Asymmetric Kumada-Corriu cross-coupling reaction with Pd 2(dba)3 and an N-Ar axially chiral mimetic-type ligand catalyst

Article abstract of DOI:10.1016/j.tet.2004.09.010

A catalyst comprised of Pd₂(dba)₃·CHCl ₃ and an N-Ar axially chiral mimetic-type ligand, (S)-N-[2-(diphenylphosphanyl)naphthalene-1-yl]-2-(piperidinylmethyl)piperidine, provides good enantioselectivities for the asymmetric

Full text of DOI:10.1016/j.tet.2004.09.010

Tetrahedron 60 (2004) 10701–10709
Asymmetric Kumada–Corriu cross-coupling reaction with
Pd2(dba)3 and an N–Ar axially chiral mimetic-type ligand catalyst
a
a
Hideo Horibe,a Yoshimasa Fukuda,b Kazuhiro Kondo,b, Hiroaki Okuno, Yasuoki Murakami
*
and Toyohiko Aoyamab,
*
aFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
bGraduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Received 30 July 2004; accepted 1 September 2004
Available online 29 September 2004
Abstract—A catalyst comprised of Pd2(dba)3$CHCl3 and an N–Ar axially chiral mimetic-type ligand, (S)-N-[2-(diphenyl-
phosphanyl)naphthalene-1-yl]-2-(piperidinylmethyl)piperidine, provides good enantioselectivities for the asymmetric Kumada–Corriu
cross-coupling reaction of 1-phenylethylmagnesium chloride and E-b-bromostyrene derivatives with which it is more difficult to achieve
high enantioselectivity. Furthermore, in the case of styrene derivatives bearing both vinyl and aryl bromide groups, the chemoselective
asymmetric cross-coupling reaction of the vinyl bromide group is observed. This N–Ar axially chiral mimetic-type ligand allows easy
synthesis of a wide variety of analogues, and starting from the initial ligand, the enantioselectivity of coupling products is improved by
modifying the structure in the ligand.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Catalytic asymmetric carbon–carbon bond formation with
metal–chiral ligand complexes, is one of the most important
reactions in synthetic organic chemistry. The development
of new chiral ligands for use in asymmetric catalysis has
continued to undergo rapid growth. For testing the new
Figure 1.
ligands, standard palladium-catalyzed asymmetric allylic
substitution with the use of (E)-1,3-diphenyl-2-propenyl
acetate as the substrate and dimethyl malonate as the
pronucleophile, has been quite often examined.1 A large
number of ligands, which exhibit enantioselectivity of more
than 90%, have been reported.1 However, there are some
successful examples of other catalytic asymmetric reactions
with these new ligands.2 Therefore, it is very important to
develop versatile chiral ligands, which afford good
enantioselectivity in a variety of reactions.
Figure 2.
We have recently developed a novel chiral ligand 1
mimicking N–Ar axial chirality, in which a chiral carbon
substitution.3 These results prompted us to explore further
application of the ligand 1. Our interest in this ligand
focused on its use in the asymmetric Kumada–Corriu cross-
coupling reaction4 of 1-phenylethylmagnesium chloride
with alkenyl halides, which has met with success using
Kumada’s P,N-ligands.5 Some ligands have been developed
for the asymmetric cross-coupling reaction of 1-phenyl-
ethylmagnesium chloride with alkenyl halides, but the best
substrate exhibiting more than 80% ee was vinyl bromide.6
One type of substrate with which it has been more difficult
to achieve high selectivity is a styrene derivative such as
center induces a preferred conformation 2a by rotation
around an N–Ar bond which is fixed by formation of a
chelate structure with metal (Figs. 1 and 2).3 Among the
designed ligands 1, 1i has been found to exhibit 99% ee
in the standard palladium-catalyzed asymmetric allylic
Keywords: Kumada–Corriu cross-coupling reaction; N–Ar Axially chiral
mimetic-type ligand; Enantioselectivity.
* Corresponding authors. E-mail addresses: kazuk@phar.nagoya-cu.ac.jp;
aoyama@phar.nagoya-cu.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.010

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H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
E-b-bromostyrene.7 There are, to date, only two examples
by Knochel8 and Saigo9 that give good enantioselectivity
with E-b-bromostyrene. Herein we would like to report our
investigation of this reaction using E-b-bromostyrene
derivatives as substrates with the ligand 1 mimicking
N–Ar axial chirality.10 The results obtained with the ligand
1 are, to the best of our knowledge, the third best
enantioselectivity in the reported literature. Additionally,
the ligand 1 is appealing, because it allows easy synthesis of
a wide variety of analogues.
Figure 3. Internal coordination of the pendant nitrogen group.
2. Results and discussion
We began to screen a variety of the ligands 1 in the
asymmetric cross-coupling reaction of 1-phenylethyl-
magnesium chloride (4) with b-bromostyrene (E/ZZ6:1,
3a). The results are shown in Table 1. Reactions were
carried out with PdCl2(CH3CN)2 (5 mol%), the ligand 1
(5 mol%), and 1-phenylethylmagnesium chloride (4)
(2 equiv, 0.5–0.7 mol/L in Et2O) in a,a,a-trifluorotoluene11
at 0 8C. The use of other solvents such as toluene,
chlorobenzene, THF, Et2O, isopropyl ether, t-butyl methyl
ether, dioxane, DME, and CH2Cl2, gave less satisfactory
results. First, the effect of a pendant substituent X with the
pyrrolidine-based ligands 1a–e was examined.12 As shown
in entries 1–5, the pendant substituent played an important
role. The ligands 1a–c possessing a pendant oxygen group
exhibited faster reaction rate than 1d and 1e possessing a
pendant nitrogen group. Among the oxygen-containing
ligands 1a–c, the ligand 1b bearing the pendant BnO group,
gave better results (entry 2, 66% yield, 66% ee). The ee of
5a was determined by HPLC analysis (Daicel Chiralcel
OD), and its absolute configuration was determined by
comparison with the reported 5a.8 The inhibition of the
reactivity observed with the ligands 1d and 1e possessing
Table 1. Initial ligand screeninga
Entryb
Ligand 1
X
n
Ar
R
Time
(h)
Yield of 5a
(%)
eec of 5a
(%)
Absolute
configur-
ation
1
2
3
4
1a
1b
1c
1d
1e
1i
1i
1j
1f
1g
1h
1k
1l
OMOM
OBn
Ot-Bu
Pyrrolidinyl
NBn2
Pyrrolidinyl
Pyrrolidinyl
Piperidinyl
OBn
Pyrrolidinyl
Pyrrolidinyl
OBn
1
1
1
1
1
2
2
2
1
1
1
1
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
—
—
—
—
—
—
—
—
—
—
—
Me
MeO
MeO
1
1
1
24
24
1
24
1
24
24
24
24
24
1
59
66
42
35
20
53
25
58
15
37
43
42
26
52
7
R
S
S
S
R
S
S
S
S
S
S
S
S
S
66
47
62
9
61
52
66
9
65
56
63
69
7
5
6
7d
8
9
p-Tolyl
p-Tolyl
2-Naphthyl
Ph
Ph
Ph
10
11
12
13
14
Pyrrolidinyl
H
1m
a
The reactions were performed using 5 mol% of PdCl2(MeCN)2 and the ligand 1, a 6:1 mixture of E- and Z-b-bromostyrene 3a, and 2 equiv of the Grignard
reagent 4 in CF3–C6H5 at 0 8C.
In all entries, a small amount of 6 was obtained with no enantioselectivity (for example, 1d afforded 6 with 2% yield and 0% ee).
Determined by HPLC analysis.
