High performance of a chiral diene-rhodium catalyst for the asymmetric 1,4-addition of arylboroxines to α,β-unsaturated ketones

Article abstract of DOI:10.1021/ol052756e

A rhodium complex coordinated with (S,S)-2,5-dibenzylbicyclo[2.2.2]octa-2, 5-diene (Bn-bod*) showed high catalytic activity and high enantioselectivity in the asymmetric 1,4-addition of arylboroxines to cyclic α,β-unsaturated ketones, 0.005-0.01 mol % of the catalyst giving high yields of the addition products with not lower than 94% ee. The turnover frequency of the catalyst is up to 1.4 × 10⁴ h^-1.

Full text of DOI:10.1021/ol052756e

ORGANIC
LETTERS
2
006
Vol. 8, No. 2
41-344
High Performance of a Chiral
Diene Rhodium Catalyst for the
Asymmetric 1,4-Addition of
3
−
Arylboroxines to
Ketones
r,â-Unsaturated
Fu-Xue Chen, Asato Kina, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
thayashi@kuchem.kyoto-u.ac.jp
Received November 14, 2005
ABSTRACT
A
rhodium complex coordinated with (S,S)-2,5-dibenzylbicyclo[2.2.2]octa-2,5-diene (Bn-bod*) showed high catalytic activity and high
enantioselectivity in the asymmetric 1,4-addition of arylboroxines to cyclic -unsaturated ketones, 0.005 0.01 mol % of the catalyst giving
high yields of the addition products with not lower than 94% ee. The turnover frequency of the catalyst is up to 1.4
r
,
â
−
4
-1
×
10
h
.
The recent development of chiral diene ligands opened new
research fields in transition-metal-catalyzed asymmetric
effective ligands, especially in rhodium-catalyzed aryl-
transfer reactions. Their rhodium complexes have displayed
higher catalytic activity and/or higher enantioselectivity than
the chiral phosphine-rhodium complexes in asymmetric 1,4-
addition of arylboronic acids to electron-deficient olefins and
the related asymmetric carbon-carbon bond-forming reac-
1
-3
reactions.
They have been demonstrated to be highly
(1) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508. (b) Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi,
T. Org. Lett. 2004, 6, 3425. (c) Tokunaga, N.; Otomaru, Y.; Okamoto, K.;
Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.
1,2
tions. Here, we report the results obtained for our studies
inquiring into the decrease of catalyst loading of the chiral
(d) Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem.
2
005, 70, 2503. (e) Shintani, R.; Kimura, T.; Hayashi, T. Chem. Commun.
005, 3213. (f) Hayashi, T.; Tokunaga, N.; Okamoto, K.; Shintani, R. Chem.
diene-rhodium complex for the asymmetric 1,4-addition of
arylboronic acids to R,â-unsaturated ketones. Although
2
4
,5
Lett. 2005, 34, 1480. (g) Shintani, R.; Okamoto, K.; Hayashi, T. Org. Lett.
005, 7, 4757. (h) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.;
2
high turnover frequency (TOF) has been reported in the
Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54. (i) Shintani, R.; Tsurusaki,
A.; Okamoto, K.; Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 3909. (j)
Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34, 1294. (k)
Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7,
6
catalytic asymmetric hydrogenation, the decrease of the
catalyst amount is still challenging in other catalytic asym-
7,8
metric reactions.
3
07. (l) Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron:
Asymmetry 2005, 16, 1673.
2) (a) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem.
(
(4) For reviews: (a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103,
2829. (b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169.
(5) For leading references: (a) Takaya, Y.; Ogasawara, M.; Hayashi,
T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579. (b) Hayashi,
T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002,
124, 5052.
Soc. 2004, 126, 1628. (b) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira,
E. M. Org. Lett. 2004, 6, 3873. (c) Paquin, J.-F.; Defieber, C.; Stephenson,
C. R. J.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 10850. (d) Paquin,
J.-F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett. 2005,
7
, 3821.
(
3) (a) L a¨ ng, F.; Breher, F.; Stein, D.; Gr u¨ tzmacher, H. Organometallics
(6) (a) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40. (b)
Noyori, R.; Kitamura, M.; Ohkuma, T. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5356 and references therein.
2
005, 24, 2997. (b) Grundl, M. A.; Kennedy-Smith, J. J.; Trauner, D.
Organometallics 2005, 24, 2831.
1
0.1021/ol052756e CCC: $33.50
© 2006 American Chemical Society
Published on Web 12/24/2005

