(Z)-Selective enol triflation of α-alkoxyacetoaldehydes: Application to synthesis of (Z)-allylic alcohols via cross-coupling reaction and [1,2]-wittig rearrangement

Article abstract of DOI:10.1021/acs.joc.5b00647

The stereoselective transformation of α-alkoxyacetoaldehydes to the corresponding (Z)-vinyl triflates was achieved by treatment with phenyl triflimide and DBU. The stereochemistry was explained by the "syn-effect," which was attributed primarily to an σ → π interaction. The β-alkoxy vinyl triflates obtained were applied to the stereoselective synthesis of structurally diverse (Z)-allylic alcohols via transition metal-catalyzed cross-coupling reaction and [1,2]-Wittig rearrangement.

Full text of DOI:10.1021/acs.joc.5b00647

Article
pubs.acs.org/joc
(Z)‑Selective Enol Triflation of α‑Alkoxyacetoaldehydes: Application
to Synthesis of (Z)‑Allylic Alcohols via Cross-Coupling Reaction and
[1,2]-Wittig Rearrangement
Fumiya Kurosawa, Takeo Nakano, Takahiro Soeta, Kohei Endo, and Yutaka Ukaji*
Division of Material Chemistry, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa,
Ishikawa 920-1192, Japan
S
* Supporting Information
ABSTRACT: The stereoselective transformation of α-alkoxyacetoalde-
hydes to the corresponding (Z)-vinyl triflates was achieved by treatment
with phenyl triflimide and DBU. The stereochemistry was explained by
the “syn-effect,” which was attributed primarily to an σ → π* interaction.
The β-alkoxy vinyl triflates obtained were applied to the stereoselective
synthesis of structurally diverse (Z)-allylic alcohols via transition metal-
catalyzed cross-coupling reaction and [1,2]-Wittig rearrangement.
alkoxyacetoaldehyde due to the low donor ability of the C−O
bond compared with the C−H bond, affording the correspond-
ing (Z)-vinyl ethers predominantly as shown in Scheme 1.12b
INTRODUCTION
■
Stereoselective synthesis of alkenes has been studied exten-
sively. The (Z)-alkenes, especially, are versatile two-carbon
units present in many biologically active compounds and are
useful starting materials for chemical transformations, although
their preparation is usually more difficult than that for the E-
isomers. One reason is that (Z)-alkenes are generally
thermodynamically less stable.1
Scheme 1. Transition State Model for Deprotonation of α-
Alkoxyacetoaldehydes in the Presence of Triisopropylsilyl
Triflate (E = i-Pr3Si, X = OTf)12b
Cross-coupling reaction is quite useful method to prepare
alkenes stereospecifically from the corresponding vinyl halides.
Vinyl triflates have been also used as synthetic intermediates
toward transition metal-mediated cross-coupling reactions in
addition to vinyl cation and alkylidene carbene precursors.2−4
For cross-coupling reactions, stereoselective preparation of (Z)-
vinyl triflates is essential for the subsequent transformation to
(Z)-alkenes. For 1,3-dicarbonyl compounds, Z-selective prep-
aration of vinyl triflates was achieved.2d,5 Chelation-controlled
preparation of (Z)-vinyl triflates from α-alkoxy ketones also has
been reported.6 Recently, Cu-catalyzed electrophilic vinyl
triflation of alkynes was reported to afford (Z)-triflates.7 For
preparation of vinyl triflates from aldehydes, a mixture of (Z)-
and (E)-vinyl triflates was formed through the use of triflic
anhydride (Tf2O) and 4-methyl-2,6-(di-t-butyl)pyridine
(DTBMP).8 Alternatively, trimethylsilyl enol ethers could be
converted to vinyl triflates by treatment with methyllithium and
Tf2O;9 however, (Z)-selective preparation of trimethylsilyl enol
ethers from an aldehyde is then an issue.10
Previously, a series of isomerization reactions and elimination
reactions using a base were performed to investigate the
stereochemistry of the isomerized and eliminated products. The
results showed that sterically unfavorable (Z)-alkenes were
formed predominantly. These results were explained by the
action of a “syn-effect,”11 caused primarily by σ → π*
interactions.12,13 Oxygen-substituted substrates always pro-
duced excellent Z-selectivities. For example, conformation T1
was preferred to conformation T2 during deprotonation of α-
Furthermore, [1,2]-Wittig rearrangement14 of the resulting
(Z)-vinyl ethers proceeded after the initial 1,4-eliminative ring
opening reaction of vinyl oxiranes and 1,4-elimination of allylic
sulfones and allylic benzoates to give (2Z)-2,4-pentadien-1-ol
derivatives in a highly stereoselective manner (Scheme 2).12c,e,f
These results demonstrate that the greatest Z-selectivity based
on the “syn-effect” for oxygen-substituted substrates could be
applied to stereoselective C−C bond formation.
Investigation of isomerization reactions revealed that α-
alkoxyacetoaldehydes were converted to the corresponding
(Z)-β-alkoxy silyl enol ethers with excellent Z-selectivities.12b,15
Thus, a (Z)-β-alkoxy vinyl triflate could be prepared if the
enolate is trapped by a triflic-cationic species instead of a silyl
cation. In addition, the resulting (Z)-vinyl triflate should be
accompanied by sequential stereoselective C−C bond for-
Received: March 23, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00647
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Next, the cross-coupling reaction was investigated using (Z)-
β-alkoxy vinyl triflate 2. Introduction of a phenyl group was
accomplished via Suziki−Miyaura coupling with PhB(OH)2
and using Pd(PPh3)4 as a catalyst17 to give the β-alkoxy
styrenes with retention of Z-stereochemistry as shown in Table
2.
Scheme 2. Previous Example of Stereoselective
Transformation by the Combination of “Syn-Effect” and
[1,2]-Wittig Rearrangement12f
Table 2. Coupling Reactions of Vinyl Triflates 2
mation via cross-coupling reaction in combination with [1,2]-
Wittig rearrangement (Scheme 3). The present report describes
the stereoselective enol triflation of α-alkoxyacetoaldehydes,
followed by cross-coupling reaction and [1,2]-Wittig rearrange-
ment to afford various (Z)-allylic alcohols stereoselectively.
a
a
entry
R1
2 (Z/E)
time
3
yield/% Z/E
b
1
Ph
A (94/6)
B (94/6)
C (94/6)
D (97/3)
E (95/5)
40 min
30 min
1 h
Aa
Ba
Ca
Da
Ea
69
49
74
65
79
95/5
93/7
95/5
95/5
97/3
Scheme 3. Strategy toward Synthesis of (Z)-Allylic Alcohols
2
3
4
2-MeC6H4
4-MeOC6H4
4-ClC6H4
20 min
c
5
i-Pr3SiCC
45 min
a
The ratios were determined by 400 MHz 1H NMR spectra.
Pd(PPh3)4 (0.03 equiv). Pd(PPh3)4 (0.10 equiv) at a reaction
b
c
temperature of 60 °C.
Suzuki−Miyaura coupling reaction of vinylic borane
compounds generated in situ was performed as shown in eq
1.18 The diene 3Ab was obtained with nearly full retention of
stereochemistry.19
RESULTS AND DISCUSSION
■
First, the enol triflation reaction of (α-benzyloxy)acetoaldehyde
(1A) using triflic anhydride (Tf2O) (1.2 equiv) and 2,6-di-tert-
butyl-4-methylpyridine (DTBMP) was conducted in CH2Cl2
under reflux conditions for 2 d.8c However, very little of the
desired vinyl triflate was obtained, while 48% of 1A was
recovered (Table 1, entry 1). The desired vinyl triflate also was
not obtained when DBU (2.0 equiv) was used as the base in
CH2Cl2 at rt (entry 2). When phenyl triflimide (PhNTf2) was
used instead of Tf2O,16 the reaction proceeded rapidly. The
stereoselectivity of the resulting vinyl triflate was high (Z/E =
95/5) (entry 3). DBU was chosen as the base because no
reaction occurred using other bases such as DTBMP and Et3N.
Other β-benzyloxy-type vinyl triflates 2B−2D were also
obtained stereoselectively from the corresponding α-alkoxya-
cetoaldehydes 1B−1D (entries 4−6). Furthermore, α-
(propargyloxy)acetoaldehyde 1E could be stereoselectively
transformed into the corresponding vinyl triflate 2E stereo-
selectively (entry 7); using 2.5 equiv of DBU improved the
chemical yield (entry 8).
Sonogashira coupling was also examined (Table 3).20 3,3-
Dimethyl-1-butyne was used as a substrate for the trans-
formation to give Z-enynes 3Ac and 3Ec in high chemical yield
with high stereoselectivity.
