Axial chirality control of tropos BIPHEP-Rh complexes by chiral dienes: Synergy effect in catalytic asymmetric hydrogenation

Article abstract of DOI:10.1039/b809683j

Diastereopure tropos Rh complexes bearing not only BIPHEP but also chiral dienes can be employed as highly enantioselective hydrogenation catalysts for an olefinic substrate. The Royal Society of Chemistry.

Full text of DOI:10.1039/b809683j

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Axial chirality control of tropos BIPHEP–Rh complexes by chiral
dienes: synergy effect in catalytic asymmetric hydrogenationwz
Kohsuke Aikawa,a Yu¯ki Takabayashi,a Susumu Kawauchib and Koichi Mikami*a
Received (in Cambridge, UK) 9th June 2008, Accepted 14th August 2008
First published as an Advance Article on the web 30th September 2008
DOI: 10.1039/b809683j
Diastereopure tropos Rh complexes bearing not only BIPHEP
but also chiral dienes can be employed as highly enantioselective
hydrogenation catalysts for an olefinic substrate.
C1-symmetric diene 211 in (CH2Cl)2 at 80 1C. The isomerization
of 1a-Rh proceeded to give a 72 : 28 ((S)-1a-Rh/2 : (R)-1a-Rh/2)
mixture of diastereomers after 24 h. Heating for 48 h afforded
the single diastereomer through complete ligand exchange
between cod and chiral diene 2, along with a by-product
In new frontiers of asymmetric catalysis, various chiral ligands
have been designed and synthesized.1 Especially, atrop-
isomeric (originating from atropos: ‘‘a’’ meaning ‘‘not’’ and
‘‘tropos’’ meaning ‘‘turn’’ in Greek2) ligands such as BINAP3
derivatives with a high rotation barrier are widely utilized
because of their rigid and effective asymmetric environments.
On the other hand, the use of tropos2 (chirally flexible) ligands
with a low rotation barrier is attractive as a powerful and
practical strategy for asymmetric catalysis. tropos BIPHEP
(2,20-bis(diphenylphosphino)-1,10-biphenyl)4 1a is not resolva-
ble at room temperature for the fast racemization. However,
the chirality of racemic BIPHEP–metal complexes can be
controlled by chiral diamines DABNs,5c,6–8 DPEN,5 DM-
DPEN,5b and their triflate derivatives such as DABNTf7c,8b
to lead to the single BIPHEP–metal enantiomer. We have thus
succeeded in axial chirality control of BIPHEP–Ru,5 Rh,6 Pd,7
and Pt8 complexes for catalytic asymmetric reactions.9 Herein,
we report the first example of complete chirality control of
tropos BIPHEP–Rh complexes by chiral dienes10–12 rather
than chiral diamines and the synergy effect of chirally con-
trolled BIPHEP and chiral dienes in catalytic asymmetric
hydrogenation of an olefinic substrate.
ꢀ
(18%). The employment of racemic 1a-Rh/cod bearing BArF
ꢀ
instead of SbF6 anion also led to the single diastereomer
under the same conditions, but the remaining 1a-Rh/cod and
by-product were obtained in significant amounts. No ligand
exchange was observed at 80 1C using pseudo-C2-symmetric
diene 312 due to more severe steric repulsion than in the
C1-symmetric diene 2.13
Kinetic chirality control without heating was also examined
using cationic Rh–diene dimer as
a starting material
(Scheme 2).14 In contrast to the thermodynamic control, the
combination of [RhCl(2)]2 and silver salt followed by the
addition of BIPHEP led to the complex (1a-Rh/2) without
formation of a by-product. Unfortunately, irrespective of
silver salt, the axial chirality control of the BIPHEP moiety
was unsuccessful ((S)-1a-Rh/2 : (R)-1a-Rh/2 = 64 : 36 to
59 : 41). The thermodynamic chirality control of the complex
(1a-Rh/2) was then attempted to convert the less favorable
diastereomer subsequently to the favorable one. The isomeri-
zation was observed to give solely (S)-1a-Rh/2 at 50 1C for
62 h, though with a by-product (20%).
