Synthesis of axially chiral C10-BridgePHOS oxides and their use as organocatalysts in enantioselective allylations of aldehydes

Article abstract of DOI:10.1016/j.tet.2013.07.030

A series of C₁₀-BridgePHOS oxides possessing different substituted groups on the diphenyl phosphine system were synthesized and tested as organocatalysts in the allylation of aldehydes with allyltrichlorosilane, providing chiral homoallylic alc

Full text of DOI:10.1016/j.tet.2013.07.030

Tetrahedron 69 (2013) 8161e8168
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Synthesis of axially chiral C10-BridgePHOS oxides and their use as
organocatalysts in enantioselective allylations of aldehydes
,b,
Jianzhong Chen a, Delong Liu b, Dongyang Fan b, Yangang Liu b, Wanbin Zhang a
*
a School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
b School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2013
Received in revised form 27 June 2013
Accepted 11 July 2013
Available online 16 July 2013
A series of C10-BridgePHOS oxides possessing different substituted groups on the diphenyl phosphine
system were synthesized and tested as organocatalysts in the allylation of aldehydes with allyltri-
chlorosilane, providing chiral homoallylic alcohols. These types of organocatalysts showed high catalytic
activity and only 2 mol% catalyst loading was required to induce short reaction times. Under optimal
reaction conditions, excellent product yields and up to 92% ee were obtained for a variety of substrates.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Axial chirality
C10-BridgePHOS oxide
Organocatalyst
Enantioselective allylation
Chiral homoallylic alcohol
1. Introduction
investigate the use of diphosphine oxides of C10-BridgePHOS (Fig.1)
as organocatalysts in the reaction between an aldehyde and
During the past decade there has been an explosive growth in
the area of organocatalysis and asymmetric synthesis because of
their stability to air and non-toxic properties.1 Besides commonly
used proline and its derivatives, not much attention has been given
to using chiral bisphosphine oxides (such as BINAPO, Fig. 1) as
potential organocatalysts in the field of asymmetric synthesis.2 Few
satisfactory examples concerning reaction activity and enantiose-
lectivity have been reported with chiral bisphosphine oxides, al-
though some progress has been made in enantioselective
allylations,3 epoxide openings,4 aldol reactions5 amongst others.6
To some extent, the development of efficient chiral bisphosphine
oxides remains a considerable challenge. Recently, our group has
focused on the development of a class of axially chiral 5,50-bridged
biphenyl diphosphine ligands (Fig. 1, Cn-BridgePHOS). The axial
chirality can be controlled by different length alkyl chains
(n¼7e12), which can affect asymmetric induction. C10-BridgePHOS
gave the best results in Pd-catalyzed asymmetric hydrogenation
reactions.7 To increase catalytic activity and selectivity, the
diphenyl phosphine groups present in the C10-BridgePHOS ligand
were modified to change its steric and electronic properties. Con-
sidering the promising applications of BINAPO, we decided to
allyltrichlorosilane.
Fig. 1. C10-BridgePHOS and its oxides.
2. Results and discussion
2.1. The synthesis of C10-BridgePHOS oxides 1ae1d
Our synthetic approach to enantiopure C10-BridgePHOS oxides
(1) is outlined in Scheme 1. Commercially available 4-
methoxyphenol was readily coupled in the presence of FeCl3 and
AlCl3 at room temperature over 6 h to give 5,50-dimethox-
ybiphenyl-2,20-diol (2) in 62% yield. Reaction of 2 with (CF3SO2)2O
in the presence of pyridine gave its triflate derivative (3) in almost
quantitative yield. The important intermediate tetraethyl 5,50-
dimethoxybiphenyl-2,20-diyldiphosphonate (4) was then obtained
by phosphorylation of 3 via Pd(OAc)2 catalysis in 86% yield.8
* Corresponding author. Tel./fax: þ86 21 5474 3265; e-mail address: wanbin@
sjtu.edu.cn (W. Zhang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.030

8162
J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
A series of aryl phosphine oxides 5ae5d could be obtained in high
yield by treating 4 with SOCl2 in DMF followed with ArMgBr in THF.
Reaction of 5ae5d with BBr3 provided their corresponding prod-
ucts 6ae6d in quantitative yield. Finally, treatment of 6ae6d with
1,10-dibromodecane in the presence of excess anhydrous K2CO3 in
DMF furnished 1ae1d in good yields. Compounds 1ae1d were
obtained optically pure via chiral preparative HPLC (Daicel Chiracel
AD-H, IE, and IC-3 Columns).
products were obtained (entries 5 and 6). With the above results in
hand, DIPEA was selected as the additive and used in subsequent
reactions.
2.3. Screening of solvent
Solvent had an obvious effect on the reaction activity and
enantioselectivity (Table 2). Use of MeCN and PhCH2CN provided
products in excellent yield and up to 41% ee in the enantioselective
allylation reactions (entries 1 and 2). DCM gave the desired product
in 91% yield but only 28% ee (entry 3). However, other halogenated
solvents such as CHCl3 and PhCl, only provided the desired prod-
ucts in low to moderate yields and enantioselectivities (entries 4
and 5). Other commonly used solvents (toluene, THF, acetone, and
Et2O) were found unsuitable for this reaction (entries 6e9). MeCN
was selected and used in subsequent reactions.
Table 2
Effect of solventa
Entry
Solvent
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
9
MeCN
PhCH2CN
DCM
CHCl3
PhCl
PhCH3
DMF
Acetone
THF
92
92
91
57
34
16
<5
<5
<5
41 (S)
41 (S)
28 (S)
16 (S)
18 (S)
0
Scheme 1. The synthetic route of C10-BridgePHOS oxides.
d
d
d
2.2. Screening of additive
a
Reactions were conducted using 4-chlorobenzaldehyde (0.60 mmol) and allyl-
trichlorosilane (0.90 mmol) in a suitable solvent (8 mL) in the presence of (S)-1a
(5 mol %) and DIPEA (5 mol %) at rt for 12 h.
Initially, 4-chlorobenzaldehyde (7d) was utilized in the reaction
at room temperature in MeCN with (S)-1a (Scheme 1) as a chiral
organocatalyst (Table 1). Only trace amounts of product were ob-
tained in the absence of an additive (entry 1). However, 92% yield
was obtained when diisopropylethylamine (DIPEA) was added to
the reaction system, albeit with moderate enantioselectivity (entry
2, 41% ee). Addition of tetrabutylammonium iodide (TBAI) showed
similar enantioselectivity but a very low reaction activity (entry 3).
A combination of DIPEA and TBAI did not provide a better result
(entry 4). Other additives such as N,N-dimethylaniline (DMA) and
diethylamine (DEA) were also examined, and only trace amounts of
b
Isolated yield.
c
Determined by HPLC.
The absolute configuration of product was assigned through comparison of the
d
sign of specific rotations with the literature data.9
2.4. Screening of catalyst
Catalysts containing different steric and electronic properties
had a significant effect on the reaction. As shown in Table 3, catalyst
(S)-1b containing a Me group provided better enantioselectivity
than (S)-1a (44% ee than 41% ee). Subsequently, (S)-1c possessing
a bulky electron-donating group was used as a catalyst, and the
desired product 8d was obtained readily in almost quantitative
yield and with 56% ee. However, catalyst (S)-1d possessing a bulky
Table 1
Effect of additivea
(S)-1a
Table 3
Effect of catalysta
Entry
Additive
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
None
DIPEA
TBAI
DIPEA/TBAI
DMA
DEA
<5
92
53
93
<5
<5
d
41 (S)
41 (S)
41 (S)
d
d
a
Reactions were conducted using 4-chlorobenzaldehyde (0.60 mmol) and allyl-
trichlorosilane (0.90 mmol) in MeCN (8 mL) in the presence of (S)-1a (5 mol %) and
additive (5 mol %) at rt for 12 h.
b
Isolated yield.