Next, an alkyl group was introduced via alkyl boron reagent
generated in situ from styrene and 9-BBN.21 However, the
reaction was sluggish, and a mixture of the desired product,
benzyl vinyl ether, and inseparable byproducts was obtained in
poor yield. After intensive investigation, Kumada−Tamao−
Corriu coupling reaction of 2A using n-BuMgCl in the presence
of NiCl2(dppp)22 resulted in the addition of a primary alkyl
Table 1. Enol Triflation of α-Alkoxyacetoaldehydes 1
a
entry
R1
triflating reagent
base
time
2 d
yield/%
Z/E
b
1
Ph
A
Tf2O
DTBMP
DBU
DBU
DBU
DBU
DBU
DBU
DBU
trace
-
-
2
3
4
5
6
7
Tf2O
12 h
-
PhNTf2
PhNTf2
PhNTf2
PhNTf2
PhNTf2
PhNTf2
10 min
10 min
10 min
10 min
10 min
10 min
84
84
82
88
37
71
95/5
95/5
95/5
94/6
92/8
95/5
2-MeC6H4
B
C
D
E
4-(MeO)C6H4
4-ClC6H4
i-Pr3SiCC
c
8
a
b
c
1
The ratios were determined by 400 MHz H NMR spectra. DTBMP (1.2 equiv) under CH2Cl2 reflux. DBU (2.5 equiv).
B
DOI: 10.1021/acs.joc.5b00647
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The Journal of Organic Chemistry
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3). Although the reaction of propargylic ethers 3Ea and 3Ec
provided rearranged alcohols at slightly lower chemical yields,
excellent Z-stereoselectivity was realized (entries 5 and 8). With
the use of a vinyl ether with a primary alkyl group at the β-
position, treatment with n-BuLi gave a complex mixture. In this
case, the addition of TMEDA using an excess amount of n-BuLi
was also effective to realize the rearrangement affording (Z)-
allylic alcohol 4Ad in good chemical yield (entry 9).
In summary, a useful synthetic scheme for (Z)-allylic alcohols
was established based on the novel (Z)-selective vinyl-triflation
of α-alkoxyacetoaldehydes followed by cross-coupling and
[1,2]-Wittig rearrangement. This synthetic scheme allowed
the preparation of a wide array of structurally diverse (Z)-allylic
alcohols in a stereoselective manner. These (Z)-allylic alcohols
are versatile synthetic intermediates for stereospecific trans-
formations such as Katsuki−Sharpless and related epoxidations
and Simmons−Smith cyclopropanation.23,24 The synthetic
method presented here can be used in place of the technique
using (Z)-allylic alcohols with triple bonds, which could not be
prepared by conventional Lindlar reduction of diynols.25
Table 3. Sonogashira Coupling Reaction of Vinyl Triflates 2
a
a
entry
1
R1
2 (Z/E)
time
3
yield/% Z/E
Ph
i-Pr3SiCC
A (95/5)
E (95/5)
20 min
1 h
Ac
Ec
88
98
95/5
b
2
96/4
a
b
1
The ratios were determined by 400 MHz H NMR spectra. 3,3-
Dimethyl-1-butyne (2 equiv); CuI (0.1 equiv).
group. Although slight isomerization was observed, the
corresponding vinyl ether 3Ad was obtained with high Z-
selectivity (Table 4, entry 1). In contrast, the coupling reaction
of propargyloxy triflate 1E underwent extensive isomerization
to give a ca. 2/1 mixture of 3Ed (entry 2).
Table 4. Introduction of an Alkyl Group via Kumada−
Tamao−Corriu Coupling
EXPERIMENTAL SECTION
■
General Method. 1H NMR spectra were recorded on a 400 MHz
NMR spectrometer. Chemical shifts δ are reported in ppm using TMS
as an internal standard. Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constant (J) and integration. 13C NMR spectra
were recorded on a 100 MHz NMR spectrometer. The chemical shifts
are reported relative to CDCl3 (δ = 77.0 ppm). The wavenumbers of
maximum absorption peaks in IR spectra are presented in cm−1.
HRMS (EI positive, ESI-TOF) spectra were measured with quadru-
pole and TOF mass spectrometers. All of the melting points were
measured with a micro melting point apparatus. THF was freshly
distilled from sodium diphenylketyl. CH2Cl2 was distilled and stored
over drying agents. Anhydrous CH3CN was purchased and stored over
drying agents.
a
a
entry
R1
2 (Z/E)
time
3
yield/%
Z/E
1
2
Ph
i-Pr3SiCC
A (94/6)
E (95/5)
15 min
2 h
Ad
Ed
81
38
91/9
68/32
a
1
The ratios were determined by 400 MHz H NMR spectra.
After establishing a procedure for addition of substituents via
cross-coupling reaction of vinyl triflates 2, the [1,2]-Wittig
rearrangement of vinyl ethers 3 was investigated. For benzyl-
type ethereal substrates 3Aa, 3Ba, 3 Da, 3Ab, and 3Ac, the
rearrangement proceeded to give the corresponding (Z)-allylic
alcohols stereoselectively (Table 5, entries 1, 2, 4, 6, and 7). In
the case of of (4-methoxyphenyl)methyl ether 3Ca, a specific
reaction conditions were required. When the 3Ca was treated
with n-BuLi (3.0 equiv) in THF, the rearrangement did not
proceed cleanly and yielded the allylic alcohol 4Ca in low yield
of 19% with 92/8 selectivity. By the addition of N,N,N′,N′-
tetramethylethylenediamine (TMEDA) using an excess amount
of n-BuLi, 4Ca was obtained in enhanced chemical yield (entry
2-((2-Methylbenzyl)oxy)ethanol. To a suspension of NaH (2.4
g, 60% in mineral oil, 60 mmol) in THF (160 mL) was added ethylene
glycol (10.0 mL, 180 mmol) in THF (40 mL) at 0 °C under N2
atmosphere. After 30 min of stirring, 1-(chloromethyl)-2-methyl-
benzene (9.66 g, 60 mmol) in THF (40 mL) and n-Bu4NI (1.11 g, 1.2
mmol) were added, and the mixture was refluxed for 1 d. Water was
added and aqueous layer was separated and extracted with Et2O. The
combined organic extracts were washed with brine, dried over Na2SO4,
and solvent was removed under reduced pressure. The crude product
was purified by silica gel column chromatography (hexane/AcOEt =
Table 5. [1,2]-Wittig Rearrangement of Vinyl Ethers 3 to Allylic Alcohols 4
a
a
entry
R1
R2
3 (Z/E)
time
yield/%
Z/E
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Aa (95/5)
Ba (>98/2)
Ca (95/5)
Da (96/4)
Ea (>98/2)
Ab (87/13)
Ac (93/7)
Ec (96/4)
Ad (91/9)
15 min
4 min
10 min
4 min
4 min
4 min
3 min
4 min
10 min
86
54
47
63
56
85
49
31
81
98/2
>98/2
97/3
2-MeC6H4
4-MeOC6H4
4-ClC6H4
i-Pr3SiCC
Ph
b,c
3
4
5
6
7
8
9
97/3
>98/2
95/5
d
t-BuCHCH
t-BuCC
t-BuCC
n-Bu
Ph
93/7
i-Pr3SiCC
>98/2
89/11
b,c
Ph
a
b
c
The ratios were determined by 400 MHz 1H NMR spectra. n-BuLi (8 equiv) and TMEDA (1 equiv) were added. Temperature was adjusted from
d
−78 °C to rt over 10 min. Ratio of (1Z,3E)-isomer/other isomers was 87/13.
C
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3/1) to give 2-((2-methylbenzyl)oxy)ethanol (7.08 g, 64%) as an oil.
1H NMR (400 MHz, CDCl3): 2.24 (s, 3H), 2.42 (brs, 2H), 3.46−3.49
(m, 2H), 3.62 (dd, J = 9.2, 5.5 Hz, 1H), 4.44 (s, 2H), 7.05−7.14 (m,
3H), 7.19−7.22 (m, 1H). 13C NMR (100 MHz, CDCl3): 18.7, 61.7,
71.4, 71.5, 125.7, 127.9, 128.6, 130.2, 135.7, 136.6. IR (neat): 3421,
2865, 1459, 1355, 1102, 893, 745 cm−1. HRMS (ESI-TOF): calcd for
C10H14O2Na [(M + Na)+] 189.0891, found 189.0887.
AcOEt = 6/1) to give 2A (948 mg, 84%, Z/E = 95/5 mixture from 1H
NMR) as an oil. 1H NMR (400 MHz, CDCl3): 4.94 (s, 2H), 6.00 (d, J
= 3.2 Hz, 1H), 6.04 (d, J = 3.2 Hz, 1H), 7.27−7.42 (m, 5 H). Selected
data of (E)-isomer; 4.77 (s, 2H), 6.57 (d, J = 10.1 Hz, 1H), 7.01 (d, J =
10.1 Hz, 1H). 13C NMR (100 MHz, CDCl3): 75.3, 118.6 (J = 320.7
Hz), 118.9, 123.7, 127.7, 128.7, 129.7, 138.5. IR (neat): 3134, 3067,
3035, 2938, 2883, 1684, 1497, 1421, 1211, 1141 987, 847, 698 cm−1.