1-Phenylethylmagnesium bromide was used.
b
c
d

H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
Table 2. Further screening of reaction conditions with the ligand 1b and 1ja
10703
Entryb
Catalyst
Additive
Temperature
(8C)
Time
(h)
Yield of 5a
(%)
eec of 5a
(%)
Absolute con-
figuration
1
2
3
PdCl2(MeCN)2/1b
PdCl2(MeCN)2/1j
PdCl2(MeCN)2/1j
Pd2(dba)3$CHCl3/ 1j
Pd2(dba)3$CHCl3/ 1j
Pd2(dba)3$CHCl3/ 1j
Pd2(dba)3$CHCl3/ 1j
Pd2(dba)3$CHCl3/ 1j
Pd2(dba)3$CHCl3/ 1j
[PdCl(h3-C3H5)]2 /1j
Ni(cod)2/1j
—
—
—
—
K10
K10
K20
K20
K30
K30
K30
K30
K40
0
24
12
24
2
NRd
66
—
71
—
74
76
73
47
—
—
58
0
—
S
—
S
S
S
NRd
67
4
5e
6
—
7
64
61
9
Trace
Trace
68
LiClf
LiIf
12
24
24
24
1
7
8
9
10
11
S
f
ZnCl2
—
—
S
—
—
—
0
15
56
—
a
The reactions were performed using 5 mol% of metal complex and the ligand 1, a 6:1 mixture of E- and Z-b-bromostyrene 3a, and 2 equiv of the Grignard
reagent 4 in CF3–C6H5.
b
c
d
e
f
In all entries, a small amount of 6 was obtained.
Determined by HPLC analysis.
No reaction occurred.
The use of 7.5–10 mol% of the ligand 1j gave the same results.
One molar equivalent of the additive was used.
the pendant nitrogen substituent, a strong coordinating
to 53% (entries 4 vs 6). The use of 1-phenylethylmagnesium
bromide in place of the corresponding chloride decreased
both chemical yield and enantioselectivity (entries 6 vs 7).
Furthermore, employing the piperidine-based ligand 1j
possessing the pendant piperidinyl group gave better results
(58% yield, 66% ee) than 1i (entries 6 vs 8). The effects of
the diarylphosphino groups, the aromatic parts and so on
were also examined (entries 9–14), but their replacements
gave less satisfactory results.
group, is considered to be due to the internal coordination of
the pendant nitrogen group to palladium (Fig. 3). Molecular
modeling studies suggested that the piperidine based-
ligand 1i avoids such a problem, because coordination of
the pendant nitrogen group to the internal palladium seemed
to be torsionally unfavorable. As expected, replacement of
the piperidine ring on the naphthalene ring enhanced the
reaction rate, and the chemical yield was increased from 35
Table 3. Substrate generalitya
Entry
Ar
Temperature
(8C)
Time
(h)
Yield of 5
(%)
eeb of 5
(%)
Absolute con-
figuration
1
2
3
4
5
6
7
8g
4-Me-C6H4– (3b)
4-i-Pr-C6H4– (3c)
4-Cl-C6H4– (3d)
4-TIPSOCH2-C6H4– (3e)
4-MeO-C6H4– (3f)
3-MeO-C6H4– (3g)
K20
K20
K10
K10
0
0
K20
K20
4
6
2
18
24
24
24
9
73c (5b)
75c (5c)
80c (5d)
61d (5e)
NRe
78
80
71
73
—
—
60
70
S
S
S
S
—
—
S
NRe
2-Br-C6H4– (3h, E/ZZ17:1)
3-Br-C6H4– (3i, E/ZZ23:1)
22c,f (5h)
65c (5i)
S
a
The reactions were performed using 2.5 mol% of Pd2(dba)3$CHCl3, 5 mol% of the ligand 1j, an E-isomer of the bromostyrene 3 except for 3h and 3i, and
2 equiv of the Grignard reagent 4 in CF3–C6H5.
Determined by HPLC analysis.
b
c
d
e
f
The desired product 5 was obtained as a mixture with 2,3-diphenylbutane. The chemical yield was calculated on the basis of 1H NMR analysis of the mixture.
Yield of 8 after desilylation.
No reaction occurred.
Remainder of mass balance was the unreacted starting bromostyrene 3h.
Since the use of (E)-1-bromo-2-(4-bromophenyl)ethene as a substrate gave a mixture of the cross-coupling product and a small amount of unknown
impurities, the chemical yield and ee of the cross-coupling product could not be determined.
g

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H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
1
Thus, in terms of both chemical yield and enantioselectivity,
the two ligands 1b and 1j were chosen as candidates for the
next screening. The effect of temperature on the reaction
was examined (entries 1–3, Table 2). In the case of the
ligand 1b, lowering the temperature from 0 to K10 8C
resulted in no reaction (entry 1). On the other hand, in the
case of the ligand 1j, the enantioselectivity was improved
(entry 2: 71% ee). Further intensive screening of other
palladium and nickel complexes (entries 4, 10 and 11)
established that Pd2(dba)3$CHCl3 is the most effective
complex. Thus, the reaction was found to proceed at lower
temperature (!K10 8C), and the best enantioselectivity
(76% ee) was observed at K30 8C (entry 5). The use of the
additives such as LiCl, LiI, and ZnCl2 with the best catalyst
gave less satisfactory results (entries 6–8).
Based on the previous H and 31P NMR study3 of the Pd-
ligand 1d complex, which is similar to the Pd-ligand 1j
complex, and the absolute configuration of the product 5
obtained by using the Pd-ligand 1j catalyst, enantiomeric
induction in the present system can be understood by
assuming the transition state in Figure 4. At first, oxidative
addition of the styryl bromide 3 to the Pd-ligand 1j complex
occurs. Next, the pendant nitrogen group of 1j coordinates
with the Mg atom of the Grignard reagent 4 (Fig. 4). This
coordination allows to undergo enantiomerselective trans-
metalation, thus giving the observed S-product.
Using the best Pd2(dba)3-ligand 1j catalyst, we examined
the cross-coupling reaction with several E-b-bromostyrenes
as shown in Table 3. Styrene derivatives bearing p-methyl
(3b), p-isopropyl (3c), p-chloro (3d) and p-triisopropylsilyl-
oxymethyl (3e) groups were found to be employable, giving
the corresponding products in good enantioselectivities
(entries 1–4, up to 80% ee). Unfortunately, the reaction with
3f and 3g bearing an electron-donating group did not
proceed (entries 5 and 6).13 The coupling product 5e with
73% ee was transformed into lipoxygenase inhibitor14 8, as
shown in Scheme 1. The ee of 5b–e were determined by
HPLC analysis (Daicel Chiralcel OD), and their absolute
configurations were determined by HPLC analysis (Daicel
Chiralpak AD) after conversion of 5b–e to the commercially
available carboxylic acid 7. Finally, the asymmetric cross-
coupling reaction with the styrene derivatives 3h and 3i
bearing both vinyl and aryl bromide groups was examined
as shown in entries 7 and 8, because it is important to control
the chemoselectivity in the Pd-catalyzed Grignard cross-
coupling.15 The styrene derivatives 3h and 3i underwent the
selective substitution of the vinyl bromide group to give
the corresponding mono-coupling product 5h and 5i,
respectively, although conversion of the reaction with
ortho-substituted bromostyrene 3h was low. Their ee and
absolute configurations were determined by HPLC analysis
after conversion to 5a as shown in Scheme 2.
Figure 4. Possible model for asymmetric induction.
3. Conclusion
We have shown that an N–Ar axially chiral mimetic-type
ligand is efficient in the asymmetric Kumada–Corriu cross-
coupling reaction16–18 of 1-phenylethylmagnesium chloride
with E-b-bromostyrene derivatives. Starting from the initial
ligand, the enantioselectivity was improved by modifying
the structure in the ligand. These findings validate the use-
fulness of ligand tuning for optimization. Further application
to other catalytic asymmetric reactions is now in progress.
