Synthesis of disubstituted dithioethers: Tert -butoxide promoted elimination/ring opening of 1,3-dithianes followed by palladium-catalyzed C-S bond formation

Article abstract of DOI:10.1021/acs.joc.5b00547

We report the tandem base-promoted elimination/ring-opening of 2-benzyl-1,3-dithianes with subsequent cross coupling of the pendent thiol with a range of aryl bromides. A simple Pd(OAc)₂/Xantphos catalyst system affects this new reaction and is

Full text of DOI:10.1021/acs.joc.5b00547

Article
pubs.acs.org/joc
Synthesis of Disubstituted Dithioethers: tert-Butoxide Promoted
Elimination/Ring Opening of 1,3-Dithianes Followed by Palladium-
Catalyzed C−S Bond Formation
Nissa Abidi and Jason R. Schmink*
Department of Chemistry, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, Pennsylvania 19010, United States
S
* Supporting Information
ABSTRACT: We report the tandem base-promoted elimination/ring-opening of 2-benzyl-1,3-dithianes with subsequent cross
coupling of the pendent thiol with a range of aryl bromides. A simple Pd(OAc)2/Xantphos catalyst system affects this new
reaction and is compatible with a wide range of functional groups, including heteroaromatic coupling partners. The
transformation proceeds in good to excellent yields (69−99%) and exhibits strong stereoselectivity, forming the E-alkene as the
major diastereomer. This new methodology provides access to nonsymmetric propylene styryl/aryl dithioethers, a previously
undisclosed motif.
to the significant advances of transition-metal catalyzed
chemistry,29−31 there has been extensive development of robust
and reliable routes to aryl sulfides mediated by transition metal
catalysts.32,33 Continued improvements to this important
methodology have expanded the scope of aryl electrophiles to
include bromide, chloride, and triflate electrophiles. Palladium-
and nickel-based catalysts have been used most widely, though
alternative catalysts, such as copper,34 have seen recent
adaptation as they offer the advantages of lower price and
toxicity. Aside from traditional cross-coupling approaches,
methods have been developed that couple disulfides with, for
example, aryl iodides,35 aryl boronic acids,36 and aryl siloxanes37
in the presence of a stoichiometric reducing agent and copper
catalyst. Recently, noncatalytic examples have illustrated that
sulfenyl chlorides react with either magnesium-38 or zinc-
based39 nucleophiles to access this important substrate class.
Thus, the value of the aryl sulfide motif continues to stimulate
significant interest, including the development of alternative
approaches to this compound class.
INTRODUCTION
■
Vinyl sulfides are useful synthetic building blocks for organic
chemists. For example, these motifs can be used as Michael
acceptors,1 as surrogates for enol ethers,2−5 and in cyclo-
addition reactions.6−8 Additionally, vinyl sulfides see utility as a
pseudohalide electrophile in transition metal C−C bond
forming reactions, predominantly with boron nucleophiles.9−12
Vinyl sulfides are found in natural products that exhibit
desirable biological activities,13−15 making this motif an
attractive target for the development of new synthetic
approaches (Figure 1). Over the years, a range of routes for
accessing vinyl sulfides have been developed, though
nucleophilic substitution via an addition−elimination pathway
is most prevalent. Either vinyl halide electrophiles or the
corresponding alkyne directly can be reacted with sulfur
nucleophiles. Although these conditions generally require
harsh conditions and are limited to a narrow range of activated
electrophiles, recent strides employing transition metal catalysts
have allowed for milder reaction conditions to be employed,
accessing vinyl thioethers from a range of vinyl or acetylene
electrophiles.16−23 This is significant as it affords the synthetic
chemist a route to this important functional class even when
unactivated alkynes or vinyl bromides are necessary, namely,
ones that cannot stabilize the strong carbanionic character that
typifies the addition/elimination pathway.
In 2014, our group40 and the Walsh41 group independently
disclosed that 2-aryl-1,3-dithianes act as competent, polarity-
reversed transmetalation reagents in palladium-catalyzed cross-
coupling reactions. During our initial investigations, we applied
our cross-coupling conditions to 2-benzyl-1,3-dithiane (5) to
probe the ability of the one-carbon homologue to undergo
cross coupling (Scheme 1). Though none of the expected
cross-coupling product was observed, we found that the starting
materials were consumed completely and converted cleanly to a
new product (6).
Similarly, aryl sulfides are an important motif found in a
range of small molecule therapeutics that show promise for
treating, for example, inflammatory and immune diseases,24
Parkinson’s and Alzheimer’s Diseases,25 HIV,26 and breast
cancer.27 In 1980, Migita and co-workers first reported the
palladium-catalyzed cross-coupling of aryl iodides with various
sulfur nucleophiles to afford aryl thioethers.28 In large part due
Received: March 11, 2015
© XXXX American Chemical Society
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Figure 1. Examples of biologically interesting vinyl and aryl thioethers.
Scheme 1. Discovery of Tandem Elimination/Ring-Opening/C−S Cross Coupling
a
Table 1. Reaction Optimization
b
entry
ligand
base
solvent
cat. %
t (°C)
yield (%)
1
NiXantphos
Xantphos
dppp
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
LiHMDS
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
CPME
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1.0
2.5
1.0
2.5
1.0
2.5
80
80
80
80
80
80
80
80
60
60
25
25
80
100
100
0
2
3
4
dppf
56
0
5
DPEPhos
XPhos
6
trace
100
100
23
20
0
7
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
8
CPME
9
CPME
10
11
12
13
CPME
CPME
CPME
0
CPME
0
a
Reactions run on a 1.0 mmol scale, 1:1 aryl bromide/benzyl dithiane, 0.2 M in the indicated solvent. Three equiv of base was used. Pd(OAc)2 and
b
bidentate ligands dosed in a 1:1 ratio at the indicated catalyst loading. For monodentate XPhos, 5% of the ligand (2:1 L/Pd) was dosed. Yield
extrapolated from GC area % of the peak for 6.
