Synthesis of chiral oxime ethers based on regio- and enantioselective allylic substitution catalyzed by iridium-pybox complex

Article abstract of DOI:10.1016/j.tet.2009.04.005

The oxygen atom of oximes acts as a reactive nucleophile in the iridium-catalyzed allylic substitution of unsymmetrical substrates to give the branched oxime ethers. Among several chiral ligands evaluated, the iridium complex of pybox ligand having phenyl

Full text of DOI:10.1016/j.tet.2009.04.005

Tetrahedron 65 (2009) 4464–4470
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Synthesis of chiral oxime ethers based on regio- and enantioselective allylic
substitution catalyzed by iridium–pybox complex
,
b
,
a
a
a,
*
Hideto Miyabe a , Akira Matsumura , Kazumasa Yoshida , Yoshiji Takemoto
*
a Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
b School of Pharmacy, Hyogo University of Health Sciences, Minatojima, Chuo-ku, Kobe 650-8530, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The oxygen atom of oximes acts as a reactive nucleophile in the iridium-catalyzed allylic substitution of
unsymmetrical substrates to give the branched oxime ethers. Among several chiral ligands evaluated, the
iridium complex of pybox ligand having phenyl group catalyzed the allylic substitution of phosphates
with high activity to form the branched oxime ethers with good enantioselectivities.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 12 March 2009
Received in revised form 2 April 2009
Accepted 2 April 2009
Available online 9 April 2009
Keywords:
Enantioselectivity
Oxime
Oxime ether
Allylic substitution
Iridium
1. Introduction
Hartwig7 and Helmchen,8 respectively.9–13 Recently, we also
reported that the iridium complex of pybox catalyzed the allylic
The transition metal-catalyzed allylic substitutions have been
developed as a fundamentally important reaction.1 The allylic
substitutions of 1,3-symmetrical substrates have been widely
studied including enantioselective versions. In contrast, the allylic
substitutions of unsymmetrical substrates are challenging, since
both regio- and enantioselectivities should be controlled to give the
desired chiral products. Although highly regio- and enantiose-
lective reactions with carbon nucleophiles have been achieved,1
little success was achieved with heteroatom nucleophiles. Palla-
dium complexes are general and versatile catalysts. However, the
palladium-catalyzed allylic substitutions of unsymmetrical sub-
strates with heteroatom nucleophiles generally give the linear
products.1,2 Recent studies show that rhodium,3 iridium,4 ruth-
enium,5a–d iron,5e and nickel5f–i complexes serve as catalysts for
allylic amination. The regioselectivities in the reaction using these
catalysts are quite different from those of palladium-catalyzed re-
action. Among them, the allylic amination and etherification using
chiral iridium complex have been a subject of current interest.6 The
control of regio- and enantioselectivities in iridium-catalyzed re-
action with heteroatom nucleophiles was mainly studied by
substitution to form the branched products with good
enantioselectivity.14,15
In comparison with allylic amination, the allylic etherification
has received much less attention due to the poor nucleophilic
property of the oxygen atom nucleophiles.16 Therefore, O-allylic
substitution had been largely limited to carboxylate and phenol
nucleophiles,17,18 except for the intramolecular reactions. We have
recently reported the utility of oximes as a soft oxygen nucleophile
in transition metal-catalyzed allylic substitution19,20 and the ap-
plication into iridium-catalyzed asymmetric reaction.14a In this
paper, we describe full details of the regio- and enantioselective
O-allylic substitution with oximes by using an iridium–pybox
complex.
2. Results and discussion
2.1. Regio- and enantioselectivities in allylic substitution
of oximes
Oximes are attractive nucleophiles for allylic substitution, since
they have oxygen and nitrogen atoms as nucleophilic sites. Re-
cently, we have shown the viability of oximes as a nucleophile in
allylic substitutions and the selective synthesis of oxime ethers and
nitrones by changing the palladium catalysts.19 Additionally, the
* Corresponding authors. Fax: þ81 75 753 4569 (Y.T.); fax: þ81 78 304 2794
(H.M.).
E-mail addresses: miyabe@huhs.ac.jp (H. Miyabe), takemoto@pharm.kyoto-u.
ac.jp (Y. Takemoto).
selective formation of the branched oxime ethers 3 from
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.005

H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
4465
% eed
Table 1
Ar
Allylic substitution of 8a with oxime 1 using Et2Zna
Et2Zn
[IrCl(cod)]2
NOH
Ar
+
O
N
Entry
Ligand
T (ꢀC)
Time (h)
% Yieldb (ratioc)
Ph
OAc
2
THF
1
2
3
4
5
6
7
8
7A
7B
7C
7D
7D
7D
7D
7D
7D
7E
7F
7F
7G
7H
7H
7I
þ20
þ20
þ20
þ20
0
2
2
75 (67:33)
68 (43:57)
6 (86:14)
81 (69:31)
77 (74:26)
70 (82:18)
29 (90:10)
Trace
80 (84:16)
77 (76:24)
81 (79:21)
71 (90:10)
71 (71:29)
73 (74:26)
64 (84:16)
60 (36:64)
67 (38:62)
43 (S)
63 (S)
5 (S)
64 (S)
65 (S)
80 (S)
93 (S)
1
3
Ph
N
20
0.5
10
10
48
48
20
8
Ar
+
Ar
Ar
O
N
+
N
O
O
ꢁ20
ꢁ40
ꢁ78
ꢁ78 to ꢁ10
þ20
þ20
ꢁ20
þ20
þ20
ꢁ20
þ20
þ20
Ph
Ph
Ph
4 (trace)
5 (not detected) 6 (not detected)
9
76 (S)
50 (S)
71 (S)
70 (S)
61 (S)
68 (S)
74 (S)
43 (S)
41 (S)
10
11
12
13
14
15
16
17
Scheme 1. Selective formation of the branched oxime ethers 3.
