Stereoselective one-pot synthesis of β-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions

Article abstract of DOI:10.1039/c4ob01011f

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob01011f

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Stereoselective one-pot synthesis of β-alkylsulfide
enol esters. Base-triggered rearrangement under
mild conditions†
Cite this: DOI: 10.1039/c4ob01011f
Adrián A. Heredia, Silvia M. Soria-Castro, Lydia M. Bouchet,
Gabriela Oksdath-Mansilla, Cecilia A. Barrionuevo, Daniel A. Caminos,
Fabricio R. Bisogno,* Juan E. Argüello and Alicia B. Peñéñory*
Received 15th May 2014,
Accepted 2nd July 2014
A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a
base-triggered rearrangement. This transition metal-free multicomponent approach can be performed
under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and gener-
ally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.
DOI: 10.1039/c4ob01011f
www.rsc.org/obc
side-reaction. Furthermore, the addition of alkoxides or eno-
lates to ketenes rendering enol esters displays high versatility
Introduction
Recently, multicomponent reactions have attracted a great deal en route to enantioenriched chiral products.20 Recently, an
of attention allowing the chemists to prepare molecules in a esterification-Pd-catalyzed olefin isomerization sequence was
more efficient manner, avoiding cost- and time-consuming elegantly realized furnishing enol esters, albeit with moderate
procedures, thus enabling molecular complexity, versatility, stereoselectivity.21 However, transition metal-free approaches
and robustness.1 It is well known that enol esters are useful in to synthesize stereodefined olefins are rather scarce but poss-
aldol-, Mannich-, and Povarov-type reactions.2 Besides, enol ible, as very recently demonstrated by the reaction of ketenes
esters are employed in polymerizations,3 as acylating agents with isocyanides and carboxylic acid,22a or aryl acetic acid and
under mild conditions,4 as substrates in asymmetric protona- isocyanides to prepare captodative alkenes.22b In another
tion,5 and recently in Ni-catalyzed Heck couplings,6 among approach, the Baeyer–Villiger oxidation of α,β-unsaturated
other valuable chemical reactions.7 Moreover, substituted enol carbonyl compounds by means of Oxone® can be successfully
esters are of great interest in asymmetric synthesis since they applied in the synthesis of enolesters.23a
can be stereoselectively hydrogenated.8 On the other hand,
Regarding alkylthio-substituted enolesters, just a couple of
vinyl sulfides (or enol thioethers) are useful reagents9 and reports can be found. In these procedures starting from pro-
building blocks in organic synthesis10 and several bioactive pargyl esters and allyl sulfides, the intermediacy of Au-catalysis
molecules bear this motif in their structure.11 Also, they offer a is always needed, featuring a rearrangement/Au-carbenoid for-
unique pattern of reactivity,12 behaving as a regiochemical mation/isomerization sequence,24 and leading to high yields
modulator in Diels–Alder cycloadditions13 and a stereochemi- of the target compounds.
cal controlling element in certain Al- and Tf2O-promoted cycli-
Here we present our results on the (Z)-selective multi-
component preparation of β-thioalkyl enol esters at room
zations,14 as well as Paternò–Büchi photoreactions.15
A common strategy to obtain enol esters is the addition of temperature in non-dried solvents under an air atmosphere
carboxylic acids to alkynes by means of metal-catalysis16 or without using transition metal catalysts. Also, mechanistic fea-
promoted by halogen-donors,17 although alkyne dimerization tures of the intramolecular rearrangement are discussed.
and stereo- and regioisomer formation occur in some cases.18
Also, the alkyne Cu- or Zr-catalyzed carbometalation–oxidation
sequence has been achieved19 with little diene formation as
Results and discussion
INFIQC-CONICET, Dpto. de Química Orgánica, Facultad de Ciencias Químicas,
In contrast to readily available α-haloketones, sulfur-contain-
ing substituents may easily be introduced.25 Likewise, we envi-
Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba,
Argentina. E-mail: fbisogno@fcq.unc.edu.ar, penenory@fcq.unc.edu.ar;
saged the use of a reagent enabling sulfur donation and facile
http://www.fcq.unc.edu.ar/infiqc
†Electronic supplementary information (ESI) available: Copies of NMR spectra
of compounds 3–28. See DOI: 10.1039/c4ob01011f
further S-deprotection, such as the versatile and commercially
available potassium thioacetate (KSAc, 1).26 Hence, phenacyl
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bromide (2) was reacted with 1 and the thioester 3 was readily
Next, a multicomponent version of the above discussed
formed. When t-BuOK and an electrophile such as MeI were reaction sequence was successfully accomplished furnishing
added, the expected α-methylated acetophenone was not comparable yields and clean reactions, thus, all the following
detected. Surprisingly, a rearranged product (4) was instead reactions were likewise conducted. In order to rationalize the
obtained as the sole isolated product (Scheme 1).27 Albeit formation of the enol esters in this approach, we propose a
similar basic conditions, no Eschenmoser’s sulfur extrusion stepwise mechanism (Scheme 2). First, SN2 reaction of 1 onto
products were noticed, likely due to the absence of thiophilic the α-carbon of haloketone 2 gives thioester 3, followed by
reagents.28 After a careful NMR and MS analysis, the structure base-promoted formation of enolate A. This anion may
of the enol acetate 4 (Scheme 1) was proposed. The SMe group undergo intramolecular nucleophilic addition to the thioester
was evident in the NMR spectra (δ = 2.36 ppm) displaying the carbonyl moiety30 through a 5-membered transition state B
nuclear Overhauser effect (nOe) with the olefinic H (δ = (instead of the three-membered one from Eschenmoser’s
6.36 ppm) and, interestingly, no nOe was noticed between this sulfur extrusion),31 and further elimination gives rise to the
methyl and ortho-hydrogens (Fig. 1). Indeed, vinylic hydrogen O-acyl derivative C bearing a free thiolate moiety. The latter
did show nOe with ortho-hydrogens, thus supporting the suffers alkylation, rendering the rearranged product 4 and pre-
assigned (Z)-configuration at the double bond.
venting reversion into the S-acyl precursor.
For the sake of comparison, preparation of (E)-configured
Further, a variety of commonly employed solvents were
enol acetate was attempted by C–C double bond photoisomeri- screened (polar, non-polar, protic, aprotic, basic, aqueous,
zation.29 Departing from the (Z)-4, a photostationary state with etc.; see Table 1, entries 1–10); from which DMF and DMSO
ca. 1 : 1 (Z,E) mixture was obtained. Unfortunately, isomers rendered smooth conversion at r.t. employing 1 equiv. of
were inseparable by standard chromatography methods; K2CO3 as the base (74% and 65%, entries 1 and 3, respecti-
however, MS and NMR analyses of the mixture allowed (E)-4 vely), meanwhile, MeCN did it to a lesser extent (55%,
characterization (Fig. 1).
entry 2).
In parallel, a set of bases was surveyed (see Table 1; entries
1 and 11–17). Unexpectedly, K2CO3 and K3PO4, which are
barely soluble in DMF, displayed the best performance (entries
1 and 13, respectively), whereas soluble nitrogen bases (TEA,
pyridine, DABCO; entries 15, 16 and 17, respectively) yielded
unsatisfactory results. When two equivalents of K2CO3 were
added, isolated yield improved (87%, entry 18).