The pseudo-C2-symmetric diene (3) was used instead of the
C1-symmetric diene (2) for more efficient enantiomer discri-
mination (Scheme 3). Under the same conditions, the complex
(1b-Rh/3) was prepared by treatment of DM-BIPHEP 1b (DM
=
3,5-dimethylphenyl) to afford a single diastereomer
(S)-1b-Rh/3 without formation of a by-product, except for
the AgSbF6 case.y The unfavorable diastereomer (R)-1b-Rh/3
was not observed by 31P NMR analysis. The use of 4 (R =
iBu) instead of 3 (R = Ph) for the chirality control also led to a
similar result.
Thermodynamic axial chirality control was first attempted
(Scheme 1). BIPHEP–Rh/diene (1a-Rh/2) complex was
synthesized by treatment of racemic 1a-Rh/cod complex and
a Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo, 152-8552, Japan. E-mail: mikami.k.ab@m.titech.ac.jp;
Fax: +81 3 5734 2776; Tel: +81 3 5734 2142
b Department of Organic and Polymeric Materials, Tokyo Institute of
Technology, Tokyo, 152-8552, Japan
w Taken from the Master thesis of Y. Takabayashi, Tokyo Institute of
Technology, February 8, 2008.
z Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b809683j
Scheme 1 Thermodynamic chirality control by C1-symmetric diene 2.
Chem. Commun., 2008, 5095–5097 | 5095
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Table 1 Asymmetric hydrogenation catalyzed by the single diaster-
eomer (S)-1b-Rh/3
Counter
anion
Conv.
(%)
Entry
Solvent
ee (%)a
1
2
3
4
5
6
MeOH
CH2Cl2
THF
THF
THF
THF
THF
THF
THF
OTf
OTf
OTf
BF4
21
69
100
100
47
97
97
31
55
14
89
91
51
60
78
40
—
21
Scheme 2 Kinetic chirality control by C1-symmetric diene 2.
PF6
ClO4
SbF6
SbF6
SbF6
7
8b
9c
Ref. 16
0
100
Rh(cod)2(OTf)
+ (S)-BINAP
a
Enantiopurity was determined by chiral GC analysis on a CP
b
Chirasil Dex CB column. Chiral diene 4 was used instead of chiral
c
diene 3. [RhCl(3)2] with 2 equiv. of AgSbF6 was used as an asym-
metric catalyst without DM-BIPHEP 1b.
Scheme 3 Kinetic chirality control by pseudo-C2-symmetric diene 3.
We have already determined the structure of racemic 1a-Rh/nbd
complex6 by X-ray analysis.14 The orientation of axial and
equatorial phenyl groups in the BIPHEP moiety is quite
similar to that of BIPHEP–Ru, Pd, and Pt complexes.5–8 In
the present enantiomer discrimination of (R)-1b-Rh complex
by pseudo-C2-symmetric diene 30, there is strong steric repul-
sion between equatorial aryl groups of BIPHEP and the Ph
and Bn groups of chiral diene 30 (Fig. 1: DFT calculations; see
ESIz). In sharp contrast, there is essentially no steric repulsion
in the diastereomeric complex (S)-1a-Rh/30. The (S)-1a-Rh/30
complex is thermodynamically more stable than the diaster-
eomer (R)-1a-Rh/30 complex by 4.9 kcal molꢀ1. As a result,
(S)-enantiomeric BIPHEPs could selectively complex with the
cationic Rh/3 complex after isomerization from the opposite
(R)-enantiomeric BIPHEPs.
With complete chirality control, the asymmetric hydrogena-
tion15 of the olefinic substrate (5) was investigated (Table 1),y
for which the atropos BINAP ligand16 gave only a low level of
enantioselectivity (21% ee). Furthermore, the cationic
Rh–diene dimer without diphosphine ([RhCl(3)]2/2AgSbF6)
was totally inactive (entry 9).
