A synthesis of (1 E,3 E)-TMS dienes from keto-xanthates via Chugaev-type elimination

Article abstract of DOI:10.1021/jo402169v

An efficient route leading to exclusively (1E,3E)-TMS dienes is described. Radical xanthate addition of keto-xanthates to vinyltrimethylsilane followed by one-pot Chugaev elimination/cyclization and in situ oxidation with m-CPBA afforded the corresponding TMS 2-sulfolenes. Isomerization to 3-sulfolenes by the action of DBU with the extrusion of sulfur dioxide in refluxing toluene gave the titled (1E,3E)-TMS dienes.

Full text of DOI:10.1021/jo402169v

Note
pubs.acs.org/joc
A Synthesis of (1E,3E)‑TMS Dienes from Keto-Xanthates via
Chugaev‑Type Elimination
Kelvin Kau Kiat Goh,†,‡ Sunggak Kim,*,† and Samir Z. Zard*,‡
†Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
‡Laboratoire de Synthes
̀
e Organique, CNRS UMR 765, Ecole Polytechnique, 91128 Palaiseau Cedex, France
S
* Supporting Information
ABSTRACT: An efficient route leading to exclusively (1E,3E)-TMS dienes is described. Radical xanthate addition of keto-
xanthates to vinyltrimethylsilane followed by one-pot Chugaev elimination/cyclization and in situ oxidation with m-CPBA
afforded the corresponding TMS 2-sulfolenes. Isomerization to 3-sulfolenes by the action of DBU with the extrusion of sulfur
dioxide in refluxing toluene gave the titled (1E,3E)-TMS dienes.
1,3-Dienes are important intermediates in modern organic
synthesis, in particular in relation to the Diels−Alder reaction.1
In addition, the silane group presents an alternate and versatile
functionality that can undergo various transformations to other
important functionalities such as allylic alcohols2 and aldehydes3
or be transformed into excellent coupling partners such as
iodides4 and boronate derivatives.5
Classical methods for preparing such dienylsilanes include a
modified Peterson olefination6 or Horner−Wadsworth−Em-
mons-type reactions.7 A more popular approach to dienylsilanes
relies on palladium- or nickel-catalyzed cross-couplings.
However, it is important to note that most of the coupling
partners are vinyl or dienyl halides,8 triflates,9 tosylates, and
phosphonates.10 This limits the coupling precursors to
predefined geometrical alkenyl halides or dithioacetals11 that
may not be commercially available or require tedious
preparations. Organometallic reagents such as stannanes12 and
organozinc13 or organotitanium derivatives14 pose technical
difficulties in the handling and synthesis of the reagents as well as
the issue of toxicity. In addition, such methods often exhibit poor
or suboptimal stereoselectivities in the formation of the
dienes.6−14
because of the lack of a convenient synthetic access. Our ongoing
efforts in discovering new applications for the xanthate radical
addition transfer reaction16 prompted us to exploit the rich
chemistry of xanthates to access these 2-sulfolenes as key
intermediates to 1,3-dienes.17
Herein we report a novel and rapid method to access
functionalized (1E,3E)-TMS dienes. We envisaged that heating
of secondary O-(2-butyl) xanthate adducts 2 would initiate
Chugaev elimination and cyclization followed by dehydration to
give 2-dihydrothiophenes 3 (Scheme 1).18 These would then be
oxidized in situ to give 2-sulfolenes 4, which can be easily isolated
via silica gel column chromatography and stored as bench-stable
solids. These 2-sulfolenes 4 can be easily isomerized to 3-
sulfolenes 5 with DBU to obtain the corresponding (1E,3E)-
TMS dienes 6 directly under the reaction conditions previously
reported by us.17
Such a protocol based on the Chugaev elimination would not
only effectively truncate possible tedious multistep workups to a
simplified one-pot process but, more importantly, would avoid
the use of acids, which may prove to be quite detrimental to
certain sensitive functionalities next to the sulfone such as the
trimethylsilyl (TMS) group.