This tandem base-promoted elimination with ring opening
followed by palladium-catalyzed C−S bond formation affords a
previously undisclosed chemical motif. Over the past decades,
there have been a handful of reports detailing the ring
B
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a
Scheme 2. Reactivity of Aryl and Herteroaryl Bromides
a
Reactions run on a 1.0 mmol scale at 0.2 M. Yield refers to yield of E:Z mixture in the bracketed ratio that is otherwise analytically pure. E:Z ratio
determined by the uncorrected relative peak integrations of the GC trace, which were confirmed by the relative integrations for the vinyl protons in
b
1
the H NMR. Run on a 5.0 mmol scale.
opening42 or the ring expansion43,44 of 1,3-dithiolanes to afford
vinyl sulfides. Additionally, we could find a single example
reporting the base-mediated ring opening of 1,3-dithianes45
when adjacent to an ether.46 Though no examples of the
resulting propylene-linked styryl-aryl dithioether have been
reported, dithioethers are known to be excellent chelators of
aqueous mercury ions.47 Taken together with the prevalence of
both aryl thioethers and vinyl thioethers in biologically active
small molecules, we felt this new transformation warranted
further examination. The wide availability of commercially
available aryl bromides should allow for a diverse range of
interesting new substrates to be synthesized, and we sought to
explore the scope and limitations of this new reaction.
palladium and Xantphos ligand with no observed loss of
reactivity (Table 1, entry 8). However, as we began our
substrate screening, 2.5% catalyst loading gave far more
consistent results and complete conversion of starting materials.
As such, we opted to continue with 2.5% catalyst loading.
With these optimized conditions in hand, we began to screen
the chemistry against a wide variety of aryl bromides.
Electronics of the aryl bromide seemed to have little impact
upon the observed reactivity of the system. Both electron-rich
and -poor aryl bromides reacted cleanly with no loss of catalytic
activity. Reacting 5 with 4-bromoanisole led to the isolation of
6 in 92% yield, and 10 was isolated in 85% yield when
employing the even more electron-rich 4-bromo-N,N-dimethy-
laniline. Similarly, examples of the electron withdrawing ketone,
ester, nitrile, and trifluoromethyl groups at the para position of
aryl bromides led to high yields for 8 (86%), 12 (77%), 14
(83%), and 19 (99%), respectively. A limitation was met when
running the reaction with 4-nitrobromobenzene (22). In this
case, only decomposition was observed, and the reaction went
without detection of any of the desired product. Attempts to
lower the reaction temperature did not improve the outcome.
The reaction tolerated the presence of aryl chlorides, and 16
was isolated in 94% yield with the carbon−chlorine bond still
intact. Repeated attempts were made to react either aryl triflate
(e.g., 24) or aryl chloride (e.g., 23) electrophiles as alternatives
to the aryl bromide in this cross coupling, though they were
met without success.49 Pyridine- and pyrimidine-derived aryl
bromides were well tolerated, providing 21 (from 3-
bromopyridine) and 15 (from 5-bromopyrimidine) in 92 and
80% yields, respectively. A notable current limitation of this
chemistry is the inability of the unprotected 5-bromoindole
(25) to engage. Finally, substitution at the ortho position was
well tolerated (7, 11, 17), though the methodology met its
steric limitations when subjecting 2-bromomesitylene 26 to the
reaction conditions, as no cross-coupling product was
observed.50 Across the substrates examined, the E:Z ratio was
RESULTS AND DISCUSSION
■
Though our initial discovery led to isolation of the title
compound in quantitative yield, we sought to screen for
improved reaction conditions before probing the limitations of
this chemistry. Of special importance is to examine the impact
of lower palladium and ligand loading and to search out
alternative ligands to replace the relatively expensive
NiXantphos.
We were pleased to find that substituting the less expensive
Xantphos led to no observed loss of reactivity.48 Dppf also
provided some of the desired transformation but ultimately
proved to be less capable than Xantphos. Other bisphosphine
ligands, as well as the monodentate XPhos, showed little to no
conversion to product. The less toxic CPME replaced 1,4-
dioxane with no negative impact on reactivity (Table 1, entry
7). Next, 80 °C proved optimal as lowering the temperature to
60 °C led to sluggish reactivity and incomplete conversion after
24 h (Table 1, entries 9 and 10). Running the reaction at room
temperature returned only starting materials, and substituting
LiHMDS for tert-butoxide furnished none of the target
compound. During this initial reaction optimization, we did
find that catalyst loading could be lowered to 1% for both
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a
high save for the case of 2-bromotoluene to yield 11. Still, the
observed 92:8 ratio would likely be synthetically useful. Our
initial attempts to engage 2-benzyl-1,3-dithiolane in the
reaction to afford ethylene-linked styryl-aryl dithioether have
been met without success. When subjecting the five-membered
dithiolane ring to our standard conditions, a very messy crude
reaction mixture was observed, and GC analysis found no mass
that corresponded to the expected product. The tendency of
1,3-dithiolanes to act differently under strongly basic conditions
than their 1,3-dithiane analogues, and their known tendency to
undergo decomposition/fragmentation in various ways has
been reported.51,52 However, work is ongoing in our lab
generate similar reactivity from 1,3-dithiolane.
Scheme 3. Role of pKa
The chemistry scaled cleanly to the gram scale, and
compound 6 was isolated in quantitative yield when the
reaction was run at the 5.0 mmol scale with 2.5% catalyst
loading. A standard aqueous/organic partition followed by
running the crude reaction through a short plug of silica gel to
remove the palladium catalyst was the only purification needed.
Next, we prepared derivatives of 2-benzyl-1,3-dithiane to
ascertain what impact, if any, there was on reactivity. As Table 2
a
All reactions run using 4-bromoanisole, Ar = 4-OCH3C6H4
Mechanistically, we envisioned two possible routes for the
elimination/ring-opening/C−S bond-forming event (Figure 2).
Route 1 outlines the convergence of two mechanisms occurring
in parallel: tert-butoxide-mediated elimination/ring-opening to
generate the thiolate anion, which then intercepts the
traditional Pd0/PdII catalytic cycle. Alternatively, we entertained
the possibility shown in Route 2, where the thiophilic
palladium(II) complex would perhaps coordinate to a sulfur
a
Table 2. Substitution of the 2-Benzyl-1,3-dithiane
yield
(%)
entry
Ar1
Ar2
product
E:Z
1
2
3
4
5
2-FC6H4 (27)
2-FC6H4 (27)
4-FC6H4 (28)
4-FC6H4 (28)
4-MeOC6H4
3-py
30
31
32
33
34
89
92
90
83
81
99:1
98.5:1.5
97:3
4-MeOC6H4
3-py
92:8
4-MeOC6H4 (29) 4-MeOC6H4
82:18
a
Reactions run on a 1.0 mmol scale at 0.2 M. Yield refers to yield of
E:Z mixture. E:Z ratio determined by uncorrected relative peak
integrations of the GC trace.
illustrates, no loss in yield was observed when cross-coupling
the 2-F, 4-F, or 4-OMe phenyl derivatives of the dithiane with
either 4-bromoanisole or 3-bromopyridine. For the most part,
the observed E:Z ratio was on par with those observed in the
unsubstituted variants, though it was noted that some erosion
of selectivity was observed when the electron-releasing methyl
ether was a part of the benzyl dithiane coupling partner (34;
Table 2, entry 5). Currently, we speculate that this loss of
selectivity might be attributed to attenuated acidity that would
be expected at the benzylic position when it is part of an
electron-rich arene.