HRMS (EI): calcd for C10H9F3O4S [M+] 282.0174, found: 282.0170.
In a similar manner, (Z)-vinyl triflates 2B−2E were obtained from
1B−1E.
2-((2-Methylbenzyl)oxy)acetaldehyde (1B). To a solution of
oxalyl chloride (1.27 mL, 15 mmol) in CH2Cl2 (50 mL) was added
DMSO (1.42 mL, 20 mmol) in CH2Cl2 (3 mL) at −78 °C. After 5
min of stirring, 2-((2-methylbenzyl)oxy)ethanol (1.66 g, 10 mmol) in
CH2Cl2 (3 mL) was added dropwise. After 15 min, Et3N (7.0 mL, 50
mmol) was added to the reaction mixture and this was allowed to
warm to rt. After 1 h of stirring, the insoluble substrate in the reaction
mixture was filtered off through a bed of Celite and solvent was
evaporated. The residue was purified by silica gel column
chromatography (hexane/AcOEt = 3/1) to give 1B (1.16 g, 71%) as
an oil. 1H NMR (400 MHz, CDCl3): 2.28 (s, 3H), 4.00 (d, J = 0.9 Hz,
2H), 4.54 (s, 2H), 7.06−7.17 (m, 3H), 7.20−7.23 (m, 1H), 9.61 (t, J =
0.9 Hz, 1H). 13C NMR (100 MHz, CDCl3): 18.7, 71.9, 75.2, 125.8,
128.3, 128.9, 130.4, 134.7, 136.9, 200.5. IR (neat): 3029, 2867, 1736,
1492, 1460, 1376, 1104, 746 cm−1. HRMS (ESI-TOF): calcd for
C10H12O2Na [(M+Na)+] 187.0735, found 187.0740.
(Z)-2-((2-Methylbenzyl)oxy)vinyl Trifluoromethanesulfonate
(2B). Compound 2B (749 mg, 84%, Z/E = 95/5) was obtained as an
oil from 1B (493 mg, 3.0 mmol), DBU (913 mg, 6.0 mmol), and
1
PhNTf2 (1.29 g, 3.6 mmol). H NMR (400 MHz, CDCl3): 2.36 (s,
3H), 4.95 (s, 2H), 5.99 (d, J = 3.2 Hz, 1H), 6.05 (d, J = 3.2 Hz, 1H),
7.20−7.30 (m, 4H). Selected data of (E)-isomer; 2.33 (s, 3H), 4.77 (s,
2H), 6.60 (d, J = 10.5 Hz, 1H), 7.01 (d, J = 10.5 Hz, 1H). 13C NMR
(100 MHz, CDCl3): 18.7, 74.0, 118.6 (J = 320.7 Hz), 118.9, 126.0,
128.9, 129.0, 130.7, 133.4, 137.1, 138.3. IR (neat): 3136, 3025, 2956,
2890, 1683, 1421, 1352, 1221, 1141, 986, 744, 693 cm−1. HRMS (EI):
calcd for C11H11F3O4S [M+] 296.0330, found: 296.0336.
(Z)-2-((4-Methoxybenzyl)oxy)vinyl Trifluoromethanesulfo-
nate (2C). Compound 2C (244 mg, 82%, Z/E = 95/5) was obtained
as an oil from 1C (180 mg, 1.0 mmol), DBU (304 mg, 2.0 mmol), and
In a similar manner, 2-alkoxyacetoaldehyde 1A,26 1C,27 and 1D28
were prepared from ethylene glycol.
1
PhNTf2 (429 mg, 1.2 mmol). H NMR (400 MHz, CDCl3): 3.82 (s,
Ethyl 2-((3-(Triisopropylsilyl)prop-2-yn-1-yl)oxy)acetate. To
a solution of 3-(triisopropylsilyl)prop-2-yn-1-ol29 (3.19 g, 15 mmol)
and HMPA (10.4 mL, 60 mmol) in THF (15 mL) was added
MeMgBr (15 mL of 1.0 M solution in THF, 15 mmol) dropwise at 0
°C under N2 atmosphere. After 10 min of stirring, ethyl bromoacetate
(2.51 g, 15 mmol) in THF (5 mL) was added, and the resulting
solution was warmed 50 °C, and stirred for 1 h. The reaction mixture
was quenched with a satd aq solution of NaHCO3 (5 mL). After
insoluble substance was filtered off through a bed of Celite, the organic
layer was dried over Na2SO4 and the solvent was evaporated. The
crude product was purified by silica gel column chromatography
(hexane/AcOEt = 20/1) to give ethyl 2-((3-(triisopropylsilyl)prop-2-
3H), 4.86 (s, 2H), 5.97 (d, J = 3.2 Hz, 1H), 6.03 (d, J = 3.2 Hz, 1H),
6.91 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H). Selected data of (E)-
isomer; 4.69 (s, 2H), 6.55 (d, J = 10.1 Hz, 1H), 6.99 (d, J = 10.1 Hz,
1H). 13C NMR (100 MHz, CDCl3): 55.2, 75.1, 114.1, 118.6 (J = 320.7
Hz), 118.8, 127.6, 129.6, 138.3, 159.9. IR (neat): 3135, 3005, 2941,
2840, 1684, 1614, 1517, 1420, 1246, 1211, 1142, 825, 692 cm−1.
HRMS (EI): calcd for C11H11F3O5S [M+] 312.0279, found: 312.0282.
(Z)-2-((4-Chlorobenzyl)oxy)vinyl Trifluoromethanesulfonate
(2D). Compound 2D (139 mg, 88%, Z/E = 94/6) was obtained as an
oil from 1D (92 mg, 0.5 mmol), DBU (152 mg, 1.0 mmol), and
1
PhNTf2 (214 mg, 0.6 mmol). H NMR (400 MHz, CDCl3): 4.91 (s,
2H), 6.01 (d, J = 3.7 Hz, 1H), 6.02 (d, J = 3.7 Hz, 1H), 7.26−7.42 (m,
4H). Selected data of (E)-isomer; 4.74 (s, 3H), 6.56 (d, J = 10.1 Hz,
1H), 6.99 (d, J = 10.1 Hz, 1H). 13C NMR (100 MHz, CDCl3): 74.5,
118.6 (J = 320.7 Hz), 119.2, 128.9, 129.0, 129.7, 134.0, 138.4. IR
(neat): 3321, 3134, 2942, 2884, 1684, 1600, 1495, 1211, 1142, 966,
812, 693 cm−1. HRMS (EI): calcd for C10H8ClF3O4S [M+] 315.9784,
found: 315.9786.
1
yn-1-yl)oxy)acetate (1.92 g, 49%) as an oil. H NMR (400 MHz,
CDCl3): 1.00 (s, 21H), 1.23 (t, J = 6.8 Hz, 3H), 4.16 (s, 2H), 4.17 (q,
J = 6.8 Hz, 2H), 4.29 (s, 2H). 13C NMR (100 MHz, CDCl3): 11.0,
14.1, 18.5, 58.9, 60.9, 65.7, 89.1, 101.7, 170.0. IR (neat): 2944, 2865,
2171, 1754, 1463, 1204, 1121, 1000, 883, 677 cm−1. HRMS (EI): calcd
for C16H30O3Si [M+] 298.1964, found 298.1981.
2-((3-(Triisopropylsilyl)prop-2-yn-1-yl)oxy)acetaldehyde
(1E). To a solution of ethyl 2-((3-(triisopropylsilyl)prop-2-yn-1-
yl)oxy)acetate (1.92 g, 7.4 mmol) in toluene (50 mL) was added
DIBAL-H (7.4 mL of 1.0 M solution in toluene, 7.4 mmol) dropwise
over 5 min at −78 °C under N2 atmosphere. After 5 min, MeOH (7
mL) was added and the reaction mixture was warmed to rt. A satd aq
solution of potassium sodium tartrate was added and the resulting
mixture was stirred for 3 h. After insoluble substance was filtered off
through a bed of Celite, the aqueous layer was separated and extracted
with Et2O. The combined organic extracts were washed with brine and
dried over Na2SO4, and the solvent was evaporated. The crude
product was purified by silica gel column chromatography (hexane/
AcOEt = 6/1) to give 1E (1.00 g, 53%) as an oil. 1H NMR (400 MHz,
CDCl3): 1.07 (s, 21H), 4.21 (s, 2H), 4.35 (s, 2H), 9.77 (s, 1H). 13C
NMR (100 MHz, CDCl3): 11.0, 18.5, 59.5, 74.3, 89.5, 101.6, 200.1. IR
(neat): 2943, 2891, 2865, 2716, 1739, 1463, 1382, 1366, 1242, 1114,
1009, 883, 678 cm−1. HRMS (EI): calcd for C14H26O2Si [M+]
254.1702, found 254.1706.
