Enantioselective arylation of aldehydes catalyzed by a soluble optically active polybinaphthols ligand

Article abstract of DOI:10.1016/j.tetlet.2008.09.072

A soluble chiral polymer ligand was synthesized by the polymerization of (R)-6,6′-dibutyl-3,3′-diformyl-2,2′-binaphthol (R-M-1) with 2,5-diaminopyridine (M-2) via a nucleophilic addition-elimination reaction. While arylboronic acids were used as the source of the transferable aryl group, the chiral polybinaphthols ligand in combination with Et₂Zn without Ti(OⁱPr)₄ exhibited higher enantioselectivity in asymmetric addition to aromatic aldehydes than alphatic aldehydes. When aromatic aldehydes with electron-withdrawing groups were chosen as substrates, the resulting diarylmethanols were produced in higher ee values than those with electron-donating groups as substrates. 2-Naphthaldehyde used as a substrate afforded product in 95% ee, which could be ascribed to the steric effect influence on this asymmetric arylation reaction. Moreover, the chiral polymer was easily recovered and reused, but exhibited a decrease of enantioselectivity in the third recycle.

Full text of DOI:10.1016/j.tetlet.2008.09.072

Tetrahedron Letters 49 (2008) 6823–6826
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Enantioselective arylation of aldehydes catalyzed by a soluble
optically active polybinaphthols ligand
a,b
a
a
a
a
a,*
Xiaobo Huang , Linglin Wu , Jinqian Xu , Lili Zong , Hongwen Hu , Yixiang Cheng
a
Key Lab of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China
College of Chemistry and Materials Engineering, Wenzhou University,Wenzhou 325027, PR China
b
a r t i c l e i n f o
a b s t r a c t
0
0
Article history:
Received 7 May 2008
Revised 7 September 2008
Accepted 12 September 2008
Available online 17 September 2008
A soluble chiral polymer ligand was synthesized by the polymerization of (R)-6,6 -dibutyl-3,3 -diformyl-
2
0
,2 -binaphthol (R-M-1) with 2,5-diaminopyridine (M-2) via a nucleophilic addition–elimination reac-
tion. While arylboronic acids were used as the source of the transferable aryl group, the chiral poly-
binaphthols ligand in combination with Et Zn without Ti(O Pr) exhibited higher enantioselectivity in
2 4
asymmetric addition to aromatic aldehydes than alphatic aldehydes. When aromatic aldehydes with
electron-withdrawing groups were chosen as substrates, the resulting diarylmethanols were produced
in higher ee values than those with electron-donating groups as substrates. 2-Naphthaldehyde used as
a substrate afforded product in 95% ee, which could be ascribed to the steric effect influence on this asym-
metric arylation reaction. Moreover, the chiral polymer was easily recovered and reused, but exhibited a
decrease of enantioselectivity in the third recycle.
i
Keywords:
Chiral BINOL-based polymer
Asymmetric addition
Enantioselectivity
Ó 2008 Elsevier Ltd. All rights reserved.
0
Optically active 1,1 -bi-2-naphthol (BINOL) is one of the most
available aryl boronic acids as the source of the transferable aryl
groups. This improved methodology broadened the scope of this
7
important C
2
symmetric compounds. The chirality of BINOL and
its derivatives is derived from the restricted rotation of the two
asymmetric addition reaction as it avoided the tedious and difficult
preparation of diarylzinc reagents. But so far this asymmetric aryl-
ation of aldehydes by using boronic acids as the aryl source has not
been extensively studied. Development of an efficient chiral ligand
for this kind of asymmetric aryl transfer reaction still remains to be
1
naphthalene rings. The versatile skeletal structure of BINOL at
0
0
0
3
,3 -, 5,5 - and 6,6 -positions can be systematically modified by
strategic placement of substituents at the well-defined molecular
level. These novel BINOL-based derivatives exhibit efficient and
stable chiral configuration as well as high chiral induction in
molecular recognition and asymmetric processes.2 In the past
decade, there have been a few reports on the design and synthesis
of a series of the polymer ligands incorporating optically active
binaphthol moiety in the polymer main chain backbone. These
chiral polybinaphthols are often used to coordinate with metal
ions such as Al(III), Ti(IV), Zn(II) and Ln(III) to generate highly
enantioselective Lewis acid catalysts for many asymmetric organic
8
an attractive topic.