The synergy effect17 of chirally controlled BIPHEP and the
chiral dienes (3 and 4) was thus examined in catalytic
asymmetric hydrogenation (entries 1–8). The use of THF
increased both the catalytic activity and enantioselectivity up
to 89% ee (entries 1, 2 vs. 3). The remarkable effect of counter
anions was observed; under similar reaction conditions, the BF4
anion was found to be the most effective, affording 6 with 91%
ee in 100% conversion (entry 4). On the other hand, the use of
the isobutyl diene (4) instead of the phenyl diene (3) gave lower
enantioselectivity to indicate the synergy effect of chiral dienes
with chirally controlled DM-BIPHEP (entries 7 vs. 8). Signifi-
cantly, it was confirmed by 31P NMR analysis that racemization
of the DM-BIPHEP moiety and decomposition of the complex
were not observed even after the hydrogenation reaction.z
In conclusion, we have succeeded in the complete chirality
control of tropos BIPHEP–Rh complexes by chiral dienes and in
the highly enantioselective hydrogenation of an olefinic
substrate catalyzed by diastereopure Rh complexes bearing
not only tropos diphosphines but also chiral dienes. While the
use of chiral dienes instead of achiral cod or nbd decreased
the catalytic activity (hence, not asymmetric activation18), the
synergy effect by chirally controlled tropos BIPHEP and chiral
dienes led to higher enantioselectivity than that by atropos
BINAP itself without chiral diene. Significantly, the hydrogena-
tion of chiral dienes and racemization of the DM-BIPHEP
moiety have not been observed even under the hydrogenation
conditions. Further applications of the enantiopure tropos
diphosphine–Rh–diene complexes in asymmetric catalysis are
now under investigation.
Fig. 1 Enantiomer discrimination by chiral diene 3: DFT calculation
of 1a-Rh/30 diastereomer.
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DPBP–Ru/DPEN: (e) K. Mikami, K. Wakabayashi and K.
Aikawa, Org. Lett., 2006, 8, 1517; (f) Q. Jing, C. A. Sandoval, Z.
Wang and K. Ding, Eur. J. Org. Chem., 2006, 3606.
6 BIPHEP–Rh: K. Mikami, S. Kataoka, Y. Yusa and K. Aikawa,
Org. Lett., 2004, 6, 3699.
7 BIPHEP–Pd: (a) K. Mikami, K. Aikawa, Y. Yusa and M. Hatano,
Org. Lett., 2002, 4, 91; (b) K. Mikami, K. Aikawa and Y. Yusa,
Org. Lett., 2002, 4, 95; (c) K. Mikami, Y. Yusa, K. Aikawa and M.
Hatano, Chirality, 2003, 15, 105.
Notes and references
y Kinetic chirality control: To a mixture of [RhCl(3)]2 (9.4 mg, 0.01 mmol)
and AgBF4 (3.7 mg, 0.019 mmol) was added dry dichloromethane
(1.0 mL) under argon atmosphere, and the mixture was stirred for 6 h
at room temperature. A solution of DM-BIPHEP 1b (12.1 mg,
0.019 mmol) in dry dichloromethane (1.0 mL), prepared in another
Schlenk tube, was then added to the reaction mixture via cannula.
After stirring for 2 h at room temperature, the AgCl precipitate was
removed by filtration under argon atmosphere through a bed of
Celites. Diastereopure (S)-1b-Rh/3 was isolated quantitatively by
concentration of the mixture in vacuo, addition of a few mL of
Et2O, removal of supernatant liquid via syringe, washing with Et2O,
and drying in vacuo.
8 BIPHEP–Pt: (a) J. J. Becker, P. S. White and M. R. Gagne, J. Am.
´
Chem. Soc., 2001, 123, 9478; (b) K. Mikami, H. Kakuno and K.
Aikawa, Angew. Chem., Int. Ed., 2005, 44, 7257; (c) S. Doherty, J.
G. Knight, C. H. Smyth, R. W. Harrington and W. Clegg, Org.
Lett., 2007, 9, 4925.