8
20
10
4
20
20
8
unsymmetrical substrates 2 was achieved by using [IrCl(cod)]2 as
a catalyst and 0.5 equiv of Et2Zn as a base (Scheme 1).21
Based on these results, we initially investigated the enantio-
selective iridium-catalyzed O-allylic substitution with oxime 1
under basic conditions (Scheme 2). As a preliminary experiment,
the phosphate 8a was employed to prove the efficiency of chiral
ligands, since it has shown excellent reactivity toward carbon
nucleophile in our previous iridium-catalyzed allylic alkylation.15
At first, the reactions of 8a with oxime 1 were evaluated in CH2Cl2
in the presence of Et2Zn.22 We have found that the iridium complex
of pybox ligands catalyzed the allylic substitution of phosphate 8a
with good catalytic activity. In general, the utility of C2-symmetric
pybox ligand in transition metal-catalyzed allylic substitution has
not wildly investigated compared with that of phosphorus
ligands.23 Table 1 outlines the optimization of the pybox ligands
7A–J.24 In the absence of the pybox ligands, the reaction of phos-
phate 8a with 1 did not proceed effectively;25 thus, it is noteworthy
that the pybox ligands enhance the catalytic activity of iridium.
To a solution of oxime 1 in CH2Cl2 was added a 1.0 M solution of
Et2Zn in hexane (0.5 equiv) at 20 ꢀC. After being stirred at 20 ꢀC for
10 min, a solution of the phosphate 8a, [IrCl(cod)]2 (4 mol %) and
chiral ligand (8 mol %) in CH2Cl2, was added to the reaction mixture
at the temperature indicated in Table 1. The iridium complex of
pybox 7A having benzyl group catalyzed the reaction to form the
branched oxime ether 3a with 43% ee and the linear product 4a in
67:33 ratio, after being stirred at 20 ꢀC for 2 h (entry 1). Although
the branched oxime ether 3a was obtained with 63% ee by using
pybox 7B having isopropyl group (entry 2), the bulky ligand 7C
having tert-butyl group was less effective (entry 3). The complex of
iridium and ligand 7D having phenyl group was a highly active
catalyst for the present reaction (entry 4). In this case, the branched
7J
a
Reactions were carried out in 0.15 M solution by using [IrCl(cod)]2 (4 mol %) in
the presence of Et2Zn (0.5 equiv).
b
Combined yields of 3a and 4a.
Ratio for 3a:4a.
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
c
d
oxime ether 3a was obtained with 64% ee, after being stirred at
20 ꢀC for only 30 min. The degree of regio- and enantioselectivities
was shown to be dependent on the reaction temperature (entries
5–9). Thus, changing the temperature from 20 ꢀC to ꢁ20 ꢀC led to
an increase in regioselectivity to 82:18 and enantioselectivity to
80% ee (entry 6). The reaction proceeded slowly even at ꢁ40 ꢀC
to afford a 29% yield of oxime ether 3a with 93% ee in 90:10 ratio
(entry 7). Although several aryl pybox ligands 7E–J were evaluated
under similar reaction conditions, the iridium–pybox 7D complex
has shown the best activity at low temperature (entries 10–17).
Based on Gamasa’s study on X-ray crystal structure of p-allyl irid-
ium complex with pybox ligand,26 the stereochemical feature of
our reaction can be rationalized by a pseudooctahedral geometry
around the iridium atom, which is bonded to the pybox ligand and
to
p
-allyl fragment as shown in Scheme 1.
We next investigated the reaction of 8a with 1 catalyzed by the
iridium–pybox 7D complex under different reaction conditions
(Scheme 3). In regard to the solvent effect, the replacement of
CH2Cl2 with toluene or THF led to a decrease in the regio- and
enantioselectivities (Table 2, entries 1–3). The concentration
influenced the regio- and enantioselectivities (entries 4–7). Both
ligand 7A-J
Ph
N
Ph
Et2Zn (0.5 eq)
NOH
O
O
Ph
N
OP(O)(OEt)2
+
N
[IrCl(cod)]2 (4 mol%)
+
Ph
8a
1
Ph
Ph
3a
4a
CH2Cl2
O
N
O
O
O
Nu
N
N
N
N
η3-Allyl
fragment
R
Ph
R
H
C
7I
7A: R = Bn
7B: R = i-Pr
7C: R = t-Bu
7D: R = Ph
H
Ar
H
O
O
N
Ir
CH
N
N
O
N
O
Ar
7E: R = 2-Naph
CH2
Ph
Ph
N
N
7F: R = 4-MeO-C6H4
7G: R = 3,4,5-(MeO)3-C6H2
7H: R = 4-F-C6H4
L
Ph
Ph
π-allyl complex A
7J
Scheme 2. Reaction of 8a with oxime 1 using iridium complex of pybox ligand.

4466
H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
Table 4
Pybox ligand 7D
Base
[IrCl(cod)]2 (4 mol%)
Allylic substitution of 8a with oxime 1 using Ba(OH)2$H2Oa
Entry
Solvent
T (ꢀC)
Time (h)
% Yieldb (ratioc)
% eed
+
8a
4a
1
3a
+
1
2
3
4
5
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.33 M)
Toluene (0.17 M)
THF (0.17 M)
þ20
ꢁ20
ꢁ20
þ20
þ20
1
20
20
5
81 (88:12)
87 (90:10)
90 (88:12)
73 (52:48)
59 (62:38)
81 (S)
95 (S)
94 (S)
80 (S)
73 (S)
Scheme 3. Reaction of 8a with oxime 1 using ligand 7D.
20
Table 2
a
Allylic substitution of 8a with oxime 1 using ligand 7Da
Reactions were carried out by using [IrCl(cod)]2 (4 mol %), ligand 7D and
Ba(OH)2$H2O (1 equiv).
b
Entry
Base
Solvent
T
(ꢀC)
Time
(h)
% Yieldb
(ratioc)
% eed
Combined yields of 3a and 4a.
Ratio for 3a:4a.
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
c
d
1
2
3
4
5
6
7
8
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Toluene (0.15 M)
Toluene (0.15 M)
THF (0.15 M)
þ20
ꢁ20
þ20
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ20
þ20
þ20
þ20
þ20
þ20
þ20
þ20
ꢁ20
þ20
0.5
20
20
48
20
20
20
10
10
10
3
3
3
3
2
20
1
76 (57:43)
64 (60:40)
46 (66:34)
29 (90:10)
47 (88:12)
48 (84:16)
58 (83:17)
61 (86:14)
NR
60 (S)
78 (S)
42 (S)
93 (S)
91 (S)
80 (S)
59 (S)
78 (S)
CH2Cl2 (0.15 M)
CH2Cl2 (0.29 M)
CH2Cl2 (0.5 M)
CH2Cl2 (1.0 M)
CH2Cl2 (0.15 M)
CH2Cl2 (0.15 M)
CH2Cl2 (0.15 M)
CH2Cl2 (0.15 M)
CH2Cl2 (0.15 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
Ph
H2, Pd(OH)2-C
3a
OH
9
MeOH
Me2Zn
DIBAL
PhMgBr
n-BuLi
KHMDS
K2CO3
Scheme 4. Conversion of 3a into 9.