Direct preparations of 1,3-dienes are usually plagued by
polymerization upon prolonged storage and difficulties in
handling. In regard to this aspect, bench-stable 2-sulfolenes can
be isomerized to 3-sulfolenes,15 which are well-known precursors
to such dienes, Unfortunately, these have been largely neglected
Received: September 30, 2013
© XXXX American Chemical Society
A
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Note
Scheme 1. Proposed Route to 1,3-TMS Dienes from Xanthate Adducts
a b
,
A preliminary experiment of the one-pot reaction using
xanthate adduct 2a was carried out. The initial results were
disheartening, as a complex mixture of products was observed
and only a 20% yield of 2-sulfolene 4a was isolated. This could
have arisen from competing intermolecular reactions between
the fragmented nucleophilic sulfur coproducts and the ketone or
thiocarbonyl of another adduct molecule. Fortunately, this was
circumvented by utilizing more dilute conditions, which greatly
favored the intramolecular cyclization and effectively curtailed
the intermolecular side reactions and gave the 2-sulfolene in
improved yields. After a series of trials, the optimized conditions
were found to be a dilution of 0.2 M and addition of m-CPBA at
room temperature, which gave 2-sulfolene 4a in 89% isolated
yield with no desilylation observed (Scheme 2).
Table 1. Preparation of TMS Xanthate Adducts
Scheme 2. Optimized Conditions for the One-Pot Reaction
To Give 2-Sulfolene
a
Conditions: To vinyltrimethylsilane (2.0 equiv) and 1 in EtOAc (1.0
M in the xanthate) heated to reflux under nitrogen was added 0.05
equiv of dilauroyl peroxide (DLP) every hour until 1 was mostly
Having demonstrated the TMS group to be tolerant of this
one-pot protocol, we decided to expand the scope by screening a
number of TMS xanthate adducts 2a−k, which were generally
synthesized in good to excellent yields (75−98%) by radical
addition of corresponding keto-xanthates 1 with vinyltrimethyl-
silane (Table 1).
Next, we attempted the one-pot conversion of the TMS
xanthate adducts to the corresponding TMS 2-sulfolenes. 2-
Sulfolenes bearing para-substituted aryls (4a−e), a methyl β to
the sulfone (4f), and a 2-naphthalenyl group α to the sulfone
(4g) as well as cyclohexyl-fused (4h) and dihydronaphthalene-
fused (4i) 2-sulfolenes were prepared in moderate to excellent
yields (63−91%; Table 2). An interesting example to note was
the 2-sulfolene bearing a thiophene 4j. Use of m-CPBA could
oxidize both the substituted thiophene and the 2-dihydrothio-
phene. This required careful manipulation of the reaction at a low
b
consumed as indicated by TLC. Isolated yields based on 1 are shown.
c
0.10 equiv of DLP was used at hourly intervals.
temperature of 0 °C, allowing oxidation to occur selectively on
the 2-dihydrothiophene instead of the electron-rich substituted
thiophene to give the desired 2-sulfolene 4j in a moderate yield of
58%.
Attempts to use methylene-substituted substrates were
unsuccessful with this method. We reasoned that this failure is
due to the favored formation of the more stable tetrasubstituted
alkene instead of the desired trisubstituted 2-dihydrothiophene.
In this respect, we tested the behavior of substrate 2k, in which
either external or internal elimination would lead to
trisubstitution. The results showed that even in such cases,
B
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Note
a b
,
Table 2. One-Pot Synthesis of TMS 2-Sulfolenes
Scheme 4. Desilylation of TMS 2-Sulfolene by DBU in the
Presence of Water
to a better ratio of silylated dienes and improved conversions in
toluene at elevated temperatures (Table 3). However,
inconsistency was observed even under the most optimized
conditions (Table 3, entry 8), which depended on the extent to
which the setup was kept strictly moisture-free. Further attempts
to completely remove moisture remained futile, and thus, we
decided to approach this problem from another perspective.