To our knowledge, there has not been any report on the
BINOL-based polymer ligand for the enantioselective arylation of
aldehydes using boronic acids as the aryl source. In this Letter,
we describe the synthesis of a soluble chiral polymer ligand and
its application in the asymmetric catalytic arylation of aldehydes.
0
The chiral ligand incorporating (R)-2,2 -binaphthol and pyridine-
based imine moieties can be alternatively organized in a regular
polymer chain. This kind of bifunctional Lewis-acid base ligand
has attracted much attention in asymmetric catalytic reactions,
3
transformations.
The enantioselective arylation of aldehydes has received in-
creased attention because it gives access to chiral diarylmethanols,
which play an important role in synthesis of some pharmacological
2
a
such as the addition of dialkylzinc to aldehydes. In order to
improve solubility of the polymer ligand in the common organic
4
0
and biologically active compounds in recent years. Since Fu and
solvents, n-butyl group is introduced into the 6,6 -positions of
co-workers first reported the enantioselective addition of diphen-
ylzinc to aldehydes by using a catalyst based on a planar-chiral
azoferrocene ligand, there have been some reports on the enantio-
BINOL as the side chain. The use of soluble chiral polymer catalyst
for asymmetric synthesis has practical advantages. First, the chiral
9
5
polymer catalyst can show excellent catalytic activity and enanti-
oselectivity due to the homogeneous reaction system. Second,
when the reaction is completed, the polymer catalyst can be easily
separated from the reaction mixture by precipitation and simple
filtration upon the addition of MeOH solvent.
selective arylation of aldehydes catalyzed by different chiral
6
ligands. Bolm and co-workers described a notable method to
synthesize various chiral diarylmethanols using commercially
The synthesis of monomer R-M-1 and the polymer ligand is
shown in Scheme 1. R-M-1 was obtained from a 7-step reaction
*
Corresponding author. Tel.: +86 25 83592709; fax: +86 25 83317761.
E-mail address: yxcheng@nju.edu.cn (Y. Cheng).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.072

6
824
X. Huang et al. / Tetrahedron Letters 49 (2008) 6823–6826
n-Bu
n
-Bu
CHO
(1) Br2
(
2) NaH/MOMCl
(1) n
-BuLi
OH
OH (3)
4)
OMOM
OH
OH
n
-BuLi
-BuBr
OMOM (2) DMF
(
n
(3) HCl
n-Bu
n
-Bu
CHO
n-Bu
Bu-n
R-BINOL
R-M-1
N
OHHO
N
H N
2
NH2 M-2
N
N
N
N
N
OHHO
[
]
n
n
-Bu
Bu-n
Scheme 1. Synthesis procedures for the chiral polymer ligand.
0
0
to ensure high enantioselectivity.2b,7,8b,12 In our study, we found
procedure from (R)-BINOL. (R)-6,6 -Dibromo-2,2 -bis(methoxy-
0
0
0
methoxy)-1,1 -binaphthyl and (R)-6,6 -dibutyl-2,2 -bis(methoxy-
methoxy)-1,1 -binaphthyl were synthesized according to reported
that the ee value (83%, entry 1) of the diarylmethanol obtained
0
i
by asymmetric addition in the presence of Ti(O Pr)
4
was lower than
1
0
0
0
0
i
literature. (R)-6,6 -Dibutyl-2,2 -bis(methoxymethoxy)-1,1 -bina-
phthyl was first lithiated with n-BuLi, and then followed by car-
bonylation to afford the MOM-protected intermediate. The crude
product R-M-1 was obtained by the removal of the protecting
groups in HCl solution. The purification of R-M-1 was carried out
by column chromatography on silica gel to afford a solid product
that without Ti(O Pr)
4
(91%, entry 2). Therefore in this Letter, chiral
Zn without
4
was used to catalyze the asymmetric addition reactions.
