Bipyridyl-based diphosphine as an efficient ligand in the rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to α,b-unsaturated ketones

Article abstract of DOI:10.1016/S0040-4039(03)01592-2

Reactions of α,b-unsaturated ketones with excess arylboronic acids in the presence of a rhodium catalyst generated in situ from Rh(acac)(C2H4)and (S)-P-Phos in dioxane/water at 100 deg C gave high yields of the corresponding products in up to 99 percent ee.

Full text of DOI:10.1016/S0040-4039(03)01592-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6505–6508
Bipyridyl-based diphosphine as an efficient ligand in the
rhodium-catalyzed asymmetric conjugate addition of arylboronic
acids to a,b-unsaturated ketones
Qian Shi,a,c Lijin Xu,a Xingshu Li,a,* Xian Jia,a Ruihu Wang,a,c Terry T.-L. Au-Yeung,a
Albert S. C. Chan,a,* Tamio Hayashi,a,b Rong Caoc and Maochun Hongc
aOpen Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis† and
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
bDepartment of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
cState Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter,
The Chinese Academy of Sciences, Fuzhou 325000, China
Received 2 May 2003; revised 28 May 2003; accepted 17 June 2003
Abstract—Reactions of a,b-unsaturated ketones with excess arylboronic acids in the presence of a rhodium catalyst generated in
situ from Rh(acac)(C2H4) and (S)-P-Phos in dioxane/water at 100°C gave high yields of the corresponding products in up to 99%
ee.
© 2003 Elsevier Ltd. All rights reserved.
The rhodium(I)-catalyzed 1,4-addition of aryl or
alkenyl boronic acids to unsaturated compounds con-
taining electron-deficient groups, first reported by
Miyaura in 1997, is emerging as a new and powerful
tool to introduce aryl or alkenyl groups to Michael
acceptors.1,2 By employing a BINAP-based rhodium
complex as catalyst, Hayashi and his co-workers devel-
oped the asymmetric version of 1,4-addition of
organoboronic acids to a,b-unsaturated ketones.3
Extension of this methodology to a,b-unsaturated
esters,4a,d,g 1-alkenylphosphonates,4b 1-nitroalkenes,4c
and a,b-unsaturated amides4e,f,g also afforded good
yields and high enantioselectivities. Among other chiral
ligands examined, including water-soluble Digm-
BINAP,5 BINOL-based diphosphonites,6 hemilabile
bidentate amidomonophosphine7 and other chelating
diphosphines,3d,4e BINAP was found to give rise to the
most active and enantioselective catalysts. Lately, the
Hayashi group disclosed a detailed study of the reac-
tion mechanism, and discovered an even more active
rhodium(I) catalyst employing (S)-BINAP as a ligand.8
More recently, Feringa et al. reported that monoden-
tate phosphoramidites could be used as ligands in this
reaction to give products in up to 89% ee.9 It becomes
obvious that the structure of the ligand has a significant
effect on the reactivity of the metal complex and enan-
tioselectivity of the products.
Recently metal complexes of bipyridyl-based diphos-
phine, e.g. P-Phos, and its derivatives have been shown
to be highly active and enantioselective catalysts in
asymmetric hydrogenations10 and carbonylations,11
suggesting that the rigidity of the bipyridyl backbone
allows good transfer of chiral information. In this
article, we wish to report results of P-Phos as a ligand
in Rh(I)-catalyzed 1,4-addition of boronic acids to
enones.
* Corresponding authors. E-mail: bcachan@polyu.edu.hk
† A University Grants Committee Area of Excellence in Hong Kong.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01592-2