the presence of aqueous KOH (1.5 M, 0.20 mL, 0.30 mmol)
in dioxane (1.8 mL) at 30 °C for 1 h. The phenylboronic
acid (3m) used for the present experiments is the com-
mercially available sample received from Tokyo Kasei
Kogyo. While the reaction in the presence of 1.0 or 0.10
mol % of the catalyst 1 gave a quantitative yield of the 1,4-
addition product 4am, further decrease of the catalyst caused
lower yields of 4am. Thus, the yield was 79% in the presence
of 0.05 mol % of catalyst 1 and no 4am was produced with
the catalyst loading of 0.01 mol %. The enantiomeric purity
of 4am was kept high (96% ee (S)) whenever it was obtained.
In the second set of experiments (entries 5-7), the loading
of catalyst 1 was kept constant (0.05 mol %) and the effects
of the amount of boronic acid 3m were studied. To our
surprise, the use of a larger amount of the boronic acid
resulted in a lower yield of the product. The reaction with
3.0 and 5.0 equiv of the boronic acid gave 4am in 37% and
0% yield, respectively. Consistent with this tendency, the
yield was higher (95%) with a smaller amount of boronic
acid (1.2 equiv). In the case of low yields, the starting enone
The catalytic activity of the rhodium complex [RhCl((S,S)-
9
Bn-bod*)]
dibenzylbicyclo[2.2.2]octa-2,5-diene,
the asymmetric 1,4-addition of phenylboronic acid (3m) to
2
(1), where (S,S)-Bn-bod* stands for (S,S)-2,5-
1c,d
was examined for
2
1
-cyclohexenone (2a). In the first set of experiments (entries
-4 in Table 1), the loading of catalyst 1 was decreased
Table 1. Rhodium-Catalyzed Asymmetric 1,4-Addition of
a
b
Phenylboronic Acid (3m) or Phenylboroxine (5m) to
-Cyclohexenone (2a) Catalyzed by [RhCl((S,S)-Bn-bod*)]
2
(1)c
2
2a was recovered in the corresponding amounts. These rather
unusual results may suggest that the phenylboronic acid used
here contains a small amount of a contaminant which
deactivates the catalyst.
Attempts to remove the impurity by recrystallization of
the boronic acid were not successful, no 1,4-addition product
being obtained with the catalyst loading of 0.01 mol %. It
3
m or 5m
catalyst 1
(mol % Rh)
yield (%)
entry
(equiv B to 2a)
of 4amd
% eee
1
2
3
4
5
6
7
PhB(OH)2 (2.0)
PhB(OH)2 (2.0)
PhB(OH)2 (2.0)
PhB(OH)2 (2.0)
PhB(OH)2 (3.0)
PhB(OH)2 (5.0)
PhB(OH)2 (1.2)
(PhBO)3 (1.2)
(PhBO)3 (2.0)
(PhBO)3 (1.2)
1.0
100
100
[79]
[0]
[37]
[0]
95
96
100
71
96 (S)
96 (S)
96 (S)
0.10
0.05
0.01
0.05
0.05
0.05
0.01
0.01
0.005
3
was found that the use of phenylboroxine ((PhBO) , 5m) in
place of phenylboronic acid (3m) greatly improved the
present catalytic reaction. The boroxine 5m, which was
obtained by dehydration of the commercially available
boronic acid 3m by azeotropic removal of water from its
benzene solution and purified by washing the crude boroxine
96 (S)
96 (S)
96 (S)
96 (S)
96 (S)
f
8
9
0
f
g
10
1
repeatedly with hexane, gave high yields of the 1,4-addition
a
Commercially available boronic acid was used as received. b Prepared
product 4am (96% ee) in the presence of 0.01 mol % of the
catalyst 1 (entries 8 and 9). Under the same conditions (0.01
mol % of Rh catalyst), the 1,4-addition did not proceed at