Seeing the potential impact of acidity at the benzylic position
upon the desired outcome, we prepared additional coupling
substrates for further investigation. First, dithianes 36 and 37
were prepared to ascertain whether the methodology could be
applied to substrates in which initial deprotonation occurred at
positions other than the electronically favorable benzylic
position. Indeed, it appears the acidity of the methyl C−H is
not sufficient, as neither of these substrates underwent the
expected transformation because only starting materials were
obtained when subjected to the reaction conditions. 2-
phenethyl-1,3-dithiane 38 also returned only starting materials
under our reaction conditions, further illustrating the
importance of pKa in this transformation.
Figure 2. Two potential mechanistic routes.
D
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atom of the dithiane. We reasoned that this might enhance the
acidity of the benzylic proton at which point the tert-butoxide
would promote tandem elimination/ring-opening/ligand ex-
change onto palladium. Both catalytic cycles finish with
reductive elimination to regenerate the active Pd0 catalyst.
We already had some inferred evidence that led us to favor
Route 1. As mentioned above, the attempted cross coupling
using 2-bromomesitylene led to clean recovery of the aryl
bromide starting material along with the free, ring-opened thiol.
We followed up this observation with two control experiments.
First, a solution of the benzyl dithiane and potassium tert-
butoxide in CPME was heated to 80 °C for 24 h. These
conditions cleanly yielded the ring-opened thiol, illustrating
that no additional activation by coordination to palladium is
necessary to promote the ring opening step.53 Our second
control experiment was a two-step procedure that first
subjected the 2-benzyl-1,3-dithiane to the basic conditions in
the absence of catalyst and aryl bromide, then dosing in 4-
bromoanisole, palladium, and ligand, and then allowing the
mixture to age for 24 h at 80 °C. After this two-step sequence,
product 6 was isolated in quantitative yield. At this point, we
cannot exclude Route 2 as a competing catalytic cycle that also
generates the desired compound, but all control experiments to
date indicate that Route 1 is the more reasonable mechanism.
sulfides. These investigations are already underway and will be
reported in due course.
EXPERIMENTAL SECTION
■
General. Unless otherwise indicated, all reactions were prepared in
a glovebox under a nitrogen atmosphere in 2-dram (8 mL) vials fit
with Teflon-coated stir bars and sealed with a Teflon-lined cap. Once
prepared, the vials were removed from the glovebox and placed on a
thermostat-controlled aluminum heating block set to the desired
temperature. All solvents, aryl halides, Pd(OAc)2, and the 1,3-dithianes
used in the synthesis of compounds 27−31 were purchased from
commercial suppliers and used without further purification. n-
Butyllithium was purchased as a 2.5 M solution in hexane and used
as received. NiXantphos and Xantphos were purchased commercially
and used as received.
Thin layer chromatography was carried out on silica gel plates, and
eluted plates were visualized with UV light (254 nm) and/or KMnO4
stain. Flash chromatography was carried out on silica gel (230−400
mesh). All yields refer to the isolated mixture of E:Z isomers that are
1
otherwise analytically pure. H and 13C NMR spectra were recorded
1
on a 400 MHz (400 MHz H, 100 MHz 13C) instrument. Spectra are
reported in ppm and referenced to residual solvent CHCl3 (7.28
ppm). 1H NMR data are presented as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, etc.), coupling constant(s) in hertz (Hz), and integration.
13C NMR data are reported in ppm relative to the solvent signal
CDCl3 (77.2 ppm). Data were collected at 25 °C. Infrared spectral
data (neat) are reported in terms of frequency of absorption (cm−1).
Low resolution, electron impact (EI) mass spectral data are presented
as follows: mass ion peak (relative intensity). For high-resolution mass
spectral data, the sample mass was recorded on a high-resolution time-
of-flight mass spectrometer using liquid injection field desorption
ionization (LIFDI). The analyte was applied to the filament in ethyl
acetate and/or dichloromethane. The solvent was allowed to evaporate
before ramping to a 12K voltage field and ramping the filament current
from zero to 85 mA. All samples were ionized at 0−40 mA with peak
ion counts of ∼0−25 mA. Chloropentafluorobenzene was used as an
internal standard locking the peak at 201.9605 Da. Data is reported as
follows: expected mass, actual mass, error (in mDa).
Scheme 4. Control Experiments
Synthesis of 2-Benzyl-1,3-dithiane (5). A dry 100 mL round-
bottom flask fit with a stir bar was capped with a septum and flushed
with dry nitrogen gas. To the prepared flask was transferred 40 mL of
CHCl3 via cannula. Phenylacetaldehyde (2.23 mL, 20 mmol) was
added followed by 1.1 equiv of 1,3-propandedithiol (2.4 mL, 22
mmol), and the reaction solution was allowed to equilibrate for 5 min.
To the reaction solution was added 1.1 equiv of BF3·OEt2 (2.7 mL 22
mmol) dropwise over the course of 20 min. The reaction was allowed
to stir overnight at room temperature. Upon complete consumption of
starting materials (TLC), the reaction was quenched with 2 M NaOH
(aq), which was allowed to stir for 10 min before transferring to a
separatory funnel. The organic layer was partitioned off and washed
sequentially with 2 M NaOH (aq), H2O, and brine. The chloroform
solution was dried over MgSO4 and concentrated by rotary
evaporation. The crude product was purified by flash column
chromatography (10% EtOAc/Hexane) to yield 2-benzyl-1,3-dithiane
5 (3.65 g, 87%) as a colorless oil that crystallized upon standing (mp
33−35 °C). Spectral data are in agreement with the literature.54 1H
NMR (400 MHz, CDCl3): δ 7.38−7.32 (m, 2H), 7.32−7.26 (m, 3H),
4.29 (t, J = 7.2 Hz, 1H), 3.07 (d, J = 7.2 Hz, 2H), 2.94−2.80 (m, 4H),
2.18−2.07 (m, 1H), 1.92−1.82 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 137.4, 129.3, 128.4, 127.0, 48.7, 41.8, 30.6, 25.8.