9
10
11
12
13
14
15
16
17
Trace
40 (66:34)
25 (71:29)
64 (89:11)
18 (98:2)
80 (86:14)
52 (89:11)
81 (88:12)
80 (S)
76 (S)
73 (S)
40 (S)
80 (S)
85 (S)
81 (S)
conditions, the formation of nitrones 5a and 6a was not observed
(entry 2). The absolute configuration of oxime ether 3a was de-
termined to be S by converting 3a into authentic alcohol (S)-9
(Scheme 4).27 The reduction of C]C and N–O bonds of 3a was
achieved by hydrogenolysis using Pd(OH)2–C.
CsOAc
Cs2CO3
CsOH$H2O
Ba(OH)2$H2O
To gain further insight into the reaction mechanism, the other
allylic reagents were tested under the optimized reaction condi-
tions using Ba(OH)2$H2O (Scheme 5). At first, racemic branched
reagents 2a and 10 were employed (Table 5). The reaction of
branched reagents 2a and 10 with oxime 1 proceeded with excel-
lent regioselectivities to afford the branched oxime ether 3a
without the formation of the linear oxime ether 4a (entries 1–4).
However, these enantioselectivities were poor. Treatment of ace-
tate 2a with 1 at ꢁ20 ꢀC gave the oxime ether 3a with 32% ee (entry
1). Surprisingly, the high reaction temperature improved the
enantioselectivity. Reaction at þ60 ꢀC gave the oxime ether 3a with
55% ee (entry 3). The reaction of carbonate 10 with oxime 1 gave
the nearly racemic oxime ether 3a (entry 4). In contrast to the re-
action of linear phosphate 8a, the reaction did not proceed effec-
tively when cinnamyl acetate 11 and cinnamyl methyl carbonate 12
were employed (entries 5 and 6). Thus, the linear phosphates such
as cinnamyl phosphate 8a are highly promising electrophiles for
the present iridium-catalyzed reaction.
a
Reactions were carried out by using [IrCl(cod)]2 (4 mol %) and ligand 7D.
Combined yields of 3a and 4a.
b
c
Ratio for 3a:4a.
d
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
selectivities were increased under the dilution conditions (entry 4).
Next, the effect of bases on reactivity and selectivities was studied
(entries 8–17). Amines such as Et3N and DBU were less effective for
the present reaction. The good selectivities and chemical efficiency
were obtained when Cs2CO3 or Ba(OH)2$H2O was employed (en-
tries 15 and 17). In the presence of Cs2CO3, the reaction proceeded
smoothly to give the oxime ether 3a in 80% yield with 80% ee even
at 20 ꢀC (entry 15). The reaction using Ba(OH)2$H2O afforded the
oxime ether 3a with 81% ee within 1 h (entry 17).
Next, the reactions of 8a with 1 were studied in the presence of
Cs2CO3 under the several reaction conditions (Table 3). As expected,
the degree of regio- and enantioselectivities was shown to be de-
pendent on the reaction temperature (entries 1–3). The reaction at
ꢁ20 ꢀC gave the oxime ether 3a with 87% ee in 92:8 ratio (entry 3).
When the reaction was carried out in 0.33 M solution, the oxime
ether 3a was obtained with 84% ee (entry 4). The replacement of
CH2Cl2 with toluene or THF led to a decrease in regioselectivity
(entries 5 and 6).
The observed effect of allylic reagents can be explained by two
different iridium complexes A and B as shown in Scheme 6. The
above results suggest that the formation of
important to achieve high enantioselectivity and the conversion of
-complex B into -allyl complex A is relatively slow. In contrast to
the predominant formation of -allyl complex A from phosphate
8a, the use of branched reagents 2a and 10 gave -complex B,
which allows two competitive pathways.28 The SN20 type reaction
of -complex B with nucleophile proceeded with excellent regio-
p-allyl complex A is
s
p
The similar trends were observed in the reaction using
Ba(OH)2$H2O as a base (Table 4). Changing the temperature from
20 ꢀC to ꢁ20 ꢀC led to an increase in regioselectivity to 90:10 and
enantioselectivity to 95% ee (entry 2). Under the optimized reaction
p
s
s
selectivity and low enantioselectivity. Additionally, it assumes that
the high reaction temperature promoted the conversion of
Table 3
a
Allylic substitution of 8a with oxime 1 using Cs2CO3
Entry
Solvent
T (ꢀC)
Time (h)
% Yieldb (ratioc)
% eed
Pybox ligand 7D
Ba(OH)2·H2O
[IrCl(cod)]2 (4 mol%)
1
2
3
4
5
6
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.17 M)
CH2Cl2 (0.33 M)
Toluene (0.17 M)
THF (0.17 M)
þ20
0
ꢁ20
ꢁ20
þ20
þ20
2
10
20
20
3
80 (86:14)
82 (88:12)
61 (92:8)
69 (91:9)
67 (73:27)
48 (74:26)
80 (S)
80 (S)
87 (S)
84 (S)
77 (S)
80 (S)
+
3a
+
2a, 10 -12
4a
1
CH2Cl2
20
Ph
Ph
OR
a
Reactions were carried out by using [IrCl(cod)]2 (4 mol %), ligand 7D and Cs2CO3
OR
(1 equiv).
11 : R = Ac
12 : R = CO2Me
2a : R = Ac
10 : R = CO2Me
b
Combined yields of 3a and 4a.
Ratio for 3a:4a.
c
d
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
Scheme 5. Reaction of allylic reagents 2a and 10–12 with oxime 1.