Determined by HPLC.
The absolute configuration of product was assigned through comparison of the
c
a
Reactions were conducted using 4-chlorobenzaldehyde (0.60 mmol) and allyl-
d
trichlorosilane (0.90 mmol) in MeCN (8 mL) in the presence of 1 (5 mol %) and DIPEA
(5 mol %) at rt for 12 h. The enantioselectivities were determined by HPLC.
sign of specific rotations with the literature data.9

J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
8163
Table 5
electron-withdrawing group showed a negative effect on reaction
activity. According to the above catalytic behavior, (S)-1c was se-
The scope of substratesa
lected as the chiral organocatalyst for further investigation.
2.5. Screening of temperature and catalyst loading
Entry
R
Time (h)
Product
Yieldb (%)
eec,d (%)
Accordingly, the effect of temperature on the reaction was
examined (Table 4). Decreasing the reaction temperature from rt
to 0 ꢀC provided the desired product in 92% yield and 56% ee after
2 h (entry 2). Further decreasing the temperature to ꢁ40 ꢀC gave
the desired product in 56% ee but an obvious decrease in re-
activity activity was observed (entry 3). Further investigation
focused on a low catalyst loading with the aim of improving re-
action efficiency. When decreasing the catalyst loading from
5 mol % to 2 mol %, the reaction still proceeded smoothly with
high reaction activity, providing similar catalytic results (entries 1
and 4). However, the product was only obtained in 83% yield
when 1% catalyst loading was used (entry 5). Following reactions
were examined at room temperature by using 2 mol % catalyst
loading.
1
2
3
4
5
6
7
8
C6H5
2-ClC6H4
3-ClC6H4
4-ClC6H4
3-FC6H4
3-BrC6H4
6
3
6
6
3
3
3
3
3
6
6
9
3
6
6
3
3
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
8q
8r
93
94
93
96
89
93
90
96
93
92
90
86
91
91
87
93
95
96
93
80
84
82
72
78
57 (S)
66 (S)
75 (S)
56 (S)
62 (S)
70 (S)
67 (S)
77 (S)
50 (S)
63 (S)
77 (S)
60 (S)
72 (S)
74 (S)
60 (S)
81 (S)
80 (S)
92 (ꢁ)
77 (S)
71 (S)
43 (S)
70 (S)
8 (R)
3-NO2C6H4
3,5-Cl2C6H3
2,6-Cl2C6H3
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
3,5-Me2C6H3
3,5-(MeO)2C6H3
3,5-(t-Bu)2C6H3
1-Naphthyl
2-Naphthyl
2-Furyl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2
6
12
12
12
6
8s
8t
8u
8v
8w
8x
Table 4
Effect of temperature and catalyst loadinga
2-Thienyl
C6H4CH2CH2
C6H4CHCH
6
16 (S)
a
Reactions were conducted using
7 (0.60 mmol) and allyltrichlorosilane
Entry
(S)-1c (mol %)
Temp (ꢀC)
Time (h)
Yieldb (%)
eec,d (%)
(0.90 mmol) in MeCN (8 mL) in the presence of (S)-1c (2 mol %) and DIPEA (5 mol %)
at rt.
1
2
3
4
5
5
5
5
2
1
rt
0
1
2
8
6
36
96
92
32
91
83
56 (S)
56 (S)
56 (S)
56 (S)
56 (S)
b
Isolated yield.
Determined by HPLC.
The absolute configuration of product was assigned through comparison of the
c
ꢁ40
d
rt
sign of specific rotations with the literature data.9
rt
a
Reactions were conducted using 4-chlorobenzaldehyde (0.60 mmol) and allyl-
trichlorosilane (0.90 mmol) in MeCN (8 mL) in the presence of (S)-1c (1e5 mol %)
and additive (5 mol %) at certain temperature.
Replacement of the phenyl ring by a naphthalene ring, such as 1-
naphthaldehyde or 2-naphthaldehyde, gave products in high yields
and with enantioselectivities of 77% and 71%, respectively (entries
19 and 20). When the phenyl ring was replaced by heterocyclic
motifs (a furan or a thiophene ring), excellent catalytic activity and
moderate to high enantioselectivities were also observed (entries
21 and 22). The present catalytic system is therefore suitable for the
allylation of a series of aldehydes.
b
Isolated yield.
Determined by HPLC.
c
d
The absolute configuration of product was assigned through comparison of the
sign of specific rotations with the literature data.9
2.6. The scope of substrate
We also performed the reactions using benzenepropanal and
cinnamyl aldehyde. The reactants provided high reaction activity
and high yield, but a low enantioselectivities (entries 23 and 24).
Finally, the allylation was carried out by using a mixture of
(E)-crotyltrichlorosilane and (Z)-crotyltrichlorosilane (E/Z¼87:13)
instead of the simple allyltrichlorosilane. The result showed that
a mixture of diastereoisomeric alcohols (syn and anti in 52:48 ratio)
was obtained in 89% yield (Scheme 2).
With the optimal reaction conditions in hand, we investigated
the applicability of this catalytic system for a series of aldehydes.
Thus, a number of simple aldehydes were subjected to the opti-
mized reaction conditions using (S)-1c (2 mol %) as an organo-
catalyst in the presence of DIPEA at rt in MeCN (Table 5). First,
benzaldehyde was used as a substrate in the reaction and the
product was obtained in excellent yield and 57% ee. Substrates with
electron-withdrawing groups located at the 2-, 3- and 4-position of
the phenyl ring were next examined. Products were obtained in
more than 90% yield, in addition to moderate to good enantiose-
lectivities were obtained, and substrates with a 3-position group on
the phenyl ring provided the best results (entries 2e4). Other
substrates with electron-withdrawing groups at the 3-position
were then examined and good enantioselectivities were also ob-
tained (entries 5e8). However, substrates with electron-
withdrawing groups at the 2- and 6-position gave lower enantio-
selectivity (entry 9). A similar phenomenon was also found for the
substrates possessing electron-donating groups located at the 2-, 3-
and 4-position of the phenyl ring motifs (entries 10e15). To our
delight, products with up to 92% ee were obtained when substrates
with 3,5-disubstituted electron-donating groups were used (en-
tries 16e18).
Scheme 2. The allylation with (E)- and (Z)-crotyltrichlorosilane.
3. Conclusions
In conclusion, a series of C10-BridgePHOS oxides possessing
different substituted groups at the phenyl rings were synthesized.
They were used as efficient organocatalysts in the allylation of

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J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
aldehydes with excellent catalytic behavior. These types of orga-
nocatalysts showed high catalytic activity, therefore only 2 mol%
catalyst loading was required to promote the reaction. Under op-
timal reaction conditions, excellent product yields and up to 92% ee
were obtained for a variety of substrates.
was separated, dried over Na2SO4, and concentrated under vacuum.
The residue was purified by column chromatography with ethyl
acetateepetrol ether as eluent to yield a white solid 4 (2.0 g, 86%).