Instead of meticulous physical removal of water, we decided to
introduce a sacrificial electrophile to trap the hydroxide anion.19
Indeed, this measure worked effectively to furnish the silylated
dienes with the complete absence of desilylation. 1,3-TMS dienes
bearing para-substituted aryls (6a−e) or 3-methyl-4-phenyl (6f),
naphthalenyl (6g), dihydronaphthalenyl (6i), or heteroaryl (6j)
substitution were obtained in moderate to good yields of 64−
88% (Table 4).20
Notably, the reaction was significantly slower on substrate 4f
bearing a methyl group at the 4′ position of the TMS 2-sulfolene,
and poor conversion (28%) was noted. However, this was
circumvented by increasing the amount of DBU to 10 equiv,
which gave 1,3-TMS diene 6f in a moderate yield of 64% (Table
4, 6f). This sluggishness is the result of steric hindrance.
In conclusion, we have demonstrated the use of secondary O-
(2-butyl) xanthate adducts to form 2-sulfolenes in a one-pot
fashion. This eliminates tedious multistep workups and, more
importantly, avoids acidic conditions, making the protocol
tolerant of an acid-sensitive group (e.g., trimethylsilyl) adjacent
to the sulfone, thus creating a new pathway to TMS 2-sulfolenes.
In addition, we were able to convert these TMS 2-sulfolenes to
the corresponding (1E,3E)-TMS dienes with the absence of
desilylation. This method offers an advantage in preparation over
previous methods since it starts from a simple precursor such as
vinyltrimethylsilane.
a
Conditions: In the first step, 2 (0.2 M in Ph2O) was heated to 200 °C
under nitrogen for 2 h. In the second step, the reaction mixture was
cooled to room temperature and diluted with CH2Cl2 (2.0 times the
volume of Ph2O), and this was followed by two additions of m-CPBA
b
c
(1.2 equiv) every 30 min. Isolated yields based on 2 are shown. The
oxidation was done at 0 °C.
elimination to give the exo-alkene is favored (Scheme 3). This
represents perhaps the main limitation of the present approach.
Scheme 3. Formation of the exo-Alkene Is Favored during
Elimination of Water
EXPERIMENTAL SECTION
■
General Experimental Methods. Proton magnetic resonance
spectra (1H NMR) were recorded at 400 MHz, and coupling constants
(J) are reported to 0.5 Hz. Chemical shifts (δ) are reported in parts per
million relative to the residual solvent peak at 7.26 ppm (CDCl3).
Carbon magnetic resonance spectra (13C NMR) were recorded in the
same instrument at 100.6 MHz, and chemical shifts are reported in parts
per million relative to the signal of chloroform-d (δ 77.00, triplet). High-
resolution mass spectra were recorded by positive electron impact
ionization (EI+) at 70 eV on a double-focusing high-resolution mass
spectrometer. The quoted masses are accurate to 5 ppm.
Regardless, with a good number of TMS 2-sulfolenes in hand,
we attempted the in situ DBU-induced isomerization and
elimination of sulfur dioxide to generate the 1,3-dienes.
Conversion to the 1,3-diene was disappointingly low with
cyclohexane, and significant desilylation was observed. To
monitor this desilylation, we first attempted to isomerize 2-
sulfolene 4a to 3-sulfolene 5a with DBU in acetonitrile. To our
surprise, we obtained the desilylated 2-sulfolene 5a′ in 87% yield
(Scheme 4).
