Preparation of chiral 7,7′-disubstituted BINAPs for Rh-catalyzed 1,4-addition of arylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2004.11.096

A series of new 7,7′-disubstituted BINAPs were readily prepared starting with an asymmetric catalytic oxidative coupling. They were applied as ligands to rhodium catalyzed 1,4-addition of arylboronic acids to enones, resulting in enantioselectivities of u

Full text of DOI:10.1016/j.tetlet.2004.11.096

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 509–512
Preparation of chiral 7,70-disubstituted BINAPs for
Rh-catalyzed 1,4-addition of arylboronic acids
Wei-Cheng Yuan, Lin-Feng Cun, Liu-Zhu Gong,* Ai-Qiao Mi and Yao-Zhong Jiang
Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan, Province and Union Laboratory of Asymmetric Synthesis,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China
Graduate School of Chinese Academy of Sciences, Beijing, PR China
Received 2 August 2004; revised 28 October 2004; accepted 2 November 2004
Available online 7 December 2004
Abstract—A series of new 7,70-disubstituted BINAPs were readily prepared starting with an asymmetric catalytic oxidative cou-
pling. They were applied as ligands to rhodium catalyzed 1,4-addition of arylboronic acids to enones, resulting in enantioselectivities
of up to 99% ee. The enantioselectivity was found to be dependent on the size of achiral substituents.
Ó 2004 Elsevier Ltd. All rights reserved.
Asymmetric conjugate addition of organometallic re-
agents to electron-deficient olefins is one of the most ver-
satile methods for forming carbon–carbon bonds.1
Organozinc addition to enones in the presence of copper
complexes of chiral phosphorus ligands has an impres-
sive advance,2 however it only provides excellent results
with alkylzinc and thus suffers from the poor efficiency
in reactions with arylzincs. Since the first example of
highly enantioselective 1,4-addition of arylboronic acids
to a,b-unsaturated carbonyl compounds catalyzed by
Rh-BINAP was reported by Miyaura and co-workers,3
it has been an attractive method for the introduction
of aryl functions.4 Although a number of bi- and
monodentate ligands have been tested for this reaction,
few chiral ligands show excellent stereocontrol. The use
of BINAP as a ligand is most frequent.4,5 Therefore, an
active search for new efficient ligands for Rh(I) cata-
lyzed 1,4-addition remains extremely valuable.
As a logical extension of this project, we were interested
to prepare 7,70-disubstituted 2,20-bis(diphenylphosph-
ino)-1,10-binaphthyls (7,70-disubstituted BINAPs 1a–e,8
Fig. 1) starting from optically pure 7,70-disubstituted
BINOLs, and to investigate their applications in the
asymmetric catalysis. Compared with BINAP, these
7,70-disubstituted BINAPs have their own structural
features: firstly, they have two electron-donating groups
at 7,70-positions; secondly the dihedral angles of these li-
gands are tunable by changing the substituent size. Sub-
tle variation of the dihedral angle and electrical density
generally leads to the improvement of catalytic perfor-
mance of the ligand,9 therefore 7,70-disubstituted BI-
NAPs might exhibit different catalytic performance
from BINAP in Rh-catalyzed 1,4-addition of arylbo-
ronic acids. Herein, we present the preparation of
7,70-disubstituted BINAPs and their application to
Rh-catalyzed highly enantioselective 1,4-addition of aryl-
boronic acids. The dramatic influence of achiral substi-
tuents on the enantioselectivity is also be reported.
Recently, we developed two types of chiral oxovan-
adium complexes, which catalyze the oxidative coupling
of 2-naphthols in very high enantioselectivity.6 On the
basis of catalytic procedures, optically pure 7,70-disub-
stituted BINOLs have been prepared conveniently, and
their application in catalytic phenylacetylene addition
to aldehydes results in excellent enantioselectivities.7
O
PPh2
PPh2
MeO
MeO
PPh2
PPh2
O
O
PPh2
PPh2
n(H2C)
O
O
n
Keywords: 7,70-Disubstituted BINAP; 1,4-Addition; Arylboronic
acids; Asymmetric catalysis.
1a
1b, n=6
1c, n=8
1d, n=1
1e, n=2
*
Corresponding author. Fax: +86 28 85223978; e-mail: gonglz@
cioc.ac.cn
Figure 1. The chiral ligands evaluated for this study.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.096