Mp 138e140 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.93 (2H, dd, J¼14.0,
8.8 Hz), 7.01 (2H, dd, J¼4.4, 2.4 Hz), 6.94 (2H, dt, J¼8.8, 2.8 Hz),
3.96e3.72 (8H, m), 3.85 (6H, s),1.11 (12H, dt, J¼21.6, 7.2 Hz); 13C NMR
4. Experimental
4.1. General
(100 MHz, CDCl3) d 161.5, 135.4, 120.1, 118.2, 117.6, 113.1, 61.9, 55.6,
16.5; 31P NMR (162 MHz, CDCl3):
d 19.88; HRMS (ESI-MS) calcd for
C
22H32O8P2 [Mþ1]þ 487.1650, found: 487.1649.
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a Varian MERCURY plus-400 spectrometer with TMS as
an internal standard. HRMS was performed at the Analysis Center
of Shanghai Jiao Tong University. Enantioselectivity was measured
by high performance liquid chromatography (HPLC) using Daicel
Chiralcel OD-H, AD-H, OJ-H, IE-H, and IC-3 columns with hexane/2-
propanol as eluent. Column chromatography was performed using
100e200 mesh silica gel. Melting points were measured with SGW
X-4 micro melting point apparatus. Optical rotations were mea-
sured on a Rudolph Research Analytical Autopol VI automatic
polarimeter using a 50 mm path-length cell at 589 nm.
4.2.4. General procedure for the synthesis of 5ae5d. In a 100 mL
three-neck flask with a condenser, 4 (1.00 g, 2.1 mmol), dry DMF
(5 mL), and thionyl chloride (10.0 equiv) were added and warmed
to 80 ꢀC under an argon atmosphere. After 5 h, the excess thionyl
chloride and DMF were evaporated under vacuum. Dry THF (5 mL)
was added, and evaporated under vacuum while stirred for 5 min.
Another small amount of THF (5 mL) was added, followed by the
dropwise addition of the Grignard reagent prepared from different
aryl bromides (6.0 equiv) and magnesium granules (20.0 equiv) at
ꢁ50 ꢀC. The reaction mixture was allowed to warm to room tem-
perature within 30 min to form a yellow solution and was further
stirred for 6 h. The reaction was quenched by addition of saturated
NH4Cl solution (5 mL). The organic layer was separated, washed
with saturated NaCl solution (3ꢂ10 mL), dried over anhydrous
Na2SO4, and evaporated under vacuum. The residue was purified by
column chromatography with petroleum ether/ethyl acetate to give
the pure products 5ae5d.
4.2. Synthesis of C10-BridgePHOS oxides 1ae1d
4.2.1. 5,50-Dimethoxybiphenyl-2,20-diol (2).10 A solution of 4-meth-
oxyphenol (6.2 g, 50.0 mmol) in dry MeNO2 (40 mL) was added
to a stirred solution of AlCl3 (0.6 equiv) in dry MeNO2 (20 mL) under
nitrogen at room temperature. After 30 min, a solution of anhy-
drous FeCl3 (1.0 equiv) in dry MeNO2 (20 mL) was added and the
mixture was continued to stir for 6 h at room temperature. The
reaction was quenched with aqueous HCl solution (1 N, 50 mL) and
the resulting mixture was extracted with EtOAc (3ꢂ50 mL). The
organic phase was dried over Na2SO4 and solvent evaporated. The
residue was purified on a silica gel column with petrol ethereEtOAc
as eluent to afford a white solid 2 (3.8 g, 62%). Mp 88e89 ꢀC; 1H
4.2.4.1. (5,50-Dimethoxybiphenyl-2,20-diyl)bis(diphenylphosphine
oxide) (5a). White solid (1.10 g, 87%); mp 246e247 ꢀC; 1H NMR
(400 MHz, CDCl3) d 7.81e7.70 (4H, m), 7.69e7.59 (4H, m), 7.55e7.40
(6H, m), 7.38e7.27 (6H, m), 7.05 (2H, dd, J¼13.6, 8.8 Hz), 6.81 (2H, t,
J¼2.8 Hz), 6.64e6.59 (2H, m), 3.48 (6H, s); 13C NMR (100 MHz,
CDCl3)
d 161.2, 161.1, 147.1, 147.0, 149.9, 146.9, 136.1, 135.9, 135.8,
134.8, 134.4, 133.3, 132.3, 132.2, 132.0, 131.9, 131.6, 131.5, 131.2, 131.1,
128.7, 128.6, 128.2, 128.1, 122.4, 121.3, 117.5, 117.4, 114.4, 114.2, 55.2;
NMR (400 MHz, CDCl3)
d
6.96 (2H, d, J¼8.4 Hz), 6.89 (2H, dd, J¼9.2,
3.2 Hz), 6.82 (2H, d, J¼2.8 Hz), 3.79 (6H, s); 13C NMR (100 MHz,
31P NMR (162 MHz, CDCl3):
d 29.15; HRMS (ESI-MS) calcd for
CDCl3)
d
154.3, 146.7, 125.5, 118.0, 116.2, 115.6, 77.6, 77.3, 77.0, 56.1.
C
38H32O4P2 [Mþ1]þ 615.1854, found: 615.1832.
4.2.2. 5,50-Dimethoxybiphenyl-2,20-diyl bis(trifluoromethanesulfon-
ate) (3). To a stirring solution of 2 (2.5 g, 10.0 mmol) and pyridine
(5 equiv) in DCM (20 mL) at 0 ꢀC was added dropwise Tf2O
(2.2 equiv) at a rate to maintain the reaction temperature below
10 ꢀC. The reaction was allowed to warm to ambient temperature
and its progress was monitored by thin layer chromatography
(TLC). When the material disappeared, the reaction was quenched
with aqueous HCl solution (1 N, 2 mL) and the resulting mixture
was extracted with DCM (3ꢂ10 mL). The combined organic phase
was dried over Na2SO4, filtered, and concentrated under vacuum at
rt. The residue was purified by flash chromatography with an ethyl
acetateepetrol ether mixture as eluent to give 3 as colorless oil
4.2.4.2. (5,50-Dimethoxybiphenyl-2,20-diyl)bis(di(4-
methylphenyl)phosphine oxide) (5b). White solid (1.20 g, 87%); mp
212e214 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.63 (4H, dd, J¼11.2,
8.0 Hz), 7.48 (4H, dd, J¼12.0, 8.0 Hz), 7.26e7.24 (4H, m), 7.10 (4H, dd,
J¼7.6, 2.0 Hz), 7.04 (2H, dd, J¼13.2, 8.8 Hz), 6.86 (2H, t, J¼2.4 Hz),
6.63 (2H, dt, J¼8.8, 1.6 Hz), 3.50 (6H, s), 2.35 (12H, d, J¼35.2 Hz); 13
C
NMR (100 MHz, CDCl3)
d 170.2, 166.7, 144.3, 141.8, 135.9, 132.3,
132.2, 132.1, 132.0, 129.4, 129.3, 128.9, 128.8, 117.6, 55.2, 29.9, 21.7;
31P NMR (162 MHz, CDCl3):
C
d 29.33; HRMS (ESI-MS) calcd for
42H40O4P2 [Mþ1]þ 671.2486, found: 671.2468.