Presumably, hydroxide anion generated by the action of DBU
with adventitious water caused the desilylation by nucleophilic
attack on the TMS group. This hypothesis was proven by a series
of trial experiments to remove water from the medium. This led
O-sec-Butyl xanthates 1 were prepared from the corresponding
chlorides or bromides with potassium O-sec-butyl carbonodithioate21
using a procedure similar to that reported in our previous publication.22
General Procedure A for the Addition of Xanthates 1 to
Vinyltrimethylsilane To Obtain TMS Xanthate Adducts 2. A
solution of the corresponding xanthate (5 mmol, 1.0 equiv) and
vinyltrimethylsilane (2.0 equiv) in EtOAc was refluxed under a nitrogen
C
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Note
Table 3. Screening of Conditions To Reduce Protodesilylation
a
entry
solvent
base (equiv)
drying agent/cobase
T (°C)
product ratio (TMS:H)
1
2
3
4
5
6
7
8
cyclohexane 3 mL
cyclohexane 1 mL
toluene 3 mL
toluene 1 mL
toluene 3 mL
toluene 3 mL
toluene 3 mL
toluene 3 mL
DBU (1.2)
DBU (1.2)
DBU (1.0)
DBU (1.0)
DBU (0.5)
DBU (0.5)
DBU (0.5)
DBU (0.5)
−
−
−
−
90
90
21:8
16:7
120
120
120
120
120
120
43:40
39:40
51:26
57:34
62:27
87:0
Et3N
DABCO
MgSO4
K2CO3
a
1
Product yield ratios were determined by H NMR analysis of isolated mixtures of compounds 6a and 6a′.
1.33 (d, 1.5H, J = 6.3 Hz), 1.27 (d, 1.5H, J = 6.3 Hz), 0.92 (t, 1.5H, J = 7.5
Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.14 (s, 4.5H), 0.14 (s, 4.5H). 13C NMR
Table 4. Synthesis of Functionalized (1E,3E)-TMS Dienes
(CDCl3, 100 MHz): diastereomers = 1/1; δ 216.2, 198.1, 165.6 (d, JCF
=
254.5 Hz), 133.3, 130.6 (d, JCF = 9.2 Hz), 115.6 (d, JCF = 21.8 Hz), 83.0,
36.9, 36.3, 28.5, 25.2, 18.7, 9.6, −2.6. HRMS (EI+) m/z: calcd for [M]+
C18H27FO2S2Si 386.1206, found 386.1209.
O-sec-Butyl S-4-(4-Bromophenyl)-4-oxo-1-(trimethylsilyl)-
1
butyl Carbonodithioate (2c). Yield: 2.17 g, 97%. Colorless oil. H
NMR (CDCl3, 400 MHz): diastereomers = 1/1; δ 7.79 (dd, 2H, J = 8.4
Hz, J = 1.2 Hz), 7.58 (d, 1H, J = 8.6 Hz), 5.53−5.67 (m, 1H), 3.26 (dd,
1H, J = 11.1 Hz, J = 3.5 Hz), 3.01−3.23 (m, 2H), 2.29−2.39 (m, 1H),
1.57−1.85 (m, 3H), 1.33 (d, 1.5H, J = 6.3 Hz), 1.28 (d, 1.5H, J = 6.3 Hz),
0.92 (t, 1.5H, J = 7.5 Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.13 (s, 4.5H), 0.13
(s, 4.5H). 13C NMR (CDCl3, 100 MHz): diastereomers = 1/1; δ 216.0,
198.5, 135.4, 131.7, 129.4, 127.9, 82.9, 36.8, 36.6, 36.1, 28.4, 25.0, 24.8,
18.6, 9.5, −2.7. HRMS (EI+) m/z: calcd for [M]+ C18H27BrO2S2Si
446.0405, found 446.0384.
