A General and Robust Method for the Preparation of (E)- and (Z)-Stereodefined Fully Substituted Enol Tosylates: Promising Cross-Coupling Partners

Article abstract of DOI:10.1055/s-0035-1562482

A robust method for preparing (E)- and (Z)-stereodefined fully substituted enol tosylates is described. α-Substituted β-keto esters undergo (E)-selective enol tosylations using TsCl-Me₂N(CH₂)₆NMe₂ as the reagent (method A, 13 examples; 63-96%) and (Z)-selective enol tosylations using TsCl-TMEDA-LiCl as the reagent (method B, 13 examples; 62-99%). A plausible mechanism for the (E)- and (Z)-enol tosylation selectivity is proposed. A ¹H NMR monitoring experiment revealed that TsCl coupled with TMEDA formed a simple N-sulfonylammonium intermediate.

Full text of DOI:10.1055/s-0035-1562482

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–I
paper
A
Y. Ashida et al.
Paper
Synthesis
A General and Robust Method for the Preparation of (E)- and
(Z)-Stereodefined Fully Substituted Enol Tosylates: Promising
Cross-Coupling Partners
method A
Yuichiro Ashida
O–
Me2N(CH2)6NMe2
Yuka Sato
TsCl
OTs
R2
Atsushi Honda
Hidefumi Nakatsuji*
Yoo Tanabe*
R2
R1
R1
–15 °C, 1 h and rt, 1 h
CO2Me
CO2Me
O
CO2Me
13 examples; 63–96%
(E/Z = 66:34 to >98:2)
R1
R1, R2 = alkyl, aryl, OMe, Cl
Li
R2
Department of Chemistry, School of Science and Technology,
Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-
1337, Japan
OTs
O
O
TMEDA, LiCl
TsCl
CO2Me
R1
e-mail_tanabe@kwansei.ac.jp
R1
OMe
0 °C, 1 h and rt, 1 h
R2
R2
method B
13 examples; 62–99%
(E/Z = 2:>98)
Received: 10.05.2016
Accepted after revision: 04.07.2016
Published online: 15.08.2016
were successfully subjected to stereoretentive Suzuki–
Miyaura (SM) cross-couplings for the synthesis of various
pharmaceutical precursors.
DOI: 10.1055/s-0035-1562482; Art ID: ss-2016-f0329-op
As part of our ongoing studies on mild but powerful sul-
fonylations3 and silylations4 of various alcohols and carbon-
yl compounds, we previously presented a series of (E)- and
(Z)-stereocomplementary enol tosylations of not only acy-
clic ‘α-nonsubstituted’ β-keto esters (R1 = alkyl or aryl, R2 =
H), but also α-formyl esters (R1 = H, R2 = alkyl or aryl),
which were conducted by the TsCl–N-methylimidazole
(NMI)–base system (Scheme 1). TsCl–NMI–Et3N was used
for the (E)-selective reactions, whereas TsCl–NMI–LiOH
controlled the (Z)-selective reactions. Subsequent highly
(E)- and (Z)-stereoretentive cross-couplings (Negishi,5a
Sonogashira,5a SM,5b,d and Kochi–Fürstner5c) were success-
fully performed to produce the corresponding stereode-
fined α,β-unsaturated esters. The current privileged robust
and cost-effective protocols have been adopted for the syn-
thesis of elaborated natural and unnatural compounds, such
as juvenile hormones 0 and I,6a,b functionalized steroids,6c
madangamine A,6d (E)- and (Z)-zimelidines,5d etc.
Abstract A robust method for preparing (E)- and (Z)-stereodefined ful-
ly substituted enol tosylates is described. α-Substituted β-keto esters
undergo (E)-selective enol tosylations using TsCl–Me2N(CH2)6NMe2 as
the reagent (method A, 13 examples; 63–96%) and (Z)-selective enol
tosylations using TsCl–TMEDA–LiCl as the reagent (method B, 13 exam-
ples; 62–99%). A plausible mechanism for the (E)- and (Z)-enol tosyla-
tion selectivity is proposed. A 1H NMR monitoring experiment revealed
that TsCl coupled with TMEDA formed a simple N-sulfonylammonium
intermediate.
Key words stereocomplementary, stereodefined olefin, enol tosylate,
tosyl chloride, TMEDA, diamine, NMR monitoring
Acyclic (E)- and (Z)-enol sulfonates (tosylates, triflates,
etc.) and phosphonates derived from readily accessible β-
keto esters are well-recognized synthetic precursors of ste-
reodefined olefins produced using stereoretentive cross-
coupling methodology.1 A number of biologically active
compounds and functionally useful materials comprise
these acyclic stereodefined olefins. Among several enol sul-
fonates, (E)- and (Z)-enol tosylates are particularly advanta-
geous due to their stability, cost-effectiveness, and suffi-
cient reactivity from the standpoints of fine and natural
product synthesis and process chemistry. Representative
examples of the synthetic utility of acyclic (E)- and (Z)-ste-
reodefined enol sulfonates are addressed as follows.
Very recently, the Merck process group reported a syn-
thesis
of
chiral
β-cyclopropyl-α-methyldihydrocin-
namates.7 This notable pharmacophore was synthesized via
(E)- and (Z)-stereocontrolled enol tosylations using a β-cy-
clopropyl-α-methyl-β-keto ester; the (E)-isomer was pre-
pared using Ts2O–NaHMDS at –78 °C, whereas the (Z)-iso-
mer was prepared using the same reagent at room tem-
perature.
The Merck process group disclosed a characteristic pro-
tocol for (E)- and (Z)-stereocomplementary enol tosylations
of specific α- or γ-nitrogen-substituted β-keto esters using
respective Ts2O–M(Li or Na)HMDS and Ts2O–amine re-
agents.2 The obtained stereodefined enol tosylate scaffolds
On the other hand, our group recently reported (E)- and
(Z)-stereocomplementary enol phosphorylations of ‘α-sub-
stituted’ β-keto esters as
a
relevant approach;8 the
(PhO)2POCl–NMI–LiOt-Bu reagent being used for preparing
(E)-isomers, whereas the (PhO)2POCl–NMI–KOt-Bu–18-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

B
Y. Ashida et al.
Paper
Synthesis
TsCl,
NMI, Et3N
Ar
Ar
Ar–M
Pd or Fe cat.
OTs
R2
R2
CO2Me
OTs
R1
R1
O
(E)-selective
enol tosylations
CO2Me
CO2Me
R1
Ar–M
Pd or Fe cat.