4.2.4.3. (5,50-Dimethoxybiphenyl-2,20-diyl)bis(di(3,5-di-tert-bu-
tyl-4-methoxyphenyl)phosphine oxide) (5c). White solid (2.19 g,
90%); mp 205e208 ꢀC, 1H NMR (400 MHz, CDCl3)
7.51 (4H, d,
(5.1 g, 98%). 1H NMR (400 MHz, CDCl3)
d
7.31 (2H, d, J¼8.8 Hz), 7.01
(2H, dd, J¼9.2, 3.2 Hz), 6.95 (2H, d, J¼3.2 Hz), 3.85 (6H, s); 13C NMR
d
(100 MHz, CDCl3)
d
159.0,140.3,130.6,122.9,120.1, 117.4,115.9, 56.1;
J¼12.8 Hz), 7.43 (4H, d, J¼12.8 Hz), 7.08 (2H, dd, J¼13.2, 8.4 Hz),
6.72 (2H, dt, J¼8.4, 2.4 Hz), 6.35 (2H, t, J¼2.8 Hz), 3.67 (12H, s),
3.30 (6H, s), 1.33 (72H, d, J¼8.0 Hz); 13C NMR (100 MHz, CDCl3)
HRMS (ESI-MS) calcd for C16H12F6O8S2 528.0222, found: 528.0233.
4.2.3. Tetraethyl 5,50-dimethoxybiphenyl-2,20-diyldiphosphonate (4).
To a three-necked flask under nitrogen, Pd(OAc)2 (0.2 equiv of 3),
DPPF (0.21 equiv), KOAc (0.02 equiv), and anhydrous DMF (5 mL)
were added and the reaction mixture was stirred under 60 ꢀC for
30 min. DIPEA (1.5 equiv) and diethylphosphite (3.0 equiv) were
added and the mixture stirred for 15 min. A solution of 3 (2.5 g,
5.0 mmol) in DMF (20 mL) was added slowly. The reaction mixture
was heated to 100 ꢀC and stirred for another 12 h. The volatiles were
removed in vacuo to give a dark brown oil. Upon biphasic work-up
(20 mL water/3ꢂ25 mL diethyl ether), the yellow organic layer
d 162.5, 162.4, 162.3, 162.2, 162.1, 160.5, 160.4, 158.4, 147.8, 147.7,
145.4, 144.2, 144.0, 143.6, 143.5, 142.8, 138.9, 135.7, 135.5, 132.0,
131.9, 130.5, 130.4, 130.1, 129.1, 129.0, 127.9, 126.9, 124.7, 124.0,
123.3, 122.3, 116.8, 116.7, 113.0, 112.9, 64.7, 64.6, 64.5, 54.7, 36.4,
36.2, 36.1, 32.3, 32.2, 32.1, 32.1; 31P NMR (162 MHz, CDCl3):
d
30.75; HRMS (ESI-MS) calcd for C74H104O8P2 [Mþ1]þ 1183.7284,
found:1183.7299.
4.2.4.4. (5,50-Dimethoxybiphenyl-2,20-diyl)bis(di(3,5-bis(trifluor-
omethyl)phenyl)phosphine oxide) (5d). White solid (1.98 g, 83%);

J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
8165
mp 217e220 ꢀC; 1H NMR (400 MHz, CDCl3)
d
8.31 (4H, d, J¼11.2 Hz),
with petroleum ether/ethyl acetate to give the pure products
1ae1d.
8.18 (4H, dd, J¼11.2, 1.6 Hz), 8.06 (2H, s), 7.90 (2H, s), 7.16 (2H, dd,
J¼14.0, 9.2 Hz), 6.73 (2H, dt, J¼8.4, 2.0 Hz), 6.36 (2H, t, J¼2.8 Hz),
3.67 (6H, s); 13C NMR (100 MHz, CDCl3)
d
162.0, 161.9, 144.8, 144.7,
4.2.6.1. 5,50-Decamethylenedioxy-2,20-bis(diphenylphosphoryl)bi-
144.6, 144.5, 138.0, 137.0, 135.5, 135.4, 134.4, 132.8, 132.7, 132.6,
132.5, 132.4, 132.3, 132.2, 132.1, 132.0, 131.9, 131.8, 131.7, 131.6, 126.1,
126.0,125.9,124.3,124.2,121.6, 121.4, 121.2, 120.1,120.0,112.9,112.7,
phenyl (1a). White solid (0.51 g, yield of two steps: 70%); mp
237e238 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.74e7.64 (4H, m),
7.62e7.55 (4H, m), 7.55e7.36 (12H, m), 7.06 (2H, dd, J¼12.8, 8.8 Hz),
6.71 (2H, dt, J¼8.8, 2.4 Hz), 6.21 (2H, t, J¼2.8 Hz), 3.82e3.76 (2H, m),
3.36e3.25 (2H, m), 1.57e0.82 (16H, m); 13C NMR (100 MHz, CDCl3)
55.5; 31P NMR (162 MHz, CDCl3):
d
23.16; 19F NMR (376 MHz,
CDCl3):
d 10.57, 10.50; HRMS(ESI-MS) calcd for C46H24F24O4P2
[Mþ1]þ 1159.0845, found: 1159.0835.
d 160.0, 156.0, 146.6, 146.5, 135.8, 135.6, 135.5, 134.7, 134.2, 133.1,
132.5, 132.4, 132.1, 132.0, 131.4, 131.3, 131.2, 131.1, 128.7, 128.6, 128.2,
128.0, 122.4, 121.3, 117.5, 117.4, 116.3, 116.4, 66.9, 28.9, 28.8, 28.5,
4.2.5. General procedure for the synthesis of 6ae6d. To a stirring
solution of 5ae5d (1.0 mmol, 1.0 equiv) in DCM (20 mL), boron
tribromide (2.0 equiv) was added dropwise over 30 min at ꢁ78 ꢀC.
After the addition the reaction mixture was warmed to room
temperature and stirred for another 8 h. The reaction was
quenched by the addition of a cold brine solution (10 mL) and
aqueous HCl solution (1 N, 10 mL). The suspension was filtered and
the obtained white precipitate was washed with hot water and
ether to give white solids, which were used without further
purification.
28.1, 24.7, 24.6; 31P NMR (162 MHz, CDCl3)
d 28.74; HRMS (ESI)
calcd for C46H46O4P2 [M]þ 724.2871, found: 724.2886; Chiral HPLC:
Daicel Chiralcel AD-H column (hexane/EtOH/2-propanol¼82:10:8,
25
0.8 mL/min, 254 nm), tR (R)¼5.99 min, tR (S)¼9.09 min; (S)-1a: [
ꢁ41.2 (c 0.50, CHCl3).