(Z)-2-(Benzyloxy)vinyl Trifluoromethanesulfonate (2A). To a
solution of 1A (597 mg, 4.0 mmol) in CH2Cl2 (35 mL) were added
DBU (1.21 g, 8.0 mmol) in CH2Cl2 (5 mL) and PhNTf2 (1.71 g, 4.8
mmol) in CH2Cl2 (10 mL) at rt under Ar atmosphere. After reaction
completion (monitored by TLC), the reaction was quenched with a
phosphate buffer solution (pH 7). The aqueous layer was separated
and extracted with Et2O. The combined organic extracts were washed
with brine, dried over Na2SO4, and solvent was evaporated. The crude
product was purified by silica gel column chromatography (hexane/
(Z)-2-((3-(Triisopropylsilyl)prop-2-yn-1-yl)oxy)vinyl Trifluor-
omethanesulfonate (2E). Compound 2E (82 mg, 71%, Z/E = 95/
5) was obtained as an oil from 1E (76 mg, 0.3 mmol), DBU (114 mg,
0.75 mmol), and PhNTf2 (129 mg, 0.36 mmol). 1H NMR (400 MHz,
CDCl3): 1.07 (s, 21H), 4.55 (s, 2H), 6.10 (d, J = 3.2 Hz, 1H), 6.23 (d,
J = 3.2 Hz, 1H). Selected data of (E)-isomer; 4.47 (s, 2H), 6.66 (d, J =
10.1 Hz, 1H), 6.96 (d, J = 10.1 Hz, 1H). 13C NMR (100 MHz,
CDCl3): 11.0, 18.4, 61.1, 91.4, 99.9, 118.7 (J = 320.7 Hz), 119.6,
136.9. IR (neat): 3137, 2946, 2868, 2170, 1685, 1425, 1245, 1117,
1045, 1009, 951, 883, 845, 706, 681 cm−1. HRMS (EI): calcd for
C15H25F3O4SSi [M+] 386.1195, found: 386.1169.
(Z)-(2-(Benzyloxy)vinyl)benzene (3Aa).30 To a solution of 2A
(282 mg, 1.0 mmol, Z/E = 94/6) in toluene (15 mL) and EtOH (2.5
mL) was added 2 M aq solution of Na2CO3 (15 mL). After Pd(PPh3)4
(37 mg, 0.03 mmol) and PhB(OH)2 (156 mg, 1.3 mmol) were added,
the reaction mixture was stirred at 80 °C for 30 min under Ar
atmosphere.17b The reaction mixture was cooled to rt and insoluble
substance was filtered off through a bed of Celite. The aqueous layer of
the filtrate was separated and extracted with Et2O. The combined
organic extracts were washed with water and brine, dried over Na2SO4,
and solvent was evaporated. The crude product was purified by silica
gel column chromatography (hexane/AcOEt = 20/1) to give 3Aa (144
mg, 69%, Z/E = 95/5) as an oil. 1H NMR (400 MHz, CDCl3): 5.00 (s,
2H), 5.27 (d, J = 6.9 Hz, 1H), 6.29 (d, J = 6.9 Hz, 1H), 7.06−7.39 (m,
8H), 7.63 (d, J = 7.3 Hz, 2H). Selected data of (E)-isomer; 4.91 (s,
2H), 5.96 (d, J = 12.8 Hz, 1H), 7.08 (d, J = 12.8 Hz, 1H). 13C NMR
D
DOI: 10.1021/acs.joc.5b00647
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The Journal of Organic Chemistry
Article
(100 MHz, CDCl3): 74.9, 106.3, 125.8, 127.2, 128.0, 128.2, 128.3,
128.6, 135.8, 137.2, 146.2.
2959, 2863, 1654, 1615, 1455, 1365, 1285, 1267, 1194, 1131, 1090,
1071, 975, 734 cm−1. HRMS (EI): calcd for C15H20O [M+] 216.1514,
found 216.1509.
In a similar manner, (Z)-vinyl ethers 3Ba−3Ea were obtained from
2B−2E.
(Z)-(((5,5-Dimethylhex-1-en-3-yn-1-yl)oxy)methyl)benzene
(3Ac). To a solution of Et3N (252 mg, 2.5 mmol), 3,3-dimethyl-1-
butyne (62 mg, 0.75 mmol), and 2A (141 mg, 0.5 mmol, Z/E = 95/5)
in MeCN (1 mL) was added Pd(PPh3)4 (29 mg, 0.025 mmol) in
MeCN (1 mL) and CuI (5 mg, 0.026 mmol) at rt under Ar
atmosphere and the reaction mixture was stirred at 60 °C for 20
min.20b The reaction mixture was cooled to rt, insoluble substance was
filtered off through a bed of Celite, and solvent of the filtrate was
evaporated. The crude product was purified by silica gel column
chromatography (hexane/AcOEt = 10/1) to give 3Ac (94 mg, 88%,
(Z)-1-Methyl-2-((styryloxy)methyl)benzene (3Ba). Compound
3Ba (55 mg, 49%, Z/E = 93/7) was obtained as an oil from 2B (148
mg, 0.50 mmol, Z/E = 94/6), Pd(PPh3)4 (29 mg, 0.025 mmol), and
1
PhB(OH)2 (79 mg, 0.65 mmol). H NMR (400 MHz, CDCl3): 2.38
(s, 3H), 4.99 (s, 2H), 5.26 (d, J = 7.4 Hz, 1H), 6.30 (d, J = 7.4 Hz,
1H), 7.12−7.38 (m, 7H), 7.61 (d, J = 7.4 Hz, 2H). Selected data of
(E)-isomer; 2.33 (s, 3H), 4.89 (s, 2H), 5.98 (d, J = 12.8 Hz, 1H). 13C
NMR (100 MHz, CDCl3): 18.9, 73.6, 106.1, 125.7, 126.0, 128.18,
128.22, 128.27, 128.29, 130.4, 135.1, 135.9, 136.5, 146.2. IR (neat):
3024, 2927, 1650, 1493, 1447, 1365, 1265, 1120, 1086, 779, 746, 694
cm−1. HRMS (EI): calcd for C16H16O [M+] 224.1201, found
224.1200.
1
Z/E = 95/5) as an oil. H NMR (400 MHz, CDCl3): 1.27 (s, 9H),
4.55 (d, J = 6.4 Hz, 1H), 4.97 (s, 2H), 6.29 (d, J = 6.4 Hz, 1H), 7.28−
7.36 (m, 5H). Selected data of (E)-isomer; 1.23 (s, 9H), 4.78 (s, 2H),
5.01 (d, J = 12.8 Hz, 1H), 6.83 (d, J = 12.8 Hz, 1H). 13C NMR (100
MHz, CDCl3): 28.2, 31.1, 72.9, 74.0, 86.8, 102.1, 127.2, 127.9, 128.5,
137.0, 153.2. IR (neat): 3065, 3034, 2967, 2927, 2866, 2222, 1632,
1455, 1364, 1264, 1123, 1051, 730, 696 cm−1. HRMS (EI): calcd for
C15H18O [M+] 214.1358, found 214.1359.
(Z)-1-Methoxy-4-((styryloxy)methyl)benzene (3Ca). Com-
pound 3Ca (156 mg, 74%, Z/E = 95/5) was obtained as an oil
from 2C (260 mg, 0.88 mmol, Z/E = 94/6), Pd(PPh3)4 (51 mg, 0.04
1
mmol), and PhB(OH)2 (139 mg, 1.14 mmol). H NMR (400 MHz,
CDCl3): 3.81 (s, 3H), 4.92 (s, 2H), 5.25 (d, J = 7.3 Hz, 1H), 6.28 (d, J
= 7.3 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 7.12−7.46 (m, 5H), 7.60 (d, J
= 8.7 Hz, 2H). Selected data of (E)-isomer; 3.78 (s, 3H), 4.83 (s, 2H),
5.95 (d, J = 12.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): 55.3, 74.6,
106.1, 113.9, 125.7, 128.16, 128.24, 129.0, 129.2, 135.9, 146.1, 159.5.
IR (neat): 3031, 2933, 2836, 1650, 1613, 1513, 1447, 1366, 1250,
1174, 1031, 823, 780, 696 cm−1. HRMS (EI): calcd for C16H16O2
[M+] 240.1150, found 240.1143.
In a similar manner, (Z)-vinyl ethers 3Ec were obtained from 2E.
(Z)-(3-((5,5-Dimethylhex-1-en-3-yn-1-yl)oxy)prop-1-yn-1-yl)-
triisopropylsilane (3Ec). Compound 3Ec (88 mg, 98%, Z/E = 96/4)
was obtained as an oil from 2E (116 mg, 0.3 mmol, Z/E = 95/5), Et3N
(152 mg, 1.5 mmol), 3,3-dimethyl-1-butyne (49 mg, 0.6 mmol),
1
Pd(PPh3)4 (20 mg, 0.017 mmol), and CuI (6 mg, 0.03 mmol). H
NMR (400 MHz, CDCl3): 1.07 (s, 21H), 1.26 (s, 9H), 4.54 (s, 2H),
4.61, (d, J = 6.4 Hz, 1H), 6.45 (d, J = 6.4 Hz, 1H). Selected data of
(E)-isomer; 4.42 (s, 2H), 5.03, (d, J = 12.8 Hz, 1H), 6.76 (d, J = 12.8
Hz, 1H). 13C NMR (100 MHz, CDCl3): 11.0, 18.5, 28.2, 31.1, 60.1,
72.6, 87.4, 89.7, 101.3, 102.2, 151.5. IR (neat): 3043, 2965, 2944, 2866,
2726, 2230, 2176, 1634, 1564, 1462, 1359, 1264, 1229, 1115, 1028,
998, 883, 727, 678 cm−1. HRMS (EI): calcd for C20H34OSi [M+]
318.2379, found 318.2370.