CONCLUSION
■
We have developed a novel C−S cross-coupling reaction that
traps ring opened 2-benzyl-1,3-dithianes to afford S-styryl/S-
aryl dithioethers under palladium catalysis. This sequence
tolerates a wide range of aryl and heteroaryl bromides, proceeds
very cleanly, and provides the title compounds in good-to-
excellent yields. Most title compounds were isolated without
extensive chromatography, simply passing the crude reaction
mixture through a plug of silica to remove ligated palladium
impurities. The reaction proceeds with high E-selectivity of the
vinyl sulfides, and the clean, high-yielding nature of the
methodology makes isolation and purification simple. Cur-
rently, our group is investigating alternatives to 2-benzyl-1,3-
dithianes (e.g., 1,3-dithiolanes, 1,3-oxathiolanes, etc.) to engage
in a similar reaction manifold. Additionally, alternative electron
withdrawing groups (e.g., nitrile, ester, etc.) might be
substituted for the phenyl ring and elicit similar electronic
effects, affording access to a diverse collection of these vinyl
General Procedure for the Synthesis of Title Compounds. In
a glovebox, three stock solutions were prepared in 8 mL vials. Solution
1: 1.0 M solution of 2-benzyl-1,3-dithiane 5 in CPME. Solution 2:
Pd(OAc)2 (0.025 M; 0.012 g in 2.2 mL CPME), and Xantphos (0.025
M; 0.0313 g in 2.2 mL CPME). Solution 3: 1.7 M solution of
potassium tert-butoxide (0.816 g in 4.2 mL CPME). The catalyst
solution was allowed to complex for 45 min. To prepare the individual
reactions, we charged an 8 mL vial containing a stir bar sequentially
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1
with 1.00 mL of the dithiane solution, 1.0 mmol of the appropriate aryl
bromide by volume for liquid aryl bromides and by mass for solids, 1.0
mL of the catalyst solution, and finally 2.0 mL of the potassium tert-
butoxide solution. The vial was capped, removed from the glovebox,
and placed on an aluminum heating block set to the indicated
temperature where it was allowed to age for 24 h. After being cooled
to room temperature, the crude reaction solution was filtered through
a plug of silica gel atop a bed of Celite, washing with ethyl acetate until
the runnings became colorless. The filtrate was transferred to a
separatory funnel, and the organic layer was adjusted to pH 7.2 and
then washed sequentially with water and brine. The organic layer was
dried over MgSO4 and concentrated by rotary evaporation. Unless
otherwise indicated, this workup provides the title compounds as
in a dark brown oil (0.279g, 85%). H NMR (400 MHz, CDCl3): δ
7.41 (d, J = 9.2 Hz, 2H), 7.37−7.32 (m, 4H), 7.29−7.23 (m, 1H), 6.76
(d, J = 15.6 Hz, 1H), 6.70 (d, J = 9.2 Hz, 2H), 6.54 (d, J = 15.6, 1H),
3.01−2.94 (m, 10H), 2.01 (quintet, J = 7.0 Hz, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ 150.0, 137.1, 134.32, 134.26, 127.4, 126.9,
125.6, 124.9, 120.1, 112.9, 40.5, 35.3, 31.2, 29.0. EI MS, m/z: 329 (90),
176 (10), 152 (100), 134 (15), 115 (10) 91 (45), 77 (10). HRMS
(LIFDI): m/z calculated for C19H23NS2, 329.1272; found, 329.1293;
error, 2.1 mDa. IR (neat): 3020, 2910, 2800, 1592, 1442, 1350, 1192,
939, 810, 735, 690 cm−1.
(2-Methylphenyl)(3-(styrylthio)propyl)sulfane (11). The title com-
pound was prepared using the general procedure with 2-bromotoluene
(0.120 mL, 1.0 mmol). Workup of the reaction resulted in a yellow oil
1
1
(0.207 g, 69%). H NMR (400 MHz, CDCl3): δ 7.34−7.26 (5H, m),
analytically pure samples (>98% purity by GC and H NMR).
7.24−7.09 (4H, m), 6.70 (d, J = 15.6 Hz, 1H), 6.52 (d, J = 15.2 Hz,
1H), 3.08 (t, J = 7.2 Hz, 2H), 2.97 (t, J = 7.0 Hz, 2H), 2.41 (3H, s),
2.06 (quintet, J = 7.1 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ
137.7, 137.0, 135.3, 130.2, 128.1, 127.7, 127.0, 126.5, 125.8, 125.6,
124.5, 31.5, 31.5, 28.6, 20.5. EI MS, m/z: 300 (30), 165 (30), 149
(20), 137 (35), 115 (25), 91 (100), 77 (35), 65 (25), 51 (20). HRMS
(LIFDI): m/z calculated for C18H20S2, 300.1006; found, 300.1016;
error, 1.0 mDa. IR (neat): 2980, 1734, 1481, 1371, 1237, 1044, 748
cm−1.
(4-Methoxyphenyl)(3-(styrylthio)propyl)sulfane (6). The title
compound was prepared using the general procedure with 4-
bromoanisole (0.125 mL, 1.0 mmol). Workup of the reaction resulted
1
in a brown oil (0.290 g, 92%). H NMR (400 MHz, CDCl3): δ 7.43
(d, J = 8.4 Hz, 2H), 7.38−7.31 (m, 4H), 7.29−7.23 (m, 1H), 6.89 (d, J
= 8.8 Hz, 2H), 6.74 (d, J = 15.6 Hz, 1H), 6.54 (d, J = 15.6 Hz, 1H),
3.80 (s, 3H), 3.01 (t, J = 7.0 Hz, 2H), 2.96 (t, J = 7.0 Hz, 2H), 2.01
(quintet, J = 7.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.1,
137.0, 133.4, 128.7, 127.5, 127.0, 126.0, 125.6, 124.8, 114.7, 55.34,
34.5, 31.2, 28.9. EI MS, m/z: 316 (100), 181 (45), 153 (50), 135 (25),
115 (20), 91 (47). HRMS (LIFDI): m/z calculated for C18H20OS2,
316.0956; found, 316.0948; error, 0.8 mDa. IR (neat): 2930, 2834,
1592, 1492, 1239, 1173, 1029, 938, 824, 738, 691 cm−1.
Ethyl 4-((3-(Styrylthio)propyl)thio)benzoate (12). The title com-
pound was prepared using the general procedure with ethyl 4-
bromobenzoate (0.163 mL, 1.0 mmol). Workup of the reaction
1
resulted in a dark orange oil (0.2753 g, 77%). H NMR (400 MHz,
CDCl3): δ 7.97−7.91 (m, 2H), 7.36−7.26 (m, 6H), 7.24−7.19 (m,
1H), 6.70 (d, J = 15.6 Hz, 1H), 6.53 (d, J = 15.6 Hz, 1H), 4.38 (q, J =
7.1 Hz, 2H), 3.16−3.13 (m, 2H), 2.95 (t, J = 6.8 Hz, 2H), 2.08
(quintet, J = 7.0 Hz, 2H), 1.41 (t, J = 7.0 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 166.2, 143.2, 136.9, 130.0, 128.7, 128.0, 127.1,
126.8, 125.6, 124.3, 60.9, 31.3, 30.7, 28.4, 28.3, 14.4. EI MS, m/z: 358
(100), 313 (15), 223 (85), 177 (20), 149 (27), 135 (30). HRMS
(LIFDI): m/z calculated for C20H22O2S2, 358.1061; found, 358.1085;
error, 2.4 mDa. IR (neat): 3024, 2979, 2877, 1708, 1592, 1270, 1105,
937, 758, 736 cm−1.