O-sec-Butyl S-4-Oxo-4-p-tolyl-1-(trimethylsilyl)butyl Carbon-
1
odithioate (2d). Yield: 1.79 g, 94%. Colorless oil. H NMR (CDCl3,
400 MHz): diastereomers = 1/1; δ 7.83 (d, 2H, J = 8.0 Hz), 7.24 (d, 2H,
J = 8.0 Hz), 5.58−5.63 (m, 1H), 3.26 (dd, 1H, J = 10.9 Hz, J = 3.5 Hz),
3.11−3.15 (m, 2H), 2.40 (s, 3H), 2.28−2.38 (m, 1H), 1.61−1.89 (m,
3H), 1.33 (d, 1.5H, J = 6.3 Hz), 1.27 (d, 1.5H, J = 6.3 Hz), 0.93 (t, 1.5H, J
= 7.4 Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.14 (s, 4.5H), 0.14 (s, 4.5H). 13C
NMR (CDCl3, 100 MHz): diastereomers = 1/1; δ 211.9, 199.4, 143.7,
134.4, 129.2, 128.1, 82.9, 36.9, 36.3, 28.5, 25.4, 25.1, 21.6, 18.7, 9.6, −2.6.
HRMS (EI+) m/z: calcd for [M]+ C19H30O2S2Si 382.1456, found
382.1472.
No product was observed from 2-sulfolene 4h because of high
volatility. The reaction was done with DBU (10 equiv), TMSCl (10
equiv), and K2CO3 (10 equiv) in toluene (5 mL).
a
O-sec-Butyl S-4-(4-Methoxyphenyl)-4-oxo-1-(trimethylsilyl)-
butyl Carbonodithioate (2e). Yield: 1.89 g, 95%. Yellow oil. 1H NMR
(CDCl3, 400 MHz): diastereomers = 1/1; δ 7.92 (d, 2H, J = 8.8 Hz),
6.92 (d, 2H, J = 8.8 Hz), 5.56−5.64 (m, 1H), 3.86 (s, 3H), 3.26 (dd, 1H,
J = 10.9 Hz, J = 3.5 Hz), 3.08−3.14 (m, 2H), 2.27−2.37 (m, 1H), 1.61−
1.88 (m, 3H), 1.34 (d, 1.5H, J = 6.3 Hz), 1.27 (d, 1.5H, J = 6.2 Hz), 0.93
(t, 1.5H, J = 7.4 Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.14 (s, 4.5H), 0.14 (s,
4.5H). 13C NMR (CDCl3, 100 MHz): diastereomers = 1/1; δ 216.1,
198.3, 163.4, 130.3, 130.0, 113.7, 82.9, 55.4, 36.7, 36.4, 28.5, 25.5, 18.7,
9.6, −2.6. HRMS (EI+) m/z: calcd for [M]+ C19H30O3S2Si 398.1406,
found 398.1406.
atmosphere for 10 min. Dilauroyl peroxide (DLP) (5 mol %) was then
added every hour until complete consumption of the xanthate was
indicated by TLC analysis. The resulting solution was concentrated
under reduced pressure, and the crude mixture was purified by flash
column chromatography (silica gel, Et2O/petroleum ether = 10/90) to
give the title TMS xanthate adduct.
O-sec-Butyl S-4-Oxo-4-phenyl-1-(trimethylsilyl)butyl Car-
bonodithioate (2a). Yield: 1.69 g, 92%. Colorless oil. 1H NMR
(CDCl3, 400 MHz): diastereomers = 1/1; δ 7.93 (d, 2H, J = 7.8 Hz),
7.54 (t, 1H, J = 7.4 Hz), 7.44 (t, 2H, J = 7.7 Hz), 5.56−5.64 (m, 1H),
3.25−3.29 (m, 1H), 3.13−3.19 (m, 2H), 2.29−2.39 (m, 1H), 1.56−1.90
(m, 3H), 1.33 (d, 1.5H, J = 6.3 Hz), 1.27 (d, 1.5H, J = 6.3 Hz), 0.93 (t,
1.5H, J = 7.4 Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.15 (s, 4.5H), 0.15 (s,
4.5H). 13C NMR (CDCl3, 100 MHz): diastereomers = 1/1; δ 216.1,
199.8, 136.9, 133.0, 128.5, 128.0, 83.0, 37.0, 36.3, 28.5, 25.3, 18.7, 9.6,
−2.6. HRMS (EI+) m/z: calcd for [M]+ C18H28O2S2Si 368.1300, found
368.1305.