4. Experimental
4.1. General
IR spectra were measured on a SHIMADZU FTIR-8100 and
84005 diffraction grating IR spectrophotometer. 1H and 13
C
NMR spectra were measured on a JEOL JNM-EX-270
NMR spectrometer, operating at 270 MHz for 1H NMR and
1
at 68 MHz at 13C NMR. H and 13C NMR spectra were
reported in d units, parts per million (ppm) downfield from
tetramethylsilane (dZ0). EI and FAB MS spectra were
measured on a JEOL JMS-SX-102A instrument. Specific
rotations (in deg cm3 gK1 LK1) were determined on a
JASCO DIP-1000 digital polarimeter.
1-Methoxy-2-(diarylphosphinyl)naphthalene,19 (S)-2-
(benzyloxymethyl)pyrrolidine,20 (S)-2-(t-butoxymethyl)-
pyrrolidine21 and 1,1-dibromo-2-(2-bromophenyl)ethene22
were prepared according to the known procedure. (S)-2-
Methylpiperidine and 1-bromo-2-phenylethene (E/ZZ6:1)
were commercially available. The syntheses of the ligands
1b, 1d, 1e, 1g, 1h and 1i were previously reported by us.3
The known (E)-1-bromo-2-arylethene shown below were
prepared according to our published procedure.23 Their
physical data were comparable to those of the corresponding
literature: (E)-1-bromo-2-(4-tolyl)ethene24 (3b), (E)-1-
bromo-2-(4-isopropylphenyl)ethene23 (3c), (E)-1-bromo-2-
(4-chlorophenyl)ethene24 (3d), (E)-1-bromo-2-(4-hydroxy-
methylphenyl)ethene,23 (E)-1-bromo-2-(4-methoxyphenyl)-
ethene24 (3f), (E)-1-bromo-2-(3-methoxyphenyl)ethene24
Scheme 1. Conversion to lipoxygenase inhibitor 8.
Scheme 2. Debromination of 5h and 5i.

H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
10705
(3g). 2,3-Diphenylbutane, and optically active and racemic
2-phenylpropionic acid were commercially available.
phosphanyl)naphthyl]-2-(pyrrolidinylmethyl)piperidine
(1j) (505 mg, 54% in 2 steps) as a colorless amorphous.
[a]2D8ZC1158 (c 1.60, dioxane). IR (nujol): nZ1300, 1275,
All reagents were available from commercial sources and
used without further purification. In general, all reactions
were performed under an argon atmosphere. a,a,a-
Trifluorotoluene was distilled from Na under a nitrogen
atmosphere. THF, Et2O, DME, and 1,4-dioxane, were
distilled from Na/benzophenone ketyl under a nitrogen
atmosphere. CH2Cl2 was distilled from CaH2 under a
nitrogen atmosphere. Other solvents were available from
commercial sources and used without further purification.
Silica gel column chromatography was performed on Fuji
silysia PSQ 60B, unless otherwise noted.
1206, 1159 cmK1 1H NMR (CDCl3): dZ0.83–2.22 (m,
.
18H), 2.66 (brd, JZ11.5 Hz, 1H!4/5), 3.01 (brd, JZ
11.2 Hz, 1H!1/5), 3.30 (brdd, JZ11.5, 10.6 Hz, 1H!4/5),
3.45–3.53 (br, 1H!1/5), 3.55–3.73 (br, 1H!4/5), 4.13–
4.28 (br, 1H!1/5), 6.89 (dd, JZ8.6, 2.4 Hz, 1H!4/5), 7.09
(dd, JZ8.6, 3.8 Hz, 1H!1/5), 7.14–7.57 (m, 13H), 7.72–
7.77 (m, 1H!1/5), 7.81 (dd, JZ6.3, 3.5 Hz, 1H!4/5), 8.05
(dd, JZ6.3, 3.5 Hz, 1H!4/5), 8.63 (dd, JZ6.3, 3.5 Hz,
1H!1/5). 13C NMR (CDCl3): 24.05, 24.29, 24.41, 25.27,
25.71, 25.93, 26.02, 27.47, 29.75, 31.59, 32.34, 54.10,
54.32, 54.93, 55.10, 57.17, 57.38, 59.20, 61.70, 62.50,
62.59, 124.80, 124.94, 125.49, 125.57, 125.78, 125.95,
126.02, 126.71, 127.44, 127.90, 127.97, 128.00, 128.13,
128.17, 128.27, 128.37, 128.63, 129.50, 131.91, 132.72,
133.00, 133.29, 133.54, 133.80, 133.95, 134.10, 134.26,
134.54, 134.66, 135.01, 135.19, 136.92, 137.40, 137.60,
138.35, 138.54, 138.81, 139.00, 139.63, 139.87, 150.99,
151.30, 153.92, 154.28. FABMS: m/zZ493 (MCC1).
Anal. Calcd for C33H37N2P: C, 80.46; H, 7.57; N, 5.69.
Found: C, 80.27; H, 7.56; N, 5.85.
4.1.1. (S)-2-(Piperidinylmethyl)piperidine. The title com-
pound was prepared according to the similar procedure
reported.25 The physical data were comparable to the
commercially available racemate. [a]2D6ZC338 (c 8.17,
dioxane).
4.2. Representative procedure for the synthesis of
ligand 1
4.2.2. (S)-N-[2-(Diphenylphosphanyl)naphthalen-1-yl]-
2-(methoxymethoxymethyl)pyrrolidine (1a). The repre-
sentative 2-step procedure was used to afford the title ligand
1a (yield 35%) as a colorless viscous oil. [a]2D4ZC988 (c
0.41, THF). IR (neat): nZ1374, 1362, 1078 cmK1. 1H NMR
(CDCl3, 55 8C): dZ1.93–2.06 (br, 3H), 2.30–2.46 (br, 1H),
3.15 (s, 3H), 3.20–3.32 (br, 2H), 3.38 (d, JZ6.3 Hz, 2H),
4.16–4.28 (br, 1H), 4.34 (s, 2H), 7.07 (dd, JZ1.5, 3.2 Hz,
1H), 7.24–7.34 (br, 10H), 7.44 (dd, JZ1.5, 3.2 Hz, 2H),
7.57 (d, JZ7.6 Hz, 1H), 7.80 (dd, JZ1.5, 3.2 Hz, 1H),
7.99–8.12 (br, 1H). 13C NMR (CDCl3): 25.15, 30.32, 54.72,
55.07, 63.43, 63.55, 71.83, 96.66, 124.44, 125.72, 126.24,
126.32, 128.11, 128.19, 128.23, 128.32, 128.62, 130.92,
133.43, 133.59, 133.73, 133.89, 135.59. FABMS: m/zZ456
(MCC1). Anal. Calcd for C29H30NO2P: C, 76.46; H, 6.64;
N, 3.07. Found: C, 76.75; H, 6.48; N, 3.11.
4.2.1. (S)-N-[2-(Diphenylphosphanyl)naphthalen-1-yl]-
2-(piperidinylmethyl)piperidine (1j). First step: to a
stirred solution of (S)-2-(piperidinylmethyl)piperidine
(700 mg, 3.84 mmol) in THF (4.0 mL) was gradually
added BuLi (2.53 mL, 4.00 mmol, 1.58 M solution in
hexane) at K30 8C, and the mixture was stirred for 2 h at
the same temperature. To this solution was then added a
solution of 1-methoxy-2-(diphenylphosphinoyl)naphthalene
(680 mg, 1.90 mmol) in THF (2.0 mL) at K30 8C. The
whole mixture was stirred for 1 h at the same temperature,
quenched with water and extracted with EtOAc. The
organic extracts were successively washed with saturated
aq. NH4Cl and brine, dried (Na2SO4) and concentrated.