polybinaphthols ligand in combination with Et
2
i
Ti(O Pr)
In order to evaluate the enantioselectivity of the chiral ligand for
asymmetric addition, both aromatic and alphatic aldehydes were
chosen as substrates, and different solvents, such as toluene, THF
1
1
in 38.4% yield. The chiral polymer was prepared in 75.9% yield
2 2
and CH Cl , were screened too. The enantioselective data are sum-
by the reaction of R-M-1 with monomer 2,5-diaminopyridine
marized in Table 1. The results showed that toluene gave the best
yield and enantioselectivity (entries 2, 3 and 4). So, asymmetric
addition reactions were conducted using arylboronic acids, Et Zn,
2
chiral polymer ligand (based on BINOL unit) and aldehyde with a
molar ratio of 2.4:7.2:0.1:1 in toluene. The resulting catalyst can
be obtained by the reaction of chiral polymer in combination with
1
2
25
(
M-2). The specific rotation value (½
is +216.0 (c 0.5, CH Cl
298.0 (c 0.1, CH Cl
a
ꢀ ) of the monomer R-M-1
D
2
2
), while the chiral polymer ligand is
) with the reversed signal. The catalytical cen-
ꢁ
2
2
0
tre of optically active 2,2 -binaphthol can orient in a well-defined
spatial arrangement. Unlike the traditional chiral polymeric cata-
lysts, which are prepared by anchoring a chiral ligand to a flexible
and sterically irregular achiral polymer backbone, these stereoreg-
ular chiral BINOL-based polymer ligands can generate regularly
oriented catalytic sites along the polybinaphthols chain backbone
and produce a well-defined microenvironment around the catalyt-
ically chiral centres. Therefore, it is possible to systematically ad-
just the microenvironment of the catalytic sites in the chiral
polymer ligand to achieve the desired catalytic activity and
2
Et Zn and the boronic acids at 60 °C for 10 h. The absolute config-
uration and ee of the corresponding alcohol product can be
assigned to R or S by comparing its HPLC data with those previ-
6
h,j,7,8g,h,14
ously reported in the literature.
As shown in Table 1, the resulting configuration of products was
R when aromatic aldehydes were used as substrates (entries 1–12),
but S when the substrates were aliphatic aldehydes (entries 13–
15). Based on Pu’s reports, the catalytic diarylzinc (prepared in
situ) occurred at the re face of the aldehydes, and the arylboronic
acids addition to aldehydes may be mechanistically similar to the
1
3
enantioselectivity.
The GPC result of the chiral polymer shows the moderate
molecular weight. The chiral polymer ligand is an air stable solid
with deep yellow colour and shows good solubility in some com-
6
j,15
diethylzinc or diphenylzinc addition to aldehydes.
It was also
noticed that aryl aldehydes undergo aryl addition in high yield
and ee (82%, entry 9 and 92%, entry 5). However, aliphatic alde-
hydes afford alcohol products in lower yields and ee values (entries
13–15). We also explored the asymmetric addition of non-aro-
matic boronic acid to benzaldehyde, and the result indicated the
use of n-butylboronic acid afforded the corresponding product in
50% yield with 83% ee (entry 16). In the case of aromatic aldehydes,
electronic effect of the substituents on aromatic aldehydes plays an
important role in asymmetric addition. Diarylmethanols were
obtained in higher ee values when aromatic aldehydes with
electron-withdrawing groups were used as substrates (entries 6
and 7). While benzaldehydes substituted with electron-donating
groups afforded the addition products in lower ee values (entries
2 2 3
mon solvents, such as THF, CH Cl , CHCl , toluene, and DMF, which
could be attributed to the twisted polymer chain backbone and the
flexible n-butyl as the side chain of the polymer. Moreover, this
soluble polymer ligand used as the catalyst for asymmetric addi-
tion of arylboronic acid to aldehydes can undergo homogeneous
reaction. The results demonstrate that the chiral polymer ligand
is a good enantioselective catalyst and can produce as high as
9
5% ee while 2-naphthaldehyde is used as a substrate (Table 1,
entry 12).
Based on the previous reports, some reactions of diethylzinc or
diarylzinc addition to aldehydes require an additive, such as dime-
i
thoxy poly(ethyleneglycol) (DiMPEG), or co-catalyst like Ti(O -Pr)
4

X. Huang et al. / Tetrahedron Letters 49 (2008) 6823–6826
6825
Table 1
a
Asymmetric arylation of aldehydes with aryl boronic acids
(
(
1) toluene, 60 C, 12h
°
OH
R2
2) the polymer ligand(10 mol%)
1
R B(OH) + Et Zn
2
2
2
R1
(3) R CHO, rt, 24 h
Entry
R1
R2
Yieldb (%)
eec (%)
Configuratione
1f
2
4-Methylphenyl
4-Methylphenyl
4-Methylphenyl
4-Methylphenyl
4-Trifluoromethylphenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
n-Butyl
4-Methylphenyl
4-Methylphenyl
4-Methylphenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
4-Trifluoromethylphenyl
4-Fluorophenyl
4-Methylphenyl
4-Methoxyphenyl
2-Chlorophenyl
2-Bromophenyl
2-Naphthyl
n-Hexyl
n-Heptyl
2-Phenylethenyl
Phenyl
Phenyl
68
75
63
68
73
80
78
81
82
77
75
65
58
60
40
50
70
68
67
83
91
35
53
R
R
R
R
R
R
R
R
R
R
R
R
S
S
S
S
R
R
R
g
3
4
h
d
5
6
7
8
9
92
d
84
d
91
71
75
81
85
95
60
53
40
83
91
89
74
10
11
12
13
14
15
16
17
18
19
i
j
Phenyl
Phenyl
k
a
Arylboronic acid:Et
Isolated yields.