a]
D
4.2.6.2. 5,50-Decamethylenedioxy-2,20-bis(di(4-methylphenyl)
phosphoryl)biphenyl (1b). White solid (0.56 g, yield of two steps:
72%); mp 229e232 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.58 (4H, dd,
J¼11.6, 8.0 Hz), 7.48 (4H, dd, J¼12.0, 8.0 Hz), 7.23 (4H, d, J¼6.0 Hz),
7.08 (4H, dd, J¼8.4, 2.0 Hz), 7.02 (2H, dd, J¼13.2, 9.2 Hz), 6.62 (2H,
dt, J¼8.4, 2.0 Hz), 6.52 (2H, s), 3.86e3.83 (2H, m), 3.64e3.61 (2H,
m), 2.36 (6H, s), 2.29 (6H, s), 1.37e0.93 (16H, m); 13C NMR
4.2.5.1. 6,60-Bis(diphenylphosphoryl)biphenyl-3,30-diol
(6a). White solid; mp>260 ꢀC; 1H NMR (400 MHz, CD3OD)
d
7.83e7.76 (4H, m), 7.72e7.66 (2H, m), 7.64e7.46 (14H, m), 7.04
(2H, dd, J¼14.2, 8.6 Hz), 6.67e6.62 (2H, m), 6.10 (2H, dd, J¼4.0,
2.4 Hz); 13C NMR (100 MHz, CDCl3)
159.6, 159.5, 147.1, 147.0, 146.9,
(100 MHz, CDCl3)
d 159.8, 159.7, 146.8, 146.7, 146.6, 146.5, 141.7,
d
141.6, 141.2, 141.1, 135.5, 135.4, 132.5, 132.4, 132.2, 132.1, 131.1,
130.0, 129.4, 129.3, 128.9, 128.8, 122.7, 121.6, 117.6, 117.5, 116.1,
116.0, 66.7, 28.8, 28.5, 28.2, 24.7, 21.7; 31P NMR (162 MHz, CDCl3)
136.5, 135.8, 135.7, 135.6, 135.5, 134.6, 132.4, 132.3, 132.0, 131.9,
131.8, 131.5, 129.1, 129.0, 128.6, 128.5, 121.2, 120.1, 119.9, 119.8, 114.4,
114.2; 31P NMR (162 MHz, CD3OD):
d
27.61; HRMS (ESI-MS) calcd
d
28.68; HRMS (ESI-MS) calcd for C50H54O4P2 [Mþ1]þ 781.3575,
for C36H28O4P2 [Mþ1]þ 587.1541, found: 587.1534.
found: 781.3571; Chiral HPLC: Daicel Chiralcel IC3-H column
(hexane/MeOH/2-propanol¼55:15:30, 0.5 mL/min, 254 nm), tR
25
4.2.5.2. 6,60-Bis(dip-tolylphosphoryl)biphenyl-3,30-diol
(S)¼19.99 min, tR (R)¼23.55 min; (S)-1b: [
a
]
ꢁ14.5 (c 0.32,
D
(6b). White solid; mp>260 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.72
CHCl3).
(4H, dd, J¼11.2, 8.0 Hz), 7.48 (4H, dd, J¼12.0, 8.0 Hz), 7.35e7.26 (8H,
m), 7.01 (2H, dd, J¼14.0, 8.4 Hz), 6.65 (2H, dt, J¼8.4, 2.4 Hz), 5.95
(2H, dd, J¼4.0, 2.4 Hz), 2.43 (12H, d, J¼28.4 Hz); 31P NMR (162 MHz,
4.2.6.3. 5,50-Decamethylenedioxy-2,20-bis(di(3,5-di-tert-butyl-4-
methoxyphenyl)phosphoryl)biphenyl (1c). White solid (0.97 g, yield
of two steps: 75%); mp 225e228 ꢀC; 1H NMR (400 MHz, CDCl3)
CDCl3)
d
42.25; HRMS (ESI-MS) calcd for C40H36O4P2 [Mþ1]þ
643.2167, found: 643.2119.
d
7.59 (4H, d, J¼13.2 Hz), 7.37 (4H, d, J¼13.2 Hz), 7.10 (2H, dd,
J¼14.0, 8.4 Hz), 6.71 (2H, dt, J¼8.4, 2.8 Hz), 6.12 (2H, dd, J¼3.2,
2.0 Hz), 3.82e3.77 (2H, m), 3.68 (12H, d, J¼1.2 Hz), 3.57e3.52 (2H,
4.2.5.3. 6,60-Bis(bis(3,5-di-tert-butyl-4-methoxyphenyl)phospho-
ryl)biphenyl-3,30-diol (6c). White solid; mp>260 ꢀC; 1H NMR
m), 1.23 (88H, d, J¼8.0 Hz); 13C NMR (100 MHz, CDCl3)
d 162.3,
(400 MHz, CDCl3)
d
7.64 (4H, d, J¼13.2 Hz), 7.31 (4H, d, J¼13.2 Hz),
162.2, 159.5, 159.4, 147.4, 147.3, 147.2, 147.1, 143.9, 143.8, 143.5,
143.4, 135.2, 135.0, 132.0, 131.9, 130.6, 130.5, 123.0, 128.9, 128.5,
127.4, 123.8, 122.7, 117.4, 117.2, 114.8, 114.7, 66.9, 64.5, 64.4, 36.2,
36.1, 32.2, 32.1, 28.9, 28.7, 27.9, 25.3; 31P NMR (162 MHz, CDCl3)
7.01 (2H, dd, J¼14.0, 8.4 Hz), 6.75 (2H, dt, J¼8.4, 2.8 Hz), 5.98 (2H,
dd, J¼3.2, 2.0 Hz), 3.78 (12H, d, J¼7.2 Hz),1.40 (72H, d, J¼8.0 Hz); 31
P
NMR (162 MHz, CDCl3)
d 44.31; HRMS (ESI-MS) calcd for
C
72H100O8P2 [Mþ1]þ 1155.6971, found: 1155.7006.
d
30.66; HRMS (ESI-MS) calcd for C82H118O8P2 [Mþ1]þ 1293.8380,
found: 1293.8391; Chiral HPLC: Daicel Chiralcel IE-H column
4.2.5.4. 6,60-Bis(bis(3,5-bis(trifluoromethyl)phenyl)phosphoryl)
biphenyl-3,30-diol (6d). White solid; mp>260 ꢀC; 1H NMR
(400 MHz, CDCl3)
(hexane/EtOH/2-propanol¼80:10:10, 0.7 mL/min, 254 nm), tR
25
(S)¼10.26 min, tR (R)¼11.91 min; (S)-1c: [
a
]
ꢁ89.3 (c 0.50,
D
d
8.49 (4H, d, J¼11.6 Hz), 8.36 (4H, dd, J¼11.6,
CHCl3).
1.6 Hz), 8.23 (2H, s), 8.09 (2H, s), 7.16 (2H, dd, J¼14.0, 8.4 Hz), 6.67
(2H, dt, J¼8.8, 2.4 Hz), 6.20 (2H, dd, J¼3.6, 2.0 Hz); 31P NMR
4 . 2 . 6 . 4 . 5 , 5 0- D e c a m e t hyl e n e d i o x y - 2 , 2 0- b i s ( d i ( 3 , 5 -
bis(trifluoromethyl)phenyl)phosphoryl)biphenyl (1d). White solid
(0.81 g, yield of two steps: 64%); mp 146e149 ꢀC; 1H NMR
(162 MHz, CDCl3) d d 17.31, 17.25;
28.88; 19F NMR (376 MHz, CDCl3)
HRMS (ESI-MS) calcd for C44H20O4P2 [Mþ1]þ 1131.0532, found:
1131.0527.