6506
Q. Shi et al. / Tetrahedron Letters 44 (2003) 6505–6508
Enones 1b–e underwent the reaction with phenyl-
boronic acid 2a smoothly, providing high yields and
enantioselectivites (entries 1–4). For example, asymmet-
ric addition of phenylboronic acid to enone 1c cata-
lyzed by the Rh(I)/(S)-P-Phos complex led to 88% yield
and 98% ee. Yet, when the (S)-BINAP-Rh(I) was used
for this addition, the yield and enantioselectivity were
reported to be 51 and 93%, respectively.3a In the reac-
tion of arylboronic acid 2b, it was found that a reduced
amount of water favored the addition, affording higher
yield (entry 5 versus 6). Using 5 equiv. of 2b and 3
mol% Rh(I)/(S)-P-Phos in dioxane/H2O (20/1) at 100°C
for 5 h, 90% yield and 99% ee were achieved, whereas
no addition product was formed using the Rh(I)/
BINAP catalyst.2b,3c Both the yield and ee suggest that
P-Phos may efficiently retard the competing hydrolysis
of the boronic acid giving methoxybenzene. In the
presence of a reduced amount of water, similarly good
results were also found in the reactions of 2b with
enones 1b and 1c (entry 7 versus 8 and entry 9 versus
10). Excellent enantioselectivities and yields were also
observed in the reactions of 2-cyclohexenone 1a with a
wide array of arylboronic acids 2c–i (entries 11–17). It
is worth noting that in the addition of arylboronic acid
2e to 2-cyclohexenone 1a catalyzed by Rh(I)/(S)-
BINAP the yield was disappointingly low.8 In contrast,
when Rh(I)/(S)-P-Phos catalyst was employed, the yield
rose to 97% (entry 13). For the ortho-substituted aryl-
boronic acid 2j, high yield and enantioselectivity were
obtained with lower-water-content solvent system, indi-
cating that steric hindrance does not cause great distur-
bance to the reaction (entry 18 versus 19). In the case of
2k, the reduced amount of water did improve the
reaction as indicated by an increase of yield from 15%
to 44% (entry 20 versus 21). Further reduction of the
water-to-dioxane ratio did not lead to improved yield
beyond 45%. Two possible intervening events may be
operative: (1) Because of the similar p-releasing prop-
erty of MeO in 2k and 2b (versus the meta-analog 2f),
hydrolysis of 2k to produce methoxybenzene may just
be as facile. (2) Considering the oxophilicity of Rh(I),
the low yield may be ascribed to the existence of
intramolecular chelation, which has been observed in
the coordination chemistry of rhodium complexes.12
In the model reaction, 2-cyclohexenone 1a was treated
with phenylboronic acid 2a in the presence of 3 mol%
[Rh(acac)((S)-P-Phos)], which was generated in situ
from equimolar of Rh(acac)(CH2=CH2)2 and (S)-P-
Phos in dioxane/H2O (10/1) at 100°C. Considering the
possibility of the hydrolysis of arylboronic acid under
the reaction conditions,2b an excess amount of phenyl-
boronic acid (5 equiv.) was added. After stirring for 1
h, the reaction went to completion to give the adduct 3a
with almost quantitative yield (>99%) and excellent ee
(99%).13 The result compares favorably with those
obtained with BINAP. According to Tomioka, the
catalytic performance of BINAP strongly depends on
the initial procedure.7a To test this effect, the same
reaction promoted by Rh(I)/(S)-P-Phos was then con-
ducted with a different initial procedure. Thus, the
reaction mixture was first allowed to warm from ambi-
ent temperature to 100°C in 10 min, followed by stir-
ring for
a further 1 h. The same yield and
enantioselectivity were obtained, implying that the cata-
lytic performance of P-Phos is independent of the initial
procedure. Table 1 summarizes the results obtained
under the former reaction conditions at various temper-
atures. It was found that high chemical yield and
enantioselectivity were dependent on the reaction tem-
perature. As can be seen from Table 1, the reaction
temperature of 100°C was found to be optimum. At
room temperature, after stirring for 5 h, no product
was observed. When the temperature was raised to
40°C, the 1,4-addition still remained sluggish, providing
3a in less than 5% yield after 5 h. At 80°C, the yield
increased to 70% after 5 h of stirring with 99% ee.
Noticeably, a higher temperature (cf. 120°C, entry 5)
decreased the otherwise good yield and ee. Similar
temperature effect was noted with Rh(I)/BINAP as a
catalyst.3d
A variety of a,b-unsaturated ketones as well as aryl-
boronic acids were coupled in the Rh(I)/(S)-P-Phos
catalyzed 1,4-conjugate addition under conditions simi-
lar to the addition of phenylboronic acid to 2-cyclo-
hexenone 1a. The results are summarized in Table 2.
Table 1. Asymmetric 1,4-addition of phenylboronic acid
2a to 2-cyclohexenone 1a catalyzed by Rh(I)/(S)-P-Phosa
In conclusion, P-Phos has been shown to be an efficient
ligand in the rhodium-catalyzed 1,4-addition of aryl-
boronic acids. The activity and stereorecognition ability
of Rh(I)/P-Phos catalyst in this addition reaction is
comparable to, or at times better than, those observed
with BINAP, BINOL-based diphosphonites and hemi-
labile bidentate amidomonophosphine.
Entry
Temp. (°C)
Time (h)
Yield (%)
Ee (%)b
1
2
3
4
5
100
25
40
80
120
1
5
5
5
5
>99
0
5
70
79
99
–
97
99
97
Acknowledgements
We thank The Hong Kong Research Grants Council
Central Allocation Fund (Project ERB003), The Uni-
versity Grants Committee Areas of Excellence Scheme
in Hong Kong (AoE P/10-01) and The Hong Kong
Polytechnic University ASD Fund for financial support
of this study.
a Reactions were carried out with 1a (0.40 momol), 2a (2.0 mmol)
under N2 in dioxane (1 ml)/H2O (0.1 ml).
b Determined by HPLC analysis using a Daicel Chiralcel OD-H chiral
stationary phase column.

Q. Shi et al. / Tetrahedron Letters 44 (2003) 6505–6508
6507
Table 2. Asymmetric 1,4-addition of arylboronic acids to a,b-unsaturated ketones catalyzed by Rh(I)/(S)-P-Phosa
Entry
Ketone 1
ArB(OH)2 (equiv. to 1)
Time (h)
Yield (%)
Ee (%)c
1
2
3
4
1b
1c
1d
1e
1a
1a
1b
1b
1c
1c
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
2a (1.4)
2a (1.4)
2a (2.5)
2a (5.0)
2b (5.0)
2b (5.0)
2b (5.0)
2b (5.0)
2b (5.0)
2b (5.0)
2c (5.0)
2d (5.0)
2e (5.0)
2f (5.0)
2g (5.0)
2h (5.0)
2i (5.0)
2j (5.0)
2j (5.0)
2k (5.0)
2k (5.0)
5
5
5
5
5
5
5
5
5
5
4
4
4
4
4
4
4
5
5
5
5
89
88
90
86
82
90
77
90
62
86
>99
97
97
95
97
94
98
74
90
15
44
97
98
90
96
99
99
99
99
99
99
99
99
96
99
99
99
97
99
99
99
99
5
6b
7
8b
9
10b
11
12
13
14
15
16
17
18
19b
20
21b
a Reactions were carried out under N2 in dioxane (1 ml)/H2O (0.1 ml) at 100°C in the presence of 3 mol% of the catalyst generated from
Rh(acac)(C2H4)2 and (S)-P-Phos.
b Dioxane (1 ml)/H2O (0.05 ml).
c Determined by HPLC analysis using Daicel Chiralcel chiral stationary phase columns.
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