H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
4467
Table 5
Allylic substitution of 2a, 10–12 with oxime 1 using Ba(OH)2$H2Oa
Pybox ligand 7D
Ba(OH)2·H2O
[IrCl(cod)]2
+
Ar
OP(O)(OEt)2
Ar
1
Entry
Reagent
T (ꢀC)
Time (h)
% Yieldb (ratioc)
% eed
8b-h
1
2
3
4
5
6
2a
2a
2a
10
11
12
ꢁ20
þ20
þ60
þ20
þ20
þ20
15
0.5
0.5
0.5
20
66 (>98:2)
85 (>98:2)
82 (>98:2)
75 (>98:2)
NR
32 (S)
42 (S)
55 (S)
Racemic
CH2Cl2, -20 °C
8b: Ar = 4-F-C6H4
8c: Ar = 3-Cl-C6H4
Ar
8d: Ar = 4-Me-C6H4
8e: Ar = 4-MeO-C6H4
8f: Ar = 1-Naph
O
O
N
N
+
20
Trace
Ph
Ph
8g: Ar = 2-Naph
8h: Ar = 2-Pyridinyl
a
Reactions were carried out in CH2Cl2 by using [IrCl(cod)]2 (4 mol %), ligand 7D
and Ba(OH)2$H2O (1 equiv).
3b-g
4b-g
b
Combined yields of 3a and 4a.
Ratio for 3a:4a.
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
Scheme 7. Reaction of phosphates 8b–h with oxime 1.
c
d
s
-complex B into
p-allyl complex A, leading to the improvement of
Table 6
Allylic substitution of 8b–h with oxime 1a
enantioselectivity.
Entry
Reagent
Mol % of [IrCl(cod)]2
Time (h)
% Yieldb (ratioc)
% eed
2.2. Regio- and enantioselective allylic substitution of several
phosphates
1
2
3
4
5
6
7
8
8b
8b
8c
8c
8d
8e
8f
4
8
4
8
4
4
4
8
4
6
4
20
40
20
40
20
20
20
35
20
30
20
48 (69:31)
89 (69:31)
38 (74:26)
86 (76:24)
84 (83:17)
35 (84:16)
38 (95:5)
83 (94:6)
70 (82:18)
81 (83:17)
NR
83
90
90
92
90
70
91
90
92
89
Finally, several phosphates 8b–h were tested under the opti-
mized reaction conditions (Scheme 7). The phosphates 8b and 8c
having electron-withdrawing substituents on aromatic ring
showed the low reactivity toward the allylic substitution (Table 6,
entries 1–4). Good yields were observed when 8 mol % of [IrCl-
(cod)]2 was employed (entries 2 and 4). In contrast, the reaction of
phosphate 8d having tolyl group proceeded smoothly to give a 90%
ee of oxime ether 3d with good regioselectivity (entry 5). However,
the reaction of phosphate 8e having an electron-donating sub-
stituent on aromatic ring gave the low yield of oxime ether 3e, due
to instability of phosphate 8e under reaction conditions (entry 6).
The phosphates 8f and 8g having bulky 1-naphtyl or 2-naphtyl
substituents worked well, allowing facile incorporation of struc-
tural variety (entries 7–10). On the other hand, the phosphate 8h
having basic 2-pyridinyl group did not work (entry 11). The abso-
lute configuration of oxime ethers 3b–g was assigned to be S, since
their high performance liquid chromatography analyses and optical
rotations showed similarity with those of oxime ether (S)-3a.
In summary, we have demonstrated that regio- and enantiose-
lectivities in O-allylic substitution of oximes are achieved by using
an iridium–pybox complex. In addition to the enantioselective
O-allylic substitution with hydroxylamines,14b the allylic sub-
stitution with oximes disclosed a broader aspect of the utility of the
oxygen nucleophiles directly connected with heteroatoms for the
synthesis of various types of functionalized allylic compounds.
8f
9
10
11
8g
8g
8h
a
Reactions were carried out in CH2Cl2 by using [IrCl(cod)]2, ligand 7D and
Ba(OH)2$H2O (1 equiv).
b
Combined yields of 3b–g and 4b–g.
Ratio for 3b–g:4b–g.
Enantiomeric excess was determined by HPLC analysis using Chiralcel OD-H.
c
d
recorded on a JASCO FT/IR-410 Fourier-transfer infrared spec-
trometer. Low and high resolution mass spectra were obtained by EI
method. Preparative TLC separations were carried out on precoated
silica gel plates (E. Merck 60F254). Optical rotations were recorded
on a JASCO DIP-360 polarimeter.
3.2. General procedure for allylic substitution of 8a using
Et2Zn and ligands 7A–J in 0.15 M solution
To a solution of oxime 1 (121 mg, 1.0 mmol) in CH2Cl2 (4.0 mL)
was added Et2Zn (1.0 M in hexane, 0.50 mL, 0.50 mmol) under ar-
gon atmosphere at 20 ꢀC. After being stirred at the same temper-
ature for 10 min, a solution of phosphate 8a (405 mg, 1.5 mmol),
[IrCl(cod)]2 (26.8 mg, 0.040 mmol), and pybox ligand 7A–J
(0.080 mmol) in CH2Cl2 (2.0 mL) was added to the reaction mixture
at the temperature indicated in Table 1. After the reaction was
completed, the reaction mixture was diluted with saturated aque-
ous potassium sodium (þ)-tartrate and then extracted with AcOEt.
The organic phase was dried over MgSO4 and concentrated under
3. Experimental
3.1. General
Melting points were taken on a YANAGIMOTO micromelting
point apparatus and are uncorrected. 1H and 13C NMR spectra were
recorded at 500 MHz and at 125 MHz, respectively. IR spectra were
Ph
Pybox ligand 7D
Ph
OP(O)(OEt)2
High enatioselectivity
Ir
[IrCl(cod)]2
Nu
8a
*
*
π-allyl complex A
slow
Ph
Ph
*
OAc
2a
fast
Pybox ligand 7D
[IrCl(cod)]2
Ph
Ir
Low enatioselectivity
*
OCO2Me
10
Nu
σ-complex B
Scheme 6. Possible reaction pathway.

4468
H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
reduced pressure. The ratio of products was determined by 1H NMR
analysis of crude products. Purification of the residue by pre-
parative TLC (hexane/AcOEt¼20:1, twofold development) afforded
the products 3a and 4a.