R2
CO2Me
CO2Me
R1 = alkyl, aryl R2 = H
R1 = H, R2 = alkyl, aryl
R1
R1
TsCl, NMI,
LiOH
several
cross-couplings
R2
R2
(Z)-selective
enol tosylations
Scheme 1 (E)- and (Z)-Stereocomplementary synthesis of (E)- and (Z)-α,β-unsaturated esters utilizing stereoselective enol tosylations and stereore-
tentive cross-couplings
crown-6 reagent was employed for the (Z)-isomers. The ap-
plication of this protocol to (E)- and (Z)-stereoretentive SM
and Negishi cross-couplings produced the corresponding
stereodefined all-carbon (fully) substituted α,β-unsaturated
esters. This approach, however, has several conspicuous
drawbacks compared with the reaction sequence via the
enol tosylations; these include: (i) harsher reaction condi-
tions (DMF, reflux) for the SM cross-coupling due to the
poor reactivity of the (PhO)2PO- group, (ii) lower atom
economy of the (PhO)2PO- group, (iii) a considerably more
tedious separation procedure of (E)- and (Z)-enol phospho-
nates by column chromatography due to their similar Rf val-
ues, and (iv) stoichiometric amounts of expensive and high-
ly toxic 18-crown-6 are required.
This background prompted us to search for a more effi-
cient enol tosylation method using less reactive ‘α-carbon-
substituted’ β-keto esters 1 (R1, R2 = alkyl and/or aryl). We
present herein a substrate-general and robust method for
(E)- and (Z)-stereocomplementary enol tosylations of 1 us-
ing the TsCl–Me2N(CH2)6NMe2 reagent for (E)-enol tosylates
(E)-2 and the TsCl–TMEDA–LiCl reagent for (Z)-enol to-
sylates (Z)-2.9
Our initial attempt was intentionally guided using ste-
reocongested methyl 2-butyl-3-oxooctanoate (1a)10 as a
much less reactive substrate probe (Table 1). As anticipated,
the reported NMI-mediated method6 resulted in almost no
reaction (Table 1, entries 1 and 2). Notably, the use of inex-
pensive Me2N(CH2)nNMe2 (n = 3 or 6)11 alone afforded posi-
Table 1 (E)- and (Z)-Stereocomplementary Enol Tosylation of 1a Using TsCl–N,N,N′,N′-Tetramethyldiamine Base with or without Additive
TsCl (1.5 equiv), base (1.5 equiv)
additive (1.5 equiv)
O
OTs
OTs
CO2Me
Bu
CO2Me
or
H11C5
H11C5
H11C5
solvent
0–5 °C, 1 h and 20–25 °C
Bu
CO2Me
(E)-2a
Bu
(Z)-2a
1a
Entry
Base
Et3N
Additive
Solvent
Yield (%)a
E/Za
1
2
NMI
C6H5Cl
THF
NR
–
–
KOt-Bu
NMI, 18-crown-6
trace
17
3
TMEDA
–
MeCN
MeCN
MeCN
MeCN
97/3
4
Me2N(CH2)3NMe2
Me2N(CH2)6NMe2
Me2N(CH2)6NMe2
Me2N(CH2)6NMe2
TMEDA
–
48
93/7
94/6
98/2
–
5
–
44
6
–
74,b 60b,c
traceb
93c
7
–
EtOAc, DMF, THF, toluene
8
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
–
MeCN
2/>98
2/>98
2/>98
2/>98
27/73
–
9
TMEDA
EtOAc
38
10
11
12
13
14
TMEDA
toluene
MeCN
50
Me2N(CH2)3NMe2
Me2N(CH2)6NMe2
Et3N
40
MeCN
66
MeCN
trace (33)d
11 (43)d
LHMDS
toluene/MeCN (1:1)
36/64
a Determined by 1H NMR of the crude products. NR = no reaction.
b Reaction conditions: –15 °C, 1 h and 20–25 °C, 1 h.
c Yield of isolated product.
d α-Chlorinated by-product of 1a; see the experimental section.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

C
Y. Ashida et al.
Paper
Synthesis
tive results for the (E)-selective reaction to give the desired
enol tosylate (E)-2a (Table 1, entries 3–5). When using
TMEDA , less reactive alcohols are prone to resist the tosyla-
tion reaction concomitant with the side production of
TsNMe2 via Hoffmann degradation of TMEDA with TsCl.3c
This information led us to use Me2N(CH2)nNMe2 (n = 3 or 6).
Optimization of the temperature and time (–15 °C, 1 h
and 20–25 °C, 1 h) allowed for improvement in both the
yield (74%) and the stereoselectivity (E/Z = >98:2) (Table 1,
entry 6). The best solvent was MeCN; EtOAc, DMF, THF, and
toluene were apparently inferior (Table 1, entry 7). On the
other hand, the (Z)-selective reaction proceeded smoothly
to give (Z)-2a in good yield (93%) with excellent selectivity
(E/Z = 2:>98) using the available combined reagent, TsCl–
TMEDA–LiCl under very accessible conditions (0–5 °C, 1 h
and 20–25 °C, 1 h) (Table 1, entry 8). The use of TMEDA pro-
duced satisfactory results eventually compared with
Me2N(CH2)nNMe2 (n = 3 or 6) (Table 1, entries 8–12). EtOAc
and toluene gave moderate yields and the best solvent was
MeCN (Table 1, entries 8–10).12
TsCl (1.5 equiv)
Me2N(CH2)6NMe2 (1.5 equiv)
OTs
method A
OMe
H11C5
MeCN
CO2Me
(Z)-2l
90% (E/Z = 31:69)
O
–15 °C, 1 h and 20–25 °C, 1 h
CO2Me
H11C5
OMe
1l
OTs
TsCl (1.5 equiv), TMEDA (1.5 equiv)
LiCl (1.5 equiv)
CO2Me
H11C5
method B
method A
MeCN
OMe
(E)-2l
91% (E/Z = >98:2)
0–5 °C, 1 h and 20–25 °C, 1 h
TsCl (1.5 equiv)
Me2N(CH2)6NMe2 (1.5 equiv)
OTs
Cl
H11C5
MeCN
CO2Me
(Z)-2m
82% (E/Z = 5:95)
–15 °C, 1 h and 20–25 °C, 1 h
O
CO2Me
H11C5
Cl
1m
OTs
TsCl (1.5 equiv), TMEDA (1.5 equiv)
LiCl (1.5 equiv)
CO2Me
H11C5
toluene
0–5 °C, 1 h and 20–25 °C 1 h
method B
Cl
(E)-2m
62% (E/Z = 91:9)
In the two cases using Et3N and LHMDS, considerable
amounts of the α-chlorinated by-product (methyl 2-butyl-
2-chloro-3-oxooctanoate) of 1a were detected (Table 1, en-
tries 13 and 14).13 The occurrence of this side reaction is as-
cribed to the fact that TsCl cannot be sufficiently activated
(vide infra, Scheme 4). Accordingly, the present method is
obviously more efficient than the NMI-mediated reactions.