all with phosphorus ligands such as binap or phosphorami-
dites, demonstrating the high catalytic activity of the diene
rhodium catalyst. A larger scale reaction is possible with
0.005 mol % of the catalyst, which gave 71% yield of 4am
in the reaction period of 1 h (entry 10), the turnover
frequency (TOF) of the catalyst being calculated to be 1.4
c
and purified by us (see text). The reaction was carried out with enone 2a
0.60 mmol) and aqueous KOH (1.5 M, 0.20 mL, 0.30 mmol) in dioxane
1.8 mL) at 30 °C for 1 h. Isolated yield of 4am by silica gel
chromatography. The yields in brackets are those obtained by H NMR
with nitromethane as an internal standard. Determined by HPLC analysis
with a chiral stationary-phase column (Chiralcel OD-H). Enone 2a (3.0
mmol) and aqueous KOH (5 M, 0.30 mL, 1.5 mmol) in dioxane (3.0 mL).
The reaction of 1.73 g (18 mmol) of enone 2a.
(
(
d
1
e
f
g
from 1.0 to 0.01 mol % for the reaction of enone 2a (0.60
mmol) with boronic acid 3m (1.2 mmol, 2 equiv to 2a) in
4
-1
×
10 h . To the best of our knowledge, this TOF number
is highest for the catalytic asymmetric carbon-carbon bond-
8
forming reactions including asymmetric 1,4-addition reac-
tions.
(
7) (a) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer-Verlag: Heidelberg, Germany, 1999.
b) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH:
New York, 2000.
8) For reports describing high TOF: (a) Long, J.; Hu, J.; Shen, X.; Ji,
11,12
(
Arylboroxine and water are known to be in a fast
13
equilibrium with arylboronic acid, and hence, the reaction
(
2
-1
B.; Ding, K. J. Am. Chem. Soc. 2002, 124, 10 (TOF ) 1.0 × 10 h ). (b)
Yoshida, T.; Morimoto, H.; Kumagai, N.; Matsunaga, S.; Shibasaki, M.
(10) Washing the solid boroxine with hexane is essential for the required
high purity.
(11) Examples of low catalyst loadings in rhodium-catalyzed asymmetric
1,4-addition: (a) Amengual, R.; Michelet, V.; Gen eˆ t, J.-P. Synlett. 2002,
1791. (b) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1999,
40, 6957. (c) Reetz, M. T.; Moulin, D.; Gosberg, A. Org. Lett. 2001, 3,
4083.
2
-1
Angew. Chem., Int. Ed. 2005, 44, 3470 (TOF ) 2.4 × 10 h ). (c) Kina,
A.; Shimada, T.; Hayashi, T. AdV. Synth. Catal. 2004, 346, 1169 (TOF )
2
-1
3
.5 × 10 h ). (d) Matsunaga, S.; Kinoshita, T.; Okada, S.; Harada, S.;
3 -1
Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 7559 (TOF ) 3.1 × 10 h ).
(
3
e) Davies, H. M. L.; Venkataramani, C. Org. Lett. 2003, 5, 1403 (TOF )
3
-1
.8 × 10 h
)
(9) The rhodium complex was obtained by treatment of (S, S)-Bn-bod*
(12) In the nonasymmetric 1,4-addition of an arylboronic acid, high TOF
1
4
-1
with [RhCl(C2H4)2]2 in chloroform. H NMR (CDCl3): δ 0.24 (m, 4H),
.52 (m, 4H), 2.76 (d, J ) 14.1 Hz, 4H), 3.52 (br, 4H), 3.54 (d, J ) 14.0
Hz, 4H), 4.03 (d, J ) 5.4 Hz, 4H), 7.21 (t, J ) 7.3 Hz, 4H), 7.29 (t, J )
.4 Hz, 8H), 7.35 (d, J ) 7.4 Hz, 8H).
(up to 1.0 × 10 h ) of [Rh(OH)(cod)]2 as a catalyst has been reported:
Itooka, R.; Iguchi, Y.; Miyaura, N. J. Org. Chem. 2003, 68, 6000.
(13) Tokunaga, Y.; Ueno, H.; Shimomura, Y.; Seo, T. Heterocycles 2002,
57, 787.
0
7
342
Org. Lett., Vol. 8, No. 2, 2006