510
W.-C. Yuan et al. / Tetrahedron Letters 46 (2005) 509–512
ref. 6
O
O
OH
OH
ref. 7
A
RO
RO
OH
OH
O
OH
2
3
4
O
PPh2
RO
RO
C
RO
RO
PPh2
OTf
B
B
RO
RO
OTf
OTf
OTf
6
7
5
O
O
N
V O
O
O
O
V O
O
1a, 64% yield
1b, 47% yield
1c, 44% yield
1d, 56% yield
1e, 49% yield
PPh2
PPh2
RO
RO
RO
RO
PPh2
PPh2
C
N
O
O
8
Chiral oxovanadium
complex
Scheme 1. Preparation of chiral 7,70-disubstituted BINAPs 1a–e. Reagents and conditions: (A) Tf2O, pyridine, dichloromethane, 0 °C, 3 h (>99%);
(B) Ph2P(O)H (2 equiv), 5 mol% Pd(OAc)2, 5 mol% dppb, iPr2NEt, DMSO, 100 °C, 8 h; (C) Cl3SiH, iPr2NEt, toluene, 110 °C, 10 h (44–64% overall
yields of four steps from 5).
Starting with an asymmetric oxidative coupling of 7-all-
oxyl-2-naphthol (2) in the presence of 5 mol% chiral
oxovanadium catalyst, optically pure 7,70-binaphthols
4 were readily prepared according to the known proce-
dure developed by this group (Scheme 1).6,7 The syn-
thetic approach to 7,70-disubstituted BINAP 1 from
7,70-disubstituted BINOLs 4 followed the reported pro-
cedures (Scheme 1).10 The reactions of 4 with trifluo-
romethane sulfonic anhydride (Tf2O) in the presence
of pyridine in CH2Cl2 provided 5 in quantitative yields.
Monophosphinylation of 5 with two equivalents of
diphenylphosphine oxide in the presence of 5 mol% of
a palladium complex, in situ generated from palladium
acetate and 1,4-bis(diphenylphosphino)butane (dppb),
gave compounds 6, which were subsequently reduced
into 7 with trichlorosilane (Cl3SiH). The reactions of 7
with diphenylphosphine oxide under similar conditions,
for the preparations of 6 from 5 furnished 8. Com-
pounds 8 were reduced with Cl3SiH again to afford the
desired chiral ligands 1a–e. Although the synthetic route
looks long, the purification of each of the intermediates
6–8 was usually unnecessary and thus the chiral ligands
1 were obtained conveniently in 44–64% overall yields.
4), same as that observed with BINAP.3 However, a
much lower enantioselectivity of 38% ee was provided
by 1e (entry 5), which has a bigger achiral crown ether
substituent than 1d. Because crown ethers are easy to
coordinate with some metal ions,12 we reasoned that
the complexation of metal ions with the crown ether
moiety of ligand 1e could produce some difference in
its catalytic performance.13 Indeed 1e, as a ligand,
showed an increased enantioselectivity by more than
10% ee by the addition of KF, NaF and LiF as guests
into the reaction solution (entries 6–8). Although the
difference are not significant, the results imply that
the supramolecular effect on the stereocontrol exist in
the cases where ligands bearing achiral crown ether sub-
stituents. The dramatic difference of the enantioselectivity
Table 1. Asymmetric 1,4-addition of phenylboronic acid to cyclohex-
enone catalyzed by ligands 1–Rhodium(I) complexes
O
O
3 mol%Rh(acac)(C2H4)2
1 (1 equiv to Rh)
+
PhB(OH)2
10a
*
dioxane/H2O (10/1)
100 o
Ph
9a
C
11aa
For screening the catalytic efficiency of chiral ligands 1,
a model reaction of cyclohexenone with phenylboronic
acid was performed under conditions developed by Hay-
ashi and co-workers3,11 As shown in Table 1, the size of
the achiral substituent on the ligand has an obvious
influence on the enantioselectivity, thus subtle alteration
of achiral substituents leads to a significantly different
catalytic performance (entries 1–5). 1a has two more
methoxyl groups at its 7,70-positions than BINAP, but
gave a much lower enantioselectivity of 36% ee (entry
1). Varying the ring size of the 7,70-substituents on the
ligands, which are shown as 1b–e, leads to significantly
different results (entries 2–5). Among these ligands, 1d
gave the best level of enantioselectivity of 97% ee (entry
Entry BINAPs Additive Time (h) Yield (%)a Ee (%)b
1
2
1a
1b
1c
1d
1e
1e
1e
1e
1d
1d
—
—
5
5
5
5
5
5
5
5
5
8
92
83
94
99
89
80
73
81
92
75
36
33
46
97
38
51
49
52
97
92
3
—
—
4
5
—
6
LiFc
NaFc
KFc
—
7
8
9
10
—
a Isolated yield based on cyclohexenone.
b Determined by HPLC and the absolute configuration is R.
c The ratio of additive to 1e = 1.2:1.