With the successful outcome in hand, Table 2 lists the
substrate generality using a variety of α-substituted β-keto
esters 1 [method A for (E)-isomers (E)-2 and method B for
(Z)-isomers (Z)-2]. The salient features are as follows. (i) All
reactions were completed under the identical optimized
conditions in good to excellent yield. (ii) With regard to ste-
reoselectivity, almost all cases produced positive and excel-
lent results (>94:6 for method A and 2:>98 for method B).
(iii) As a limitation, the (E)-selectivity using α,β-diaryl sub-
strates (E)-1j and (E)-1k was moderate (Table 2, entries 19
and 21). This tendency coincides with discussions in the
precedent report5d which ascribes to the nature of intrinsi-
cally more stable (Z)-isomers. Fortunately, these crude
products could be enriched to the pure (E)-products, (E)-2j
and (E)-2k, by recrystallization. It should be noted that all
of these stereodefined (E)- and (Z)-enol tosylates 2 are nov-
el compounds.
Scheme 2 (E)- and (Z)-Stereocomplementary enol tosylations of α-he-
teroatom-substituted β-keto esters
The (E)- and (Z)-stereochemistry was determined on
the basis of the hitherto reported study.5 In addition, NOE
measurements exemplified by enol tosylates (E)-2d and
(Z)-2d, determined unambiguous assignments (Figure 1).
OTs
OTs
CO2Me
CO2Me
NOE
NOE
(E)-2d
(Z)-2d
Figure 1 NOE measurement of (Z)-2d
A plausible mechanism for the successful emergence of
(E)- and (Z)-enol tosylation selectivity is illustrated in
Scheme 3.14 The (E)-selective reaction with highly reactive
intermediate I proceeds via a non-chelation pathway to give
(E)-2; Me2N(CH2)6NMe2 plays two different roles as a base
reagent and as
a partner of I through equilibrium.
Me2N(CH2)6NMe2 aids (E)-enolate formation through di-
pole–dipole repulsive interactions between the oxy anion
and ester function. In clear contrast, the (Z)-selective reac-
tion proceeds via a chelation mechanism to give (Z)-2; the
Li cation facilitates (Z)-enolate formation.
Next, an extension to α-heteroatom (MeO and Cl) sub-
stituted β-keto esters 1l and 1m was examined (Scheme 2).
Gratifyingly, the reactions proceeded smoothly to give the
desired functionalized products (E)-, (Z)-2l and (E)-, (Z)-
2m. (Note: due to the sequence rule, reverse configurations
are indicated.)
As depicted in Scheme 4 and Figure 2, a careful 1H NMR
monitoring experiment (–40 °C in CD3CN) revealed that
TsCl coupled with TMEDA formed a simple N-sulfonylam-
monium intermediate IA rather than a plausible N,N′-che-
late-type intermediate IB (see a brief discussion in the Sup-
porting Information). The apparent downfield chemical
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

D
Y. Ashida et al.
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Synthesis
Table 2 (E)- and (Z)-Stereocomplementary Enol Tosylation of 1 Using TsCl–Me2N(CH2)6NMe2 (Method A) and TsCl–TMEDA–LiCl (Method B)
method A
OTs
TsCl (1.5 equiv), Me2N(CH2)6NMe2 (1.5 equiv)
R2
R1
MeCN
O
–15 °C, 1 h and 20–25 °C, 1 h
CO2Me
(E)-2
CO2Me
R1
TsCl (1.5 equiv), TMEDA (1.5 equiv)
LiCl (1.5 equiv)
R2
OTs
CO2Me
1
R1
MeCN
method B
R2
(Z)-2
0–5 °C, 1 h and 20–25 °C, 1 h
Entry
R1
Me
R2
Substrate
Method
Product
Yield (%)
E/Za
1
n-Bu
n-Bu
i-Pr
i-Pr
Me
1b
1b
1c
1c
1d
1d
1e
1e
A
B
A
B
A
B
A
B
(E)-2b
(Z)-2b
(E)-2c
(Z)-2c
(E)-2d
(Z)-2d
(E)-2e
(Z)-2e
81
95
84
85
74
94
77
85
97/3
2
Me
2/>98
>98/2
2/>98
>98/2
2/>98
>98/2
2/>98
3b
4c
5
Me
Me
n-pentyl
n-pentyl
Cl(CH2)4
Cl(CH2)4
6
Me
7
Me
8
Me
9
1f
1f
A
B
(E)-2f
(Z)-2f
63
91
95/5
8
7
7
10
2/>98
8
11
12
13
14
15
16
17
18
n-pentyl
n-pentyl
Ph
n-Bu
n-Bu
Me
1a
1a
1g
1g
1h
1h
1i
A
B
A
B
A
B
A
B
(E)-2a
(Z)-2a
(E)-2g
(Z)-2g
(E)-2h
(Z)-2h
(E)-2i
74
93
89
90
80
89
94
96
>98/2
2/>98
94/6
Ph
Me
2/>98
94/6
p-MeC6H4
p-MeC6H4
p-ClC6H4
p-ClC6H4
Me
Me
2/>98
>98/2
2/>98
Me
Me
1i
(Z)-2i
74/26
(>98/2)
19
20
21
22
Ph
Ph
Ph
Ph
Ph
1j
A
B
A
B
(E)-2j
(Z)-2j
(E)-2k
(Z)-2k
96 (49)d
93
Ph
1j
2/>98
66/34
(>98/2)
p-MeOC6H4
p-MeOC6H4
1k
1k
95 (26)d
99
2/>98
a Determined by 1H NMR of the crude products.
b TsCl (3.0 equiv) and Me2N(CH2)6NMe2 (3.0 equiv) were used.
c TsCl (3.0 equiv), TMEDA (3.0 equiv), and LiCl (3.0 equiv) were used.
d Yield after recrystallization; see the experimental section for details.