Purification by silica gel column (Fuji Silysia Chromatorex
NH, EtOAc/hexaneZ1:5) gave a mixture (724 mg) of 1-(S)-
N-[2-(diphenylphosphonyl)naphthalen-1-yl]-2-(piperidinyl-
methyl)piperidine and small amounts of impurities. This
mixture was used for the next step without further
4.2.3. (S)-N-[2-(Diphenylphosphanyl)naphthalen-1-yl]-
2-(t-butoxymethyl)pyrrolidine (1c). The representative
2-step procedure was used to afford the title ligand 1c (yield
44%) as a colorless amorphous. [a]2D7ZC1158 (c 2.26,
separation. IR (neat): nZ1308, 1254, 1192, 1161 cmK1
.
1H NMR (CDCl3): dZ0.75–1.15 (m, 8H), 1.24–1.45 (m,
2H), 1.60–1.94 (m, 7H), 2.46 (dd, JZ13.3, 5.9 Hz, 1H),
2.92 (brd, JZ11.1 Hz, 1H), 3.36 (dd, JZ11.1, 11.1 Hz, 1H),
3.51–3.62 (br, 1H), 6.97 (dd, JZ12.1, 8.6 Hz, 1H), 7.35–
7.57 (m, 10H), 7.65–7.87 (m, 4H), 8.23 (d, JZ8.4 Hz, 1H).
13C NMR (CDCl3): 24.29, 24.90, 25.47, 25.63, 31.38, 54.80,
56.09, 60.55, 62.23, 125.15, 125.42, 125.62, 126.21, 127.02,
127.95, 128.13, 128.65, 129.02, 129.22, 129.77, 130.74,
131.09, 131.23, 131.37, 131.94, 132.07, 134.15, 134.65,
135.09, 135.22, 135.66, 136.22, 136.63, 155.14. FABMS:
m/zZ509 (MCC1). Second step: the above mixture was
dissolved in p-xylene (7.0 mL), and Et3N (2.10 mL,
15.1 mmol) and HSiCl3 (1.4 mL, 14 mmol) were added at
0 8C. The whole mixture was heated at 140 8C for 2 h. After
being cooled to rt, the reaction mixture was carefully poured
into 10% NaOH, and the whole mixture was extracted with
EtOAc. The organic extracts were successively washed with
water and brine, dried (Na2SO4), and concentrated.
Purification by silica gel column (Fuji Silysia Chromatorex
NH, hexane/EtOAcZ20:1) gave (S)-N-[2-(diphenyl-
1
dioxane). IR (neat): nZ1374, 1362, 1078 cmK1. H NMR
(CDCl3, 50 8C): dZ0.93 (s, 9H), 1.91–2.06 (m, 3H), 2.26–
2.43 (br, 1H), 3.09–3.31 (m, 4H), 4.00–4.14 (br, 1H), 7.05
(br d, JZ8.4 Hz, 1H), 7.21–7.33 (m, 10H), 7.43 (br dd, JZ
4.2, 4.2 Hz, 2H), 7.57 (d, JZ8.4 Hz, 1H), 7.77–7.84 (br,
1H), 7.96–8.12 (br, 1H). 13C NMR (CDCl3): 25.05, 27.54,
30.33, 54.70, 54.76, 64.04, 64.12, 65.65, 72.17, 124.67,
125.52, 126.15, 126.22, 128.04, 128.08, 128.15, 128.25,
128.36, 128.65, 130.73, 133.38, 133.50, 133.67, 133.80,
135.68, 139.02, 139.25, 150.32, 150.65. FABMS: m/zZ468
(MCC1). Anal. Calcd for C31H34NOP: C, 79.63; H,
7.33; N, 3.00. Found: C, 79.39; H, 7.35; N, 3.24. The
physical data of the coupling product in the first step, (S)-N-
[2-(diphenylphosphinoyl)naphthalen-1-yl]-2-(t-butoxy-
methyl)pyrrolidine, with small amounts of inseparable
impurities are shown below. This mixture was used for
the second step, the reduction reaction, without further
separation. IR (neat): nZ1387, 1364, 1196, 1115 cmK1. 1H

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H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
NMR (CDCl3): dZ0.89 (s, 9H), 1.70–1.82 (m, 3H), 2.04–
2.20 (br, 1H), 2.71–2.89 (br, 1H), 2.96–3.05 (m, 1H), 3.11
(dd, JZ9.1, 4.1 Hz, 1H), 3.23–3.35 (br, 1H), 4.16–4.31 (br,
1H), 7.16 (dd, JZ12.7, 8.6 Hz, 1H), 7.37–7.60 (m, 9H),
7.65–7.81 (m, 4H), 7.84 (d, JZ7.8 Hz, 1H), 8.23 (br d, JZ
7.8 Hz, 1H). 13C NMR (CDCl3): 24.60, 27.35, 29.45, 54.02,
64.32, 64.50, 71.93, 124.78, 124.98, 125.41, 126.02, 127.38,
127.87, 128.06, 128.49, 129.31, 129.50, 130.79, 130.83,
130.88, 130.92, 131.21, 131.35, 131.63, 131.77, 133.72,
133.92, 135.25, 135.48, 136.72, 136.75, 152.08, 152.14.
FABMS: m/zZ484 (MCC1).
2.88–3.04 (br, 1H), 3.12–3.23 (m, 2H), 4.22 (s, 2H), 6.89–
7.02 (m, 2H), 7.06–7.13 (m, 2H), 7.15–7.49 (m, 9H), 7.61–
7.76 (m, 5H). FABMS: m/zZ482 (MCC1).
4.2.6.
(S)-N-[2-(Diphenylphosphanyl)-6-methoxyl-
phenyl]-2-(pyrrolidinylmethyl)pyrrolidine (1l). The
representative 2-step procedure was used to afford the title
ligand 1l (yield 31%) as a colorless viscous oil. The physical
data were comparable to those reported.18a
4.2.7.
(S)-N-[2-(Diphenylphosphanyl)-6-methoxyl-
4.2.4. (S)-N-[2-(Di-p-tolylphosphanyl)naphthalen-1-yl]-
2-(benzyloxymethyl)pyrrolidine (1f). The representative
2-step procedure was used to afford the title ligand 1f (yield
48%) as a colorless viscous oil. [a]2D4ZC818 (c 0.47, THF).
phenyl]-2-methylpiperidine (1m). The representative
2-step procedure was used to afford the title ligand 1m
(yield 30%) as a colorless amorphous. [a]2D5ZK238 (c 3.51,
dioxane). IR (neat): nZ1283, 1258 cmK1 1H NMR
.