(Z)-1-Chloro-4-((styryloxy)methyl)benzene (3Da). Compound
3Da (79 mg, 65%, Z/E = 95/5) was obtained as an oil from 2D (190
mg, 0.60 mmol, Z/E = 97/3), Pd(PPh3)4 (35 mg, 0.03 mmol), and
1
PhB(OH)2 (95 mg, 0.78 mmol). H NMR (400 MHz, CDCl3): 4.93
(s, 2H), 5.28 (d, J = 7.3 Hz, 1H), 6.23 (d, J = 7.3 Hz, 1H), 7.13−7.36
(m, 7H), 7.60 (d, J = 7.3 Hz, 2H). Selected data of (E)-isomer; 4.87 (s,
2H), 5.95 (d, J = 12.8 Hz, 1H), 7.05 (d, J = 12.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): 74.1, 106.7, 125.9, 127.1, 128.2, 128.3, 128.5,
128.8, 133.8, 135.6, 145.9. IR (neat): 3085, 3031, 2928, 2972, 1651,
1600, 1492, 1447, 1403, 1365, 1266, 1200, 1088, 1014, 806, 779, 695
cm−1. HRMS (EI): calcd for C15H13ClO [M+] 244.0655, found
244.0656.
(Z)-Triisopropyl(3-(styryloxy)prop-1-yn-1-yl)silane (3Ea).
Compound 3Ea (74 mg, 79%, 97/3) was obtained as an oil from
2E (116 mg, 0.3 mmol, Z/E = 95/5), Pd(PPh3)4 (35 mg, 0.03 mmol,
10 mol %), and PhB(OH)2 (48 mg, 0.39 mmol). 1H NMR (400 MHz,
CDCl3): 1.07 (s, 21H), 4.56 (s, 2H), 5.34 (d, J = 6.8 Hz, 1H), 6.37 (d,
J = 6.8 Hz, 1H), 7.13−7.16 (m, 1H), 7.24−7.36 (m, 2H), 7.58−7.61
(m, 2H). Selected data of (E)-isomer; 4.54 (s, 2H), 5.99 (d, J = 12.8
Hz, 1H). 13C NMR (100 MHz, CDCl3): 11.1, 18.5, 60.4, 89.4, 101.8,
107.3, 125.9, 128.1, 128.4, 135.6, 144.6. IR (neat): 2942, 2864, 2725,
2174, 1652, 1493, 1462, 1450, 1356, 1274, 1086, 1034, 999, 883, 777,
693, 678, 666 cm−1. HRMS (EI): calcd for C20H30OSi [M+] 314.2066,
found 314.2070.
(Z)-((Hex-1-en-1-yloxy)methyl)benzene (3Ad). To a solution
of 2A (141 mg, 0.5 mmol, Z/E = 94/6) in toluene (3 mL) were added
NiCl2(dppp) (28 mg, 0.05 mmol) and n-BuMgCl (1.1 mL of 0.91 M
solution in THF, 1.0 mmol) and the reaction mixture was stirred at rt
for 30 min under Ar atmosphere.22d The reaction was quenched with a
satd aq solution of NH4Cl and insoluble substance was filtered off
through a bed of Celite. The aqueous layer of the filtrate was separated
and extracted with Et2O. The combined organic extracts were washed
with water and brine, dried over Na2SO4, and solvent was evaporated.
The crude product was purified by silica gel column chromatography
(hexane/AcOEt = 10/1) to give 3Ad (77 mg, 81%, Z/E = 91/9) as an
oil. 1H NMR (400 MHz, CDCl3): 0.87−0.91 (m, 3H), 1.25−1.37 (m,
4H), 2.09−2.15 (m, 2H), 4.39 (dt, J = 6.0, 7.3 Hz, 1H), 4.79 (s, 2H),
6.00 (dt, J = 6.0, 1.4 Hz, 1H), 7.26−7.36 (m, 5H). Selected data of
(E)-isomer; 1.90−1.95 (m, 2H), 4.71 (s, 2H), 4.88 (dt, J = 12.8, 7.3
Hz, 1H), 6.32 (d, J = 12.8 Hz, 1H). 13C NMR (100 MHz, CDCl3):
13.9, 22.3, 23.7, 31.9, 73.5, 108.0, 127.2, 127.7, 128.4, 137.8, 144.3. IR
(neat): 3065, 3031, 2956, 2926, 2871, 1668, 1463, 1362, 1271, 1209,
1129, 1095, 1027, 732, 695 cm−1. HRMS (EI): calcd for C13H18O
[M+] 190.1358, found 190.1362.
((((1Z,3E)-5,5-Dimethylhexa-1,3-dien-1-yl)oxy)methyl)-
benzene (3Ab). To a solution of 3,3-dimethyl-1-butyne (123 mg, 1.5
mmol) in THF (1 mL) was added 9-BBN (3.0 mL of 0.5 M solution
in THF, 1.5 mmol) and stirred 1 d.18 To the solution, 2 M aq solution
of Na2CO3 (5 mL) and 2A (141 mg, 0.5 mmol, Z/E = 94/6) in THF
(1 mL), and Pd(PPh3)4 (29 mg, 0.025 mmol,) in EtOH (1 mL) were
added and the reaction mixture was stirred at 80 °C for 30 min. The
reaction mixture was cooled to rt and insoluble substance was filtered
off through a bed of Celite. The aqueous layer of the filtrate was
separated and extracted with Et2O. The combined organic extracts
were washed with water and brine, dried over Na2SO4, and solvent was
evaporated. The crude product was purified by silica gel column
chromatography (hexane/benzene = 1/1) to give 3Ab (59 mg, 61%,
In a similar manner, vinyl ethers 3Ed were obtained from 2E.
(3-(Hex-1-en-1-yloxy)prop-1-yn-1-yl)triisopropylsilane
(3Ed). Compound 3Ed (44 mg, 38%, Z/E = 68/32) was obtained as
an oil from 2E (77 mg, 0.2 mmol, Z/E = 95/5), NiCl2(dppp) (11 mg,
0.02 mmol), and n-BuMgCl (0.43 mL of 0.94 M solution in THF, 0.4
1
mmol). H NMR (400 MHz, CDCl3): 0.86−0.91 (m, 3H), 1.07 (s,
21H), 1.30−1.35 (m, 4H), 2.05−2.11 (m, 2H), 4.38 (s, 2H), 4.48 (dt,
J = 6.4, 7.4 Hz, 1H), 6.06 (d, J = 6.4 Hz, 1H). Selected data of (E)-
isomer; 1.89−1.95 (m, 2H), 4.37 (s, 2H), 4.92 (dt, J = 12.4, 7.4 Hz,
1H), 6.24 (d, J = 12.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): (Z)-
isomer; 11.1, 13.9, 18.5, 22.3, 23.6, 31.9, 59.5, 88.3, 102.6, 109.1,
143.0; (E)-isomer; 11.1, 13.9, 18.5, 22.0, 27.3, 32.6, 57.4, 88.2, 102.3,
106.3, 144.3. IR (neat): 3035, 2943, 2865, 2175, 1666, 1617, 1463,
1382, 1353, 1274, 1134, 1092, 997, 919, 883, 731, 677 cm−1. HRMS
1
1Z,3E/others = 87/13) as an oil. H NMR (400 MHz, CDCl3): 1.04
(s, 9H), 4.85 (s, 2H), 5.07 (dd, J = 6.0, 11.0 Hz, 1H), 5.60 (d, J = 15.6
Hz, 1H), 5.96 (d, J = 6.0 Hz, 1H), 6.36, (dd, J = 11.0, 15.6 Hz, 1H),
7.24−7.35 (m, 5H). 13C NMR (100 MHz, CDCl3): 29.7, 33.2, 74.0,
108.0, 117.6, 127.4, 127.9, 128.5, 137.4, 142.7, 144.0. IR (neat): 3034,
E
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(ESI-TOF): calcd for C18H34OSiNa [(M + Na)+] 317.2277, found
317.2268.