shifts of the tosyl moiety in IA are related to the higher re-
activity of the present system. Based on the result, IA is
likely to function as the key active species.15,16
In conclusion, we have developed a general and conve-
nient protocol for (E)- and (Z)-stereocomplementary enol
tosylations of α-substituted β-keto esters using the TsCl–
Me2N(CH2)6NMe2 reagent (method A) and the TsCl–
TMEDA–LiCl reagent (method B), respectively. A plausible
mechanism for the successful (E)- and (Z)-enol tosylation
selectivity is proposed. A H NMR monitoring experiment
1
revealed that TsCl coupled with TMEDA formed a simple N-
sulfonylammonium intermediate. Further investigation on
various (E)- and (Z)-stereoretentive cross-couplings using
the obtained fully substituted enol tosylates, a pair of latent
and potential scaffolds, is now under progress in our labo-
ratory.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

E
Y. Ashida et al.
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Synthesis
(0 ppm) for H NMR. For 13C NMR, chemical shifts are reported rela-
tive to CDCl3 (77.00 ppm) as an internal reference. Mass spectra were
measured on a JEOL JMS-T100LC spectrometer. β-Keto esters 1a, 1b,
1c, 1d, 1e, 1g, 1h, 1i, and 1j are known compounds, whilst 1f, 1k, and
1m are new compounds and were prepared by Ti-Claisen condensa-
tion or alkylation in a single step and on gram scale. Detailed proce-
dures and physical and spectroscopic data are described in the Sup-
porting Information.
1
O–
OTs
Me2N(CH2)6NMe2
I
I
R2
CO2Me
OTs
R2
R1
R1
O
CO2Me
Li
CO2Me
R1
O
O
LiCl
R2
CO2Me
R1
R1
OMe
R2
R2
Scheme 3 A mechanistic investigation into the (E)- and (Z)-stereose-
lective enol tosylations
(E)-Enol Tosylation of β-Keto Esters (Method A); General Proce-
dure
TsCl (286 mg, 1.50 mmol) in MeCN (1.0 mL) was added to a stirred
suspension of a β-keto ester (1.00 mmol) and Me2N(CH2)6NMe2 (258
mg, 1.50 mmol) in MeCN (1.0 mL) at –15 °C, and the mixture was
stirred at the same temperature for 1 h and at 20–25 °C for 1 h. H2O (a
large amount) was added to the mixture, which was extracted twice
with EtOAc. The combined organic phase was washed with H2O, sat.
aq NaHCO3 solution and brine, then dried (Na2SO4), and concentrated.
The obtained crude product was purified by SiO2 column chromatog-
raphy (hexane/EtOAc = 50:1 to 15:1) to give the desired product.
TsCl + Me2N(CH2)2NMe2
Me Me
Me Me
N+
O
Me
Me
O
N
N
S
Me
S
Me
+
O
O
Cl–
N
Cl–
Me Me
IB
IA
sulfonylammonium intermediate
(Z)-Enol Tosylations of β-Keto Esters (Method B); General Proce-
dure
Scheme 4 Formation of sulfonylammonium intermediate I monitored
by 1H NMR measurements at –40 °C
TsCl (286 mg, 1.50 mmol) in MeCN (1.0 mL) was added to a stirred
suspension of a β-keto ester (1.00 mmol), TMEDA (258 mg, 1.50
mmol), and LiCl (64 mg, 1.50 mmol) in MeCN (1.0 mL) at 0–5 °C, and
the mixture was stirred at the same temperature for 1 h and at 20–
25 °C for 1 h. H2O (a large amount) was added to the mixture, which
was extracted twice with EtOAc. The combined organic phase was
washed with H2O, sat. aq NaHCO3 solution and brine, then dried
(Na2SO4), and concentrated. The obtained crude product was purified
by SiO2 column chromatography (hexane/EtOAc = 50:1 to 10:1) to
give the desired product.
(E)-2a (Method A); Typical Gram-Scale Procedure
TsCl (4.29 g, 22.5 mmol) in MeCN (15 mL) was added to a stirred solu-
tion of methyl 2-butyl-3-oxooctanoate (1a) (3.42 g, 15.0 mmol) and
Me2N(CH2)6NMe2 (4.85 mL, 22.5 mmol) in MeCN (15.0 mL) at –15 °C,
and the mixture was stirred at the same temperature for 1 h and at
20–25 °C for 1 h. H2O was added to the mixture, which was extracted
twice with EtOAc. The combined organic phase was washed with
H2O, sat. aq NaHCO3 solution and brine, then dried (Na2SO4), and con-
centrated. The obtained crude product was purified by SiO2 column
chromatography (hexane/EtOAc = 15:1) to give the desired product
(E)-2a (3.46 g, 60%, E/Z = >98/2).
Figure 2 A 1H NMR monitoring study using a 1:1 mixture of TsCl and
TMEDA at –40 °C
(Z)-2a (Method B); Typical Gram-Scale Procedure
TsCl (4.29 g, 22.5 mmol) in MeCN (15 mL) was added to a stirred sus-
pension of methyl 2-butyl-3-oxooctanoate (1a) (3.42 g, 15.0 mmol),
TMEDA (3.35 mL, 22.5 mmol), and LiCl (954 mg, 22.5 mmol) in MeCN
(15 mL) at 0–5 °C, and the mixture was stirred at the same tempera-
ture for 1 h and at 20–25 °C for 1 h. H2O was added to the mixture,
which was extracted twice with EtOAc. The combined organic phase
was washed with H2O, sat. aq NaHCO3 solution and brine, then dried
(Na2SO4), and concentrated. The obtained crude product was purified
by SiO2 column chromatography (hexane/EtOAc = 10:1) to give the
desired product (Z)-2a (4.74 g, 82%, E/Z = 2/>98).
All reactions were carried out in oven-dried glassware under an ar-
gon atmosphere. Flash column chromatography was performed with
silica gel (Merck 60, 230–400 mesh ASTM). TLC analysis was per-
formed on 0.25 mm silica gel Merck 60 F254 plates. Melting points
were determined on a hot stage microscope apparatus (AS ONE, ATM-
01) and are uncorrected. IR spectra were recorded on a JASCO FT/IR-
5300 spectrophotometer. NMR spectra were recorded on a JEOL DEL-
TA 300 or JEOLRESONANCE ECX-500 spectrometer, operating at 300
MHz or 500 MHz for 1H NMR and 75 MHz or 125 MHz for 13C NMR.
Chemical shifts (δ) (ppm) in CDCl3 are reported downfield from TMS
Methyl (E)-2-Butyl-3-(tosyloxy)oct-2-enoate [(E)-2a]
Yield: 282 mg (74%); colorless oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

F
Y. Ashida et al.
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Synthesis
IR (neat): 2956, 2931, 2872, 1720, 1644, 1598, 1435, 1374 cm–1
.