Determined by HPLC on Chiralcel OD-H column.
Determined by HPLC on Chiralcel OB-H column.
2
Zn:ligand:aldehyde = 2.4:7.2:0.1:1.
b
c
d
e
f
Determined by comparison with literature data.
i
0
.1 equiv of Ti(O Pr)
4
was added.
g
h
i
Using THF as solvent.
Using CH Cl as solvent.
2
2
First recycled and reused.
Second recycled and reused.
Third recycled and reused.
j
k
8
and 9). With regard to the positions of the substituent in the
References and notes
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2
3
.
.
.
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(
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9
1%, 89% and 74% ee, respectively (entries 17–19). The results
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recycle.
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5
.
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i
nation with Et
2
Zn without Ti(O Pr)
4
had been developed as an effi-
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arylboronic acids are used as the source of the transferable aryl
group. The results show that benzaldehydes with electron-with-
drawing groups and bigger steric groups as substrates can afford
diarylmethanols in high ee values. The chiral polymer could be eas-
ily recovered and reused, but exhibits a decrease of ee in the third
recycle.
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Acknowledgements
This work was supported by the National Natural Science Foun-
dation of China (Nos. 20474028, 20774042) and the Scientific
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826
X. Huang et al. / Tetrahedron Letters 49 (2008) 6823–6826
9
.
(a) Fan, Q.; Ren, C.; Yeung, C.; Hu, W.; Chan, A. S. C. J. Am. Chem. Soc. 1997, 121,
precipitate the polymer. A brown solid was filtered off and washed with
methanol several times. Further purification was conducted by dissolving the
polymer in CH Cl , and then precipitated in methanol again. The polymer was
dried under vacuum at room temperature for 24 h. The final yield was 75.9%
7
407–7408; (b) Salvadori, P.; Pini, D.; Petri, A. J. Am. Chem. Soc. 1997, 119,
6
929–6930.
2
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1
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2
5
2 w n
). M = 5720, M H
= 2450, PDI = 2.33. 1
(
b) Wu, L.; Zheng, L.; Zong, L.; Xu, J.; Cheng, Y. Tetrahedron 2008, 64, 2651–
(576.1 mg). ½ Cl
a
ꢀ
ꢁ298.0 (c 0.1, CH
2
D
2
657; (c) Zhang, S.; Liu, Y.; Huang, H.; Zheng, L.; Wu, L.; Cheng, Y. Synlett 2008,
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3
8
53–857.
4H), 2.76–2.71 (m, 4H), 7.24–7.22 (m, 4H), 7.32–7.25 (m, 3H), 7.71–7.67 (m,
2H), 8.11–8.09 (m, 2H), 8.93 (s, 1H), 9.76 (s, 1H), 12.69 (s, 1H), 13.16 (s, 1H); IR
1
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ꢁ
1
(KBr): 3391, 2954, 2926, 2855, 1613, 1589, 1508, 1252, 1134 cm ; Anal. Calcd
for C35 : C, 79.67; H, 6.30; N, 7.96. Found: C, 79.66; H, 6.48; N, 7.82.
2
001, 57, 805–814.
33 3 2
H N O
1
2. Procedure for the chiral polymer (see Dong, C.; Zhang, J.; Zheng, W.; Zhang, L.;
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2
454): A mixture of R-M-1 (655.0 mg, 1.44 mmol) and 2,5-diaminopyridine
157.0 mg, 1.44 mmol) was dissolved in THF (60 mL) and kept refluxing for
2 h. The solvent was removed under reduced pressure and the residue was
dissolved in a small quantity of THF and 100 mL of methanol was added to
(
1