9H), 2.18 (d, J = 3.2 Hz, 1H), 5.59 (dd, J = 10.5, 0.9 Hz, 1H), 5.79
(dd, J = 8.2, 3.2 Hz, 1H), 5.99 (J = 10.5, 8.2 Hz, 1H), 7.26−7.46 (m,
5H). Selected data of (E)-isomer: 1.22 (s, 9H), 5.22−5.24 (m, 1H),
6.19 (dd, J = 15.6, 6.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): 28.2,
30.9, 72.0, 75.1, 104.8, 110.4, 125.7, 127.6, 128.5, 142.67, 142.71. IR
(neat): 3342, 2968, 2928, 2866, 2213, 1602, 1493, 1475, 1453, 1362,
1266, 1203, 1036, 1003, 854, 744, 698 cm−1. HRMS (EI): calcd for
C15H18O [M+] 214.1358, found 214.1355.
(Z)-1,3-Diphenylprop-2-en-1-ol (4Aa).31 To a solution of 3Aa
(63 mg, 0.3 mmol, Z/E = 95/5) in THF (3 mL) was added n-BuLi
(0.56 mL of 1.62 M solution in hexane, 0.9 mmol) at 0 °C under Ar
atmosphere and the reaction mixture was stirred at 0 °C for 10 min.
The reaction was quenched with water. The aqueous layer was
separated and extracted with Et2O. The combined organic extracts
were washed with brine, dried over Na2SO4, and solvent was
evaporated. The crude product was purified by silica gel column
chromatography (hexane/AcOEt = 6/1) to give 4Aa (48 mg, 86%, Z/
E = 98/2) as an oil. 1H NMR (400 MHz, CDCl3): 1.97 (brs, 1H), 5.64
(d, J = 9.2 Hz, 1H), 5.94 (dd, J = 11.4, 9.2 Hz, 1H), 6.70 (d, J = 11.4
Hz, 1H), 7.26−7.47 (m, 10H). Selected data of (E)-isomer: 5.40 (d, J
= 6.9 Hz 1H), 6.39 (dd, J = 16.0, 6.9 Hz, 1H). 13C NMR (100 MHz,
CDCl3): 70.0, 126.3, 127.5, 127.8, 128.3, 128.7, 128.8, 131.4, 133.2,
136.3, 143.1.
(Z)-8,8-Dimethyl-1-(triisopropylsilyl)nona-4-en-1,6-diyn-3-ol
(4Ec). Compound 4Ec (14 mg, 31%, Z/E = >98/2) was obtained as
an oil from 3Ec (45 mg, 0.15 mmol, Z/E = 96/4) and n-BuLi (0.27
1
mL of 1.65 M solution in hexane, 0.45 mmol). H NMR (400 MHz,
CDCl3): 1.07 (s, 21H), 1.26 (s, 9H), 2.08 (d, J = 5.0 Hz, 1H), 5.37
(dd, J = 8.3, 5.0 Hz, 1H), 5.61 (dd, J = 10.6, 0.9 Hz, 1H), 5.93 (dd, J =
10.6, 8.3 Hz, 1H). 13C NMR (100 MHz, CDCl3): 11.1, 18.6, 28.2,
30.8, 60.7, 74.2, 86.3, 105.8, 106.4, 112.0, 139.4. IR (neat): 3383, 2945,
2865, 2212, 2170, 1616, 1463, 1385, 1363, 1266, 1038, 883, 678 cm−1.
HRMS (EI): calcd for C20H34OSi [M+] 318.2379, found 318.2384.
(Z)-1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-ol (4Ca). To a
solution of 3Ca (21 mg, 0.09 mmol, Z/E = 95/5) and N,N,N′,N′-
tetramethylethylenediamine (TMEDA) (15 μL, 0.09 mmol) in THF
(1 mL) was added n-BuLi (0.45 mL of 1.60 M solution in hexane, 0.72
mmol) at −78 °C under Ar atmosphere and the reaction mixture was
warmed to rt over 10 min. The reaction was quenched with water. The
aqueous layer was separated and extracted with Et2O. The combined
organic extracts were washed with brine, dried over Na2SO4, and
solvent was evaporated. The crude product was purified by silica gel
column chromatography (hexane/AcOEt = 8/1) to give 4Ca (10 mg,
In a similar manner, (Z)-allylic alcohols 4Ba, 4Da, 4Ea, 4Ab, 4Ac,
and 4Ec were obtained from the corresponding (Z)-vinyl ethers 3Ba, 3
Da, 3Ea, 3Ab, 3Ac, and 3Ec, respectively.
(Z)-3-Phenyl-1-(o-tolyl)prop-2-en-1-ol (4Ba). Compound 4Ba
(28 mg, 54%, Z/E = >98/2) was obtained as a solid from 3Ba (52 mg,
0.23 mmol, Z/E = >98/2) and n-BuLi (0.42 mL of 1.65 M solution in
1
hexane, 0.69 mmol). Mp 84−86 °C (from AcOEt). H NMR (400
MHz, CDCl3): 1.89 (d, J = 4.1 Hz, 1H), 2.11 (s, 3H), 5.72 (dd, J = 4.1,
9.2 Hz, 1H), 5.89 (dd, J = 9.2, 11.4 Hz, 1H), 6.66 (d, J = 11.4 Hz, 1H),
7.13−7.37 (m, 8H), 7.58 (d, J = 7.3 Hz, 1H). 13C NMR (100 MHz,
CDCl3): 18.9, 67.6, 125.4, 126.3, 127.4, 127.6, 128.3, 128.7, 130.6,
131.5, 132.6, 135.6, 136.4, 141.5. IR (KBr): 3274, 3022, 2925, 1492,
1458, 1209, 1039, 997, 870, 770, 751 cm−1. Anal. Calcd for C16H16O:
C, 85.68; H, 7.19. Found: C, 85.59; H, 7.33.
1
47%, Z/E = 97/3) as an oil. H NMR (400 MHz, CDCl3): 3.82 (s,
3H), 5.60 (d, J = 9.2 Hz, 1H), 5.95 (dd, J = 11.4, 9.2 Hz, 1H), 6.67 (d
J = 11.4 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 7.26−7.38 (m, 7H), the
signal of OH proton was not clearly observed. Selected data of (E)-
isomer; 5.25 (d, J = 6.9 Hz, 1H), 6.27 (dd, J = 13.8, 6.9 Hz, 1H).32 13C
NMR (100 MHz, CDCl3): 55.3, 69.7, 114.0, 127,4, 127.6, 128.3,
128.8, 130.9, 133.4, 135.4, 136.4, 159.2. IR (neat): 3371, 3057, 3021,
2956, 2934, 2835, 1610, 1509, 1463, 1302, 1247, 1173, 1032, 831, 699
cm−1. HRMS (EI): Calcd for C16H16O2 [M+] 240.1150, found
240.1148.
(Z)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-ol (4Da). Com-
pound 4Da (50 mg, 63%, Z/E = 97/3) was obtained as an oil from
3Da (80 mg, 0.33 mmol, Z/E = 96/4) and n-BuLi (0.61 mL of 1.65 M
solution in hexane, 1.0 mmol). 1H NMR (400 MHz, CDCl3): 1.98 (d,
J = 3.2 Hz, 1H), 5.62 (dd, J = 9.2, 3.2 Hz, 1H), 5.87 (dd, J = 11.5, 9.2
Hz, 1H), 6.71 (d, J = 11.5 Hz, 1H), 7.26−7.39 (m, 9H). Selected data
of (E)-isomer; 6.33 (dd, J = 16.0, 6.8 Hz, 1H), 6.68 (d, J = 16.0 Hz,
1H). 13C NMR (100 MHz, CDCl3): 69.4, 127.6, 127.7, 128.4, 128.70,
128.73, 131.8, 132.7, 133.4, 136.1, 141.5. IR (neat): 3337, 3057, 3023,
2927, 1597, 1491, 1446, 1408, 1213, 1091, 1046, 1013, 867, 827, 801,
771, 701 cm−1. HRMS (EI): Calcd for C15H13ClO [M+] 244.0655,
found 244.0652.
(Z)-1-Phenyl-5-(triisopropylsilyl)pent-1-en-4-yn-3-ol (4Ea).
Compound 4Ea (40 mg, 56%, Z/E = >98/2) was obtained as an oil
from 3Ea (72 mg, 0.23 mmol, >98/2) and n-BuLi (0.42 mL of 1.65 M
solution in hexane, 0.69 mmol). 1H NMR (400 MHz, CDCl3): 1.01 (s,
21H), 1.97 (d, J = 5.0 Hz, 1H), 5.17 (dd, J = 5.0, 8.7 Hz, 1H), 5.76
(dd, J = 8.7, 11.0 Hz, 1H), 6.55 (d, J = 11.0 Hz, 1H), 7.22−7.30 (m,
5H). 13C NMR (100 MHz, CDCl3): 11.1, 18.6, 59.5, 86.9, 107.3,
127.6, 128.3, 129.0, 130.9, 131.2, 136.0. IR (neat): 3343, 3059, 3025,
2942, 2864, 2170, 1494, 1462, 1383, 1026, 883, 701, 677 cm−1. HRMS
(EI): Calcd for C20H30OSi [M+] 314.2066, found 314.2068.
In a similar manner, (Z)-allylic alcohol 4Ad was obtained from the
corresponding (Z)-vinyl ether 3Ad.