3.3.5. (E)-(S)-O-[1-(3-Chlorophenyl)prop-2-enyl]benzaldehyde
oxime (3c)
A colorless oil. IR (CHCl3) 2911, 1476, 1448, 1429 cmꢁ1. 1H NMR
(CDCl3) d 8.18 (1H, s), 7.59–7.50 (2H, m), 7.40–7.23 (7H, m), 6.10 (1H,
ddd, J¼17.2, 10.6, 6.1 Hz), 5.66 (1H, d, J¼6.1 Hz), 5.33 (1H, d,
J¼17.2 Hz), 5.30 (1H, d, J¼10.6 Hz). 13C NMR (CDCl3)
d 149.6, 142.4,
3.3. General procedure for allylic substitution of 8a–h using
Cs2CO3 or Ba(OH)2$H2O in 0.17 M solution
137.0, 134.3, 132.1, 130.0, 129.7, 128.7, 128.0, 127.5, 127.2, 125.5, 117.9,
85.3. MS (EIþ) m/z: 271 (Mþ, 1), 151 (100). HRMS calcd for
C16H14ClNO: 271.0764, Found: 271.0767. HPLC (Chiralcel OD-H,
A mixture of oxime 1 (121 mg, 1.0 mmol) and Cs2CO3 or
Ba(OH)2$H2O (1.0 mmol) in CH2Cl2 (4.0 mL) was stirred under ar-
gon atmosphere at 20 ꢀC for 10 min. To the reaction mixture was
added a solution of phosphate 8a–h (1.5 mmol), pybox 7D (0.080–
0.16 mmol), and [IrCl(cod)]2 (0.040–0.080 mmol) in CH2Cl2
(2.0 mL) at ꢁ20 ꢀC. After the reaction was completed, the reaction
mixture was diluted with saturated aqueous NH4Cl and then
extracted with AcOEt. The organic phase was dried over MgSO4 and
concentrated under reduced pressure. The ratio of products was
determined by 1H NMR analysis of crude products. Purification of
the residue by preparative TLC (hexane/AcOEt¼5:1 to 25:1, twofold
development) afforded the products 3a–g and 4a–g.
hexane/2-propanol¼90:10, 0.5 mL/min, 254 nm) tr (S)¼8.8 min, tr
28
(R)¼12.1 min. A sample of 90% ee (S) by HPLC analysis gave [
a]
D
ꢁ65.0 (c 1.05, CHCl3).
3.3.6. (E)-O-[3-(3-Chlorophenyl)prop-2-enyl]benzaldehyde
oxime (4c)
A colorless oil. IR (CHCl3) 2925, 1477, 1447, 1425 cmꢁ1. 1H NMR
(CDCl3) d 8.13 (1H, s), 7.63–7.56 (2H, m), 7.43–7.33 (4H, m), 7.28–7.17
(3H, m), 6.59 (1H, d, J¼15.9 Hz), 6.42 (1H, dt, J¼15.9, 5.5 Hz), 4.82
(2H, d, J¼5.5 Hz). 13C NMR (CDCl3)
d 149.1, 138.6, 134.5, 132.2, 131.8,
129.9, 129.8, 128.7, 127.7, 127.1, 126.9,126.5,124.8, 74.5. MS (EIþ) m/z:
271 (Mþ, 3),151 (100). HRMS calcd for C16H14ClNO: 271.0764, Found:
271.0764.
3.3.1. (E)-(S)-O-(1-Phenylprop-2-enyl)benzaldehyde oxime (3a)
A colorless oil. IR (CHCl3) 2908, 1494, 1450, 1414 cmꢁ1. 1H NMR
(CDCl3) d 8.18 (1H, s), 7.60–7.50 (2H, m), 7.45–7.23 (8H, m), 6.16 (1H,
3.3.7. (E)-(S)-O-[1-(4-Methylphenyl)prop-2-enyl]benzaldehyde
oxime (3d)
ddd, J¼17.1, 10.5, 6.3 Hz), 5.71 (1H, d, J¼6.3 Hz), 5.34 (1H, d,
A colorless oil. IR (CHCl3) 2945, 1513, 1493, 1448, 1413 cmꢁ1. 1H
J¼17.1 Hz), 5.29 (1H, d, J¼10.5 Hz). 13C NMR (CDCl3)
d
149.2, 140.1,
NMR (CDCl3) d 8.17 (1H, s), 7.58–7.52 (2H, m), 7.35–7.32 (3H, m),
137.6,132.3, 129.8, 128.6,128.4, 127.9, 127.4, 127.1, 117.3. MS (EIþ) m/z:
237 (Mþ, 0.2), 117 (100). HRMS calcd for C16H15NO: 237.1154, Found:
237.1156. HPLC (Chiralcel OD-H, hexane/2-propanol¼90:10, 0.5 mL/
7.29 (2H, d, J¼7.9 Hz), 7.18 (2H, d, J¼7.9 Hz), 6.16 (1H, ddd, J¼17.4,
10.5, 6.3 Hz), 5.67 (1H, d, J¼6.3 Hz), 5.33 (1H, d, J¼17.4 Hz), 5.28
(1H, d, J¼10.5 Hz), 2.34 (3H, s). 13C NMR (CDCl3)
d 149.1, 137.8, 137.6,
min, 254 nm) tr (S)¼8.8 min, tr (R)¼13.2 min. A sample of 95% ee (S)
137.2, 132.4, 129.8, 129.1, 128.6, 127.4, 127.1, 117.1, 86.0, 21.1. MS (EIþ)
m/z: 251 (Mþ, <0.1), 131 (100). HRMS calcd for C17H17NO: 251.1310,
Found: 251.1306. HPLC (Chiralcel OD-H, hexane/2-propanol¼90:10,
26
by HPLC analysis gave [
a]
D ꢁ62.3 (c 1.03, CHCl3).
3.3.2. (E)-O-(3-Phenylprop-2-enyl)benzaldehyde oxime (4a)
A colorless oil. IR (CHCl3) 2926, 1494, 1448 cmꢁ1 1H NMR
0.5 mL/min, 254 nm) tr (S)¼8.0 min, tr (R)¼11.0 min. A sample of
28
.
90% ee (S) by HPLC analysis gave [
a
]
ꢁ72.9 (c 1.01, CHCl3).