(2-Methoxyphenyl)(3-(styrylthio)propyl)sulfane (7). The title
compound was prepared using the general procedure with 2-
bromoanisole (0.125 mL, 1.0 mmol). Workup of the reaction resulted
in a yellow oil (0.3062 g, 87%). 1H NMR (400 MHz, CDCl3): δ 7.35−
7.26 (m, 5H), 7.27−7.20 (m, 2H), 7.01−6.93 (m, 1H), 6.92−6.87 (m,
1H), 6.70 (d, J = 15.6 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 3.91 (s, 3H),
3.07 (t, J = 7.0 Hz, 2H), 2.97 (t, J = 7.2 Hz, 2H), 2.06 (quintet, J = 7.0
Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 157.6, 137.1, 129.9,
128.7, 127.50, 127.46, 127.0, 125.6, 124.8, 124.0, 121.2, 110.7, 55.8,
31.5, 30.9, 28.7. EI MS, m/z: 316 (100), 181 (60), 153 (35), 135 (20),
115 (15), 91 (40), 65 (10). HRMS (LIFDI): m/z calculated for
C18H20OS2, 316.0956; found, 316.0949; error, 0.7 mDa. IR (neat):
3023, 2878, 1594, 1475, 1431, 1270, 1239, 1070, 1023, 936, 715, 690
cm−1.
3-((3-(Styrylthio)propyl)thio)thiophene (13). The title compound
was prepared using the general procedure with 3-bromothiophene
(0.094 mL, 1.0 mmol). Workup of the reaction resulted in a brown oil
1
(0.2095 g, 72%). H NMR (400 MHz, CDCl3): δ 7.31 (m, 5H), 7.21
(m, 2H), 7.10−7.07 (m, 1H), 6.71 (d, J = 15.6 Hz, 1H), 6.52 (d, J =
15.6 Hz, 1H), 3.01 (t, J = 7.2 Hz, 2H), 2.95 (t, J = 7.2 Hz, 2H), 2.02
(q, J = 6.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 137.0,
131.3, 129.8, 128.7, 127.7, 127.0, 126.4, 125.6, 124.6, 124.0, 34.0, 31.2,
28.9. EI MS, m/z: 292 (50), 157 (50), 129 (50), 115 (80), 91 (100),
71 (40), 51 (15). HRMS (LIFDI): m/z calculated for C15H16S3,
292.0414; found, 292.0443; error, 2.9 mDa. IR (neat): 3100, 3019,
2914, 1595, 1493, 1244, 936, 851, 736, 690 cm−1.
Phenyl(4-((3-(styrylthio)propyl)thio)phenyl)methanone (8). The
title compound was prepared using the general procedure with 4-
bromobenzophenone (0.2609 g, 1.0 mmol). Workup of the reaction
1
resulted in a red brown oil (0.3359g, 86%). H NMR (400 MHz,
CDCl3): δ 7.82−7.72 (m, 4H), 7.60 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.4
Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 7.33−7.26 (m, 4H), 7.23−7.18 (m,
1H), 6.72 (d, J = 15.6 Hz, 1H), 6.55 (d, J = 15.6, 1H), 3.19 (t, J = 7.0
Hz, 2H), 2.98 (t, J = 6.8, 2H), 2.13 (quintet, J = 7.0 Hz, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ 195.7, 143.2, 137.8, 136.8, 134.3, 132.3,
130.8, 130.1, 129.9, 128.7, 128.3, 128.0, 127.1, 126.6, 125.6, 124.3,
31.4, 30.7, 28.5. EI MS, m/z: 390 (90), 225 (75), 214 (20), 177 (25),
135 (30), 105 (100), 77 (50). HRMS (LIFDI): m/z calculated for
C24H22OS2, 390.1086; found, 390.1112; error, 2.6 mDa. IR (neat):
3054, 2876, 1732, 1650, 1588, 1282, 1272, 936, 921, 730, 696 cm−1.
Phenyl(3-(styrylthio)propyl)sulfane (9). The title compound was
prepared using the general procedure with bromobenzene (0.104 mL,
1.0 mmol). Workup of the reaction resulted in a dark orange oil
(4-Cyanophenyl)(3-(styrylthio)propyl)sulfane (14). The title com-
pound was prepared using the general procedure with 4-
bromobenzonitrile (0.182 g, 1.0 mmol). Workup of the reaction
resulted in a brown oil (0.2580 g, 83%). 1H NMR (400 MHz, CDCl3):
δ 7.50−7.46 (m, 2H), 7.34−7.26 (m, 6.8 H, overlapping E/Z isomer),
6.70 (d, J = 15.6 Hz, 1H), 6.53 (d, J = 15.6 Hz, 2H), 3.13 (t, J = 7.2
Hz, 2H), 2.95 (t, J = 6.8 Hz, 2H), 2.08 (quintet, J = 7.0 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 137.0, 131.4, 129.8, 128.74,
127.7, 127.1, 126.4, 125.6, 124.6, 124.0, 34.0, 31.2, 29.0. EI MS, m/z:
311 (100), 176 (65), 148 (45), 115 (15), 91 (48). HRMS (LIFDI):
m/z calculated for C18H17NS2, 311.0802; found, 311.0837; error, 3.5
mDa. IR (neat): 3021, 2876, 2224, 1590, 1233, 1123, 1086, 738 cm−1.
5-((3-(Styrylthio)propyl)thio)pyrimidine (15). The title compound
was prepared using the general procedure with 5-bromopyrimidine
(0.159 g, 1.0 mmol). Workup of the reaction resulted in an orange oil
(0.2294 g, 80%). 1H NMR (400 MHz, CDCl3): δ 9.04 (s, 1H), 8.72 (s,
2H), 7.34−7.28 (m, 5H), 6.67 (d, J = 15.2 Hz, 1H), 6.54 (d, J = 15.6
Hz, 1H), 3.14 (t, J = 7.2 Hz, 2H), 2.96 (t, J = 6.8 Hz, 2H), 2.06
(quintet, J = 7.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 157.0,
156.2, 136.7, 132.5, 128.7, 128.3, 127.2, 125.6, 123.9, 32.1, 31.1, 28.6.