Colorless oil.
IR (neat): 2958, 2873, 1727, 1467, 1436, 1314, 1244, 1208 cm–1
1H NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.2 Hz, 3 H), 0.91 (t, J = 7.2
Hz, 3 H), 1.20–1.43 (m, 8 H), 1.62 (quin, J = 7.2 Hz, 2 H), 2.04–2.25 (m,
2 H), 2.58 (dt, J = 7.2 Hz, Jgem = 17.9 Hz, 1 H), 2.72 (dt, J = 7.2 Hz, Jgem
17.5 Hz, 1 H), 3.81 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 13.7 (2 C), 22.3, 22.4, 23.5, 26.1, 30.9,
36.3, 37.9, 53.4, 75.9, 168.0, 200.8.
HRMS (ESI): m/z [M + Na]+ calcd for C13H23ClO3Na: 285.1233; found:
285.1247.
1H NMR (300 MHz, CDCl3): δ = 0.81 (t, J = 7.2 Hz, 3 H), 0.82 (t, J = 7.2
Hz, 3 H), 1.10–1.27 (m, 8 H), 1.43 (quin, J = 7.2 Hz, 2 H), 2.18 (t, J = 7.2
Hz, 2 H), 2.46 (s, 3 H), 2.60 (t, J = 7.6 Hz, 2 H), 3.74 (s, 3 H), 7.31–7.40
(m, 2 H), 7.80–7.88 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.6, 13.8, 21.5, 22.1, 22.4, 26.7, 27.6,
30.2, 31.0, 32.0, 51.8, 125.8, 127.7 (2 C), 129.8 (2 C), 134.2, 145.2,
156.6, 168.1.
.
=
HRMS (ESI): m/z [M + Na]+ calcd for C20H30O5SNa: 405.1712; found:
405.1710.
Methyl (Z)-2-Butyl-3-(tosyloxy)oct-2-enoate [(Z)-2a]
Methyl (E)-2-Isopropyl-3-(tosyloxy)but-2-enoate [(E)-2c]
Yield: 356 mg (93%); colorless oil.
IR (neat): 2959, 2872, 1728, 1655, 1599, 1458, 1375, 1310 cm–1
Yield: 131 mg (84%) (0.5 mmol scale); pale yellow oil.
IR (neat): 1968, 1725, 1667, 1598, 1435, 1372, 1276, 1193 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.94 (d, J = 6.9 Hz, 6 H), 2.04 (s, 3 H),
2.46 (s, 3 H), 2.85 (sept, J = 6.9 Hz, 1 H), 3.75 (s, 3 H), 7.33–7.39 (m, 2
H), 7.80–7.87 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 18.9, 20.3 (2 C), 21.5, 27.2, 51.5, 127.8
(2 C), 129.8 (2 C), 131.4, 133.8, 145.3, 147.0, 167.9.
HRMS (ESI): m/z [M + Na]+ calcd for C15H20O5SNa: 335.0929; found:
.
.
1H NMR (300 MHz, CDCl3): δ = 0.78–0.95 (m, 6 H), 1.12–1.53 (m, 10
H), 2.25 (t, J = 7.6 Hz, 2 H), 2.31 (t, J = 7.6 Hz, 2 H), 2.45 (s, 3 H), 3.59 (s,
3 H), 7.29–7.38 (m, 2 H), 7.75–7.85 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.7 (2 C), 21.5, 22.17, 22.22, 26.2, 29.0,
30.8, 30.9, 31.1, 51.7, 125.0, 127.9 (2 C), 129.6 (2 C), 134.0, 144.9,
151.2, 167.1.
335.0928.
Methyl (E)-2-Butyl-3-(tosyloxy)but-2-enoate [(E)-2b]
Yield: 263 mg (81%); colorless oil.
IR (neat): 2956, 1719, 1650, 1598, 1435, 1372, 1279, 1088 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.81 (t, J = 6.9 Hz, 3 H), 1.10–1.26 (m, 4
H), 2.17 (t, J = 6.9 Hz, 2 H), 2.27 (s, 3 H), 2.46 (s, 3 H), 3.74 (s, 3 H),
7.33–7.42 (m, 2 H), 7.80–7.88 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.6, 19.4, 21.6, 22.5, 27.4, 30.3, 51.8,
125.4, 127.8 (2 C), 129.9 (2 C), 134.1, 145.3, 153.4, 168.0.
HRMS (ESI): m/z [M + Na]+ calcd for C16H22O5SNa: 349.1086; found:
349.1097.
Methyl (Z)-2-Isopropyl-3-(tosyloxy)but-2-enoate [(Z)-2c]
.
Yield: 133 mg (85%) (0.5 mmol scale); pale yellow oil.
IR (neat): 2929, 2859, 1718, 1621, 1442, 1254, 1200, 1089 cm–1
1H NMR (300 MHz, CDCl3): δ = 1.08 (d, J = 6.9 Hz, 6 H), 2.05 (s, 3 H),
2.45 (s, 3 H), 2.62 (sept, J = 6.9 Hz, 1 H), 3.55 (s, 3 H), 7.30–7.38 (m, 2
H), 7.76–7.82 (m, 2 H).
.
13C NMR (75 MHz, CDCl3): δ = 16.8, 20.7 (2 C), 21.6, 28.7, 51.4, 127.9
(2 C), 129.6 (2 C), 130.7, 133.8, 143.9, 145.0, 166.5.
Methyl (E)-2-Methyl-3-(tosyloxy)oct-2-enoate [(E)-2d]
Methyl (Z)-2-Butyl-3-(tosyloxy)but-2-enoate [(Z)-2b]
Yield: 253 mg (74%); colorless oil.
IR (neat): 2954, 1720, 1650, 1598, 1435, 1373, 1276, 1191 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.83 (t, J = 7.2 Hz, 3 H), 1.10–1.26 (m, 4
H), 1.43 (quin, J = 7.2 Hz, 2 H), 1.73 (s, 3 H), 2.47 (s, 3 H), 2.68 (t, J = 7.2
Hz, 2 H), 3.74 (s, 3 H), 7.33–7.40 (m, 2 H), 7.81–7.88 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (2 C), 21.5, 22.1, 26.6, 31.1, 32.0,
51.8, 120.8, 127.7 (2 C), 129.8 (2 C), 134.1, 145.3, 158.6, 167.8.
HRMS (ESI): m/z [M + Na]+ calcd for C17H24O5SNa: 363.1242; found:
Yield: 312 mg (95%); colorless oil.