O-sec-Butyl S-3-Methyl-4-oxo-4-phenyl-1-(trimethylsilyl)-
1
butyl Carbonodithioate (2f). Yield: 1.78 g, 93%. Yellow oil. H
NMR (CDCl3, 400 MHz): diastereomers = 1/1/1/1; δ 7.92−7.98 (m,
2H), 7.52−7.56 (m, 1H), 7.40−7.48 (m, 2H), 5.36−5.67 (m, 1H),
3.70−3.85 (m, 1H), 3.07−3.42 (m, 1 H), 1.92−2.52 (m, 1H), 1.41−1.90
(m, 3H), 1.35 (dd, 2H, J = 15.1 Hz, J = 6.3 Hz), 1.24 (dd, 2.5H, J = 13.8
Hz, J = 6.5 Hz), 1.17 (dd, 1.5H, J = 7.2 Hz, J = 1.5 Hz), 0.95 (m, 1.5H),
0.86 (t, 0.75H, J = 7.4 Hz), 0.73 (t, 0.75H, J = 7.5 Hz), 0.13 (s, 2.25H),
0.12 (s, 2.25H), 0.09 (s, 2.25H), 0.09 (s, 2.25H). 13C NMR (CDCl3, 100
MHz): diastereomers = 1/1/1/1; δ 215.9, 215.0, 203.9, 203.4, 136.5,
135.9, 132.9, 128.6, 83.1, 82.8, 38.9, 35.2, 34.5, 34.1, 33.7, 33.0, 28.6,
O-sec-Butyl S-4-(4-Fluorophenyl)-4-oxo-1-(trimethylsilyl)-
1
butyl Carbonodithioate (2b). Yield: 1.89 g, 98%. Colorless oil. H
NMR (CDCl3, 400 MHz): diastereomers = 1/1; δ 7.93−7.96 (m, 2H),
7.11 (t, 2H, J = 8.6 Hz), 5.55−5.64 (m, 1H), 3.26 (dd, 1H, J = 11.1 Hz, J
= 3.5 Hz), 3.05−3.15 (m, 2H), 2.28−2.37 (m, 1H), 1.59−1.87 (m, 3H),
D
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Note
28.4, 28.2, 19.5, 18.7, 18.5, 18.1, 16.6, 9.6, −3.0. HRMS (EI+) m/z: calcd
6.77 (t, 1H, J = 3.0 Hz), 2.82−3.03 (m, 2H), 2.75−2.79 (m, 1H), 0.30 (s,
9H). 13C NMR (CDCl3, 100 MHz): δ 144.8, 132.0, 129.3, 128.7, 127.8,
126.6, 50.1, 27.1, −2.9. HRMS (EI+) m/z: calcd for [M]+ C13H18O2SSi
266.0797, found 266.0792.
5-(4-Fluorophenyl)-2-(trimethylsilyl)-2,3-dihydrothiophene
1,1-Dioxide (4b). Yield: 472 mg, 83%. White solid, mp 138−140 °C.
1H NMR (CDCl3, 400 MHz): δ 7.66 (dd, 2H, J = 8.7 Hz, J = 5.3 Hz),
for [M]+ C19H30O2S2Si 382.1456, found 382.1461.