(Z)-1-Phenylhept-2-en-1-ol (4Ad).25 Compound 4Ad (57 mg,
81%, Z/E = 89/11) was obtained as an oil from 3Ad (70 mg, 0.37
mmol, Z/E = 91/9), TMEDA (54 μL, 0.36 mmol), and n-BuLi in
1
hexane (1.76 mL, 1.65 M solution in hexane, 2.9 mmol). H NMR
(400 MHz, CDCl3): 0.92 (t, J = 6.9 Hz, 3H), 1.30−1.43 (m, 4H), 1.81
(d, J = 2.7 Hz, 1H), 2.14−2.30 (m, 2H), 5.52−5.59 (m, 3H), 7.24−
7.80 (m, 5H). Selected data of (E)-isomer: 2.03−2.09 (m, 2H), 5.17
(d, J = 6.9 Hz, 1H), 5.67 (dd, J = 15.6, 6.9 Hz, 1H), 5.77 (dt, J = 15.6,
6.4 Hz, 1H).33 13C NMR (100 MHz, CDCl3): 13.9, 22.3, 27.4, 31.7,
69.7, 125.9, 127.4, 128.5, 131.8, 132.4, 143.7.
ASSOCIATED CONTENT
■
S
* Supporting Information
(2Z,4E)-6,6-Dimethyl-1-phenylhepta-2,4-dien-1-ol (4Ab).
Compound 4Ab (47 mg, 85%, 2Z,4E/2E,4E = 95/5) was obtained
as an oil from 3Ab (55 mg, 0.25 mmol, 1Z,3E/others = 87/13) and n-
1
Copies of H NMR and 13C NMR spectra of products. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.joc.5b00647.
1
BuLi (0.45 mL of 1.65 M solution in hexane, 0.75 mmol). H NMR
(400 MHz, CDCl3): 1.06 (s, 9H), 1.88 (brs, 1H), 5.51 (dd, J = 10.6,
9.2 Hz, 1H), 5.72 (d, J = 9.2, Hz, 1H), 5.83 (d, J = 15.6 Hz, 1H), 6.11
(dd, J = 11.0, 10.6 Hz, 1H), 6.40 (dd, J = 15.6, 11.0 Hz, 1H), 7.26−
7.42 (m, 5 H). Selected data of (E,E)-isomer: 1.02 (s, 9H), 5.96 (dd, J
= 15.6, 10.6 Hz, 1H), 6.26 (dd, J = 15.6, 11.0 Hz, 1H). 13C NMR (100
MHz, CDCl3): 29.4, 33.5, 69.9, 119.5, 125.8, 127.4, 128.5, 130.6,
130.9, 143.4, 149.0. IR (neat): 3340, 3030, 2959, 2901, 2864, 1650,
1602, 1452, 1389, 1362, 1037, 1020, 985, 950, 743, 698 cm−1. HRMS
(EI): calcd for C15H20O [M+] 216.1514, found 216.1515.
(Z)-6,6-Dimethyl-1-phenylhept-2-en-4-yn-1-ol (4Ac). Com-
pound 4Ac (21 mg, 49%, Z/E = 93/7) was obtained as an oil from
3Ac (43 mg, 0.20 mmol, Z/E = 93/7) and n-BuLi (0.36 mL of 1.65 M
solution in hexane, 0.6 mmol). 1H NMR (400 MHz, CDCl3): 1.29 (s,
AUTHOR INFORMATION
Corresponding Author
*E-mail:ukaji@staff.kanazawa-u.ac.jp
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported in part by a Grant-in-Aid
for Scientific Research from the Japan Society for the
Promotion of Science (JSPS).
F
DOI: 10.1021/acs.joc.5b00647
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(13) Stereoselective productions of (Z)-alkenes by elimination or
isomerization reactions were reported. (a) Margot, C.; Matsuda, H.;
Schlosser, M. Tetrahedron 1990, 46, 2425−2430. (b) Guillam, A.;
Maddaluno, J.; Duhamel, L. J. Chem. Soc., Chem. Commun. 1996,
1295−1296. (c) Guillam, A.; Toupet, L.; Maddaluno, J. J. Org. Chem.
1998, 63, 5110−5122. (d) Tayama, E.; Sugai, S. Synlett. 2006, 849−
852. (e) Tayama, E.; Sugai, S.; Hara, M. Tetrahedron Lett. 2006, 47,
7533−7535. (f) Pichon, N.; Harrison-Marchand, A.; Toupet, L.;
Maddaluno, J. J. Org. Chem. 2006, 71, 1892−1901. (g) Tayama, E.;
Hashimoto, R. Tetrahedron Lett. 2007, 48, 7950−7952. (h) Xu, L.;
REFERENCES
■
(1) (a) Siau, W.-Y.; Zhang, Y.; Zhao, Y. Top. Curr. Chem. 2012, 327,
33−58. (b) Oger, C.; Balas, L.; Durand, T.; Galano, J.-M. Chem. Rev.
2013, 113, 1313−1350. Recent examples of stereoselective synthesis
of (Z)-alkenes: (c) Zhuo, L.-G.; Yao, Z.-K.; Yu, Z.-X. Org. Lett. 2013,
15, 4634−4637. (d) Chen, C.; Dugan, T. R.; Brennessel, W. W.; Weix,
D. J.; Holland, P. L. J. Am. Chem. Soc. 2014, 136, 945−955. (e) Singh,
K.; Staig, S. J.; Weaver, J. D. J. Am. Chem. Soc. 2014, 136, 5275−5278.
(f) Bronner, S. M.; Herbert, M. B.; Patel, P. R.; Marx, V. M.; Grubbs,
R. H. Chem. Sci. 2014, 5, 4091−4098. (g) Koh, M. J.; Khan, R. K. M.;
Torker, S.; Yu, M.; Mikus, M. S.; Hoveyda, A. H. Nature 2015, 517,
181−186.
(2) (a) Stang, P. J. Acc. Chem. Res. 1978, 11, 107−114. (b) Stang, P.
J.; Hanack, M.; Subramanian, L. R. Synthesis 1982, 85−126.
(c) Baraznenok, I. L.; Nenajdenko, V. G.; Balenkova, E. S. Tetrahedron
2000, 56, 3077−3119. (d) Chassaing, S.; Specklin, S.; Weibel, J.-M.;
Pale, P. Tetrahedron 2012, 68, 7245−7273.
̀
Regnier, T.; Lemiegre, L.; Cardinael, P.; Combret, J.-C.; Bouillon, J.-P.;
Blanchet, J.; Rouden, J.; Harrison-Marchand, A.; Maddaluno, J. Org.
Lett. 2008, 10, 729−732. (i) Prantz, K.; Mulzer, J. Angew. Chem., Int.
Ed. 2009, 48, 5030−5033. (j) Song, Z.; Lei, Z.; Gao, L.; Wu, X.; Li, L.
Org. Lett. 2010, 12, 5298−5301. (k) Gan, Z.; Wu, Y.; Gao, L.; Sun, X.;
Lei, J.; Song, Z.; Li, L. Tetrahedron 2012, 68, 6928−6934. (l) Tayama,
E.; Toma, Y. Tetrahedron 2015, 71, 554−559 and references cited
therein.
(3) Examples of the reviews of cross-coupling reactions: (a) Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457−2483. (b) Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; John
Wiley & Sons, Inc.: New York, 2002. (c) Palladium-Catalyzed
Coupling Reactions; Molnar
Metal-Catalyzed Cross-Coupling Reactions and More; de Meijere, A.,
(14) (a) Schollkoph, U. Angew. Chem., Int. Ed. 1970, 9, 763−773.
̈
(b) Rautenstrauch, V.; Buchi, G.; Wuest, H. J. Am. Chem. Soc. 1974,
̈
̈
96, 2576−2580. (c) Marshall, J. A. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 3, pp 979−981.
(d) Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann./Recl. 1997,
1275−1281. (e) Tomooka, K. J. Syn. Org. Chem. Jpn. 2001, 59, 322−
330. (f) Giampietro, N. C.; Kampf, J. W.; Wolfe, J. P. J. Am. Chem. Soc.
2009, 131, 12556−12557. (g) Giampietro, N. C.; Wolfe, J. P. Angew.
Chem., Int. Ed. 2010, 49, 2922−2924 and references cited therein.
(15) Preference of syn-conformation of aldehydes was also pointed
out. For example: (a) Wintner, C. E. J. Chem. Educ. 1987, 64, 587−
590. (b) Deslongchamps, G.; Deslongchamps, P. Org. Biomol. Chem.
2011, 9, 5321−5333.
́
́
, A., Ed.; Wiley-VCH: Weinheim, 2013. (d)
Brase, S., Oestreich, M., Eds.; Wiley-VCH: Weinheim, 2014.
̈
(4) Cross-coupling reactions of vinyl triflates; reviews: (a) Scott, W.
J.; McMurry, J. E. Acc. Chem. Res. 1988, 21, 47−54. (b) Ritter, K.