IR (neat): 2956, 1724, 1598, 1370, 1306, 1196, 1164, 1090 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 7.2 Hz, 3 H), 1.21–1.42 (m, 4
H), 2.02 (s, 3 H), 2.23 (t, J = 7.2 Hz, 2 H), 2.44 (s, 3 H), 3.57 (s, 3 H),
7.30–7.39 (m, 2 H), 7.75–7.84 (m, 2 H).
.
.
13C NMR (75 MHz, CDCl3): δ = 13.5, 17.7, 21.4, 22.0, 28.9, 30.2, 51.5,
124.7, 127.8 (2 C), 129.5 (2 C), 133.5, 145.0, 147.3, 166.6.
363.1246.
Methyl 2-Butyl-2-chloro-3-oxooctanoate (By-Product; Figure 3)
Methyl (Z)-2-Methyl-3-(tosyloxy)oct-2-enoate [(Z)-2d]
O
O
Yield: 319 mg (94%); colorless oil.
H11C5
OMe
IR (neat): 2954, 2863, 1715, 1598, 1434, 1372, 1306, 1180 cm–1
.
Bu
Cl
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 7.2 Hz, 3 H), 1.11–1.32 (m, 4
H), 1.38–1.52 (m, 2 H), 1.89 (s, 3 H), 2.32 (t, J = 7.2 Hz, 2 H), 2.45 (s, 3
H), 3.60 (s, 3 H), 7.30–7.39 (m, 2 H), 7.76–7.87 (m, 2 H).
Figure 3 Structure of by-product
13C NMR (75 MHz, CDCl3): δ = 13.7, 14.8, 21.5, 22.1, 25.9, 31.0, 31.3,
51.7, 119.7, 127.9 (2 C), 129.6 (2 C), 134.1, 145.0, 151.9, 167.0.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

G
Y. Ashida et al.
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Synthesis
Methyl (E)-7-Chloro-2-methyl-3-(tosyloxy)hept-2-enoate [(E)-2e]
13C NMR (75 MHz, CDCl3): δ = 14.8, 21.5, 51.8, 123.1, 127.6 (2 C),
127.8 (2 C), 128.7 (2 C), 129.2, 129.3 (2 C), 133.4, 133.8, 144.8, 151.6,
168.4.
HRMS (ESI): m/z [M + Na]+ calcd for C18H18O5SNa: 369.0773; found:
369.0758.
Yield: 276 mg (77%); pale yellow oil.
IR (neat): 2952, 1719, 1648, 1435, 1371, 1278, 1191, 1177 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.57–1.72 (m, 4 H), 1.73 (s, 3 H), 2.47
(s, 3 H), 2.75 (t, J = 6.5 Hz, 2 H), 3.46 (t, J = 6.5 Hz, 2 H), 3.75 (s, 3 H),
7.34–7.41 (m, 2 H), 7.81–7.88 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.7, 21.4, 24.0, 31.1, 31.5, 44.2, 51.8,
121.3, 127.6 (2 C), 129.8 (2 C), 133.7, 145.4, 157.4, 167.5.
Methyl (Z)-2-Methyl-3-phenyl-3-(tosyloxy)prop-2-enoate [(Z)-2g]
Yield: 312 mg (90%); colorless oil.
IR (neat): 2952, 1715, 1598, 1434, 1374, 1308, 1255, 1002 cm–1
.
HRMS (ESI): m/z [M + Na]+ calcd for C16H21O5ClSNa: 383.0696; found:
383.0678.
1H NMR (300 MHz, CDCl3): δ = 1.94 (s, 3 H), 2.35 (s, 3 H), 3.81 (s, 3 H),
7.04–7.10 (m, 2 H), 7.14–7.30 (m, 5 H), 7.38–7.45 (m, 2 H).
Methyl (Z)-7-Chloro-2-methyl-3-(tosyloxy)hept-2-enoate [(Z)-2e]
13C NMR (75 MHz, CDCl3): δ = 15.6, 21.1, 51.8, 120.9, 127.5 (2 C),
127.6 (2 C), 128.9 (2 C), 129.0 (2 C), 129.1, 131.8, 133.7, 144.3, 147.9,
166.9.
Yield: 306 mg (85%); pale yellow oil.
IR (neat): 2952, 1720, 1598, 1435, 1371, 1307, 1108, 1086 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.58–1.83 (m, 4 H), 1.90 (s, 3 H), 2.38
(t, J = 6.9 Hz, 2 H), 2.45 (s, 3 H), 3.46 (t, J = 6.5 Hz, 2 H), 3.59 (s, 3 H),
7.32–7.38 (m, 2 H), 7.79–7.85 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.6, 21.3, 23.3, 30.2, 31.3, 44.0, 51.5,
120.1, 127.6 (2 C), 129.5 (2 C), 133.5, 145.0, 150.5, 166.5.
Methyl (E)-2-Methyl-3-(4-tolyl)-3-(tosyloxy)prop-2-enoate [(E)-
2h]
Yield: 864 mg (80%) (3 mmol scale); colorless oil.
IR (neat): 1717, 1651, 1597, 1435, 1371, 1240, 1190 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.03 (s, 3 H), 2.29 (s, 3 H), 2.43 (m, 3
H), 3.53 (s, 3 H), 6.92–6.97 (m, 2 H), 7.01–7.06 (m, 2 H), 7.08–7.14 (m,
2 H), 7.43–7.49 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 14.6, 21.1, 21.3, 51.6, 122.1, 127.7 (2
C), 128.2 (2 C), 128.5 (2 C), 129.2 (2 C), 130.3, 133.7, 139.2, 144.6,
151.7, 168.4.
Methyl (E)-2-(Non-8-en-1-yl)-3-(tosyloxy)trideca-2,12-dienoate
[(E)-2f]
Yield: 327 mg (63%); colorless oil.
IR (neat): 2927, 2854, 1720, 1640, 1598, 1376, 1192, 1178 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.08–1.49 (m, 22 H), 1.96–2.08 (m, 4
H), 2.17 (t, J = 7.6 Hz, 2 H), 2.46 (s, 3 H), 2.60 (t, J = 7.6 Hz, 2 H), 3.74 (s,
3 H), 4.89–5.05 (m, 4 H), 5.81 (ddt, J = 6.9, 10.3, 16.9 Hz, 2 H), 7.33–
7.39 (m, 2 H), 7.81–7.87 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.6, 27.1, 27.9, 28.1, 28.83, 28.85,
28.91, 28.98, 29.02 (2 C), 29.09, 29.2, 29.3, 32.2, 33.7 (2 C), 51.8, 114.1
(2 C), 125.8, 127.8 (2 C), 129.8 (2 C), 134.3, 139.1 (2 C), 145.2, 156.7,
168.1.