It is noteworthy that the use of inexpensive inorganic bases
represents a great benefit since conjugated acids can be
removed by liquid–liquid partition and, after passing through
silica plug and solvent evaporation, a practically pure product
could be obtained (around 80% isolated yield) without the
need for further purification.
Scheme 1 Formation of β-alkylsulfide enol ester (4) and possible com-
petitive reactions. Conditions: KSAc (1, 0.44 mmol), phenacyl bromide
(2, 1 equiv.) stirred in DMF (1 mL) at r.t. then MeI (2 equiv.) and t-BuOK
(1 equiv.) were added and continued stirring for 5 h.
Fig. 1 Representative 1H- and 13C-NMR chemical shifts (in grey and
black, respectively, in ppm) of (Z)- and (E)-4. Curved arrows show found
nOe, thus indicating (Z)-configuration for the multicomponent-obtained
enol ester 4.
Scheme 2 Proposed reaction pathway for the multicomponent
reaction.32
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Table 1 Solvent and base screening for the synthesis of (Z)-enol esters
Entrya
Solvent
Base
Yield %b
1
2
3
4
5
6
7
8
DMF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaHCO3
K3PO4
t-BuOK
TEA
74
55
65
35
<1
<1
<1
<1
<1
26
53
30
79
72
15
<1
<1
87
MeCN
DMSO
EtOH
Water
DCM
Toluene
THF
1,4-Dioxane
DME
DMF
DMF
DMF
DMF
DMF
9
10
11
12
13
14
15
16
17
18c
DMF
DMF
DMF
Pyridine
DABCO
K2CO3
a Reactions performed with KSAc (0.44 mmol), phenacyl bromide
(1 equiv.), MeI (2 equiv.) and base (1 equiv.) unless otherwise stated in
1 mL of solvent at r.t. and air atmosphere for 5 h. b Quantified by GC
using the internal standard method. c 2 equiv. of the base were
employed.
Once established standard conditions as 1 equiv. of halo-
ketone, 1 equiv. of thiocarboxylate nucleophile, 2 equiv. of
K2CO3, 1 equiv. of electrophile (2 equiv. in case of MeI), DMF
as solvent, room temperature and air atmosphere, the scope of
this multicomponent reaction was studied (Scheme 3).
Different haloketones, thiocarboxylates and electrophiles were
explored. When aromatic haloketones were employed, after
5 h, products were smoothly obtained at room temperature.33
Remarkably, after aqueous work-up and passing through a
short silica pad, the products were obtained with high purity.
Isolated yields were good to excellent (69–98%), except for
compounds coming from aliphatic α-haloketones that
rendered somewhat lower yields (32–68%) probably due to
instability of the enol ester functionality during the work-up;23a
however, the stereochemistry of the obtained enol esters was
not impaired at all. Although less likely, another reason for
lower yields starting from aliphatic haloketones as compared
to aromatic ones is the lower rate of enolate formation.23b We
have performed experiments with K2CO3 (mild and small) and
t-BuOK (stronger and bulkier) affording similar results (32%
and 36%, respectively, see Scheme 3, compound 23). However,
when 4 equiv. of K2CO3 were used, a two-fold yield increase
was achieved. Since these bases are barely soluble in DMF, its
availability in solution may be the issue. As can be noticed, no
detrimental effects were exerted by the electron-donating
(82–89% yield for p-methyl and p-methoxy substituents,
respectively) or electron-withdrawing (92–98% yield for p-nitro
Scheme 3 One-pot synthesis of (Z)-enol esters. Conditions: halo-
ketone (0.44 mmol), 1 (1 equiv.), K2CO3 (2 equiv.) and electrophile
(1 equiv.); except for SMe compounds (2 equiv. of MeI were applied).
Isolated yield in parentheses. aPhenacyl chloride as the substrate and
1 equiv. of the base. bHSBz and an extra equiv. of the base were used.
cHaloketone (0.44 mmol, 1 equiv.), potassium ethyl xanthate (1 equiv.),
K2CO3 (2 equiv.) and electrophile (1 equiv.) were employed. dGram-scale
reaction (1.55 g, 3.81 mmol of isolated product). eK2CO3 (2 equiv. stan-
dard cond.), t-BuOK (1 equiv.), K2CO3 (4 equiv.) respectively.
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and p-cyano substituents, respectively) substituents in the aro-
matic ring in any of the substrates. Steric hindrance was not
an issue since ortho-substitution does not affect the reaction
yield, as shown for compounds 9 (75% yield) and 10 (95%
yield). Besides, functional groups such as nitro, cyano,
methoxy, methylen dioxo, alkyl, alkenyl, alkynyl, hydroxy,
phthalimido, ester, haloaryl, etc. are well tolerated. Regarding
the late S-alkylation, several electrophiles were tested bearing
different leaving groups (I, Br, Cl, OTs) with similar good reac-
tivity and selectivity (see the Experimental section). Moreover,
when thiobenzoic acid or potassium ethyl xanthate was
employed, acyl migration was not impaired. It must be empha-
sized that the protocol was very efficient when performed on
the gram scale (compound 20, 93% isolated yield, 1.55 g). All
these features account for the versatility and operational sim-
plicity of the here described methodology to prepare stereo-
defined compounds. To gain some insight into the reaction
mechanism, we tested the effect of the phenacyl halide, the
electrophile and the base concentration on the formation of 4.
Thus, at low conversion, there was no significant difference
by using phenacyl bromide or chloride. Assuming that with a
poorer leaving group the overall process will slow down, the
experimental results would suggest that the first SN234 is not
rate-determining (Scheme 2). The addition of 2 or 3 equiv. of
MeI did not affect the reaction rate as well, indicating that the
final S-alkylation step was not crucial. A different scenario
took place when 2 equiv. of K2CO3 were employed instead of 1
equiv. In 1 h, almost 67% of the final product was already
formed and 78% and 87% at 2 h and 5 h, respectively. Mean-
while, when 1 equiv. of the base was used, in 2 h, only 53% of
the product was obtained. These data suggest that the proton
abstraction would be the critical pathway in the reaction mech-
anism. However, deeper studies must be conducted in order to
unambiguously establish the rate-determining step.
Scheme 5 Dependency on the nucleophile in the reaction outcome.
Conditions: nucleophile (0.44 mmol), phenacyl bromide (2, 1 equiv.),
Mel (2 equiv.), K2CO3 (2 equiv.), in DMF (1 mL), stirring at R.T. for 5 h
under an air atmosphere.
1
ducted and analysed by GC and H-NMR, indicating that the
enol ester is exclusively formed in (Z)-form.
In contrast to the observed thiocarboxylate anions, with
nucleophiles such as thiourea and sodium acetate, different
reaction outcomes were noticed (Scheme 5). These findings
suggest unique reactivity pattern for the thioacid analogues35
under the selected conditions.