Synthesis 1993, 735−762. (c) Cacchi, S. Pure Appl. Chem. 1996, 68,
45−52. Recent examples: (d) Scheiper, B.; Bonnekessel, M.; Krause,
H.; Furstner, A. J. Org. Chem. 2004, 69, 3943−3949. (e) Shirakawa, E.;
̈
Sato, T.; Imazaki, Y.; Kimura, T.; Hayashi, T. Chem. Commun. 2007,
4513−4515. (f) Wu, X.-F.; Neumann, H.; Beller, M. Angew. Chem., Int.
Ed. 2010, 49, 5284−5288. (g) Saini, V.; Sigman, M. S. J. Am. Chem.
Soc. 2012, 134, 11372−11375. (h) Winkler, C. K.; Clay, D.; Davies, S.;
O’Neill, P.; McDaid, P.; Debarge, S.; Steflik, J.; Karmilowicz, M.;
Wong, J. W.; Faber, K. J. Org. Chem. 2013, 78, 1525−1533.
(5) (a) Xie, H.; Shao, Y.; Becker, J. M.; Naider, F.; Gibbs, R. A. J. Org.
Chem. 2000, 65, 8552−8563. (b) Babinski, D.; Soltani, O.; Frantz, D.
E. Org. Lett. 2008, 10, 2901−2904. (c) Specklin, S.; Bertus, P.; Weibel,
J.-M.; Pale, P. J. Org. Chem. 2008, 73, 7845−7848.
(16) (a) McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24,
979−982. (b) Scott, W. J.; Pena, M. R.; Sward, K.; Stoessel, S. J.; Stille,
̃
̈
J. K. J. Org. Chem. 1985, 50, 2302−2308.
(17) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981,
11, 513−519. (b) Spivey, A. C.; Fekner, T.; Spey, S. E.; Adams, H. J.
Org. Chem. 1999, 64, 9430−9443.
(18) (a) Colberg, J. C.; Rane, A.; Vaquer, J.; Soderquist, J. A. J. Am.
Chem. Soc. 1993, 115, 6065−6071. (b) Mjalli, A. M. M.; Polisetti, D.
R.; Quada, J. C.; Yarragunta, R. R.; Andrews, R. C.; Xie, R.;
Subramanian, G. PCT Int. Appl., 2007089857.
(6) Sosa, J. R.; Tudjarian, A. A.; Minehan, T. G. Org. Lett. 2008, 10,
5091−5094.
(7) Suero, M. G.; Bayle, E. D.; Collins, B. S. L; Gaunt, M. J. J. Am.
Chem. Soc. 2013, 135, 5332−5335.
(19) Although the Heck reaction of the vinyl triflate 2A with methyl
acrylate was examined,34 the serious isomerization occurred to give a
ca. 1/1 mixture of the product.35
(8) (a) Stang, P. J.; Treptow, W. Synthesis 1980, 283−284.
(b) Martínez, A. G.; Herrera, A.; Martínez, R.; Teso, E.; García, A.;
Osío, J.; Pargada, L.; Unanue, R.; Subramanian, L. R.; Hanack, M. J.
Heterocycl. Chem. 1988, 25, 1237−1241. (c) Wright, M. E.; Pulley, S.
R. J. Org. Chem. 1989, 54, 2886−2889. (d) Sato, Y.; Watanabe, S.;
Shibasaki, M. Tetrahedron Lett. 1992, 33, 2589−2592. (e) Niwa, H.;
Watanabe, M.; Inagaki, H.; Yamada, K. Tetrahedon 1994, 50, 7385−
7400.
(9) Stang, P. J.; Mangum, M. G.; Fox, D. P.; Haak, P. J. Am. Chem.
Soc. 1974, 96, 4562−4569.
(10) The stereoselective preparation of (Z)-tris(trimethylsilyl)silyl
enol ether from propionaldehyde was reported: Boxer, M. B.;
Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 48−49.
(11) The “syn-effect” is herein defined as an effect which stabilizes the
syn-conformation against the steric hindrance at the transition state.
(12) Related representative studies on the “syn-effect”: (a) Hirata, T.;
Sasada, Y.; Ohtani, T.; Asada, T.; Kinoshita, H.; Senda, H.; Inomata, K.
Bull. Chem. Soc. Jpn. 1992, 65, 75−96. (b) Guha, S. K.; Shibayama, A.;
Abe, D.; Sakaguchi, M.; Ukaji, Y.; Inomata, K. Bull. Chem. Soc. Jpn.
2004, 77, 2147−2157. (c) Takeda, N.; Chayama, T.; Takenaka, H.;
Ukaji, Y.; Inomata, K. Chem. Lett. 2005, 34, 1140−1141. (d) Inomata,
K. J. Synth. Org. Chem. Jpn. 2009, 67, 1172−1182. (e) Horii, S.;
Ishimaru, I.; Ukaji, Y.; Inomata, K. Chem. Lett. 2011, 40, 521−523.
(f) Nakano, T.; Soeta, T.; Endo, K.; Inomata, K.; Ukaji, Y. J. Org.
Chem. 2013, 78, 12654−12661 and references cited therein.
(20) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467−4470. (b) Li, C. C.; Xie, Z. X.; Zhang, Y. D.; Chen, J.
H.; Yang, Z. J. Org. Chem. 2003, 68, 8500−8504.
(21) Oh-e, T.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58, 2201−
2208.
(22) (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. (c) Tamao, K.; Sumitani, K.; Kiso, Y.;
Zembayashi, M.; Fujioka, A.; Kodama, S.; Nakajima, I.; Minato, A.;
Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49, 1958−1969. (d) Busacca,
C. A.; Eriksson, M. C.; Fiaschi, R. Tetrahedron Lett. 1999, 40, 3101−
3104.
(23) Examples of stereospecific transformation of allylic alcohols:
(a) Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Chapter 18.1.
(b) Adam, W.; Wirth, T. Acc. Chem. Res. 1999, 32, 703−710. (c) Lebel,
H.; Marcoux, J.-F; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103,
G
DOI: 10.1021/acs.joc.5b00647
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
977−1050. (d) Olivares-Romero, J. L.; Li, Z.; Yamamoto, H. J. Am.
Chem. Soc. 2013, 135, 3411−3413.
(24) (Z)-2-En-4-yn-1-ols were useful precursors for furan synthesis:
(a) Du, X.; Chen, H.; Liu, Y. Chem.Eur. J. 2008, 14, 9495−9498.
(b) Du, X.; Song, F.; Lu, Y.; Chen, H.; Liu, Y. Tetrahedron 2009, 65,
1839−1845.
(25) Unique stereoselective synthesis of (Z)-allylic alcohols was
reported: Jeon, S.-J.; Fisher, E. L.; Carroll, P. J.; Walsh, P. J. J. Am.
Chem. Soc. 2006, 128, 9618−9619.
(26) Maulucci, N.; Izzo, I.; Bifulco, G.; Aliberti, A.; Cola, C. D.;
Comegna, D.; Gaeta, C.; Napolitano, A.; Pizza, C.; Tedesco, C.; Flot,
D.; Riccardis, F. D. Chem. Commun. 2008, 3927−3929.
(27) Kamptmann, S. B.; Bruckner, R. Eur. J. Org. Chem. 2013, 6584−
̈
6600.
(28) Collins, I.; Caldwell, J.; Fonseca, T.; Donald, A.; Bavetsias, V.;
Hunter, L.-J. K.; Garrett, M. D.; Rowlands, M. G.; Aherne, G. W.;
Davies, T. G.; Berdini, V.; Woodhead, S. J.; Davis, D.; Seavers, L. C. A.;
Wyatt, P. G.; Workman, P.; McDonald, E. Bioorg. Med. Chem. 2006,
14, 1255−1273.
(29) Mukherjee, S.; Kontokosta, D.; Patil, A.; Rallapalli, S.; Lee, D. J.
Org. Chem. 2009, 74, 9206−9209.
(30) Ding, B.; Bentrude, W. G. J. Am. Chem. Soc. 2003, 125, 3248−
3259.
(31) Banert, K.; Hagedorn, M.; Liedtke, C.; Melzer, A.; Schoffler, C.
̈
Eur. J. Org. Chem. 2000, 257−267.
(32) Arai, N.; Azuma, K.; Nii, N.; Ohkuma, T. Angew. Chem., Int. Ed.
2008, 47, 7457−7460.
(33) Wu, H.-L.; Wu, P.-Y.; Uang, B.-J. J. Org. Chem. 2007, 72, 5935−
5937.
(34) Scott, W. J.; Pefia, M. R.; Sward, K.; Stoessel, S. J.; Stille, J. K. J.
Org. Chem. 1985, 50, 2302−2308.
(35) Lebold, T. P.; Gallego, G. M.; Marth, C. J.; Sarpong, R. Org. Lett.
2012, 14, 2110−2113.
H
DOI: 10.1021/acs.joc.5b00647
J. Org. Chem. XXXX, XXX, XXX−XXX