HRMS (ESI): m/z [M + Na]+ calcd for C19H20O5SNa: 383.0929; found:
383.0926.
Methyl (Z)-2-Methyl-3-(4-tolyl)-3-(tosyloxy)prop-2-enoate [(Z)-
2h]
Yield: 970 mg (89%) (3 mmol scale); colorless crystals; mp 94–96 °C.
IR (neat): 1726, 1645, 1425, 1369, 1258, 1179, 1134 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.92 (s, 3 H), 2.30 (s, 3 H), 2.36 (s, 3 H),
HRMS (ESI): m/z [M + Na]+ calcd for C30H46O5SNa: 541.2964; found:
3.78 (s, 3 H), 6.95–7.01 (m, 2 H), 7.04–7.13 (m, 4 H), 7.39–7.46 (m, 2
H).
541.2944.
Methyl (Z)-2-(Non-8-en-1-yl)-3-(tosyloxy)trideca-2,12-dienoate
[(Z)-2f]
13C NMR (125 MHz, CDCl3): δ = 15.9, 21.2, 21.4, 52.0, 120.6, 127.9 (2
C), 128.5 (2 C), 129.1 (2 C), 129.2 (2 C), 129.3, 134.2, 140.0, 144.3,
148.5, 167.3.
Yield: 474 mg (91%); colorless oil.
IR (neat): 2926, 2855, 1726, 1640, 1599, 1376, 1194, 1180 cm–1
.
Methyl (E)-2-Methyl-3-(4-chlorophenyl)-3-(tosyloxy)prop-2-
enoate [(E)-2i]
1H NMR (300 MHz, CDCl3): δ = 1.15–1.52 (m, 22 H), 2.03 (q, J = 6.9 Hz,
4 H), 2.24 (t, J = 7.6 Hz, 2 H), 2.30 (t, J = 7.6 Hz, 2 H), 2.45 (s, 3 H), 3.59
(s, 3 H), 4.89–5.04 (m, 4 H), 5.80 (ddt, J = 6.9, 10.3, 16.9 Hz, 1 H), 5.81
(ddt, J = 6.9, 10.3, 16.9 Hz, 1 H), 7.31–7.37 (m, 2 H), 7.78–7.85 (m, 2
H).
Yield: 982 mg (94%) (3 mmol scale); colorless crystals; mp 71–73 °C.
IR (neat): 1722, 1651, 1593, 1487, 1371, 1244, 1190 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.06 (s, 3 H), 2.40 (s, 3 H), 3.54 (s, 3 H),
13C NMR (75 MHz, CDCl3): δ = 21.5, 26.5, 28.6, 28.70, 28.75, 28.82,
28.91, 28.93, 28.98, 29.0 (2 C), 29.16, 29.18, 30.9, 33.6 (2 C), 51.6,
114.1 (2 C), 125.0, 127.9 (2 C), 129.5 (2 C), 134.0, 138.86, 138.89,
144.9, 151.1, 167.0.
7.04–7.12 (m, 4 H), 7.13–7.17 (m, 2 H), 7.42–7.48 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 14.7, 21.5, 52.0, 123.5, 127.8 (2 C),
127.9 (2 C), 129.4 (2 C), 130.2 (2 C), 131.8, 133.7, 135.3, 145.2, 150.5,
168.0.
HRMS (ESI): m/z [M + Na]+ calcd for C18H17O5ClSNa: 403.0383; found:
403.0377.
Methyl (E)-2-Methyl-3-phenyl-3-(tosyloxy)prop-2-enoate [(E)-2g]
Yield: 309 mg (89%); colorless crystals; mp 68–69 °C.
IR (neat): 1714, 1657, 1599, 1439, 1364, 1322, 1191, 1176 cm–1
1H NMR (300 MHz, CDCl3): δ = 2.06 (s, 3 H), 2.36 (s, 3 H), 3.51 (s, 3 H),
.
Methyl (Z)-2-Methyl-3-(4-chlorophenyl)-3-(tosyloxy)prop-2-
enoate [(Z)-2i]
Yield: 1.01 g (96%) (3 mmol scale); colorless oil.
7.07–7.27 (m, 7 H), 7.41–7.46 (m, 2 H).
IR (neat): 1732, 1595, 1489, 1435, 1314, 1248, 1161 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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Synthesis
1H NMR (400 MHz, CDCl3): δ = 1.92 (s, 3 H), 2.38 (s, 3 H), 3.80 (s, 3 H),
Methyl (Z)-2-Methoxy-3-(tosyloxy)oct-2-enoate [(Z)-2l]
7.09–7.18 (m, 4 H), 7.13–7.15 (m, 2 H), 7.41–7.46 (m, 2 H).
Yield: 322 mg (90%); pale yellow oil.
13C NMR (100 MHz, CDCl3): δ = 15.8, 21.4, 52.1, 121.7, 127.8 (2 C),
128.2 (2 C), 129.2 (2 C), 129.5, 130.6 (2 C), 133.9, 135.5, 144.8, 146.9,
166.9.
IR (neat): 2935, 1725, 1642, 1598, 1371, 1297, 1179, 1024 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.85 (t, J = 7.2 Hz, 3 H), 1.14–1.34 (m, 4
H), 1.50 (quin, J = 7.6 Hz, 2 H), 2.45 (s, 3 H), 2.71 (t, J = 7.6 Hz, 2 H),
3.42 (s, 3 H), 3.81 (s, 3 H), 7.30–7.37 (m, 2 H), 7.83–7.91 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.7, 21.5, 22.1, 26.2, 30.6, 30.9, 52.0,
60.0, 127.8 (2 C), 129.5 (2 C), 134.4, 139.4, 144.9, 151.2, 163.9.
Methyl (E)-2,3-Diphenyl-3-(tosyloxy)prop-2-enoate [(E)-2j]
Yield: 3.91 g (96%, E/Z = 74:26), 2.02 g (49%, E/Z = >98:2 after recrys-
tallization from EtOAc) (10 mmol scale); colorless crystals; mp 149–
152 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C17H24O6SNa: 379.1191; found:
379.1199.
IR (neat): 1717, 1651, 1595, 1445, 1368, 1302, 1273, 1215, 1175 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.35 (s, 3 H), 3.50 (s, 3 H), 6.94–7.03
(m, 2 H), 7.17–7.50 (m, 12 H).