(400 MHz, CDCl3)
d
8.35 (4H, d, J¼11.6 Hz), 8.26 (4H, dd, J¼11.6,
1.6 Hz), 8.03 (2H, s), 7.87 (2H, s), 7.11 (2H, dd, J¼14.0, 8.4 Hz), 6.71
(2H, dt, J¼8.8, 2.4 Hz), 6.22 (2H, dd, J¼3.6, 2.0 Hz), 3.99e3.83 (4H,
4.2.6. General procedure for the synthesis of 1ae1d. A solution of
6ae6d obtained from the previous step (1.0 equiv) and 1,10-
dibromodecane (1.1 equiv) in DMF (200 mL) was added slowly to
a suspension of anhydrous K2CO3 (10 equiv) in DMF (200 mL) at
80 ꢀC. The mixture was stirred for 36 h before the solvent was re-
moved under reduced pressure. The residue was extracted with
ether, and the combined extracts were washed with water, brine,
and dried over Na2SO4. After evaporation of solvent, a solid was
obtained and was purified by column chromatography on silica gel
m), 1.66e1.03 (16H, m); 13C NMR (100 MHz, CDCl3)
d 161.2, 161.1,
145.0, 144.9, 144.8, 144.7, 137.6, 136.5, 136.4, 134.9, 134.8, 134.7,
133.9, 132.9, 132.8, 132.6, 132.5, 132.3, 132.2, 132.1, 132.0, 131.7,
131.6, 126.1, 126.0, 124.3, 124.2, 121.6, 121.5, 121.4, 120.3, 118.9, 117.7,
117.6, 117.4, 117.3, 67.9, 28.8, 28.6, 27.5, 24.9; 31P NMR (162 MHz,
CDCl3)
(ESI-MS) calcd for
1269.1957; Chiral HPLC: Daicel Chiralcel IE-H column (hexane/2-
d d 14.75, 14.66; HRMS
23.10; 19F NMR (376 MHz, CDCl3)
C
54H38O4P2 [Mþ1]þ 1269.1940, found:

8166
J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
propanol¼99.5:0.5, 0.5 mL/min, 254 nm); tR (S)¼11.50 min, tR (R)¼
excess was determined by HPLC with a Chiralcel OD-H column
(hexane/2-propanol¼98:2, 0.8 mL/min, 210 nm), tmajor¼18.4 min
(S), tminor¼22.0 min (R), ee¼70%.
15.91 min; (S)-1d: [
a]
25 ꢁ30.6 (c 0.22, CHCl3).
D
4.3. General procedure for the enantioselective allylation of
aldehydes
4.4.7. 1-(3-Nitrophenyl)-3-buten-1-ol (8g).13 As
(105 mg, 90%); 1H NMR (400 MHz, CDCl3)
8.23 (1H, s), 8.13 (1H, d,
a
yellow oil
d
To a stirred solution of 1 (0.012 mmol) in acetonitrile (8 mL) at
room temperature, an aldehyde (0.6 mmol) and DIPEA (3.0 mmol)
were added. Allyltrichlorosilane (0.9 mmol) was then added
dropwise by means of a syringe. The reaction was detected by thin
layer chromatography (TLC) until the starting material dis-
appeared and was then quenched by the addition of a saturated
aqueous solution of NaHCO3 (3 mL). Saturated NaCl (6 mL) and
EtOAc (10 mL) were added and the organic phase was separated,
dried over Na2SO4, filtered, and concentrated under vacuum at
room temperature. The residue was purified on a flash chroma-
tography with different ethyl acetateepetrol ether mixtures as
eluent to give pure product for the determination of ee by chiral
HPLC.
J¼1.2 Hz), 7.75 (1H, d, J¼1.2 Hz), 7.52e7.40 (1H, m), 5.91e5.70 (1H,
m), 5.26e5.12 (2H, m), 4.90e4.82 (1H, m), 2.65e2.50 (3H, m). En-
antiomeric excess was determined by HPLC with a Chiralcel IC-3
column (hexane/2-propanol¼92:8, 0.8 mL/min, 210 nm),
tmajor¼13.3 min (S), tminor¼14.0 min (R), ee¼67%.
4.4.8. 1-(3,5-Dichlorophenyl)but-3-en-1-ol (8h).14 As a pale yellow
oil (125 mg, 96%); 1H NMR (400 MHz, CDCl3)
d 7.24e7.26 (3H, m),
5.82e5.71 (1H, m), 5.21e5.15 (2H, m), 4.68 (1H, dd, J¼8.0, 4.8 Hz),
2.55e2.37 (2H, m), 2.12 (1H, br s). Enantiomeric excess was de-
termined by HPLC with a Chiralcel OJ-H column (hexane/2-
propanol¼98:2, 0.8 mL/min, 210 nm), tmajor¼13.5 min (S),
tminor¼14.4 min (R), ee¼77%.
4.4. Analytical data
4.4.9. 1-(2,6-Dichlorophenyl)but-3-en-1-ol (8i).9b As a colorless oil
(121 mg, 93%); 1H NMR (400 MHz, CDCl3)
d
7.28 (2H, d, J¼8.0 Hz),
4.4.1. 1-Phenylbut-3-en-1-ol (8a).11 As a pale yellow oil (83 mg,
7.14 (1H, t, J¼8.0 Hz), 5.86e5.81 (1H, m), 5.53e5.50 (1H, m),
5.15e5.08 (2H, m), 2.90 (1H, d, J¼9.8 Hz), 2.87e2.82 (1H, m),
2.71e2.65 (1H, m). Enantiomeric excess was determined by HPLC
with a chiralcel OD-H column (hexane/2-propanol¼98:2, 0.7 mL/
min, 230 nm), tmajor¼11.7 min (S), tminor¼12.7 min (R), ee¼50%.
93%); 1H NMR (400 MHz, CDCl3)
d 7.40e7.25 (5H, m), 5.90e5.75
(1H, m), 5.18e5.06 (2H, m), 4.75 (1H, d, J¼7.4 Hz), 2.50e2.38 (2H,
m), 2.10 (1H, br s). Enantiomeric excess was determined by HPLC
with
a
Chiralcel OD-H column (hexane/2-propanol¼97.5:2.5,
1.0 mL/min, 254 nm), tminor¼13.1 min (R), tmajor¼14.9 min (S),
ee¼57%.
4.4.10. 1-o-Tolylbut-3-en-1-ol (8j).15 As a pale yellow oil (89 mg,
92%); 1H NMR (400 MHz, CDCl3)
d
7.49 (1H, d, J¼7.8 Hz), 7.23 (1H, t,
4.4.2. 1-(2-Chlorophenyl)-but-3-en-1-ol (8b).11 As
(103 mg, 94%); 1H NMR (400 MHz, CDCl3)
1.6 Hz), 7.27e7.20 (2H, m), 7.13 (1H, t, J¼7.6 Hz), 5.85e5.74 (1H, m),
5.14e5.11 (3H, m), 2.59e2.52 (1H, m), 2.37e2.27 (1H, m), 2.09 (1H,
s). Enantiomeric excess was determined by HPLC with a Chiralcel
IE-H column (hexane/2-propanol¼99:1, 0.8 mL/min, 210 nm),
tminor¼10.9 min (R), tmajor¼12.6 min (S), ee¼66%.
a
yellow oil
J¼7.2 Hz), 7.18 (1H, t, J¼7.2 Hz), 7.13 (1H, d, J¼7.2 Hz), 5.89e5.83
(1H, m), 5.20e5.15 (2H, m), 4.97 (1H, dd, J¼8.4, 4.2 Hz), 2.53e2.49
(1H, m), 4.46e2.41 (1H, m), 2.34 (3H, s), 1.96 (1H, br s). Enantio-
meric excess was determined by HPLC with a Chiralcel OD-H col-
umn (hexane/2-propanol¼98:2, 0.6 mL/min, 210 nm),
tmajor¼20.3 min (S), tminor¼21.2 min (R), ee¼63%.