1
IR (neat): nZ1374, 1308, 1113 cmK1. H NMR (CDCl3,
(CDCl3): dZ0.67 (d, JZ6.3 Hz, 3H), 1.03–1.35 (m, 4H),
1.48 (brd, JZ8.3 Hz, 1H), 1.60–1.68 (br, 1H), 2.46 (brd,
JZ11.1 Hz, 1H), 2.94 (ddd, JZ11.1, 11.1, 3.3 Hz 1H),
3.20–3.32 (m, 1H), 3.77 (s, 3H), 6.36 (brd, JZ8.1 Hz 1H),
6.81 (d, JZ8.1 Hz, 1H), 7.02 (dd, JZ8.1, 8.1 Hz, 1H),
7.22–7.36 (m, 10H). 13C NMR (CDCl3): 20.03, 20.08,
25.40, 25.84, 35.20, 52.41, 54.98, 55.18, 111.90, 124.71,
126.09, 126.11, 127.77, 127.82, 127.87, 127.92, 133.87,
134.12, 134.18, 134.42, 138.04, 138.22, 138.91, 139.12,
141.67, 141.79, 141.82, 141.97, 158.83, 158.86. FABMS:
m/zZ390 (MCC1). Anal. Calcd for C25H28NOP: C, 77.10;
H, 7.25; N, 3.60. Found: C, 76.96; H, 7.33; N, 3.41. The
physical data of the coupling product in the first step, (S)-N-
[2-(diphenylphosphinoyl)-6-methoxylphenyl]-2-methyl-
piperidine, with small amounts of inseparable impurities are
shown below. This mixture was used for the second step, the
reduction reaction, without further separation. IR (nujol):
nZ1283, 1267, 1190 cmK1. 1H NMR (CDCl3): dZ0.52 (d,
JZ6.4 Hz, 3H), 0.83–1.00 (m, 1H), 1.08–1.34 (m, 4H),
1.79–1.91 (br, 1H), 2.87–2.95 (m, 2H), 3.16–3.30 (m, 1H),
3.80 (s, 3H), 6.62 (ddd, JZ13.5, 7.3, 1.6 Hz, 1H), 6.99–7.10
(m, 2H), 7.36–7.50 (m, 6H), 7.73–7.83 (m, 4H). 13C NMR
(CDCl3): 19.75, 24.88, 25.42, 34.06, 54.29, 55.19, 55.85,
115.59, 115.62, 125.50, 125.73, 125.88, 126.06, 127.62,
127.73, 127.80, 127.90, 130.48, 130.50, 130.52, 130.54,
131.19, 131.32, 131.56, 131.69, 133.53, 134.00, 135.07,
135.55, 144.08, 144.15, 159.84, 159.99. FABMS: m/zZ406
(MCC1).
50 8C): dZ1.90–2.09 (br, 3H), 2.22–2.45 (m, 7H), 3.20–
3.41 (m, 4H), 4.10–4.30 (br, 3H), 6.98–8.25 (m, 19H). 13C
NMR (CDCl3): 21.32, 25.24, 30.26, 54.63, 63.22, 63.32,
72.88, 74.61, 125.58, 126.04, 126.15, 127.02, 127.22,
127.90, 127.98, 129.01, 129.11, 133.44, 133.58, 133.74,
133.88, 137.84, 137.95, 138.81. FABMS: m/zZ530 (MCC
1). Anal. Calcd for C36H36NOP: C, 81.64; H, 6.85; N, 2.64.
Found: C, 81.35; H, 6.70; N, 2.65. The physical data of the
coupling product in the first step, (S)-N-[2-(di-p-tolyl-
phosphinoyl)naphthalen-1-yl]-2-(benzyloxymethyl)pyrroli-
dine, with small amounts of inseparable impurities are
shown below. This mixture was used for the second step, the
reduction reaction, without further separation. IR (neat): nZ
1383, 1310, 1186, 1113 cmK1. 1H NMR (CDCl3): dZ1.56–
1.73 (br, 1H), 1.78–1.94 (m, 2H), 2.12–2.29 (br, 1H), 2.36
(s, 6H), 2.80–2.99 (br, 1H), 3.11–3.27 (m, 2H), 3.28–3.46
(br, 1H), 4.11 (s, 2H), 4.27–4.48 (br, 1H), 7.03 (br d, JZ
6.8 Hz, 2H), 7.11–7.32 (m, 8H), 7.36–7.67 (m, 7H), 7.83 (d,
JZ8.1 Hz, 1H), 8.14–8.24 (br, 1H). 13C NMR (CDCl3):
21.58, 24.81, 29.57, 54.21, 63.38, 72.56, 73.88, 124.80,
124.99, 125.47, 125.73, 126.88, 126.95, 127.43, 127.87,
128.69, 128.75, 128.83, 128.88, 128.93, 129.50, 129.69,
130.34, 130.81, 131.34, 131.48, 131.67, 131.81, 132.40,
136.72, 138.71, 141.19, 141.23, 141.27, 151.86. FABMS:
m/zZ546 (MCC1).
4.2.5. (S)-N-[2-(Diphenylphosphanyl)-6-methylphenyl]-
2-(benzyloxymethyl)pyrrolidine (1k). The representative
2-step procedure was used to afford the title ligand 1l (yield
50%) as a colorless viscous oil. [a]2D4ZC508 (c 0.647,
1
4.2.8. (E)-1-Bromo-2-(4-triisopropylsilyloxymethyl-
phenyl)ethene (3e). To a stirred solution of (E)-1-bromo-
2-(4-hydroxymethylphenyl)ethene (134 mg, 0.632 mmol)
and imidazole (94.2 mg, 1.37 mmol) in DMF (0.6 mL)
was gradually added TIPSCl (240 mg, 1.24 mmol) at 0 8C.
The reaction mixture was stirred for 1.5 h at rt and purified
directly by silica gel column (hexane) to gave 1-bromo-2-
(4-triisopropylsilyloxymethylphenyl)ethene (3e) (230 mg,
99%) as a colorless oil. IR (neat): nZ1462, 1094 cmK1. 1H
NMR (CDCl3): dZ0.97–1.24 (m, 3H), 1.09 (d, JZ5.6 Hz,
18H), 4.81 (s, 2H), 6.74 (d, JZ14.0 Hz, 1H), 7.09 (d,
JZ14.0 Hz, 1H), 7.26 (d, JZ8.3 Hz, 2H), 7.31 (d, JZ
8.3 Hz, 2H). 13C NMR (CDCl3): dZ12.00, 18.01, 64.63,
105.68, 125.73, 125.87, 134.23, 136.82, 141.71. EIMS:
THF). IR (neat): nZ1095 cmK1. H NMR (CDCl3): dZ
1.49–1.90 (m, 3.5H), 1.99–2.20 (m, 1.2H), 2.27 (s, 3H),
2.60–2.80 (m, 0.6H), 2.85 (dd, JZ7.6, 7.6 Hz, 0.9H), 3.09–
3.36 (m, 2H), 3.64–3.80 (m, 0.8H), 4.27 (s, 2H), 6.61–6.84
(br, 0.8H), 7.01 (dd, JZ7.4, 7.4 Hz, 1H), 6.97–7.40 (16.2H).
FABMS: m/zZ466 (MCC1). EIMS: m/zZ344 (MCK
CH2OBn, bp), 91. HRMS (MCKCH2OBn): calcd for
C23H23NP: 344.1568; found: 344.1549. The physical data
of the coupling product in the first step, (S)-N-[2-
(diphenylphosphinoyl)-6-methylphenyl]-2-(benzyloxy-
methyl)pyrrolidine, with small amounts of inseparable
impurities are shown below. This mixture was used for
the second step, the reduction reaction, without further
separation. IR (neat): nZ1454, 1418, 1200, 1113 cmK1. 1H
NMR (CDCl3, 50 8C): dZ1.30–1.51 (br, 1H), 1.54–1.72 (m,
2H), 1.90–2.05 (m, 2H), 2.29 (s, 3H), 2.43–2.68 (br, 1H),
m/zZ370 (MC), 368 (MC), 325 (bp), 195. HRMS: m/z
79
calcd for C18H BrOSi: 368.1171; found: 368.1180.
29

H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
10707
4.3. Representative procedure for the stereoselective
(Daicel chiralcel OD, hexane/i-PrOHZ100:1, 0.3 mL/min,
254 nm): tR/minZ34.9 (S), 37.1 (R). The absolute con-
figuration was determined by comparison of the reported
specific rotation.8 The physical data were comparable to
those reported.8
synthesis of (E)-1-bromo-2-arylethene (3)23
4.3.1. 1-Bromo-2-(2-bromophenyl)ethene (3h). To a
stirred solution of 1,1-dibromo-2-(2-bromophenyl)ethene
(580 mg, 1.72 mmol) and EtOAc (302 mg, 3.44 mmol) in
THF (5.7 mL) was gradually added LiAlH4 (130 mg,
3.44 mmol) at K40 8C. The mixture was stirred for 8 h at
the same temperature and quenched with a small amount of
acetone. To the mixture was then added Na2SO4$10H2O.