EI MS, m/z: 289 (100), 214 (10), 153 (90), 135 (50), 115 (25), 104
1
(0.2807g, 98%). H NMR (400 MHz, CDCl3): δ 7.49−7.42 (m, 2H),
7.42−7.32 (m, 6H), 7.32−7.23 (2H), 6.78 (d, J = 15.6 Hz, 1H), 6.59
(d, J = 15.6 Hz, 1H), 3.14 (t, J = 7.0 Hz, 2H), 3.00 (t, J = 7.0 Hz, 2H),
2.10 (quintet, J = 7.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ
137.1, 136.2, 129.4, 129.1, 128.8, 127.6, 127.1, 126.2, 125.7, 124.7,
32.4, 31.3, 28.8. EI MS, m/z: 286 (100), 151 (85), 135 (40), 123 (50),
109 (35, 91 (50), 73 (38). HRMS (LIFDI): m/z calculated for
C17H18S2, 286.0850; found, 286.0879; error, 2.9 mDa. IR (neat): 2980,
1733, 1438, 1371, 1238, 1044, 937, 909, 734, 690, 497 cm−1.
N,N-Dimethyl-4-((3-(styrylthio)propyl)thio)aniline (10). The title
compound was prepared using the general procedure with 4-
bromoaniline (0.200 g, 1.0 mmol). Workup of the reaction resulted
F
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The Journal of Organic Chemistry
Article
(11), 91 (68), 73 (23). HRMS (LIFDI): m/z calculated for
C15H16N2S2, 288.0755; found, 288.0772; error, 1.7 mDa. IR (neat):
3023, 2877, 1595, 1538, 1416, 1401, 936, 737, 719, 690, 625 cm−1.
(4-Chlorophenyl)(3-(styrylthio)propyl)sulfane (16). The title com-
pound was prepared using the general procedure with 4-
chlorobromobenzene (0.1970 g, 1.0 mmol). Workup of the reaction
3-((3-(Styrylthio)propyl)thio)pyridine (21). The title compound
was prepared using the general procedure with 3-bromopyridine
(0.096 mL, 1.0 mmol). Workup of the reaction resulted in a dark
1
orange oil (0.2586 g, 90%). H NMR (400 MHz, CDCl3): δ 8.60 (s,
1H), 8.41 (s, 1H), 6.66 (d, J = 8.0 Hz, 1H), 7.32−7.24 (m, 4H), 7.22−
7.13 (m, 2H), 6.66 (d, J = 15.6 Hz, 1H), 6.49 (d, J = 15.6 Hz, 1H),
3.06 (t, J = 7.0 Hz, 2H), 2.90 (t, J = 7.0 Hz, 2H), 1.99 (p, J = 7.0 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 150.4, 147.3, 137.0, 136.8,
128.7, 127.9, 127.1, 125.6, 124.3, 123.7, 32.3, 31.2, 28.6. EI MS, m/z:
287 (80), 213 (15), 152 (100), 135 (45), 124 (47), 111 (15), 91 (83),
78 (10), 51 (8). HRMS (LIFDI): m/z calculated for C16H17NS2,
287.0802; found, 287.0787; error, 1.5 mDa. IR (neat): 2980, 2927,
1732, 1371, 1238, 1044, 938, 794, 737, 691 cm−1
General Procedure (B) for the Synthesis of Substituted 2-benzyl-
1,3-dithianes (27−29). A solution of 1,3-dithiane (0.66 g, 5.5 mmol)
in dry THF was cooled in a dry ice/acetone bath. To this cooled
solution was added n-BuLi (2.8 mL, 2.5 M in hexanes, 5.5 mmol)
dropwise over 20 min, and the solution was then allowed to stir for an
hour. After complete addition, the reaction solution was removed from
the cooling bath and then allowed to warm to ∼0 °C. The reaction
flask was placed back into the cooling bath before adding 5.0 mmol of
the appropriate benzyl bromide or chloride dropwise over 30 min. The
reaction was allowed to stir for 10 min, removed from the cooling
bath, and allowed to stir at room temperature overnight. The reaction
was subjected to a standard aqueous:organic partition by washing the
organic layer sequentially with sodium bicarbonate, water, then brine
before drying the organic layer over magnesium sulfate. After the
desiccant was filtered away, the solution was concentrated in vacuo,
and the crude product was purified by either flash chromatography or
recrystallization.
1
resulted in a dark orange oil (0.3016 g, 94%). H NMR (400 MHz,
CDCl3): δ 7.43−7.24 (m, 10H, cis isomer included), 6.76 (d, J = 15.6
Hz, 1H), 6.58 (d, J = 15.6 Hz, 1H), 3.09 (t, J = 7.0 Hz, 2H), 2.98 (t, J
= 7.0 Hz, 2H), 2.06 (quintet, J = 7.1 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 136.9, 134.6, 132.1, 130.7, 129.2, 128.7, 127.9, 127.1,
125.6, 124.4, 32.5, 31.2, 28.6. EI MS, m/z: 320 (100), 185 (80), 157
(55), 134 (80), 105 (55), 91 (100), 77 (100), 51 (50). HRMS
(LIFDI): m/z calculated for C17H17ClS2, 320.0460; found, 320.0434;
error, 2.6 mDa.
Naphthalen-1-yl(3-(styrylthio)propyl)sulfane (17). The title com-
pound was prepared using the general procedure with 1-
bromonapthalene (0.139 mL, 1.0 mmol). Workup of the reaction
resulted in a brown oil (0.2934 g, 93%). 1H NMR (400 MHz, CDCl3):
δ 8.56 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.0
Hz, 1H), 7.71−7.58 (m, 3H), 7.48 (t, J = 7.6 Hz, 1H), 7.46−7.42 (m,
5H), 6.77 (d, J = 15.2 Hz, 1H), 6.59 (d, J = 15.6 Hz, 1H), 3.20 (t, J =
6.8 Hz, 2H), 3.01 (t, J = 7.0 Hz, 1H), 2.10 (quintet, J = 7.0 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 137.1, 134.1, 133.3, 133.2,
128.77, 128.76, 128.4, 127.7, 127.5, 127.1, 126.6, 126.4, 125.73,
125.68, 125.2, 124.7, 32.97, 31.4, 28.9. EI MS, m/z: 336 (70), 201
(10), 173 (40), 159 (42), 134 (44), 115 (100), 91 (65), 77 (30), 51
(15). HRMS (LIFDI): m/z calculated for C21H20S2, 336.1006; found,
336.1035; error, 2.9 mDa. IR (neat): 3052, 2877, 1595, 1381, 936, 798,
788, 769, 736, 690 cm−1.