Table 2. Effects of Phenol on Rhodium-Catalyzed Asymmetric
Scheme 1
a
1
,4-Addition of Phenylboroxine (5m) to 2-Cyclohexenone (2a)
b
Catalyzed by Rh/(S,S)-Bn-bod* Complex 1 or 6
Although the 1,4-addition was not completely suppressed,
we suppose that the formation of phenoxy complex 6 is
responsible for the deactivation of the catalyst.
phenol
(equiv to Rh)
catalyst
(0.05 mol % Rh)
yield (%)
of 4amc
entry
% eed
Considering that the phenoxy complex 6 is likely to
undergo the ligand exchange under the reaction conditions
1
2
3
4
5
0
1
1
1
1
6
95
96 (S)
96 (S)
92 (S)
-
with H
2
O (or OH ) giving [Rh(OH)((S,S)-Bn-bod*)]
2
, which
2.0
3.0
5.0
0
[56]
[24]
[0]
15
is assumed to be a catalytically active species, the low yield
(11%) does not contradict our supposition that the phenoxy
complex is not catalytically active for the 1,4-addition.
As shown in Scheme 2, the addition of phenylboroxine
[11]
94 (S)
a
Prepared and purified by us (see text). b The reaction was carried out
with enone (2a, 0.60 mmol), phenylboroxine (5m, 1.2 equiv B to 2a),
aqueous KOH (1.5 M, 0.20 mL, 0.30 mmol), and 1 or 6 (0.05 mol % Rh)
c
in dioxane (1.8 mL) at 30 °C for 1 h. Isolated yield of 4am by silica gel
1
chromatography. The yields in brackets are those obtained by H NMR
with nitromethane as an internal standard. Determined by HPLC analysis
d
Scheme 2
with a chiral stationary-phase column (Chiralcel OD-H).
starting from phenylboronic acid and that starting from
arylboroxine in water should result in the same outcome.
The much higher yield observed here with phenylboroxine
5m than with boronic acid 3m indicates that the impurity
present in the boronic acid was removed during the prepara-
1
tion and purification of the boroxine. H NMR analysis of
the commercially available phenylboronic acid revealed that
it contains 0.05 ( 0.02 mol % of phenol, and it was supposed
that the phenol is the impurity that deactivates the rhodium
catalyst. To verify the deactivation caused by phenol, control
experiments were carried out by addition of phenol to the
reaction system consisting of 2-cyclohexenone (2a), phen-
ylboroxine (5m), and [RhCl((S,S)-Bn-bod*)]
2
(1, 0.05 mol
%
Rh), which otherwise gives a high yield of the 1,4-addition
product 4am (entry 1 in Table 2). As more phenol was added,
the yield of 4am was decreased. Thus, the addition of 2.0
and 3.0 equiv (to Rh) of phenol gave 4am in 56% and 24%
yield, respectively (entries 2 and 3), and the reaction was
completely suppressed by the addition of 5.0 equiv of phenol
(
5m) to 2-cyclopentenone (2b) was also efficiently catalyzed
by 0.01 mol % of the Rh/(S,S)-Bn-bod* catalyst to give 93%
yield of (S)-3-phenylcyclopentanone (4bm) with 94% enan-
tioselectivity. Arylboroxines substituted with 4-fluoro and
4
-methoxy groups, which were prepared and purified in a
(entry 4). These results are in very good agreement with those
manner similar to 5m, were successfully applied to the
asymmetric addition to 2-cyclohexenone as well. The cor-
responding 1,4-addition products 4an and 4ao were obtained
in high yields with high enantioselectivity. Linear enones
were less reactive than cyclic ones, but 0.05 mol % of the
chiral diene-rhodium complex 1 efficiently catalyzed the
asymmetric addition of boroxine 5m to 5-methyl-3-hexen-
observed in the reaction using phenylboronic acid (3m) in
the presence of 0.05 mol % (Rh) of the catalyst (entries 3,
5, and 6 in Table 1), where the boronic acid contains 0.05
(
0.02 mol % of phenol.
On addition of 1 equiv of KOPh to [RhCl((S,S)-Bn-bod*)]
2
1
(1) at 40 °C in THF-d
8
, we observed ( H NMR) exclusive
formation of a new rhodium species which is assigned to be
1
6
14
2-one (2c) and 3-nonen-2-one (2d).
phenoxy complex [Rh(OPh)((S,S)-Bn-bod*)]
2
(6) (Scheme
In summary, the rhodium complex coordinated with chiral
diene ligand (S,S)-Bn-bod* showed its high performance as
a catalyst in the asymmetric 1,4-addition of arylboroxines
1
). The use of phenoxy complex 6 as a catalyst (0.05 mol %
of Rh) for the reaction of 2a with boroxine 5m gave 11%
yield of the 1,4-addition product 4am (entry 5 in Table 2).
1
(
14) H NMR (THF-d8): δ 0.26 (m, 4H), 0.37 (m, 4H), 1.76 (d, J )
(15) A hydroxorhodium complex, [Rh(OH)(binap)]2, was reported to be
an active catalyst for the asymmetric 1,4-addition (ref 5b).
(16) The use of 0.05 mol % of catalyst 1 for the addition of boroxine
5m to R,â-unsaturated esters and amides failed probably due to their lower
reactivity.
1
3.8 Hz, 4H), 2.78 (d, J ) 6.1 Hz, 4H), 2.98 (d, J ) 14.0 Hz, 4H), 3.90 (d,
J ) 5.6 Hz, 4H), 6.72 (t, J ) 7.2 Hz, 2H), 7.09 (d, J ) 7.6 Hz, 4H), 7.15
(
(
t, J ) 7.6 Hz, 4H), 7.31 (t, J ) 7.4 Hz, 4H), 7.41 (t, J ) 7.6 Hz, 8H), 7.46
d, J ) 7.8 Hz, 8H).
Org. Lett., Vol. 8, No. 2, 2006
343

to R,â-unsaturated ketones. The catalyst loading of 0.005-
.01 mol % efficiently catalyzed the reaction without loss
of enantioselectivity. The deactivation of catalyst caused by
a small amount of phenol, which is found during this study,
provides us with a significant information on the mechanism
of rhodium-catalyzed 1,4-addition reactions.
Education, Culture, Sports, Science and Technology, Japan.
A.K. thanks the Japan Society for the Promotion of Science
for the award of a fellowship for graduate students.
0
Supporting Information Available: Experimental pro-
cedures and spectroscopic data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research, the Ministry of
OL052756E
344
Org. Lett., Vol. 8, No. 2, 2006