The whole mixture was stirred for 1 h at rt and filtered to
remove white precipitates. After concentration, purification
by silica gel column (hexane) gave 1-bromo-2-(2-bromo-
phenyl)ethene (3h) (283 mg, 65%) as a 17:1 mixture of
E- and Z-isomers. a colorless oil. IR (neat): nZ1605, 1462,
4.5. Representative procedure for the cross-coupling
reaction with Pd2(dba)3-the ligand 1j catalyst (entry 5,
Table 2)
1-Phenylethylmagnesium chloride (2.10 mL, 1.50 mmol,
0.70 mol/L in Et2O) was added to the mixture of Pd2-
(dba)3$CHCl3 (19.1 mg, 0.0180 mmol) and the ligand 1j
(18.2 mg, 0.0369 mmol) in a,a,a-trifluorotoluene
(2.10 mL) at K30 8C, and the solution was stirred at
the same temperature for 30 min. To the solution was added
b-bromostyrene (E/ZZ6:1, 3a) (133 mg, 0.727 mmol) at
K30 8C. The resulting solution was stirred for 7 h at
K30 8C. After usual work-up, purification by silica gel
column (hexane) afforded (S)-(E)-1,3-diphenyl-1-butene
(5a) (96.9 mg, 64%, 76% ee) as a colorless oil. The ee
was determined by HPLC analysis with Daicel chiralcel
OD. The absolute configuration was determined by
comparison of the reported specific rotation.8 The physical
data were comparable to those reported.8
1
1435 cmK1. H NMR (CDCl3): dZ6.76 (d, JZ14.0 Hz,
1H), 7.15 (ddd, JZ7.7, 7.7, 1.6 Hz, 1H), 7.27 (ddd, JZ7.7,
7.7, 1.2 Hz, 1H), 7.39 (dd, JZ7.7, 1.6 Hz, 1H), 7.43 (d, JZ
14.0 Hz, 1H), 7.55 (dd, JZ7.7, 1.2 Hz, 1H). 13C NMR
(CDCl3): dZ109.14, 122.63, 126.95, 127.53, 129.44,
132.99, 135.78, 136.03. EIMS: m/zZ264 (MC), 262
(MC), 260 (MC), 181 (bp), 75. HRMS: m/z calcd for
C8H769Br2: 259.8836; found: 259.8839.
4.3.2. 1,1-Dibromo-2-(3-bromophenyl)ethene. The pub-
lished procedure26 was used to afford the title dibromo-
alkene (yield 99%) as a pale yellow oil. IR (neat): nZ1589,
1560, 1470 cmK1. 1H NMR (CDCl3): dZ7.23 (dd, JZ7.6,
7.9 Hz, 1H), 7.41 (s, 1H), 7.43 (d, JZ7.9 Hz, 1H), 7.47 (d,
JZ7.6 Hz, 1H), 7.68 (s, 1H). 13C NMR (CDCl3): dZ91.37,
122.31, 126.85, 129.79, 131.01, 131.34, 135.24, 137.08.
EIMS: m/zZ344 (MC), 342 (MC), 340 (MC, bp) 338
(MC), 261, 180. HRMS: m/z calcd for C8H579Br3: 337.7941;
found: 337.7953.
4.5.1. (S)-(E)-1-(4-Tolyl)-3-phenyl-1-butene (5b). Yield
73%, 78% ee. The desired product 5b was obtained as a
mixture with 2,3-diphenylbutane. The chemical yield of 5b
1
was calculated on the basis of H NMR analysis of the
mixture. The protons of these compounds were assigned,
respectively, by comparison with the authentic sample
(G)-5b, which was prepared by Wittig olefination of
2-phenylpropionaldehyde with Ph3P]CH(4-tolyl), and
commercially available 2,3-diphenylbutane. The ee was
determined by HPLC analysis with Daicel chiralcel OD
(hexane/i-PrOHZ200:1), and its absolute configuration was
determined by HPLC analysis with Daicel Chiralpak AD
(hexane/i-PrOH/TFAZ9:1:0.1) after conversion ((i) OsO4,
NMO, t-BuOH–H2O, (ii) RuO2, NaIO4, CCl4-MeCN–H2O,
0 8C) of 5b to 2-phenylpropionic acid 7 of known
configuration. Physical data of the authentic sample
(G)-(E)-5b. A colorless oil. IR (neat): nZ1603, 1456,
4.3.3. (E)-1-Bromo-2-(3-bromophenyl)ethene (3i). The
above representative procedure was used to afford the title
bromoalkene (yield 65%, E/ZZ23: 1) as a colorless oil. IR
1
(neat): nZ1605, 1593, 1562, 1475, 1470 cmK1. H NMR
(CDCl3): dZ6.80 (d, JZ14.0 Hz, 1H), 7.04 (d, JZ14.0 Hz,
1H), 7.18–7.24 (m, 2H), 7.38–7.48 (m, 2H). 13C NMR
(CDCl3): dZ108.13, 122.82, 124.61, 128.85, 130.17,
131.03, 135.62, 137.75. EIMS: m/zZ264 (MC), 262 (MC,
bp), 260 (MC), 102, 75. HRMS: m/z calcd for C8H679Br2:
259.8836; found: 259.8823.
1
967 cmK1. H NMR (CDCl3): dZ1.46 (d, JZ6.9 Hz, 3H),
2.32 (s Hz, 3H), 2.87 (sept, JZ6.9 Hz, 1H), 3.57–3.68 (m,
1H), 6.33–6.37 (m, 2H), 7.06–7.35 (m, 9H). EIMS: m/zZ
222 (MC), 207 (MCKCH3, bp). HRMS (MC): calcd for
C17H18 222.1409; found: 222.1401.
4.4. Representative procedure for the cross-coupling
with PdCl2(MeCN)2-the ligand 1j catalyst (entry 2,
Table 2)
4.5.2. (S)-(E)-1-(4-Isopropylphenyl)-3-phenyl-1-butene
(5c). Yield 75%, 80% ee. The desired product 5c was
obtained as a mixture with 2,3-diphenylbutane. The
1-Phenylethylmagnesium chloride (2.10 mL, 1.50 mmol,
0.70 mol/L in Et2O) was added to the mixture of PdCl2-
(MeCN)2 (9.3 mg, 0.036 mmol) and the ligand 1j (18.2 mg,
0.0369 mmol) in a,a,a-trifluorotoluene (2.10 mL) at 0 8C,
and the solution was stirred at the same temperature for
30 min (CAUTION: stirring at 0 8C for 30 min for the
favorable complexation of Pd and ligand 1j is needed.). To
the solution was added b-bromostyrene (E/ZZ6:1, 3a)
(133 mg, 0.727 mmol) at K10 8C. The resulting solution
was stirred for 6 h at K10 8C. After usual work-up,
purification by silica gel column (hexane) afforded (S)-
(E)-1,3-diphenyl-1-butene (5a) (105 mg, 69%, 71% ee) as a
colorless oil. The ee was determined by HPLC analysis
1
chemical yield of 5c was calculated on the basis of H
NMR analysis of the mixture. The protons of these
compounds were assigned, respectively, by comparison
with the authentic sample (G)-5c, which was prepared by
Wittig olefination of 2-phenylpropionaldehyde with
Ph3P]CH(4-i-Pr-C6H4), and commercially available 2,3-
diphenylbutane. The ee was determined by HPLC analysis
with Daicel chiralcel OD (hexane/i-PrOHZ200:1), and its
absolute configuration was determined by HPLC analysis
with Daicel Chiralpak AD (hexane/i-PrOH/TFAZ9:1:0.1)
after conversion of 5c to 2-phenylpropionic acid 7 of known

10708
H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
configuration. Physical data of the authentic sample (G)-
respectively, by comparison with the authentic sample
(G)-5i, which was prepared by Wittig olefination of
2-phenylpropionaldehyde with Ph3P]CH(3-Br-C6H4), and
commercially available 2,3-diphenylbutane. The ee and
absolute configuration were determined by HPLC analysis
with Daicel chiralcel OD and OD-H (hexane/i-PrOHZ
400:1) after conversion (t-BuLi, THF, K40 8C) of 5i to 5a
of known configuration. Physical data of the authentic
sample (G)-5i. A colorless oil. IR (neat): nZ1591, 1558,
1493, 1474, 1450 cmK1. 1H NMR (CDCl3): dZ1.46 (d, JZ
6.9 Hz, 3H), 3.63 (dq, JZ6.9, 6.9 Hz, 1H), 6.27–6.44 (m,
2H), 7.08–7.37 (m, 8H), 7.50 (s, 1H). EIMS: m/zZ288
(E)-5c. A colorless oil. IR (neat): nZ1603, 1453, 968 cmK1
.