2-(2-Fluorophenyl)methyl-1,3-dithiane (27). Reagent was pre-
pared using general procedure B with 2-fluorobenzyl bromide (0.603
mL, 5.0 mmol). Workup resulted in a solid that was recrystallized in
(4-tert-Butylphenyl)(3-(styrylthio)propyl)sulfane (18). The title
compound was prepared using the general procedure with 4-tert-
butyl bromobenzene (0.175 mL, 1.0 mmol). Workup of the reaction
1
1
resulted in a red orange oil (0.3171 g, 93%). H NMR (400 MHz,
ethanol (0.616 g, 54%). H NMR (400 MHz, CDCl3): δ 7.29−7.24
CDCl3): δ 7.44−7.35 (m, 8H), 7.32−7.26 (m, 1H), 6.80 (d, J = 15.6
Hz, 1H), 6.61 (d, J = 15.6 Hz, 1H), 3.14 (d, J = 7.0 Hz, 2H), 3.02 (t, J
= 7.0 Hz, 2H), 2.11 (quintet, J = 7.0 Hz, 2H), 1.37 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3): δ 149.5, 137.1, 132.5, 129.7, 129.6, 128.8,
127.6, 127.0, 126.2, 125.7, 124.8, 34.6, 32.8, 31.5, 31.4, 28.9. EI MS,
m/z: 342 (100), 207 (75), 177 (30), 149 (37), 115 (25), 91 (45).
HRMS (LIFDI): m/z calculated for C21H26S2, 342.1476; found,
342.1481; error, 0.5 mDa. IR (neat): 3022, 2958, 2855, 1735, 1494,
1239, 1119, 937, 819, 737, 690, 547 cm−1.
(m, 2H), 7.12−7.04 (m, 2H), 4.32 (t, 1H), 3.12 (d, J = 7.6 Hz, 2H),
2.88−2.85 (m, 4H), 2.16−2.10 (m, 1H), 1.94−1.88 (m, 1H). 13C{1H}
1
NMR (100 MHz, CDCl3): 161.2 (d, 1JC−F = 244 Hz), 131.7 (d, JC−F
= 4.4 Hz), 128.8 (d, 1JC−F = 8.2 Hz), 124.4 (d, 1JC−F = 15.5 Hz), 123.8
1
1
(d, JC−F = 3.2 Hz), 115.4 (d, JC−F = 21.8 Hz), 47.1, 36.1, 30.2, 25.7.
EI MS, m/z: 228 (5), 119 (100), 109 (20). HRMS (LIFDI): m/z
calculated for C11H13FS2, 228.0443; found, 228.0417; error, 2.6 mDa.
2-(4-Fluorophenyl)methyl-1,3-dithiane (28). Reagent was pre-
pared using general procedure B with 4-fluorobenzyl bromide (0.68
mL, 5.0 mmol). Workup and column chromatography with 5%
EtOAc/heptane resulted in a light yellow oil (0.833g, 73%). Spectral
data are in agreement with the literature.55 1H NMR (400 MHz,
CDCl3): δ 7.24−7.18 (m, 2H), 7.03−6.96 (m, 2H), 4.22 (t, J = 7.2 Hz,
1H), 3.01 (d, J = 7.6 Hz, 2H), 2.86−2.77 (m, 4H), 2.14−2.02 (m,
1H), 1.92−1.79 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.9
(d, 1JC−F = 243.6 Hz), 131.1 (d, 4JC−F = 3.3 Hz), 130.8 (d, 3JC−F = 8.1
Styryl(3-((4-(trifluoromethyl)phenyl)thio)propyl)sulfane (19). The
title compound was prepared using the general procedure with 4-
bromobenzotrifluoride (0.140 mL, 1.0 mmol). Workup of the reaction
1
resulted in a dark orange oil (0.2807 g, 98%). H NMR (400 MHz,
CDCl3): δ 7.63−7.50 (m, 2H), 7.47−7.31 (m, 6H), 7.31−7.24 (m,
1H), 6.77 (d, J = 15.6 Hz, 1H), 6.61 (d, J = 15.6 Hz, 1H), 3.19 (t, J =
7.0 Hz, 2H), 2.99 (t, J = 7.0 Hz, 2H), 2.12 (quintet, J = 7.0 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3): δ 141.96, 141.95, 136.9, 128.8,
128.0 127.5, 127.2, 125.8, 125.8, 125.7, 124.4, 31.3, 31.0, 28.4. EI MS,
m/z: 354 (100), 219 (75), 191 (50), 135 (40), 91 (50), 73 (30).
HRMS (LIFDI): m/z calculated for C18H17F3S2, 354.0724; found,
354.0712; error, 1.2 mDa. IR (neat): 3022, 2919, 1605, 1323, 1117,
1093, 1062, 1012, 822, 736, 690 cm−1.
2
Hz), 115.1 (d, JC−F = 21.3 Hz), 48.6, 41.0, 30.5, 25.7. EI MS, m/z:
228 (5), 119 (100), 109 (20).
2-(4-Methoxyphenyl)methyl-1,3-dithiane (29). Reagent was pre-
pared using general procedure B with 4-methoxybenzyl chloride (0.68
mL, 5.0 mmol). Neutral workup resulted in a solid that was
recrystallized in ethanol (0.6481 g, 54%). Spectral data are in
agreement with the literature.56 1H NMR (400 MHz, CDCl3): δ 7.19
(d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 4.23 (t, J = 7.2 Hz, 1H),
3.81 (s, 3H), 2.99 (d, J = 7.2 Hz, 2H), 2.87−2.84 (m, 4H), 2.14 (m,
1H), 1.89 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.6,
130.2, 129.4, 113.75, 55.2, 49.01, 40.94, 30.56, 25.82. EI MS, m/z: 240
(10), 119 (100).