Conclusions
In summary, we have developed a practical one-pot stereo-
selective methodology to synthesize β-sulfur-substituted enol
esters in
a multicomponent fashion with high atom
economy.36 The described transition metal-free protocol toler-
ates air atmosphere and can be conducted at room tempera-
ture in non-dried polar aprotic solvents. Moreover, several
functional groups are perfectly compatible with this method-
ology, including electron-donating and -withdrawing substitu-
ents. Most of the obtained compounds are bench stable (for
months). The availability of several α-haloketones and alkyl
halides makes the system a powerful tool to create chemical
diversity in a straightforward manner.37
In line with the proposed mechanism (Scheme 2), when the
S-alkylation is not efficient, e.g. with (E)-β-bromostyrene as an
electrophile, the obtained product is the corresponding thio-
ester 3, supporting the reversibility of the reaction until such a
stage (Scheme 4).
The equilibrium between the charged species A and C
through a cyclic transition state accounts for the perfect
(Z)-selectivity of this methodology (Scheme 2). Since the alkyl
(pseudo)halide is present as soon as the charged species are
formed, the S-alkylation takes place readily. To rule out (Z→E)
conversion when the final S-alkylation is delayed, an experi-
ment adding MeI 5 h after the addition of the base was con-
Experimental section
General methods
1H and 13C NMR spectra were recorded at 400.16 and
100.62 MHz respectively on a Bruker 400 spectrometer, and
chemical shifts were reported in δ (ppm) relative to TMS with
CDCl3 as the solvent. GC-FID measurements were performed
on an Agilent 6890 apparatus equipped with a 30 m capillary
column of a 0.32 mm × 0.25 μm film thickness, with a 5% phe-
nylpolysiloxane phase. GC-MS analyses were performed on a
Shimadzu apparatus by electronic impact (70 eV) positive
mode employing a 30 m × 0.25 mm × 0.25 μm with a 5%
Scheme 4 The use of a poorer electrophile prevents acyl migration
rendering the corresponding thioester.
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phenylpolysiloxane phase column. HRMS were recorded on a dried over anhydrous Na2SO4. Solvent was evaporated to afford
MicroTOF Q II equipment, operated with an ESI source and pure 3 as a brownish oil (83.2 mg, quant. yield). 1H NMR
positive mode, using nitrogen as the nebulizing and drying (400.16 MHz, CDCl3, 30 °C): δ = 8.00 (d, J = 7.5 Hz, 2H), 7.60 (t,
gas and sodium formate 10 mM as the internal calibrant. J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 4.41 (s, 2H), 2.41 (s, 3H)
IR spectra were obtained on an FT-IR Avatar 360 spectrometer. ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 194.2, 193.2,
Melting points were recorded on capillary tubes in regular 135.5, 133.7, 128.7, 128.5, 36.6, 30.2 ppm. MS (EI): m/z (%) =
Electrothermal IA9100 apparatus.
152 (8) [M − CH2CO]+, 105 (100), 77 (33), 43 (19).
(Z)-2-(Methylthio)-1-phenylvinyl acetate (4)40
General experimental methods
All reactions were performed under an air atmosphere in a The typical above described procedure was followed using pot-
10 mL round-bottom flask. DMF, MeCN and DMSO were used assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
without further purification and stored over molecular sieves (2, 87.6 mg, 0.44 mmol), methyl iodide (50.4 μL, 0.88 mmol)
(4 Å). Toluene, dioxane, THF, DME, and DCM were distilled by and K2CO3 (121.4 mg, 0.88 mmol). After extraction, the crude
standard procedures and stored over molecular sieves (4 Å). residue was passed through a silica gel pad (eluting with
Ultrapure water and ethanol were used without further purifi- petroleum ether–diethyl ether = 70 : 30) to afford pure 4 as a
cation. Commercially available reagents were used without yellow solid (88.4 mg, 87%); mp 56–58 °C. 1H NMR
further purification. α-Haloketones were prepared from the (400.16 MHz, CDCl3, 30 °C): δ = 7.38–7.27 (m, 4H), 7.27–7.21
corresponding ketones following standard procedures.38 The (m, 1H), 6.35 (s, 1H), 2.36 (s, 3H), 2.30 (s, 3H) ppm. 13C NMR
identity of all products was confirmed by 1H and 13C NMR, MS (100.62 MHz, CDCl3, 30 °C): δ = 168.0, 143.9, 134.0, 128.6,
and IR.
128.0, 123.7, 116.6, 20.5, 17.0 ppm. IR (neat, cm−1) 2960, 2920,
2850, 1759, 1198, 1180, 1041, 1024, 752. MS (EI): m/z (%) = 208
(12) [M]+, 166 (100), 151 (41), 123 (12), 105 (20), 88 (17), 77
(29), 45 (14), 43 (19). HRMS (ESI+) calcd for C11H12NaO2S
General procedure for the multicomponent synthesis of
β-alkylsulfide enol esters
The reactions were carried out in a 10 mL round-bottom flask, [M + Na]+ 231.0450; found 231.0465.
equipped with a magnetic bar. The flask was charged keeping
the following addition order to ensure best yields: DMF
(1.0 mL), thiocarboxylate (0.44 mmol), α-haloketone
Procedure for gram-scale synthesis of (Z)-2-((2-iodobenzyl)-
thio)-1-phenylvinyl acetate (20)
(0.44 mmol), alkyl or benzyl halide (generally 0.44 mmol, In a 50 mL round-bottom flask, equipped with a magnetic
except for MeI, 0.88 mmol) and the base (0.88 mmol) were stirrer, DMF (10 mL), potassium thioacetate (1, 0.468 g,
added and the mixture was stirred at room temperature for 4.1 mmol), 2-chloroacetophenone (0.631 g, 4.1 mmol), 2-iodo-
5 h. Then, ethyl acetate (2 mL) and water (2 mL) were added benzyl bromide (1.242 g, 4.6 mmol) and K2CO3 (1.215 g,
and the mixture was stirred. The organic layer was separated 8.2 mmol) were added and the mixture was stirred at room
and the aqueous layer was extracted with ethyl acetate (2 × temperature for 5 h. Ethyl acetate (15 mL) and water (15 mL)
2 mL). The combined organic extract was dried over anhydrous were added and the mixture was stirred. The organic layer was
Na2SO4 and the products were isolated by filtration through a separated and the aqueous layer was extracted with ethyl
silica gel pad from the crude reaction mixture.
acetate (2 × 15 mL). The combined organic extract was dried
over anhydrous Na2SO4 and the crude residue was purified by
flash column chromatography on silica gel (eluting with
Procedure for the photoisomerization experiment
A 50 mL Schlenk tube equipped with a nitrogen gas inlet and petroleum ether–dichloromethane = 50 : 50) to afford pure 20
a magnetic stirrer was dried under vacuum, filled with N2, and as a yellow solid (1.55 g, 3.81 mmol, 93%).
then loaded with 40 mL of dried acetone. To the degassed
(Z)-2-(Methylthio)-1-(p-tolyl)vinyl acetate (5)
solvent, 76.5 mg of 4 (0.368 mmol, 9.2 mM) were added and,
while stirring, the reaction was irradiated at 300 nm. During The typical above described procedure was followed using pot-
the irradiation (12 h), the reaction progress was analyzed by assium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1-(4-
GC-MS. Finally, the solvent was evaporated and the residue tolyl)ethanone (93.4 mg, 0.44 mmol), methyl iodide (50.4 μL,
dissolved in CDCl3 for both 1H and 13C NMR analysis.