1H NMR (CDCl3): dZ1.23 (d, JZ6.9 Hz, 3H!2), 1.45 (d,
JZ7.1 Hz, 3H), 2.87 (sept, JZ6.9 Hz, 1H), 3.62 (dt, JZ6.9,
6.9 Hz, 1H), 6.28–6.46 (m, 2H), 7.10–7.34 (m, 9H). 13C
NMR (CDCl3): 21.34, 24.04, 33.88, 42.56, 126.00, 126.04,
126.44, 127.20, 128.23, 128.33, 134.21, 135.08, 145.66,
147.72. EIMS: m/zZ250 (MC), 207 (bp). HRMS (MC):
calcd for C19H22 250.1722; found: 250.1715.
4.5.3. (S)-(E)-1-(4-Chlorophenyl)-3-phenyl-1-butene
(5d). Yield 80%, 71% ee. The desired product 5d was
obtained as a mixture with 2,3-diphenylbutane. The
(MC), 286 (MC), 207 (bp), 192, 130. HRMS (MC): calcd
79
1
for C16H Br: 286.0357; found: 286.0369.
15
chemical yield of 5d was calculated on the basis of H
NMR analysis of the mixture. The protons of these
compounds were assigned, respectively, by comparison
with the known 5d27 and commercially available 2,3-
diphenylbutane. The ee was determined by HPLC analysis
with Daicel chiralcel OD (hexane/i-PrOHZ200:1), and its
absolute configuration was determined by HPLC analysis
with Daicel Chiralpak AD (hexane/i-PrOH/TFAZ9:1:0.1)
after conversion of 5d to 2-phenylpropionic acid 7.
Acknowledgements
We thank the Ministry of Education, Science and Culture,
Japan for support. K.K. was financially supported by
Sankyo Award in Synthetic Organic Chemistry, Japan.
4.5.4. (S)-(E)-1-(4-Hydroxymethylphenyl)-3-phenyl-1-
butene (8). The ee of 5e was determined by HPLC analysis
with Daicel chiralpak AD (hexane/i-PrOHZ20:1), and its
absolute configuration was determined by HPLC analysis
with Daicel Chiralpak AD (hexane/i-PrOH/TFAZ9:1:0.1)
after conversion of 5e to 2-phenylpropionic acid of known
configuration. Since the desired product 5e was obtained as
a mixture with 2,3-diphenylbutane, the desilylation was
performed without further separation. The solution of the
above mixture and TBAF (187 mg, 0.717 mmol) in THF
(1.2 mL) were stirred for 1 h at 0 8C, and purified directly by
silica gel column (EtOAc/hexaneZ1:2) to gave (S)-(E)-1-
(4-hydroxymethylphenyl)-3-phenyl-1-butene (8) (81 mg,
61%, 2 steps, 73% ee) as a pale yellow oil. [a]2D3ZK368
References and notes
1. Trost, B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96,
395–422.
2. (a) Ojima, I. Catalytic Asymmetric Synthsis II; Wiley-VCH:
New York, 2000. (b) Jacobsen, E. N.; Pfaltz, A.; Yamamoto,
H. In Comprehensive Asymmetric Catalysis, Vol. 1–3;
Springer: Berlin, 1999.
3. Kondo, K.; Kazuta, K.; Fujita, H.; Sakamoto, Y.; Murakami,
Y. Tetrahedron 2002, 58, 5209–5214.
4. Grignard cross-coupling reaction is called the Kumada–Corriu
reaction: (a) Tamao, K.; Sumitani, K.; Kumada, M. J. Am.
Chem. Soc. 1972, 94, 4374–4376. (b) Corriu, R. J. P.; Masse,
J. P. J. Chem. Soc., Chem. Commun. 1972, 144.
1
(c 2.08, THF). IR (neat): nZ1491, 1451, 1011 cmK1. H
NMR (CDCl3): dZ1.46 (d, JZ7.1 Hz, 3H), 1.68–1.76 (br,
1H), 3.58–3.67 (m, 1H), 4.63 (s, 2H), 6.34–6.43 (m, 2H),
7.17–7.35 (m, 9H). 13C NMR (CDCl3): dZ21.26, 42.59,
65.12, 126.14, 126.23, 127.12, 127.20, 128.03, 128.40,
135.29, 136.98, 139.52, 145.46. EIMS: m/zZ238 (MC),
115 (bp). Anal. Calcd for C17H18O: C, 85.67; H, 7.61.
Found: C, 85.27; H, 7.68.
5. (a) Hayashi, T.; Fukushima, M.; Konishi, M.; Kumada, M.
Tetrahedron Lett. 1980, 21, 79–82. (b) Hayashi, T.; Konishi,
M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika, M.;
Kumada, M. J. Am. Chem. Soc. 1982, 104, 180–186.
(c) Hayashi, T.; Hagihara, T.; Katsuro, Y.; Kumada, M. Bull.
Chem. Soc. Jpn 1983, 56, 363–364. (d) Hayashi, T.; Konishi,
M.; Fukushima, M.; Kanehira, K.; Hioki, T.; Kumada, M.
J. Org. Chem. 1983, 48, 2195–2202. (e) Hayashi, T.;
Yamamoto, A.; Hojo, M.; Ito, Y. J. Chem. Soc., Chem.
Commun. 1989, 495–496.
4.5.5. (S)-(E)-1-(2-Bromophenyl)-3-phenyl-1-butene
(5h). Yield 22%, 60% ee. The desired product 5h was
obtained as a mixture with 2,3-diphenylbutane. The
1
chemical yield of 5h was calculated on the basis of H
6. (a) Vriesema, B. K.; Kellogg, R. M. Tetrahedron Lett. 1986,
27, 2049–2052. (b) Cross, G.; Vriesema, B. K.; Boven, G.;
Kellogg, R. M.; van Bolhuis, F. J. Organomet. Chem. 1989,
370, 357–381. (c) Baker, K. V.; Brown, J. M.; Cooley, N. A.;
Hughes, G. D.; Taylar, R. J. J. Organomet. Chem. 1989, 370,
397–406. (d) Jedlicka, B.; Kratky, C.; Weissensteiner, W.;
Widhalm, M. J. Chem. Soc., Chem. Commun. 1993,
1329–1330. (e) Pellet-Rostaing, S.; Saluzzo, C.; Halle, R. T.;
Breuzard, J.; Vial, L.; Guyader, F. L.; Lemaire, M.
Tetrahedron: Asymmetry 2001, 12, 1983–1985.