D
(CDCl3) d 8.13 (1H, s), 7.63–7.48 (2H, m), 7.46–7.16 (8H, m), 6.67 (1H,
d, J¼15.9 Hz), 6.42 (1H, dt, J¼15.9, 6.2 Hz), 4.83 (2H, d, J¼6.2 Hz). 13C
3.3.8. (E)-O-[3-(4-Methylphenyl)prop-2-enyl]benzaldehyde
oxime (4d)
NMR (CDCl3)
d 148.9, 136.6, 133.5, 132.2, 129.8, 128.7, 128.5, 127.8,
127.1, 126.6, 125.1, 74.9. MS (EIþ) m/z: 237 (Mþ, 1.5), 117 (100). HRMS
A colorless crystal. Mp 70–72 ꢀC (hexane). IR (CHCl3) 2925, 1512,
calcd for C16H15NO: 237.1154, Found: 237.1155.
1493, 1448, 1414 cmꢁ1. 1H NMR (CDCl3)
d 8.14 (1H, s), 7.63–7.56 (2H,
m), 7.40–7.34 (3H, m), 7.31 (2H, d, J¼7.9 Hz), 7.12 (2H, d, J¼7.9 Hz),
3.3.3. (E)-(S)-O-[1-(4-Fluorophenyl)prop-2-enyl]benzaldehyde
oxime (3b)
6.65 (1H, d, J¼15.9 Hz), 6.38 (1H, dt, J¼15.9, 6.4 Hz), 4.83 (2H, d,
J¼6.4 Hz), 2.34 (3H, s). 13C NMR (CDCl3)
d 148.9, 137.7, 133.9, 133.5,
A colorless oil. IR (CHCl3) 2906, 1509, 1447, 1415 cmꢁ1. 1H NMR
132.3, 129.8, 129.3, 128.7, 127.1, 126.5, 124.0, 75.0, 21.1. MS (EIþ) m/z:
251 (Mþ, 1.4), 131 (100). HRMS calcd for C17H17NO: 251.1310, Found:
251.1314. Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found:
C, 81.54; H, 6.92; N, 5.53.
(CDCl3)
d 8.17 (1H, s), 7.58–7.53 (2H, m), 7.40–7.32 (5H, m), 7.08–
7.02 (2H, m), 6.13 (1H, ddd, J¼17.0, 10.6, 6.2 Hz), 5.68 (1H, d,
J¼6.2 Hz), 5.32 (1H, d, J¼17.0 Hz), 5.31 (1H, d, J¼10.6 Hz). 13C NMR
(CDCl3)
d
162.4 (d, J¼246 Hz), 149.3, 137.4, 136.0, 132.2, 129.9, 129.1
(d, J¼7.2 Hz), 128.6, 127.1, 117.5, 115.3 (d, J¼20.7 Hz), 85.3. MS (EIþ)
m/z: 255 (Mþ, 0.2), 135 (100). HRMS calcd for C16H14FNO: 255.1059,
Found: 255.1065. HPLC (Chiralcel OD-H, hexane/2-prop-
3.3.9. (E)-(S)-O-[1-(4-Methoxyphenyl)prop-2-enyl]benzaldehyde
oxime (3e)
A colorless oil. IR (CHCl3) 2935, 1512, 1463, 1446, 1416 cmꢁ1. 1H
anol¼90:10, 0.5 mL/min, 254 nm) tr (S)¼8.6 min, tr (R)¼12.8 min.
NMR (CDCl3) d 8.16 (1H, s), 7.58–7.51 (2H, m), 7.40–7.29 (5H, m),
28
A sample of 90% ee (S) by HPLC analysis gave [
a
]
D ꢁ53.7 (c 1.04,
6.90 (2H, d, J¼8.0 Hz), 6.16 (1H, ddd, J¼17.0, 10.6, 6.2 Hz), 5.66 (1H,
CHCl3).
d, J¼6.2 Hz), 5.32 (1H, d, J¼17.0 Hz), 5.28 (1H, d, J¼10.6 Hz), 3.80
(3H, s). 13C NMR (CDCl3)
d 159.4, 149.1, 137.8, 132.4, 132.2, 129.8,
3.3.4. (E)-O-[3-(4-Fluorophenyl)prop-2-enyl]benzaldehyde
oxime (4b)
128.8, 128.6, 127.1, 117.0, 113.8, 85.7, 55.2. MS (EIþ) m/z: 267 (Mþ,
<0.1), 147 (100). HRMS calcd for C17H17NO2: 267.1259, Found:
267.1258. HPLC (Chiralcel OD-H, hexane/2-propanol¼90:10,
A colorless crystal. Mp 54–57 ꢀC (hexane). IR (CHCl3) 2926, 1509,
1447, 1414 cmꢁ1. 1H NMR (CDCl3)
d
8.14 (1H, s), 7.63–7.57 (2H, m),
0.5 mL/min, 254 nm) tr (S)¼10.0 min, tr (R)¼15.9 min. A sample of
28
7.42–7.34 (5H, m), 7.05–6.97 (2H, m), 6.65 (1H, d, J¼15.8 Hz), 6.34
70% ee (S) by HPLC analysis gave [
a]
D ꢁ60.4 (c 1.04, CHCl3).
(1H, dt, J¼15.8, 6.1 Hz), 4.82 (2H, d, J¼6.1 Hz). 13C NMR (CDCl3)
d
162.5 (d, J¼247 Hz),149.0,132.8,132.3,132.2,129.8,128.7,128.1 (d,
3.3.10. (E)-O-[3-(4-Methoxyphenyl)prop-2-enyl]benzaldehyde
oxime (4e)
J¼8.3 Hz), 127.1, 124.9, 115.4 (d, J¼21.7 Hz), 74.7. MS (EIþ) m/z: 255
(Mþ, 0.5), 135 (100). HRMS calcd for C16H14FNO: 255.1059, Found:
255.1062. Anal. Calcd for C16H14FNO: C, 75.28; H, 5.53; N, 5.49; F,
7.44. Found: C, 75.33; H, 5.72; N, 5.45; F, 7.46.
A colorless oil. IR (CHCl3) 2935, 1512, 1464, 1445 cmꢁ1. 1H NMR
(CDCl3)
d 8.14 (1H, s), 7.63–7.57 (2H, m), 7.40–7.28 (5H, m), 6.84 (2H,
d, J¼8.6 Hz), 6.63 (1H, d, J¼15.9 Hz), 6.29 (1H, dt, J¼15.9, 6.5 Hz),

H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
4469
26
4.81 (2H, d, J¼6.5 Hz), 3.78 (3H, s). 13C NMR (CDCl3)
d
159.4, 148.8,
136.0888, Found: 136.0888. A sample of 95% ee gave [
(c 1.01, hexane).
a]
ꢁ49.0
D
133.3, 132.3, 129.8, 129.4, 128.7, 127.8, 127.1, 122.7, 113.9, 75.1, 55.2.