W.-C. Yuan et al. / Tetrahedron Letters 46 (2005) 509–512
511
Table 3. Asymmetric 1,4-addition of phenylboronic acids to enones 9
catalyzed by Rh(I) complex of 1d
depending on the substituent size and the supramolecu-
lar effects might be attributed to the bite angle effect.5c,9
It is noteworthy that decreasing the catalyst loading
from 3 mol% to 0.5 mol% does not lead to a pro-
nounced decrease in catalytic efficiency (entries 9 and
10). A high enantioselectivity of 97% ee and yield of
92% was maintained by 1 mol% catalyst (entry 9). As
little as 0.5 mol% of the catalyst still gave a high enantio-
selectivity of 92% ee, but the yield dropped to 75% and
the reaction time needed to be prolonged (entry 10).
O
3 mol%Rh(acac)(C H )
2
4 2
O
Ph
*
1d (1 equiv to Rh)
1
2
+
PhB(OH)
10a
R
R
2
2
1
R
R
dioxane/H O (10/1)
2
9a-d
11aa-da
o
100
C
Entry
1
Enones 9
Time (h)
5
Yield (%)a
99
Ee (%)b
97
O
(9a)
O
To determine if the optimal catalyst generated from
Rh(acac)(C2H4) and the ligand 1d maintains a generally
high enantioselectivity for arylboronic acids, the 1,4-
addition of a range of arylboronic acids bearing either
electron donating or withdrawing substituents to cyclo-
hexenone were conducted. As shown in Table 2, the pres-
ent catalyst tolerates a broad scope of substrates. The
reactions proceeded successfully to give corresponding
products in high yields and excellent enantioselectivities
ranging from 94% to 99% ee. In most cases, the enantio-
selectivities for Rh(I)–1d were as high as those for
Rh(I)–BINAP,3 but was more enantioselective than
Rh(I) complexes of some monodentate ligands5a,d,e
and bidentate ligands such as diphosphonite5c and
diphosphines5f under similar reaction conditions. Nota-
bly, the addition of 4-methoxyphenylboronic acid (10c)
to cyclohexenone does not take place to give 3-(4-meth-
oxyphenyl)cyclohexanone 11ac using Rh-BINAP as a
catalyst,3 and thus a lithium trimethyl 4-methoxyphen-
ylborate has to be used to replace methoxyphenylbo-
ronic acid (10c) for a successful transformation.14
However, the reaction of methoxyphenylboronic acid
(10c) with cylcohexenone catalyzed by Rh-1d proceeded
smoothly in 90% yield and 96% ee (entry 3).
2
3
4
5
5
5
90
82
88
90c
90
(9b)
O
(9c)
O
97
(9d)
a Isolated yield based on unsaturated ketone.
b Determined by HPLC and the absolute configuration is R.
c Determined by GC and the absolute configuration is R.
(entry 1), both more and less flexible enones, for exam-
ple, cyclopentenone (9b) and cycloheptenone (9c) affor-
ded products with lower yield, but still high
enantioselectivities of 90% ee values, respectively (entries
2 and 3). An acyclic alkenone 9d reacted with phenyl-
boronic acid to furnish 11da with a yield of 88% and
an excellent enantioselectivity of 97% ee (entry 4).
In summary, 7,70-disubstituted BINAPs 1 have been
readily prepared on the basis of our chiral oxovanadium
complex catalyzed asymmetric oxidative coupling of 7-
alloxyl-2-naphthol. Their applications to rhodium cata-
lyzed 1,4-additions of arylboronic acids to enones led to
products with enantioselectivities of up to more than
99% ee. We found that the achiral substituents on the li-
gands play an important role in controlling of stereo-
chemistry. The dependence of catalytic performance of
ligands on the substituent size could be due to the subtle
variation of bite angle. Our preliminary results demon-
strate that the new 7,70-disubstituted BINAPs are useful
in asymmetric catalysis. Applications of these new
ligands to other asymmetric reactions are now in
progress.
Different types of unsaturated ketones as 1,4-addition
acceptors were finally test to further determine the scope
and limitation of the new catalyst. Once again, the rho-
dium complex of 1d showed high catalytic activity and
enantioselectivity for enones with different structural
features (Table 3). Compared with cyclohexenone 9a
Table 2. Asymmetric 1,4-addition of arylboronic acids to cyclohex-
enone catalyzed by Rh(I) complex of 1d
O
O
3 mol%Rh(acac)(C2H4)2
1d (1 equiv to Rh)
+
ArB(OH)2
10a-g
*
dioxane/H2O (10/1)
100 o
Ar
Acknowledgements
9a
11aa-ag
C
Entry ArB(OH)2 Ar
Time (h) Yield Ee (%)b
(%)a
We are grateful for financial support from the National
Natural Science Foundation of China (Projects
203900505 and 20325211) and Sichuan province.
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10f
10g
Ph
4-ClC6H4
5
5
5
5
5
5
5
99
85
90
92
86
84
97
97
98
4-MeOC6H4
3-MeOC6H4
4-tBuC6H4
4-CF3C6H4
4-CH3C6H4
96
96
References and notes
>99
>99
94
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