NMR analysis of the mixture. The protons of these
compounds were assigned, respectively, by comparison
with the known 5h28 and commercially available 2,3-
diphenylbutane. The ee and absolute configuration were
determined by HPLC analysis with Daicel chiralcel OD and
OD-H (hexane/i-PrOHZ400:1) after conversion (t-BuLi,
THF, K40 8C) of 5h to 5a.
4.5.6. (S)-(E)-1-(3-Bromophenyl)-3-phenyl-1-butene (5i).
Yield 65%, 70% ee. The desired product 5i was obtained as
a mixture with 2,3-diphenylbutane. The chemical yield of 5i
¨
7. (a) Kreuzfeld, H.-J.; Dobler, C.; Abicht, H.-P. J. Organomet.
¨
Chem. 1987, 336, 287–292. (b) Dobler, C.; Kreuzfeld, H.-J.
1
was calculated on the basis of H NMR analysis of the
mixture. The protons of these compounds were assigned,
J. Organomet. Chem. 1988, 344, 249–252. (c) Uemura, M.;
Miyake, R.; Nishimura, H.; Matsumoto, Y.; Hayashi, T.

H. Horibe et al. / Tetrahedron 60 (2004) 10701–10709
10709
Tetrahedron: Asymmetry 1992, 3, 213–216. (d) Yamago, S.;
Yanagawa, M.; Nakamura, E. J. Chem. Soc., Chem. Commun.
1994, 52, 2093–2094. (e) Richards, C. J.; Hibbs, D. E.;
Hursthouse, M. B. Tetrahedron Lett. 1995, 36, 3745–3748.
(f) Yamago, S.; Yanagawa, M.; Mukai, H.; Nakamura, E.
Tetrahedron 1996, 52, 5091–5102. (g) Lloyd-Jones, G. C.;
Butts, C. P. Tetrahedron 1998, 54, 901–914.
K.-G.; Miyake, Y.; Uemura, S. J. Chem. Soc., Perkin Trans. 1
¨
2000, 2725–2729. (j) Holzer, B.; Hoffmann, R. W. Chem.
Commun. 2003, 732–733.
17. Another type of catalytic asymmetric cross-coupling, the
Suzuki and Miyaura reaction, has been reported, see: (a) Cho,
S. Y.; Shibasaki, M. Tetrahedron: Asymmetry 1998, 9,
´
3751–3754. (b) Cammidge, A. N.; Crepy, K. V. L. Chem.
8. Schwink, L.; Knochel, P. Chem. Eur. J. 1998, 4, 950–968.
9. Hayashi, M.; Takaoki, K.; Hashimoto, Y.; Saigo, K.
Enantiomer 1997, 2, 293–296.
Commun. 2000, 1723–1724. (c) Chung, K.-G.; Miyake, Y.;
Uemura, S. J. Chem. Soc., Perkin Trans. 1 2000, 15–18.
(d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122,
12051–12052. (e) Castanet, A.-S.; Colobert, F.; Broutin, P.-E.;
Obringer, M. Tetrahedron: Asymmetry 2002, 13, 659–665.
18. For recent chiral P,N(sp3)-ligands, see: (a) Mino, T.; Tanaka,
Y.; Sato, Y.; Saito, A.; Sakamoto, M.; Fujita, T. Tetrahedron
Lett. 2003, 44, 4677–4679. (b) Shibatomi, K.; Uozumi, Y.
Tetrahedron: Asymmetry 2002, 13, 1769–1772. (c) Jin, M.-J.;
Kim, S.-H.; Lee, S.-J.; Kim, Y.-M. Tetrahedron Lett. 2002, 43,
7409–7411. (d) Okuyama, Y.; Nakano, H.; Hongo, H.
Tetrahedron: Asymmetry 2000, 11, 1193–1198. (e) Suzuki,
Y.; Abe, I.; Hiroi, K. Heterocycles 1999, 50, 89–94. (f) Cahill,
J. P.; Cunneen, D.; Guiry, P. J. Tetrahedron: Asymmetry 1999,
10, 4157–4173. (g) Bourghida, M.; Widhalm, M. Tetrahedron:
Asymmetry 1998, 9, 1073–1083. (h) Hattori, T.; Komuro, Y.;
Hayashizaka, N.; Takahashi, H.; Miyano, S. Enantiomer 1997,
2, 203–213 and references cited therein.
10. For our preliminary communication, see: Horibe, H.; Kazuta,
K.; Kotoku, M.; Kondo, K.; Okuno, H.; Murakami, Y.;
Aoyama, T. Synlett 2003, 2047–2051.
11. Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450–451.
12. Use of the ligand 1n possessing a pendant methoxy group
resulted in no reaction. For the ligand 1n, see: (a) Miyano, S.;
Hattori, T.; Komuro, Y.; Kumobayashi, H. Jpn. Kokai Tokkyo
koho H09241277; Chem. Abstr. 1997, 127, 302486h. (b) Mino,
T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Heterocycles 2000,
53, 1485–1488.
19. Hattori, T.; Sakamoto, J.; Hayashizaka, N.; Miyano, S.
Synthesis 1994, 199–202.
13. The use of 1-propenyl bromide as a substrate resulted in no
reaction.
20. Madsen, R.; Roberts, C.; Fraser-Reid, B. J. Org. Chem. 1995,
60, 7920–7926.
14. Durette, P. L.; Gallagher, T. F. U.S. patent 4760161.
15. Kamikawa, T.; Hyashi, T. Tetrahedron Lett. 1997, 38,
7087–7090.
21. Vedejs, E.; Gingras, M. J. Am. Chem. Soc. 1994, 116,
579–588.
16. For other catalytic asymmetric Grignard cross-couplings, see:
(a) Tamao, K.; Minato, A.; Miyake, N.; Matsuda, T.; Kiso, Y.;
Kumada, M. Chem. Lett. 1975, 133–136. (b) Tamao, K.;
Yamamoto, H.; Matsumoto, H.; Miyake, N.; Hayashi, T.;
Kumada, M. Tetrahedron Lett. 1977, 1389–1392. (c) Hayashi,
T.; Konishi, M.; Okamoto, Y.; Kabeta, K.; Kumada, M. J. Org.
Chem. 1986, 51, 3772–3781. (d) Iida, A.; Yamashita, M. Bull.
Chem. Soc. Jpn 1988, 61, 2365–2367. (e) Hayashi, T.;
Hayashizaki, K.; Kiyoi, T.; Ito, Y. J. Am. Chem. Soc. 1988,
110, 8153–8156. (f) Hayashi, T.; Hayashizaki, K.; Ito, Y.
Tetrahedron Lett. 1989, 30, 215–218. (g) Hayashi, T.;
Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi, Y. J. Am.
Chem. Soc. 1995, 117, 9101–9102. (h) Kamikawa, T.;
Hayashi, T. Tetrahedron 1999, 55, 3455–3466. (i) Chung,
¨
22. Tietze, L. F.; Nobel, T.; Spescha, M. J. Am. Chem. Soc. 1998,
120, 8971–8977.
23. Horibe, H.; Kondo, K.; Okuno, H.; Aoyama, T. Synthesis
2004, 986–988.
24. Kuang, C.; Senboku, H.; Tokuda, M. Tetrahedron 2002, 58,
1491–1496.
25. Asami, M.; Ohno, H.; Kobayashi, S.; Mukaiyama, T. Bull.
Chem. Soc. Jpn 1978, 51, 1869–1873.
26. Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc.
1962, 84, 1745–1747.
27. Shen, Y.; Yao, J. J. Org. Chem. 1996, 61, 8658–8661.
28. Blake, A.; Harding, M.; Sharp, J. T. J. Chem. Soc., Perkin
Trans. 1 1994, 3149–3161.