(E/Z)-(2-Fluorostyryl)(3-((4-methoxyphenyl)thio)propyl)sulfane
(30). The title compound was prepared using the general procedure
with 2-(2-fluorobenzyl)-1,3-dithiane (0.2058 g, 0.9 mmol) and 4-
bromoanisole (0.113 mL, 0.9 mmol). Neutral workup resulted in a
dark orange oil (0.297 g, 89%). 1H NMR (400 MHz, CDCl3): δ 7.43−
7.37 (m, 2H), 7.37−7.31 (m, 1H), 7.21−7.14 (m, 1H), 7.12−7.01 (m,
2H), 6.91−6.79 (m, 3H), 6.60 (d, J = 15.6 Hz, 1H), 3.78 (s, 3H), 2.99
(t, J = 6.2 Hz, 2H), 2.96 (t, J = 6.2 Hz, 2H), 1.99 (quintet, J = 7.0 Hz,
(4-Fluorophenyl)(3-(styrylthio)propyl)sulfane (20). The title com-
pound was prepared using the general procedure with 4-
fluorobromobenzene (0.110 mL, 1.0 mmol). Workup of the reaction
resulted in a brown oil (0.2549 g, 84%). 1H NMR (400 MHz, CDCl3):
δ 7.41−7.35 (m, 2H), 7.35−7.26 (m, 4H), 7.25−7.19 (m, 1H), 7.00 (t,
J = 8.4 Hz, 2H), 6.68 (d, J = 15.6 Hz, 1H), 6.51 (d, J = 15.6 Hz, 1H),
3.03 (t, J = 7.2 Hz, 2H), 2.94 (t, J = 7.0 Hz, 2H), 2.00 (quintet, J = 7.0
Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.9 (d, 1JC−F = 245
Hz), 136.9, 132.5 (d, 3JC−F = 7.9 Hz), 128.7, 127.8, 127.1, 125.6, 124.5,
2
116.1 (d, JC−F = 21.7 Hz), 33.7, 31.2, 28.7. EI MS, m/z: 304 (100),
169 (75), 141 (50), 115 (10), 91 (45), 73 (12). HRMS (LIFDI): m/z
calculated for C17H17FS2, 304.0756; found, 304.0746; error, 1.0 mDa.
IR (neat): 2980, 1733, 1489, 1371, 1237, 1044, 938, 823, 736, 691
cm−1.
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The Journal of Organic Chemistry
Article
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 160.74, 159.07, 158.26,
133.45, 133.40, 132.26, 128.02, 127.97, 127.94, 127.91, 127.73, 126.
82, 126.78, 125.90, 124.91, 124.78, 124.24, 124.21, 119.37, 119.34,
115.88, 115.78, 116.66, 114.70, 114.62, 55.31, 34.46, 31.00, 28.78
(complexities due to carbon−fluorine splitting). EI MS, m/z: 334
(100), 195 (40), 181 (30), 167 (35), 153 (48), 139 (45), 109 (50).
HRMS (LIFDI): m/z calculated for C18H19FOS2, 334.0861; found,
334.0887; error, 2.6 mDa. IR (neat): 3033, 2878, 1592, 1491, 1481,
1283, 1241, 1224, 1029, 939, 822, 749 cm−1.
fluorine coupling). EI MS, m/z: 346 (100), 181 (65), 153 (90), 139
(85), 121 (80), 77 (40). HRMS (LIFDI): m/z calculated for
C19H22O2S2, 346.1061; found, 346.1052; error, 0.9 mDa. IR (neat):
3025, 2879, 2224, 1591, 1506, 1492, 1240, 1226, 1030, 823 cm−1.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR of all title compounds. This material is free of
charge via the Internet at http://pubs.acs.org.
(E/Z)-3-((3-((2-Fluorostyryl)thio)propyl)thio)pyridine (31). The
title compound was prepared using the general procedure from 2-
(2-fluorobenzyl)-1,3-dithiane (0.2285 g, 1.0 mmol) with 3-bromopyr-
idine (0.096 mL, 1.0 mmol), 1.0 mL of catalyst stock solution (0.025
mmol), and potassium tert-butoxide (2.0 mL stock solution, 3.0
AUTHOR INFORMATION
Corresponding Author
*E-mail: jschmink@brynmawr.edu.
■
1
mmol). Neutral workup resulted in a brown oil (0.281 g, 81%). H
Notes
NMR (400 MHz, CDCl3): δ 8.63−8.56 (m, 1H), 8.46−8.38 (m, 1H),
7.69−7.63 (m, 1H), 7.26−7.16 (m, 3H), 7.08−6.93 (m, 2H), 6.57 (d, J
= 15.6 Hz, 1H), 6.46 (d, J = 16.6 Hz), 3.08 (t, J = 7.0 Hz, 2H), 2.94 (t,
J = 7.0 Hz, 2H), 2.01 (quintet, J = 7.0 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 163.1, 160.7, 150.3, 147.3, 137.0, 133.2, 133.1, 133.0,
130.4, 130.2, 127.1, 127.0, 126.8, 124.0, 123.9, 123.7, 115.6, 155.4,
115.3, 115.0, 34.0, 32.3, 32.0, 31.2, 31.0, 29.2, 28.6. EI MS, m/z: 305
(50), 231 (35), 152 (100), 124 (38), 109 (75). HRMS (LIFDI): m/z
calculated for C16H16FNS2, 305.0708; found, 305.0729; error, 2.1
mDa. IR (neat): 3032, 1595, 1481, 1223, 1196, 939, 749, 704, 617,
492, 460 cm−1.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Bryn Mawr College and the Isabel H. Benham Fund for Faculty
Research are acknowledged for funding support. N.A. acknowl-
edges the Bryn Mawr College Dean’s Fellowship for financial
support. The authors acknowledge the National Science
Foundation for a Major Research Instrumentation award
(CHE-0958996), which paid for the NMR spectrometer used
in these studies. The authors acknowledge Mr. Jesse McAtee
(University of Delaware) for HRMS data.
(E)-(4-Fluorostyryl)(3-((4-methoxyphenyl)thio)propyl)sulfane
(32). The title compound was prepared using the general procedure
from 2-(4-fluorobenzyl)-1,3-dithiane (0.188 mL, 1 mmol) with 4-
bromoanisole (0.125 mL, 1.0 mmol). Neutral workup resulted in a
REFERENCES
1
■
brown oil (0.301, 90%). H NMR (400 MHz, CDCl3): δ 7.39 (d, J =
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̈
8.8 Hz, 2H), 7.24 (dd, J = 8.8 Hz, 2H), 7.00 (t, J = 8.6 Hz, 2H), 6.86
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1H), 3.78 (s, 3H), 2.98 (t, J = 6.8 Hz, 2H), 2.92 (t, J = 7.0, 2H), 1.98
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1
oil (0.254 g, 83%). H NMR (400 MHz, CDCl3): δ 8.60−8.56 (m,
1H), 8.42−8.38 (m, 1H), 7.66−7.60 (m, 1H), 7.25−7.13 (m, 4H),
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H
DOI: 10.1021/acs.joc.5b00547
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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DOI: 10.1021/acs.joc.5b00547
J. Org. Chem. XXXX, XXX, XXX−XXX