d
7.49 (1H, dd, J¼7.6,
4.4.11. 1-m-Tolylbut-3-en-1-ol (8k).16 As a pale yellow oil (87 mg,
4.4.3. 1-(3-Chlorophenyl)but-3-en-1-ol (8c).11 As
(102 mg, 93%); 1H NMR (400 MHz, CDCl3)
7.22 (1H, s), 7.17e7.09
(3H, m), 5.69e5.60 (1H, m), 5.17e5.02 (2H, m), 4.60e4.55 (1H, m),
2.43e2.28 (2H, m), 2.04 (1H, s). Enantiomeric excess was de-
termined by HPLC with a Chiralcel AD-H column (hexane/2-
propanol¼98.5:1.5, 0.8 mL/min, 230 nm), tminor¼14.4 min (R),
tmajor¼15.4 min (S), ee¼75%.
a
yellow oil
90%); 1H NMR (400 MHz, CDCl3)
d 7.20e7.04 (4H, m), 5.80e5.72
d
(1H, m), 5.13e5.08 (2H, m), 4.63 (1H, dd J¼7.2, 5.4 Hz), 2.49e2.42
(2H, m), 2.32 (3H, s), 2.11 (1H, br s). Enantiomeric excess was de-
termined by HPLC with a Chiralcel OD-H column (hexane/2-
propanol¼98:2, 0.8 mL/min, 210 nm), tminor¼14.9 min (R),
tmajor¼19.4 min (S), ee¼77%.
4.4.12. 1-p-Tolylbut-3-en-1-ol (8l).9b As a pale yellow oil (84 mg,
4.4.4. 1-(4-Chlorophenyl)-but-3-en-1-ol (8d).11 As
(106 mg, 96%); 1H NMR (400 MHz, CDCl3):
7.25e7.18 (4H, m),
5.73e5.65 (1H, m), 5.10e4.97 (2H, m), 4.65e4.61 (1H, m),
2.46e2.33 (2H, m), 2.07 (1H, s). Enantiomeric excess was de-
termined by HPLC with a Chiralcel IE-H column (hexane/2-
propanol¼99.9:0.1, 1.0 mL/min, 230 nm), tminor¼26.1 min (R),
tmajor¼27.6 min (S), ee¼56%.
a
yellow oil
86%); 1H NMR (400 MHz, CDCl3)
d
7.26 (2H, d, J¼5.6 Hz), 7.15 (2H, d,
d
J¼7.6 Hz), 5.83e5.80 (1H, m), 5.15 (2H, q, J¼5.0 Hz), 4.72 (1H, t,
J¼4.0 Hz), 2.50 (2H, t, J¼8.0 Hz), 2.35 (3H, s), 1.98 (1H, br s). En-
antiomeric excess was determined by HPLC with a Chiralcel OD-H
column (hexane/2-propanol¼98:2, 0.6 mL/min, 210 nm),
tminor¼21.4 min (R), tmajor¼22.5 min (S), ee¼60%.
4.4.13. 1-(2-Methoxyphenyl)-but-3-en-1-ol (8m).11 As a pale yellow
4.4.5. 1-(3-Fluorophenyl)-3-buten-1-ol (8e).12 As a pale yellow oil
oil (97 mg, 91%); 1H NMR (400 MHz, CDCl3)
d
7.25 (1H, d, J¼8.4 Hz),
(89 mg, 89%); 1H NMR (400 MHz, CDCl3)
d
7.34e7.25 (1H, m),
7.19e7.15 (1H, m), 6.88 (1H, t, J¼7.6 Hz), 6.80 (1H, d, J¼8.4 Hz),
5.82e5.72 (1H, m), 5.09e5.01 (2H, m), 4.90e4.87 (1H, m), 3.77 (3H,
s), 2.55e2.39 (3H, m). Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (hexane/2-propanol¼98:2,
0.8 mL/min, 210 nm), tmajor¼16.5 min (S), tminor¼18.6 min (R),
ee¼72%.
7.13e7.05 (2H, m), 6.99e6.91 (1H, m), 5.85e5.70 (1H, m), 5.20e5.12
(2H, m), 4.70 (1H, t, J¼6.4 Hz), 2.57e2.38 (2H, m), 2.25 (1H, s).
Enantiomeric excess was determined by HPLC with a Chiralcel IC-3
column (hexane/2-propanol¼98:2, 0.8 mL/min, 210 nm),
tminor¼11.2 min (R), tmajor¼12.0 min (S), ee¼62%.
4.4.6. 1-(3-Bromo-phenyl)but-3-en-1-ol (8f).12 As
(126 mg, 93%); 1H NMR (400 MHz, CDCl3)
7.52 (1H, s), 7.41e7.28
a
yellow oil
4.4.14. 1-(3-Methoxyphenyl)-but-3-en-1-ol (8n).11 As a pale yellow
d
oil (97 mg, 91%); 1H NMR (400 MHz, CDCl3)
d 7.20e7.16 (1H, m),
(1H, m), 7.27e7.19 (2H, m), 5.84e5.72 (1H, m), 5.19e5.14 (2H, m),
4.72e4.68 (1H, m), 2.54e2.40 (2H, m), 2.11 (1H, s). Enantiomeric
6.86e6.84 (2H, m), 6.75e6.73 (1H, m), 5.78e5.68 (1H, m),
5.12e5.05 (2H, m), 4.65e4.62 (1H, m), 3.74 (3H, s), 2.47e2.39 (2H,

J. Chen et al. / Tetrahedron 69 (2013) 8161e8168
8167
m), 2.03 (1H, s). Enantiomeric excess was determined by HPLC with
a Chiralcel IC-3 column (hexane/2-propanol¼98:2, 0.8 mL/min,
210 nm), tmajor¼38.9 min (S), tminor¼43.3 min (R), ee¼74%.
7.00e6.98 (2H, m), 5.79e5.87 (1H, m), 5.23e5.16 (2H, m),
5.04e5.00 (1H, m), 2.67e2.59 (2H, m), 2.24 (1H, d, J¼4.0 Hz). En-
antiomeric excess was determined by HPLC with a Chiralcel OD-H
column (hexane/2-propanol¼99:1, 1.0 mL/min, 210 nm),
tminor¼22.5 min (R), tmajor¼23.6 min (S), ee¼70%.
4.4.15. 1-(4-Methoxyphenyl)but-3-en-1-ol (8o).11 As a pale yellow
oil (93 mg, 87%); 1H NMR (400 MHz, CDCl3)
d
7.28 (2H, d, J¼8.8 Hz),
6.87 (2H, d, J¼8.8 Hz), 5.83e5.76 (1H, m), 5.18e5.11 (2H, m), 4.65
(1H, t, J¼6.4 Hz), 3.80 (3H, s), 2.51 (2H, t, J¼6.8 Hz), 2.01 (1H, s).
Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (hexane/2-propanol¼98:2, 0.7 mL/min, 230 nm),
tminor¼20.2 min (R), tmajor¼24.6 min (S), ee¼60%.