0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac-
tion, the crude residue was passed through a silica gel pad
Synthesis of S-phenacyl thioacetate (3)39
(eluting with petroleum ether–diethyl ether = 70 : 30) to afford
1
The reaction was carried out in a 10 mL round-bottom flask, pure 5 as a yellow oil (77.6 mg, 82%). H NMR (400.16 MHz,
equipped with a magnetic bar. The flask was charged with CDCl3, 30 °C): δ = 7.24 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz,
DMF (1.0 mL), potassium thioacetate (1, 50.2 mg, 0.44 mmol) 2H), 6.28 (s, 1H), 2.37 (s, 3H), 2.32 (s, 3H), 2.30 (s, 3H) ppm.
and phenacyl bromide (2, 87.3 mg, 0.44 mmol). The mixture 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.1, 144.2, 138.0,
was stirred at room temperature for 10 minutes. Ethyl acetate 131.3, 129.3, 123.7, 115.3, 21.2, 20.5, 17.0 ppm. IR (neat, cm−1
)
(2 mL) and water (2 mL) were added. The organic layer was 2966, 2926, 2837, 1757, 1196, 1174, 1039, 1024, 796, 825.
separated and the aqueous layer was extracted with ethyl MS (EI): m/z (%) = 222 (12) [M]+, 181 (11), 180 (100), 165 (50),
acetate (2 × 2 mL). The organic layers were pooled together, 137 (13), 119 (50), 91 (44), 88 (22), 65 (21), 45 (14), 43 (23).
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HRMS (ESI+) calcd for C12H15O2S [M + H]+ 223.0787, found 2-(Methylthio)-3,4-dihydronaphthalen-1-yl acetate (9)
223.0809.
The typical above described procedure was followed using potass-
ium thioacetate (1, 50.2 mg, 0.44 mmol), 2-chloro-3,4-dihydro-
(Z)-1-(p-Methoxyphenyl)-2-(methylthio)vinyl acetate (6)
naphthalen-1(2H)-one (79.5 mg, 0.44 mmol), methyl iodide
(50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After
extraction, the crude residue was purified by column chromato-
graphy on silica gel (eluting with petroleum ether–diethyl ether =
90 : 10) to afford pure 9 as a yellow solid (77.2 mg, 75%); mp
63.5–65.1 °C. 1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.19–7.10
(m, 3H), 7.04–7.02 (m, 1H), 2.97–2.92 (m, 2H), 2.67–2.63 (m, 2H),
2.35 (s, 3H), 2.30 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3,
30 °C): δ = 168.3, 141.7, 134.6, 130.7, 127.4, 127.3, 126.6, 123.9,
120.4, 28.0, 26.4, 20.5, 14.2 ppm. IR (neat, cm−1) 3024, 2931,
2854, 1758, 1187, 1049, 894, 740. MS (EI): m/z (%) = 234 (15) [M]+,
192 (100), 177 (51), 149 (19), 116 (13), 115 (63), 43 (17). HRMS
(ESI+) calcd for C13H14NaO2S [M + Na]+ 257.0607, found 257.0624.
The typical above described procedure was followed using
potassium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1-(4-
methoxyphenyl)ethanone (100.5 mg, 0.44 mmol), methyl
iodide (50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol).
After extraction, the crude residue was passed through a silica
gel pad (eluting with petroleum ether–diethyl ether = 70 : 30)
to afford pure 6 as a white solid (90.0 mg, 89%); mp. 71–73 °C.
1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.28 (d, J = 9.0 Hz,
2H), 6.84 (d, J = 9.0 Hz, 2H), 6.18 (s, 1H), 3.79 (s, 3H), 2.36 (s,
3H), 2.30 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ
= 168.1, 159.6, 144.2, 126.9, 125.3, 114.0, 114.0, 55.3, 20.5,
17.0 ppm. IR (neat, cm−1) 2980, 2926, 2850, 1755, 1200, 1178,
1039, 1257, 741, 796, 825. MS (EI): m/z (%) = 238 (18) [M]+,
196 (100), 181 (68), 135 (22), 107 (16), 92 (12), 77 (21), 43 (20).
HRMS (ESI+) calcd for C12H15O3S [M + H]+ 239.0736, found
239.0738.
(Z)-1-(2-Bromophenyl)-2-(methylthio)vinyl acetate (10)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1-(2-
bromophenyl)ethanone (121.4 mg, 0.44 mmol), methyl iodide
(50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After
extraction, the crude residue was passed through a silica gel
pad (eluting with petroleum ether–diethyl ether = 80 : 20) to
afford pure 10 as a brownish oil (119.5 mg, 95%). 1H NMR
(400.16 MHz, CDCl3, 30 °C): δ = 7.55 (dd, J = 8.0, 1.0 Hz, 1H),
7.40 (dd, J = 7.7, 1.7 Hz, 1H), 7.27 (td, J = 7.6, 1.1 Hz, 1H), 7.13
(td, J = 7.7, 1.7 Hz, 1H), 6.14 (s, 1H), 2.36 (s, 3H), 2.20 (s, 3H)
ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 167.9, 142.7,
135.9, 133.5, 130.7, 129.6, 127.3, 121.4, 121.3, 20.5, 16.9 ppm.
IR (neat, cm−1) 3455, 2915, 2854, 1758, 1187, 1018, 756. MS
(EI): m/z (%) = 288 (4) [M]+, 246 (39), 244 (39), 165 (100), 150
(61), 43 (43). HRMS (ESI+) calcd for C11H11BrNaO2S [M + H]+
286.9736, found 286.9735.
(Z)-1-(p-Cyanophenyl)-2-(methylthio)vinyl acetate (7)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1-(4-
cyanophenyl)ethanone (98.2 mg, 0.44 mmol), methyl iodide
(50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After
extraction, the crude residue was passed through a silica gel
pad (eluting with diethyl ether) to afford pure 7 as a yellow
solid (98.3 mg, 98%); mp 79–81 °C. 1H NMR (400.16 MHz,
CDCl3, 30 °C): δ = 7.58 (d, J = 8.8 Hz, 2H), 7.40 (d, J = 8.8 Hz,
2H), 6.61 (s, 1H), 2.42 (s, 3H), 2.32 (s, 3H) ppm. 13C NMR
(100.62 MHz, CDCl3, 30 °C): δ = 167.8, 141.5, 138.0, 132.4,
123.8, 121.8, 118.7, 110.9, 20.4, 17.0 ppm. IR (neat, cm−1
)
2958, 2920, 2850, 2224, 1757, 1180, 1035, 1020, 741, 795, 833.
MS (EI): m/z (%) = 233 (7) [M]+, 191 (100), 176 (30), 148 (11),
130 (15), 102 (21), 45 (13), 43 (43). HRMS (ESI+) calcd for
C12H12NO2S [M + H]+ 234.0583, found 234.0583.