MS (EIþ) m/z: 267 (Mþ, 6), 147 (100). HRMS calcd for C17H17NO2:
267.1259, Found: 267.1253.
Acknowledgements
3.3.11. (E)-(S)-O-[1-(1-Naphthyl)prop-2-enyl]benzaldehyde
oxime (3f)
This work was supported in part by a Grant-in-Aid for Scientific
Research (C) (H.M.) and for Scientific Research (B) (Y.T.) from the
Ministry of Education, Culture, Sports, Science and Technology of
Japan, and Astellas Foundation for Research on Metabolic Disorders
(to H.M.).
A colorless oil. IR (CHCl3) 2944, 1511, 1447 cmꢁ1. 1H NMR (CDCl3)
d
8.21 (1H, s), 8.20 (1H, d, J¼11.0 Hz), 7.85 (1H, d, J¼7.9 Hz), 7.80 (2H,
d, J¼8.3 Hz), 7.61–7.44 (6H, m), 7.34–7.28 (3H, m), 6.43 (1H, d,
J¼5.5 Hz), 6.35 (1H, ddd, J¼17.0, 9.2, 5.5 Hz), 5.37 (1H, d, J¼17.0 Hz),
5.34 (1H, d, J¼9.2 Hz). 13C NMR (CDCl3)
d 149.3, 137.1, 135.6, 134.0,
132.3, 131.2, 129.8, 128.8, 128.7, 128.6, 127.2, 126.1, 125.6, 125.5,
125.3, 124.3, 117.8, 83.6. MS (EIþ) m/z: 287 (Mþ, 0.2), 167 (100).
HRMS calcd for C20H17NO: 287.1310, Found: 287.1313. HPLC (Chir-
alcel OD-H, hexane/2-propanol¼90:10, 0.5 mL/min, 254 nm) tr
References and notes
1. For some reviews, see: (a) Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron:
Asymmetry 1992, 3, 1089; (b) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395; (c) Johannsen, M.; Jorgensen, K. A. Chem. Rev. 1998, 98, 1689; (d) Pfaltz, A.;
Lautens, M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, Germany, 1999; Vol. 2, pp 833–884; (e)
Helmchen, G. J. Organomet. Chem. 1999, 576, 203; (f) Trost, B. M.; Lee, C. B. In
Catalytic Asymmetric Synthesis II; Ojima, I., Ed.; Wiley-VCH: Weinheim, Ger-
many, 2000; pp 593–650; (g) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1; (h)
Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921; (i) Graening, T.; Schmalz,
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of unsymmetrical substrates, see: (a) Hayashi, T.; Kishi, K.; Yamamoto, A.; Ito, Y.
Tetrahedron Lett. 1990, 31, 1743; (b) Trost, B. M.; Krische, M. J.; Radinov, R.;
Zanoni, G. J. Am. Chem. Soc. 1996, 118, 6297; (c) Trost, B. M.; Toste, F. D. J. Am.
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Trost, B. M.; Brennan, M. K. Org. Lett. 2007, 9, 3961.
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Evans, P. A.; Robinson, J. E. Org. Lett. 1999, 1, 1929; (c) Evans, P. A.; Leahy, D. K. J.
Am. Chem. Soc. 2000, 122, 5012; (d) Evans, P. A.; Robinson, J. E.; Moffett, K. K.
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7882; (f) Evans, P. A.; Leahy, D. K.; Andrews, W. J.; Uraguchi, D. Angew. Chem.,
Int. Ed. 2004, 43, 4788; (g) Evans, P. A.; Lai, K. W.; Zhang, H.-R.; Huffman, J. C.
Chem. Commun. 2006, 844; For a review, see: (h) Leahy, D. K.; Evans, P. A. In
Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, Germany, 2005; Chapter 10, pp 191–214.
(S)¼12.0 min, tr (R)¼13.6 min. A sample of 90% ee (S) by HPLC
28
analysis gave [
a]
D ꢁ17.1 (c 1.04, CHCl3).
3.3.12. (E)-O-[3-(1-Naphthyl)prop-2-enyl]benzaldehyde oxime (4f)
A colorless oil. IR (CHCl3) 2925, 1507, 1493, 1446 cmꢁ1. 1H NMR
(CDCl3)
d
8.17 (1H, s), 8.12 (1H, d, J¼7.9 Hz), 7.82 (1H, d, J¼6.4 Hz),
7.75 (1H, d, J¼8.2 Hz), 7.68–7.55 (3H, m), 7.51–7.30 (7H, m), 6.44
(1H, dt, J¼15.8, 6.1 Hz), 4.94 (2H, d, J¼6.1 Hz), 3.78 (3H, s). 13C NMR
(CDCl3)
d 149.0, 134.5, 133.6, 132.3, 131.2, 130.6, 129.9, 128.7, 128.5,
128.4, 128.1, 127.1, 126.1, 125.8, 125.6, 124.1, 123.8, 75.0. MS (EIþ)
m/z: 287 (Mþ, 10.1), 167 (100). HRMS calcd for C20H17NO: 287.1310,
Found: 287.1311.