1H NMR (300 MHz, CDCl3) d 0.60 (d, J = 13.2 Hz, 1H), 0.66 (d, J =
13.2 Hz, 1H), 0.91 (s, 3H), 1.69 (s, 3H), 2.17 (s, 6H), 2.20 (s, 3H), 2.31
(s, 6H), 2.34 (s, 6H), 2.46 (s, 6H), 2.82 (d, J = 14.1 Hz, 1H), 3.52 (d, J
= 15.9 Hz, 1H), 3.71 (d, J = 15.9 Hz, 1H), 4.28 (m, 1H), 4.62 (d, J =
6.3 Hz, 1H), 5.86–5.89 (m, 1H), 6.00–6.03 (m, 1H), 6.66–7.55 (m,
27H), 7.87–7.93 (m, 1H). 31P NMR (121 MHz, CDCl3) d 21.7 (dd,
JRh–P, JP–P = 157.9, 46.0 Hz), 27.4 (dd, JRh–P, JP–P=161.8, 46.0 Hz).
Anal. Calcd for C68H70BF4OP2Rhꢂ2CH2Cl2: C, 63.46; H, 5.63%.
9 Chirality control by chiral anions: (a) J. Lacour and V. Hebbe-
Viton, Chem. Soc. Rev., 2003, 32, 373. Chirality control of tropos
NUPHOS ligands: ; (b) S. Doherty, C. R. Newman, R. K. Rath, H.
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3863.
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Chem. Soc., 2003, 125, 11508; (b) N. Tokunaga, Y. Otomaru, K.
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Soc., 2004, 126, 13584.
11 C. Fischer, C. Defieber, T. Suzuki and E. M. Carreira, J. Am.
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12 J. Paquin, C. Defieber, C. R. J. Stephenson and E. M. Carreira, J.
Am. Chem. Soc., 2005, 127, 10850.
27
Found: C, 63.71; H, 5.58%. [a]D = +34.0 (c = 0.08 in CHCl3).
Asymmetric hydrogenation: To a mixture of (S)-1b-Rh/3 (11.5 mg,
0.01 mmol), prepared by kinetic chirality control as described above,
and 2-acetamidoacrylic acid methyl ester 5 (7.2 mg, 0.05 mmol) in a
10 mL Schlenk tube was added dry dichloromethane (0.5 mL) under
argon atmosphere. The mixture was charged with hydrogen gas using
a balloon (1 atm), then stirred for 24 h at 0 1C. The solvent was con-
centrated under reduced pressure. The product 6 was isolated quanti-
tatively by flash chromatography using dichloromethane–MeOH
(19 : 1). Ee values were determined by chiral GC analysis; GC
(column: CP Chirasil Dex CB, i.d. 0.32 mm ꢃ 25 m, CHROMPACK;
carrier gas: nitrogen 75 kPa; column temperature: 100 1C; injection
and detection temperature: 130 1C), tR (S isomer) = 10.9 min, tR
(R isomer) = 11.7 min.
13 (a) C. Defieber, H. Grutzmacher and E. M. Carreira, Angew.
¨
Chem., Int. Ed., 2008, 47, 4482; (b) F. R. Hartley, Chem. Rev.,
1973, 73, 163.
14 Recently, Faller et al. reported the resolution of diastereopure
(S)-1a-Rh/7 by recrystallization from the diastereomeric mixture
((S)-1a-Rh/7 : (R)-1a-Rh/7 = 3 : 1) after the kinetic chirality
control. The structure was proved by X-ray analysis: J. W. Faller
and J. C. Wilt, J. Organomet. Chem., 2006, 691, 2207
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BIPHEP is measured to be only (22 ꢄ 1) kcal molꢀ1, which
suggests that axial rotation takes place at temperatures around
or above 25 1C: O. Desponds and M. Schlosser, Tetrahedron Lett.,
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38, 495; (b) T. Korenaga, K. Aikawa, M. Terada, S. Kawauchi and
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thus prepared can be further evolved into more activated catalysts
with higher catalytic activity and enantioselectivity by ligation of
chiral activators (‘‘Asymmetric Activation’’, see ref. 18). However,
the additional ligation does not necessarily lead to higher catalytic
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(effect)’’ leading to higher enantioselectivity without an increase in
the catalytic activity (even with a decrease).
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Chem. Commun., 2008, 5095–5097 | 5097