(Z)-2-(Methylthio)-1,2-diphenylvinyl acetate (11)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1,2-
diphenylethanone (121 mg, 0.44 mmol), methyl iodide
(50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After
extraction, the crude residue was passed through a silica gel
pad (eluting with diethyl ether) to afford pure 11 as a light
yellow solid (63.7 mg, 51%). 1H NMR (400.16 MHz, CDCl3,
30 °C): δ = 7.30–7.23 (m, 5H), 7.11–7.06 (m, 5H), 2.29 (s, 3H),
1.86 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ =
168.8, 143.2, 135.3, 135.2, 130.6, 128.8, 128.5, 128.3, 127.9,
127.8, 127.7, 20.8, 14.8 ppm. IR (neat, cm−1) 3054, 2915, 2854,
1758, 1434, 1187, 1064, 756, 694. MS (EI): m/z (%) = 284 (10)
[M]+, 243 (17), 242 (100), 194 (14), 165 (21), 149 (60), 121 (46),
105 (22), 77 (38), 43 (17). HRMS (ESI+) calcd for C17H16NaO4S
[M + Na]+ 307.0763, found 307.0783.
(Z)-2-(Methylthio)-1-(p-nitrophenyl)vinyl acetate (8)
The typical above described procedure was followed using
potassium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-1-(4-
nitrophenyl)ethanone (105.4 mg, 0.44 mmol), methyl iodide
(50.4 μL, 0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After
extraction, the crude residue was passed through a silica gel
pad (eluting with diethyl ether) to afford pure 8 as an orange
solid (98.6 mg, 92%); mp 95–97 °C. 1H NMR (400.16 MHz,
CDCl3, 30 °C): δ = 8.14 (d, J = 9.0 Hz, 2H), 7.44 (d, J = 9.0 Hz,
2H), 6.70 (s, 1H), 2.44 (s, 3H), 2.34 (s, 3H) ppm. 13C NMR
(100.62 MHz, CDCl3, 30 °C): δ = 167.8, 146.7, 141.2, 139.8,
124.1, 123.8, 123.0, 20.4, 17.0 ppm. IR (neat, cm−1) 2926, 2850,
1757, 1107, 1585, 1508, 1196, 1180, 1036, 1020, 854, 833, 800,
748. MS (EI): m/z (%) = 253 (7) [M]+, 212 (17), 211 (100), 150
(Z)-2-(Methylthio)-1-phenylvinyl benzoate (12)41
(35), 121 (16), 104 (13), 76 (15), 43 (68). HRMS (ESI+) calcd for The typical above described procedure was followed using first
C11H12NO4S [M + H]+ 254.0482, found 254.0497.
thiobenzoic acid (51.4 μL, 0.44 mmol) with K2CO3 (60.7 mg,
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0.44 mmol) in order to in situ deprotonate it, then phenacyl (Z)-2-(Butylthio)-1-phenylvinyl acetate (15)
bromide (2, 87.3 mg, 0.44 mmol), methyl iodide (50.4 μL,
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
(2, 87.3 mg, 0.44 mmol), n-butyl bromide (95 μL, 0.88 mmol)
and K2CO3 (121.4 mg, 0.88 mmol). After extraction, the crude
residue was passed through a silica gel pad (eluting with pet-
roleum ether–diethyl ether = 70 : 30) to afford pure 15 as a
yellow oil (87.7 mg, 83%). 1H NMR (400.16 MHz, CDCl3,
30 °C): δ = 7.36–7.20 (m, 5H), 6.39 (s, 1H), 2.76 (t, J = 7.4 Hz,
2H), 2.29 (s, 3H), 1.65 (q, J = 7.4 Hz, 2H), 1.43 (sex, J = 7.4 Hz,
2H), 0.92 (t, J = 7.4 Hz, 3H) ppm. 13C NMR (100.62 MHz,
CDCl3, 30 °C): δ = 168.0, 144.1, 134.1, 128.6, 127.9, 123.7,
115.3, 33.6, 32.4, 21.7, 20.5, 13.6 ppm. IR (neat, cm−1) 2958,
2929, 2866, 1761, 1196, 1180, 1041, 1024, 752. MS (EI): m/z (%)
= 250 (10) [M]+, 208 (54), 152 (12), 134 (12), 120 (52), 105 (100),
77 (30), 45 (16), 43 (29), 41 (14). HRMS (ESI+) calcd for
C14H19O2S [M + H]+ 251.1100, found 251.1121.
0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol) were added.
After extraction, the crude residue was passed through a silica
gel pad (eluting with petroleum ether–dichloromethane =
1
50 : 50) to afford pure 12 as a brownish oil (62.4 mg, 78%). H
NMR (400.16 MHz, CDCl3, 30 °C): δ = 8.23 (d, J = 7.4 Hz, 2H),
7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.4 Hz, 2H), 7.41 (d, J = 7.2
Hz, 2H), 7.31 (t, J = 7.2 Hz, 2H), 7.25 (t, J = 7.2 Hz, 1H), 6.47 (s,
1H), 2.39 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C):
δ = 163.7, 143.9, 134.0, 133.7, 130.3, 129.1, 128.6 (2C), 128.0,
123.8, 116.8, 17.1 ppm. IR (neat, cm−1) 2956, 2918, 2850, 1757,
1194, 1178, 1041, 1024, 750. MS (EI): m/z (%) = 270 (8) [M]+,
106 (8), 105 (100), 77 (33), 51 (7). HRMS (ESI+) calcd for
C16H15O2S [M + H]+ 271.0787, found 271.0799.
(Z)-O-Ethyl-O-(2-(methylthio)-1-phenylvinyl) carbonothioate (13)
The typical above described procedure was followed using pot-
assium ethyl xanthate (70.4 mg, 0.44 mmol), phenacyl
bromide (2, 87.3 mg, 0.44 mmol), methyl iodide (50.4 μL,
0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac-
tion, the crude residue was purified by column chromato-
graphy on silica gel (eluting with ethyl acetate–pentane =
20 : 80) to afford pure 13 as a yellow oil (70.4 mg, 63%). 1H
NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.39–7.31 (m, 4H),
7.29–7.25 (m, 1H), 6.41 (s, 1H), 4.57 (q, J = 7.1 Hz, 2H), 2.40
(s, 3H), 1.44 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (100.62 MHz,
CDCl3, 30 °C): δ = 192.3, 145.9, 133.6, 128.7, 128.1, 123.9,
117.6, 70.5, 17.1, 13.7 ppm. IR (neat, cm−1) 3039, 2977, 2931,
2852, 174.3, 1604, 1280, 1187, 1002, 817, 756, 694. MS (EI): m/z
(%) = 254 (39) [M]+, 207 (46), 166 (51), 151 (81), 137 (96), 134
(100), 105 (96), 103 (28), 88 (42), 77 (97), 51 (29), 45 (33). HRMS
(ESI+) calcd for C12H14NaO2S2 [M + Na]+ 277.0327, found
277.0323.
(Z)-2-(Allylthio)-1-phenylvinyl acetate (16)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
(2, 87.3 mg, 0.44 mmol), allyl bromide (74.0 μL, 0.88 mmol)
and K2CO3 (121.4 mg, 0.88 mmol). After extraction, the crude
residue was passed through a silica gel pad (eluting with pet-
roleum ether–dichloromethane = 50 : 50) to afford pure 16 as
an orange oil (96.9 mg, 94%). 1H NMR (400.16 MHz, CDCl3,
30 °C): δ = 7.36–7.21 (m, 5H), 6.37 (s, 1H), 5.88 (ddt, J = 16.9,
10.0, 7.2 Hz, 1H), 5.25 (ddt, J = 16.9, 1.3, 0.8 Hz, 1H), 5.19 (dd,
J = 10.0, 1.3 Hz, 1H), 3.38 (dt, J = 7.2, 0.8 Hz, 2H), 2.31 (s, 3H)
ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.0, 144.6,
134.1, 133.82, 128.6, 128.0, 123.8, 118.2, 113.4, 36.3, 20.5 ppm.