13C NMR (125 MHz, CDCl3): δ = 21.5, 52.3, 127.3, 127.7 (2 C), 128.0 (2
C), 128.1 (2 C), 128.2, 128.6 (2 C), 129.0 (2 C), 129.2 (2 C), 129.8, 132.2,
133.2, 133.4, 144.6, 149.1, 167.6.
Methyl (E)-2-Methoxy-3-(tosyloxy)oct-2-enoate [(E)-2l]
Yield: 325 mg (91%); pale yellow oil.
IR (neat): 2934, 2862, 1725, 1598, 1436, 1376, 1294, 1208 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 7.6 Hz, 3 H), 1.11–1.30 (m, 4
H), 1.43 (quin, J = 7.6 Hz, 2 H), 2.40 (t, J = 7.6 Hz, 2 H), 2.46 (s, 3 H),
3.60 (s, 3 H), 3.68 (s, 3 H), 7.30–7.40 (m, 2 H), 7.77–7.87 (m, 2 H).
.
HRMS (ESI): m/z [M + Na]+ calcd for C23H20O5SNa: 431.0929; found:
431.0907.
13C NMR (75 MHz, CDCl3): δ = 13.8, 21.6, 22.1, 25.7, 29.1, 31.0, 51.9,
60.2, 128.1 (2 C), 129.6 (2 C), 133.5, 141.1, 145.3, 150.0, 162.2.
Methyl (Z)-2,3-Diphenyl-3-(tosyloxy)prop-2-enoate [(Z)-2j]
Yield: 381 mg (93%); colorless crystals; mp 111–112 °C.
IR (neat): 1726, 1448, 1431, 1369, 1253, 1209, 1174, 1053 cm–1
1H NMR (300 MHz, CDCl3): δ = 2.38 (s, 3 H), 3.80 (s, 3 H), 6.96–7.06
(m, 4 H), 7.08–7.22 (m, 8 H), 7.47–7.53 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.5, 52.5, 126.9, 127.0, 127.7 (2 C),
128.0 (2 C), 128.1, 128.3 (2 C), 129.3 (2 C), 129.7 (2 C), 129.9 (2 C),
131.9, 133.1, 134.0, 144.7, 148.5, 166.5.
Methyl (Z)-2-Chloro-3-(tosyloxy)oct-2-enoate [(Z)-2m]
.
Yield: 296 mg (82%); colorless oil.
IR (neat): 2959, 2866, 1724, 1615, 1384, 1262, 1180, 1047 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.86 (t, J = 6.9 Hz, 3 H), 1.20–1.33 (m, 4
H), 1.50–1.62 (m, 2 H), 2.47 (s, 3 H), 2.92 (t, J = 7.6 Hz, 2 H), 3.82 (s, 3
H), 7.34–7.40 (m, 2 H), 7.86–7.93 (m, 2 H).
.
13C NMR (75 MHz, CDCl3): δ = 13.7, 21.5, 22.0, 26.5, 30.9, 32.5, 53.0,
116.2, 128.0 (2 C), 129.8 (2 C), 133.6, 145.7, 159.6, 162.7.
HRMS (ESI): m/z [M + Na]+ calcd for C16H21ClO5SNa: 383.0696; found:
Methyl (E)-3-(4-Methoxyphenyl)-2-phenyl-3-(tosyloxy)acrylate
[(E)-2k]
383.0711.
Yield: 4.17 g (95%, E/Z = 66:34), 1.14 g (26%, E/Z = >98:2, after recrys-
tallization from toluene) (10 mmol scale); colorless crystals; mp 116–
118 °C.
Methyl (E)-2-Chloro-3-(tosyloxy)oct-2-enoate [(E)-2m]
IR (neat): 1720, 1633, 1605, 1506, 1435, 1375, 1206 cm–1
.
Yield: 261 mg (62%); colorless oil.
IR (neat): 2955, 2862, 1734, 1622, 1597, 1435, 1382, 1256 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.35 (s, 3 H), 3.53 (s, 3 H), 3.82 (s, 3 H),
6.73–6.83 (m, 2 H), 6.94–7.07 (m, 2 H), 7.14–7.30 (m, 5 H), 7.34–7.44
(m, 4 H).
13C NMR (125 MHz, CDCl3): δ = 21.5, 52.3, 55.2, 113.4 (2 C), 125.6,
126.1, 127.8 (2 C), 128.0 (3 C), 129.0 (2 C), 129.2 (2 C), 130.2 (2 C),
132.5, 133.4, 144.5, 149.3, 160.7, 167.8.
1H NMR (300 MHz, CDCl3): δ = 0.85 (t, J = 6.9 Hz, 3 H), 1.16–1.30 (m, 4
H), 1.42–1.56 (m, 2 H), 2.47 (s, 3 H), 2.53 (t, J = 7.6 Hz, 2 H), 3.70 (s, 3
H), 7.33–7.41 (m, 2 H), 7.80–7.89 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.7, 21.6, 22.1, 25.3, 30.9, 32.3, 52.9,
118.4, 128.2 (2 C), 129.8 (2 C), 133.3, 145.7, 155.1, 161.6.
HRMS (ESI): m/z [M + Na]+ calcd for C24H22O6SNa: 461.1035; found:
461.1030.
Acknowledgment
Methyl (Z)-3-(4-Methoxyphenyl)-2-phenyl-3-(tosyloxy)acrylate
[(Z)-2k]
This research was partially supported by Grant-in-Aids for Scientific
Research on Basic Areas (B) ‘18350056’, Priority Areas (A) ‘17035087’
and ‘18037068’, and Exploratory Research ‘17655045’ from the Min-
istry of Education, Culture, Sports, Science and Technology (MEXT).
Yield: 13.04 g (99%) (30 mmol scale); colorless crystals; mp 123–
125 °C.
IR (neat): 1726, 1636, 1608, 1433, 1317, 1252, 1192 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.40 (s, 3 H), 3.72 (s, 3 H), 3.77 (s, 3 H),
6.47–7.56 (m, 2 H), 6.90–7.00 (m, 2 H), 7.06–7.24 (m, 7 H), 7.48–7.59
(m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 21.5, 52.3, 55.1, 113.2 (2 C), 124.1,
125.6, 127.9, 128.0 (2 C), 128.3 (2 C), 129.2 (2 C), 129.7 (2 C), 131.5 (2
C), 133.5, 134.2, 144.6, 148.8, 160.2, 166.6.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562482.
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Synthesis
References
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I