3.3.13. (E)-(S)-O-[1-(2-Naphthyl)prop-2-enyl]benzaldehyde
oxime (3g)
A colorless oil. IR (CHCl3) 2944,1507,1446 cmꢁ1. 1H NMR (CDCl3)
d
8.21 (1H, s), 7.90–7.77 (4H, m), 7.58–7.42 (5H, m), 7.35–7.26 (3H,
m), 6.24 (1H, ddd, J¼17.0, 10.5, 6.0 Hz), 5.87 (1H, d, J¼6.0 Hz), 5.38
(1H, d, J¼17.0 Hz), 5.32 (1H, d, J¼10.5 Hz). 13C NMR (CDCl3)
d 149.3,
137.7, 137.6, 133.3, 133.1, 132.3, 129.8, 128.6, 128.2, 128.1, 127.7, 127.2,
126.4, 126.1, 126.0, 125.3, 117.6, 86.2. MS (EIþ) m/z: 287 (Mþ, <0.1),
167 (100). HRMS calcd for C20H17NO: 287.1310, Found: 287.1308.
HPLC (Chiralcel OD-H, hexane/2-propanol¼90:10, 0.5 mL/min,
4. (a) Takeuchi, R.; Ue, N.; Tanabe, K.; Yamashita, K.; Shiga, N. J. Am. Chem. Soc.
2001, 123, 9525; (b) Takeuchi, R.; Shiga, N. Org. Lett. 1999, 1, 265; For a review,
see: (c) Takeuchi, R. Synlett 2002, 1954.
254 nm) tr (S)¼9.9 min, tr (R)¼16.3 min. A sample of 89% ee (S) by
28
5. (a) Kondo, T.; Ono, H.; Satake, N.; Mitsudo, T.; Watanabe, Y. Organometallics
1995, 14, 1945; (b) Morisaki, Y.; Kondo, T.; Mitsudo, T. Organometallics 1999, 18,
4742; (c) Mbaye, M. D.; Renaud, J.-L.; Demerseman, B.; Bruneau, C. Chem.
Commun. 2004, 1870; (d) Onitsuka, K.; Okuda, H.; Sasai, H. Angew. Chem., Int. Ed.
2008, 47, 1454; (e) Enders, E.; Finkam, M. Synlett 1993, 401; (f) Bricout, H.;
Carpentier, J.-F.; Mortreux, A. J. Chem. Soc., Chem. Commun. 1995, 1863; (g)
Bricout, H.; Carpentier, J.-F.; Mortreux, A. Tetrahedron 1998, 54, 1073; (h) Ber-
kowitz, D. B.; Bose, M.; Choi, S. Angew. Chem., Int. Ed. 2002, 41, 1603; (i) Ber-
kowitz, D. B.; Maiti, G. Org. Lett. 2004, 6, 2661; (j) Ito, H.; Ito, S.; Sasaki, Y.;
Matsuura, K.; Sawamura, M. J. Am. Chem. Soc. 2007, 129, 14856.
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Commun. 2007, 675; (b) Takeuchi, R.; Kezuka, S. Synthesis 2006, 3349; (c)
Miyabe, H.; Takemoto, Y. Synlett 2005, 1641; (d) Takemoto, Y.; Miyabe, H. In
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Mingos, D. M. P., Eds.; Elsevier: Oxford, 2006; Vol. 10.15, pp 695–724.
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Shu, C.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 14272; (c) Shu, C.;
Leitner, A.; Hartwig, J. F. Angew. Chem., Int. Ed. 2004, 43, 4797; (d) Leitner, A.;
Shekhar, S.; Pouy, M. J.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 15506; (e)
Leitner, A.; Shu, C.; Hartwig, J. F. Org. Lett. 2005, 7, 1093; (f) Shekhar, S.; Trantow,
B.; Leitner, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 11770; (g) Yamashita, Y.;
Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7508; (h) Pouy, M.
J.; Leitner, A.; Weix, D. J.; Ueno, S.; Hartwig, J. F. Org. Lett. 2007, 9, 3949; (i)
Markovic´, D.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 11680; (j) Leitner, A.; Shu,
C.; Hartwig, J. F. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5830; (k) Lo´pez, F.;
Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 3426; (l) Shu, C.; Hartwig,
J. F. Angew. Chem., Int. Ed. 2004, 43, 4794.
HPLC analysis gave [
a
]
D ꢁ76.3 (c 1.00, CHCl3).
3.3.14. (E)-O-[3-(2-Naphthyl)prop-2-enyl]benzaldehyde oxime (4g)
A colorless crystal. Mp 70–73 ꢀC (hexane). IR (CHCl3) 2927, 1506,
1446 cmꢁ1. 1H NMR (CDCl3)
d 8.16 (1H, s), 7.83–7.75 (4H, m), 7.66–
7.58 (3H, m), 7.49–7.34 (5H, m), 6.85 (1H, d, J¼15.9 Hz), 6.56 (1H, dt,
J¼15.9, 6.1 Hz), 4.90 (2H, d, J¼6.1 Hz). 13C NMR (CDCl3)
d 149.0,
134.1, 133.6, 133.1, 132.2, 129.9, 128.7 (2C), 128.2, 128.0, 127.7, 127.1,
126.7, 126.3, 126.0, 125.5, 123.6, 75.0. MS (EIþ) m/z: 287 (Mþ, 5.5),
167 (100). HRMS calcd for C20H17NO: 287.1310, Found: 287.1312.
Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.72;
H, 5.97; N, 4.83.
3.4. Reduction of oxime ether 3a
A suspension of oxime ether 3a (119 mg, 0.50 mmol) and 20%
Pd(OH)2–C (30 mg) in MeOH (2.5 mL) was stirred under a hydrogen
atmosphere at 20 ꢀC for 3 h. After the reaction mixture was filtered,
the filtrate was concentrated under reduced pressure. Purification
of the residue by preparative TLC (hexane/AcOEt¼5:1) afforded
product 9 (47.6 mg, 70%). A colorless oil. IR (CHCl3) 3428, 2969,
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1493, 1455, 1380 cmꢁ1 1H NMR (CDCl3)
. d 7.37–7.20 (5H, m), 4.55
(1H, t, J¼6.6 Hz), 2.12 (1H, br s), 1.84–1.67 (2H, m), 0.89 (3H, t,
J¼7.5 Hz). 13C NMR (CDCl3)
d 144.6, 128.4, 127.4, 126.0, 75.9, 31.7,
10.0. MS (EIþ) m/z: 136 (Mþ, 9.0), 91 (100). HRMS calcd for C9H12O:

4470
H. Miyabe et al. / Tetrahedron 65 (2009) 4464–4470
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26. The structure of
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