IR (neat, cm−1) 2918, 2850, 1759, 1194, 1186, 1039, 1032, 750.
MS (EI): m/z (%) = 234 (13) [M]+, 192 (50), 151 (100), 123 (26),
105 (71), 87 (19), 77 (51), 51 (17), 45 (32), 43 (56), 41 (20).
HRMS (ESI+) calcd for C13H15O2S [M + H]+ 235.0787, found
235.0807.
(Z)-2-((3-(1,3-Dioxoisoindolin-2-yl)propyl)thio)-1-phenylvinyl
acetate (14)
(Z)-1-Phenyl-2-(prop-2-yn-1-ylthio)vinyl acetate (17)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide The typical above described procedure was followed using pot-
(2, 87.3 mg, 0.44 mmol), 2-(3-bromopropyl)isoindoline- assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
1,3-dione (235.9 mg, 0.88 mmol) and K2CO3 (121.4 mg, (2, 87.3 mg, 0.44 mmol), prop-2-yn-1-yl-p-methylbenzenesulfo-
0.88 mmol). After extraction, the crude residue was purified by nate (179 mg, 0.85 mmol) and K2CO3 (121.4 mg, 0.88 mmol).
column chromatography on silica gel (eluting with petroleum After extraction, the crude residue was purified by column
ether–diethyl ether = 50 : 50) to afford pure 14 as a white solid chromatography on silica gel (eluting with petroleum ether–
(112.5 mg, 69%); mp 113–115 °C. 1H NMR (400.16 MHz, dichloromethane = 50 : 50) to afford pure 17 as a brownish oil
CDCl3, 30 °C): δ = 7.85 (dd, J = 5.4, 3.1 Hz, 2H), 7.72 (dd, J = (72 mg, 71%). 1H NMR (400.16 MHz, CDCl3, 30 °C): δ =
5.4, 3.1 Hz, 2H), 7.38–7.22 (m, 5H), 6.39 (s, 1H), 3.82 (t, J = 7.1 7.46–7.17 (m, 5H), 6.58 (s, 1H), 3.46 (d, J = 2.6 Hz, 2H), 2.32 (t,
Hz, 2H), 2.81 (t, J = 7.1 Hz, 2H), 2.29 (s, 3H), 2.07 (q, J = 7.1 Hz, J = 2.6 Hz, 1H), 2.30 (s, 3H) ppm. 13C NMR (100.62 MHz,
2H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.3, CDCl3, 30 °C): δ = 167.9, 145.7, 133.9, 128.7, 128.4, 124.1,
168.0, 145.1, 134.0, 134.0, 132.1, 128.6, 128.1, 123.9, 123.3, 112.3, 79.0, 72.3, 21.2, 20.5 ppm. IR (neat, cm−1) 3292, 2960,
114.1, 36.8, 31.2, 29.4, 20.5 ppm. IR (neat, cm−1) 2955, 2931, 2920, 2860, 1761, 1198, 1180, 1041, 1026, 752. MS (EI): m/z (%)
2852, 1768, 1755, 1705, 1200, 1180, 1039, 1024, 752. HRMS = 232 (66) [M]+, 190 (100), 173 (83), 172 (28), 171 (85), 128 (38),
(ESI+) calcd for C21H20NO4S [M
382.1129.
+
H]+ 382.1108, found 115 (27), 77 (10), 45 (28), 43 (40). HRMS (ESI+) calcd for
C13H12NaO2S [M + Na]+ 255.0450, found 255.0470.
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(Z)-2-((2-Hydroxyethyl)thio)-1-phenylvinyl acetate (18)
(Z)-2-(((6-Bromobenzo[d][1,3]dioxol-5-yl)methyl)thio)-1-
phenylvinyl acetate (21)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide The typical above described procedure was followed using pot-
(2, 87.3 mg, 0.44 mmol), 2-hydroxyethyl iodide (69 μL, assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
0.88 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac- (2, 87.3 mg, 0.44 mmol), 5-bromo-6-(bromomethyl)benzo[d]-
tion, the crude residue was passed through a silica gel pad [1,3]dioxole (139.3 mg, 0.44 mmol) and K2CO3 (121.4 mg,
(eluting with petroleum ether–dichloromethane = 50 : 50) to 0.88 mmol). After extraction, the crude residue was purified by
afford pure 18 as a yellow oil (67.0 mg, 79%). 1H NMR column chromatography on silica gel (eluting with petroleum
(400.16 MHz, CDCl3, 30 °C): δ = 7.35–7.22 (m, 5H), 6.43 (s, ether–dichloromethane = 50 : 50) to afford pure 21 as a yellow
1H), 3.79 (t, J = 5.8 Hz, 2H), 2.90 (tb, J = 5.8 Hz, 2H), 2.90 (1H, solid (154 mg, 86%); mp 91–94 °C. 1H NMR (400.16 MHz,
OH, overlapped), 2.31 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 7.34–7.20 (m, 5H), 6.99 (s, 1H), 6.90 (s, 1H),
CDCl3, 30 °C): δ = 168.4, 145.4, 128.7, 128.6, 128.3, 123.9, 6.44 (s, 1H), 5.94 (s, 2H), 4.01 (s, 2H), 2.29 (s, 3H) ppm.
114.3, 62.1, 36.8, 20.6 ppm. IR (neat, cm−1) 3464, 2960, 2929, 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.0, 147.9, 147.7,
2875, 1755, 1201, 1184, 1041, 1026, 754. MS (EI): m/z (%) = 144.9, 133.9, 130.0, 128.6, 128.2, 123.9, 114.9, 113.2, 112.8,
238 (41) [M]+, 178 (26), 105 (100), 87 (57), 77 (29), 43 (70). 110.3, 102.0, 37.9, 20.6 ppm. IR (neat, cm−1) 2958, 2924, 2861,
HRMS (ESI+) calcd for C12H15O3S [M + H]+ 239.0736, found 1761, 1198, 1180, 1039, 1204, 933, 966, 752. MS (EI): m/z (%) =
239.0736.
408 (5), 406 (5) [M]+, 366 (10), 364 (10), 215 (100), 213 (97),
78 (13), 77 (16), 43 (23). HRMS (ESI+) calcd for C18H16BrO4S
[M + H]+ 406.9947, found 406.9958.
