ee of 2-cyclohexen-1-ol: column, CP-Chirasil-
Dex-CB; i.d. 0.25 mm × 25 m, CHROMPACK.; carrier gas, nitrogen (75
kPa); column temp, 75 °C; injection temp, 105 °C; split ratio, 100:1, tR of
S-isomer, 17.2 min (100%); tR of R-isomer, 18.7 min (0%).
ee) was equally high as that (99.9% ee) actually obtained
by the enantiopure (R)-1 catalyst (run 1 vs 2).
In conclusion, the racemic BINAP-Ru(II) (1) can be
completely resolved with 0.5 equiv of the enantiopure DM-
DABN (2) and used as a catalyst equally effective to the
enantiopure 1 for asymmetric hydrogenation. The success
with DM-DABN will provide a guiding principle for rational
design of a chiral deactivator for enantiomeric catalysts
discrimination and asymmetric catalysis therewith.
Acknowledgment. We are grateful to Drs. H. Kumo-
bayashi, T. Miura, and N. Sayo of Takasago International
Corp. for providing BINAP ligands. This work was finan-
cially supported by the Ministry of Education, Science, Sports
and Culture of Japan (09238209 and 10208204).
(12) Hydrogenation of â-keto esters by enantiopure RuCl2(binap): (a)
Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi,
H.; Akutagawa, S. J. Am. Chem. Soc. 1987, 109, 5856-5858. (b) Review:
Ager, D. J.; Laneman, S. A. Tetrahedron: Asymmetry 1997, 8, 3327-
3355 and references therein.
OL0256567
Org. Lett., Vol. 4, No. 10, 2002
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