4.4.23. 1-Phenylhex-5-en-3-ol (8w).4b As a pale yellow oil (76 mg,
72%); 1H NMR (400 MHz, CDCl3)
d 7.33e7.26 (2H, m), 7.23e7.18 (3H,
m) 5.88e5.76 (1H, m), 5.18 (2H, dd, J¼14.0, 1.2 Hz), 3.72e3.65 (1H,
m), 2.82e2.77 (1H, m), 2.74e2.69 (1H, m), 2.35e2.28 (1H, m),
2.22e2.14 (1H, m), 1.82e1.77 (2H, m), 1.67 (1H, d, J¼5.2 Hz). En-
antiomeric excess was determined by HPLC with a Chiralcel OD-H
column (hexane/2-propanol¼85:15, 0.5 mL/min, 210 nm),
tminor¼10.7 min (S), tmajor¼14.1 min (R), ee¼8%.
4.4.16. 1-(3,5-Dimethylphenyl)-but-3-en-1-ol (8p).11 As a pale yel-
low oil (98 mg, 93%); 1H NMR (400 MHz, CDCl3)
d 6.88 (2H, s), 6.83
(1H, s), 5.78e5.68 (1H, m), 5.10 (1H, s), 5.06 (1H, d, J¼2.8 Hz), 4.56
(1H, t, J¼5.6 Hz), 2.45e2.35 (2H, m), 2.24 (6H, s), 1.98 (1H, s). En-
antiomeric excess was determined by HPLC with a Chiralcel
IC-3 column (hexane/2-propanol¼98:2, 0.8 mL/min, 210 nm),
tmajor¼10.1 min (S), tminor¼11.1 min (R), ee¼81%.
4.4.24. 1-Phenyl-hexa-1,5-dien-3-ol (8x).4b As a pale yellow oil
(81 mg, 78%); 1H NMR (400 MHz, CDCl3)
d 7.38e7.12 (5H, m), 6.53
(1H, d, J¼16.0 Hz), 6.18 (1H, dd, J¼16.0, 6.4 Hz), 5.82e5.74 (1H, m),
5.17e5.06 (2H, m), 4.32e4.27 (1H, m), 2.41e2.27 (2H, m), 1.78 (1H,
s). Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (hexane/2-propanol¼95:5, 1.0 mL/min, 210 nm),
tmajor¼13.8 min (S), tminor¼18.0 min (R), ee¼16%.
4.4.17. 1-(3,5-Dimethoxyphenyl)but-3-en-1-ol (8q).17 As a yellow oil
(121 mg, 95%); 1H NMR (400 MHz, CDCl3)
d
6.56 (2H, d, J¼2.4 Hz),
6.40 (1H, d, J¼2.4 Hz), 5.87e5.81 (1H, m), 5.22e5.16 (2H, m),
4.71e4.68 (1H, m), 3.82 (6H, s), 2.56e2.47 (2H, m). Enantiomeric
excess was determined by HPLC with a Chiralcel OD-H column
(hexane/2-propanol¼95:5, 0.8 mL/min, 210 nm), tminor¼19.1 min
(R), tmajor¼25.0 min (S), ee¼80%.
4.4.25. 2-Methyl-1-phenylbut-3-en-1-ol (8y).5a As a pale yellow oil
(86 mg, 89%, syn/anti¼52:48); syn-isomer
d 7.38e7.26 (5H, m),
5.78e5.70 (1H, m), 5.06e4.99 (2H, m), 4.60 (1H, d, J¼5.2 Hz),
2.61e2.54 (1H, m), 1.02 (3H, d, J¼7.6 Hz); 1H NMR: anti-isomer
d
7.38e7.26 (5H, m), 5.85e5.76 (1H, m), 5.22e5.21 (1H, m),
4.4.18. 1-(3,5-Di-tert-butylphenyl)but-3-en-1-ol (8r). As a yellow
5.20e5.15 (1H, m), 4.36 (1H, d, J¼7.6 Hz), 2.51e2.45 (1H, m), 0.86
(3H, d, J¼7.2 Hz). Enantiomeric excess was determined by HPLC
with a Chiralcel IC-3 column (hexane/2-propanol¼97.5:2.5, 0.6 mL/
min, 210 nm), syn-isomer, tminor¼10.6 min (1S,2R), tmajor¼11.5 min
(1R,2S), ee¼74%; anti-isomer tminor¼12.3 min (1R,2R),
tmajor¼13.2 min (1S,2S), ee¼54%.
oil (150 mg, 96%); 1H NMR (400 MHz, CDCl3)
d 7.36 (1H, s), 7.22 (2H,
s), 5.93e5.83 (1H, m), 5.18 (2H, t, J¼14.0 Hz), 4.73 (1H, t, J¼6.4 Hz),
2.55e2.51 (2H, m), 2.05 (1H, br s), 1.34 (1H, s); 13C NMR (100 MHz,
CDCl3)
d 151.1, 143.3, 135.2, 121.9, 120.2, 118.3, 74.3, 44.1, 35.1, 31.7;
HRMS (ESI-MS) calcd for
259.2056. Enantiomeric excess was determined by HPLC with
C
18H28
O
[Mꢁ1]ꢁ 259.2062, found:
a Chiralcel IC-3 column (hexane/2-propanol¼98:2, 0.6 mL/min,
Acknowledgements
25
210 nm). tminor¼6.9 min, tmajor¼7.7 min, ee¼92%; [
a
]
ꢁ29.4 (c
D
0.37, CHCl3).
This work was partly supported by the National Nature Science
Foundation of China (No. 21172143, 21172145 and 21232004), Sci-
ence and Technology Commission of Shanghai Municipality (No.
09JC1407800), Nippon Chemical Industrial Co. Ltd, Shanghai Jiao
Tong University (SJTU) and the Instrumental Analysis Center of
SJTU. We thank Prof. Tsuneo Imamoto and Dr. Masashi Sugiya for
helpful discussions.
4.4.19. 1-(Naphthalen-1-yl)but-3-en-1-ol (8s).9b As a pale yellow oil
(110 mg, 93%); 1H NMR (400 MHz, CDCl3)
8.08 (1H, d, J¼8.0 Hz),
d
7.89 (1H, d, J¼7.2 Hz), 7.79 (1H, d, J¼8.0 Hz), 7.67 (1H, d, J¼7.2 Hz),
7.53e7.46 (3H, m), 5.99e5.89 (1H, m), 5.56e5.52 (1H, m), 5.24e5.17
(2H, m), 2.78e2.74 (1H, m), 2.63e2.57 (1H, m), 2.25 (1H, s). Enan-
tiomeric excess was determined by HPLC with a Chiralcel OD-H
column (hexane/2-propanol¼90:10, 1.0 mL/min, 210 nm),
tmajor¼12.1 min (S), tminor¼21.6 min (R), ee¼77%.
Supplementary data
4.4.20. 2-(Naphthalen-1-yl)but-3-en-1-ol (8t).18 As a pale yellow oil
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.07.030.
(95 mg, 80%); 1H NMR (400 MHz, CDCl3)
d 7.87e7.80 (4H, m),
7.52e7.45 (3H, m), 5.90e5.80 (1H, m), 5.22e5.18 (1H, m), 5.16e5.12
(1H, m), 4.92 (1H, dd, J¼7.6, 4.8 Hz), 2.66e2.54 (2H, m), 2.16 (1H, br
s). Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (hexane/2-propanol¼95:5, 1.0 mL/min, 210 nm),
tmajor¼16.5 min (S), tminor¼18.0 min (R), ee¼71%.
References and notes
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d
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7.26e7.24 (1H, m),
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