(1Z,1′Z)-(Pentane-1,5-diylbis(sulfanediyl))bis(1-phenylethene-
2,1-diyl) diacetate (19)
(Z)-2-(Benzylthio)-1-phenylvinyl acetate (22)
The typical above described procedure was followed using
3 mL of DMF with potassium thioacetate (1, 100.4 mg,
0.88 mmol), phenacyl bromide (2, 175 mg, 0.88 mmol), 1,5-
dibromopentane (59 μL, 0.44 mmol) and K2CO3 (242.9 mg,
1.76 mmol). After extraction, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum
ether–diethyl ether = 70 : 30) to afford pure 19 as a brownish
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide
(2, 87.3 mg, 0.44 mmol), benzyl bromide (52.2 μL, 0.44 mmol)
and K2CO3 (121.4 mg, 0.88 mmol). After extraction, the crude
residue was passed through a silica gel pad (eluting with pet-
roleum ether–diethyl ether = 70 : 30) to afford pure 22 as a
yellow solid (101.4 mg, 84%); mp 80–82 °C. 1H NMR
(400.16 MHz, CDCl3, 30 °C): δ = 7.35–7.27 (m, 10H), 6.34 (s,
1H), 3.97 (s, 2H), 2.29 (s, 3H) ppm. 13C NMR (100.62 MHz,
CDCl3, 30 °C): δ = 168.0, 144.6, 137.1, 134.0, 129.0, 128.8,
128.6, 128.1, 127.5, 123.8, 113.6, 37.8, 20.6 ppm. IR (neat,
cm−1) 2960, 2918, 2850, 1751, 1198, 1178, 1037, 1024, 752. MS
(EI): m/z (%) = 242 (32) [M]+, 151 (12), 105 (20), 91 (100),
77 (15), 65 (10), 43 (23). HRMS (ESI+) calcd for C17H17O2S
[M + H]+ 285.0944, found 285.0965.
1
oil (135.4 mg, 71%). H NMR (400.16 MHz, CDCl3, 30 °C): δ =
7.37–7.21 (m, 10H), 6.37 (s, 2H), 2.77 (t, J = 7.3 Hz, 4H), 2.30 (s,
6H), 1.70 (q, J = 7.3 Hz, 4H), 1.59–1.49 (m, 2H) ppm. 13C NMR
(100.62 MHz, CDCl3, 30 °C): δ = 168.0, 144.5, 134.1, 128.6,
128.0, 123.7, 114.9, 33.7, 29.9, 27.3, 20.6 ppm. IR (neat, cm−1
)
2927, 2850, 1757, 1195, 1178, 1039, 1024, 750. HRMS (ESI+)
calcd for C25H29O4S2 [M + H]+ 457.1502, found 457.1485.
(Z)-2-((2-Iodobenzyl)thio)-1-phenylvinyl acetate (20)
4-(tert-Butyl)-2-(methylthio)cyclohex-1-en-1-yl acetate (23)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), phenacyl bromide The typical above described procedure was followed using pot-
(2, 87.3 mg, 0.44 mmol), 2-iodobenzyl bromide (130.6 mg, assium thioacetate (1, 50.2 mg, 0.44 mmol), 2-bromo-4-(tert-
0.44 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac- butyl)cyclohexanone (102.5 mg, 0.44 mmol), methyl iodide
tion, the crude residue was passed through a silica gel pad (50.4 μL, 0.88 mmol) and K2CO3 (242.8 mg, 1.76 mmol). After
(eluting with petroleum ether–dichloromethane = 50 : 50) to extraction, the crude residue was purified by column chrom-
afford pure 20 as a yellow solid (168 mg, 96%); mp 103–105 °C. atography on silica gel (eluting with petroleum ether–diethyl
1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.85 (dd, J = 7.7, 1.1 ether = 95 : 5) to afford pure 23 as a colorless oil (64 mg, 60%).
Hz, 1H), 7.40 (dd, J = 7.7, 1.6 Hz, 1H), 7.35–7.31 (m, 1H), 1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 2.37–2.31 (m, 1H),
7.31–7.21 (m, 5H), 6.95 (td, J = 7.7, 1.6 Hz, 1H), 6.42 (s, 1H), 2.31–2.23 (m, 1H), 2.19 (s, 3H), 2.17 (s, 3H), 2.13–2.37 (m, 1H),
4.07 (s, 2H), 2.29 (s, 3H) ppm. 13C NMR (100.62 MHz, CDCl3, 2.13–2.04 (m, 1H), 1.91–1.83 (m, 1H), 1.49–1.41 (m, 1H),
30 °C): δ = 168.0, 145.1, 139.9, 139.9, 134.0, 130.2, 129.3, 128.6, 1.40–1.30 (m, 1H), 0.91 (s, 9H) ppm. 13C NMR (100.62 MHz,
128.6, 128.2, 123.9, 113.2, 100.6, 42.9, 20.6 ppm. IR (neat, CDCl3, 30 °C): δ = 168.7, 145.4, 119.6, 44.5, 32.3, 29.8, 29.2,
cm−1) 3057, 2926, 2850, 1759, 1198, 1180, 1041, 1024, 750. MS 27.3, 23.8, 20.8, 14.0 ppm. 1H–1H COSY NMR (CDCl3) δH/δH
(EI): m/z (%) = 410 (9) [M]+, 369 (15), 368 (85), 217 (100), 151 2.38–2.31/2.13–2.04, 2.38–2.31/1.49–1.41, 2.31–2.23/2.13–2.37,
(43), 135 (17), 107 (20), 105 (42), 90 (44), 89 (22), 77 (33), 43 2.31–2.23/1.91–1.83, 2.31–2.23/1.40–1.30, 2.13–2.37/1.91–1.83,
(56). HRMS (ESI+) calcd for C17H16IO2S [M + H]+ 410.9910, 2.13–2.37/1.40–1.30, 2.13–2.04/1.49–1.41, 1.91–1.83/1.49–1.41,
found 410.9908.
1.91–1.83/1.40–1.30, 1.49–1.41/1.40–1.30. 1H–13C HSQC NMR
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(CDCl3) δH/δC 2.38–2.31/29.8, 2.31–2.23/29.2, 2.19/14.0, 2.17/ benzyl bromide (52.2 μL, 0.44 mmol) and K2CO3 (121.4 mg,
20.8, 2.13–2.37/29.2, 2.13–2.04/29.8, 1.91–1.83/23.8, 1.49–1.41/ 0.88 mmol). After extraction, the crude residue was passed
44.5, 1.40–1.30/23.8, 0.91/27.3. 1H–13C HMBC NMR (CDCl3) through a silica gel pad (eluting with petroleum ether) to
δH/δC
2.38–2.31/145.4,
2.38–2.31/119.6,
2.38–2.31/44.5, afford pure 26 as a yellow solid (60.2 mg, 40%); mp
2.38–2.31/23.8, 2.31–2.23/145.4, 2.31–2.23/119.6, 2.31–2.23/ 93.1–93.9 °C. 1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.31 (d,
44.5, 2.31–2.23/23.8, 2.19/119.6, 2.17/168.7, 2.13–2.37/145.4, J = 4.2 Hz, 4H), 7.28–7.22 (m, 1H), 5.55 (s, 1H), 3.83 (s, 2H),
2.13–2.37/44.5, 2.13–2.37/29.8, 2.13–2.37/23.8, 2.13–2.04/145.4, 2.19 (s, 3H), 1.98 (s, 3H), 1.71–1.61 (m, 12H) ppm. 13C NMR
2.13–2.04/119.6, 2.13–2.04/44.5, 2.13–2.04/32.3, 2.13–2.04/23.8, (100.62 MHz, CDCl3, 30 °C): δ = 167.8, 155.9, 137.5, 129.0,
1.91–1.83/145.4, 1.91–1.83/32.3, 1.91–1.83/29.2, 1.49–1.41/32.3, 128.5, 127.2, 108.4, 39.7, 38.6, 37.9, 36.6, 28.1, 20.5 ppm.
1.49–1.41/27.3, 1.49–1.41/23.8, 1.40–1.30/154.4, 1.40–1.30/44.5, IR (neat, cm−1) 3471, 3070, 2915, 2854, 2669, 1743, 1187, 1033.
1.40–1.30/29.8, 1.40–1.30/29.2, 0.91/44.5, 0.91/32.3. IR (neat, MS (EI): m/z (%) = 342 (3) [M]+, 300 (51), 207 (24), 135 (55),
cm−1) 2960, 2920, 2868, 1755, 1217, 1174, 1039. MS (EI): m/z 91 (100), 79 (11), 43 (21). HRMS (ESI+) calcd for C21H26O2S
(%) = 242 (5) [M]+, 200 (100), 143 (11), 116 (31), 95 (14), 73 (15), [M + H]+ 343.1726, found 343.1728.
57 (20), 55 (13), 43 (31), 41 (19). HRMS (ESI+) calcd for
2-Oxo-2-phenylethyl acetate (27)42
C13H23O2S [M + H]+ 243.1413, found 243.1417.
The typical above described procedure was followed using
sodium acetate (36.1 mg, 0.44 mmol), phenacyl bromide (2,
87.3 mg, 0.44 mmol), methyl iodide (50.4 μL, 0.88 mmol) and
K2CO3 (121.4 mg, 0.88 mmol). After extraction, the crude
residue was passed through a silica gel pad (eluting with pet-
roleum ether) to afford pure 27 as a yellow solid (33.7 mg, 43%).
1H NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.92–7.89 (m, 2H),
7.62–7.58 (m, 1H), 7.50–7.46 (m, 2H), 5.33 (s, 2H), 2.22 (s, 3H).
13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 192.2, 170.4, 134.2,
133.9, 128.9, 127.8, 66.0, 20.6 ppm. IR (neat, cm−1) 3054, 2931,
2854, 1743, 1697, 1218, 1080, 971, 755, 694. MS (EI): m/z (%) =
118 (4) [(M − AcOH)]+, 105 (100), 77 (33), 51 (10), 43 (16).
(Z)-Ethyl 2-acetoxy-3-(benzylthio)acrylate (24)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), ethyl 3-bromo-2-
oxopropanoate (85.4 mg, 0.44 mmol), benzyl bromide (52.2 μL,
0.44 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac-
tion, the crude residue was purified by column chromato-
graphy on silica gel (eluting with dichloromethane) to afford
1
pure 24 as a yellow oil (83.6 mg, 68%). H NMR (400.16 MHz,
CDCl3, 30 °C): δ = 7.37–7.27 (m, 5H), 7.28 (s, 1H), 4.19 (q, J = 7.1
Hz, 2H), 4.02 (s, 2H), 2.22 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H) ppm.
13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.0, 160.2, 136.2,
134.2, 131.6, 128.9, 128.9, 127.9, 61.3, 37.9, 20.2, 14.1 ppm. IR
(neat, cm−1) 3054, 2977, 2931, 2854, 1758, 1712, 1234, 1187, 4-Phenylthiazol-2-amine (28)43
1095, 1018, 740, 694. MS (EI): m/z (%) = 264 (34), 173 (20), 91
The typical above described procedure was followed using
(100), 87 (16), 85 (33), 65 (11), 57 (17), 43 (40). HRMS (ESI+)
calcd for C14H16NaO4S [M + Na]+ 303.0662, found 303.0671.
thiourea (33.4 mg, 0.44 mmol), phenacyl bromide (2, 87.3 mg,
0.44 mmol), methyl iodide (50.4 μL, 0.88 mmol) and K2CO3
(121.4 mg, 0.88 mmol). After extraction, the crude residue was
passed through a silica gel pad (eluting with dichloromethane)
to afford pure 28 as a light yellow solid (47.2 mg, 61%). 1H
NMR (400.16 MHz, CDCl3, 30 °C): δ = 7.78–7.75 (m, 2H),
7.40–7.35 (m, 2H), 7.31–7.26 (m, 1H), 6.71 (s, 1H), 5.24 (s, 2H)
ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 167.4, 151.4,
134.7, 128.6, 127.7, 126.0, 102.8 ppm. IR (neat, cm−1) 3440,
3255, 3116, 3070, 2915, 2854, 1743, 1697, 694. MS (EI): m/z (%)
= 176 (100) [M]+, 134 (65), 104 (11), 90 (15), 89 (18). HRMS
(ESI+) calcd for C9H8N2S [M + H]+ 177.0481, found 177.0498.
(Z)-1-((2-Iodobenzyl)thio)oct-1-en-2-yl acetate (25)
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), 1-bromooctan-2-
one (91.0 mg, 0.44 mmol), 2-iodobenzyl bromide (130.6 mg,
0.44 mmol) and K2CO3 (121.4 mg, 0.88 mmol). After extrac-
tion, the crude residue was passed through a silica gel pad
(eluting with petroleum ether) to afford pure 25 as a colorless
1
oil (93.2 mg, 52%). H NMR (400.16 MHz, CDCl3, 30 °C): δ =
7.83 (dd, J = 7.9, 1.1 Hz, 1H), 7.37–7.28 (m, 2H), 6.94 (td, J =
7.7, 1.8 Hz, 1H), 5.56 (s, 1H), 3.92 (s, 2H), 2.22–2.18 (m, 2H),
2.14 (s, 3H), 1.4 (m, 2H), 1.30–1.25 (m, 6H), 0.87 (t, J = 6.9 Hz,
3H) ppm. 13C NMR (100.62 MHz, CDCl3, 30 °C): δ = 168.1,
150.1, 140.2, 139.8, 130.1, 128.9, 128.4, 109.6, 100.5, 42.9, 33.8,
31.5, 28.6, 26.3, 22.5, 20.7, 14.1 ppm. IR (neat, cm−1) 3054,
2977, 2931, 2854, 1758, 1712, 1234, 1187, 1095, 740, 709. MS
(EI): m/z (%) = 418 (2) [M]+, 376 (46), 217 (100), 135 (15), 90
(36), 43 (57). HRMS (ESI+) calcd for C17H23INaO2S [M + Na]+
441.0356, found 441.0375.
Acknowledgements
Authors acknowledge INFIQC-CONICET and Universidad
Nacional de Córdoba (UNC). This work was partly supported
by CONICET, SECyT-UNC and FONCyT. SMS-C, AAH, and
LMB, acknowledge CONICET for the receipt of a fellowship.
(Z)-1-((3r,5r,7r)-Adamantan-1-yl)-2-(benzylthio)vinyl acetate (26)
Notes and references
The typical above described procedure was followed using pot-
assium thioacetate (1, 50.2 mg, 0.44 mmol), 1-((3r,5r,7r)-
adamantan-1-yl)-2-bromoethanone (113.1 mg, 0.44 mmol),
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