O-sec-Butyl S-4-(Naphthalen-2-yl)-4-oxo-1-(trimethylsilyl)-
butyl Carbonodithioate (2g). Yield: 1.67 g, 80%. White solid, mp
71−75 °C. 1H NMR (CDCl3, 400 MHz): diastereomers = 1/1; δ 8.45
(s, 1H), 8.02 (dd, 1H, J = 8.6 Hz, J = 1.7 Hz), 7.95 (d, 1H, J = 7.9 Hz),
7.87 (dd, 2H, J = 8.1 Hz, J = 6.1 Hz), 7.52−7.62 (m, 2H), 5.56−5.63 (m,
1H), 3.26−3.34 (m, 3H), 2.36−2.45 (m, 1H), 1.56−2.04 (m, 3H), 1.32
(d, 1.5H, J = 6.3 Hz), 1.26 (d, 1.5H, J = 6.2 Hz), 0.91 (t, 1.5H, J = 7.5
Hz), 0.88 (t, 1.5H, J = 7.5 Hz), 0.18 (s, 4.5H), 0.17 (s, 4.5H). 13C NMR
(CDCl3, 100 MHz): diastereomers = 1/1; δ 216.2, 199.7, 135.5, 134.2,
132.5, 129.7, 129.5, 128.3, 127.7, 126.7, 123.8, 83.0, 37.0, 36.3, 28.5,
25.4, 18.7, 9.6, −2.6. HRMS (EI+) m/z: calcd for [M]+ C22H30O2S2Si
418.1456, found 418.1458.
7.08 (t, 2H, J = 8.7 Hz), 6.72 (t, 1H, J = 2.9 Hz), 2.91−3.02 (m, 2H),
2.76−2.83 (m, 1H), 0.29 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 163.4
(d, JCF = 249.9 Hz), 144.2, 131.7, 128.8 (d, JCF = 8.4 Hz), 124.1 (d, JCF
=
3.4 Hz), 116.0 (d, JCF = 21.9 Hz), 50.1, 27.2, −2.7. HRMS (EI+) m/z:
calcd for [M]+ C13H17FO2SSi 284.0703, found 284.0704.
5-(4-Bromophenyl)-2-(trimethylsilyl)-2,3-dihydrothiophene
1,1-Dioxide (4c). Yield: 539 mg, 78%. Yellow solid, mp 167−170 °C.
1H NMR (CDCl3, 400 MHz): δ 7.50−7.55 (m, 4H), 6.77−6.78 (m,
O-sec-Butyl S-2-(2-Oxocyclohexyl)-1-(trimethylsilyl)ethyl
1
1H), 2.91−3.01 (m, 2H), 2.73−2.82 (m, 1H), 0.29 (s, 9H). 13C NMR
(CDCl3, 100 MHz): δ 144.2, 132.4, 132.1, 128.2, 126.9, 123.8, 50.2,
27.3, −2.7. HRMS (EI+) m/z: calcd for [M]+ C13H17BrO2SSi 343.9902,
found 343.9898.
Carbonodithioate (2h). Yield: 1.51 g, 87%. Colorless oil. H NMR
(CDCl3, 400 MHz): diastereomers = 1/1/1/1; δ 5.58−5.66 (m, 1H),
3.15−3.30 (m, 1H), 2.26−2.46 (m, 4H), 1.53−2.09 (m, 7H), 1.22−1.46
(m, 4H), 0.79−1.03 (m, 4H), 0.12 (s, 2.25H), 0.12 (s, 2.25H), 0.09 (s,
2.25H), 0.09 (s, 2.25H). 13C NMR (CDCl3, 100 MHz): diastereomers =
1/1/1/1; δ 213.3, 212.8, 194.8, 82.8, 48.9, 48.2, 42.7, 42.2, 35.8, 35.5,
33.4, 33.2, 31.2, 30.9, 28.6, 27.9, 25.6, 25.2, 18.7, 9.6, −2.9. HRMS (EI+)
m/z: calcd for [M]+ C16H30O2S2Si 346.1456, found 346.1456.
O-sec-Butyl S-2-(1-Oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-
1-(trimethylsilyl)ethyl Carbonodithioate (2i). Yield: 1.50 g, 75%.
Yellow oil. 1H NMR (CDCl3, 400 MHz): diastereomers = 1/1/1/1; δ
8.00 (t, 1H, J = 7.5 Hz), 7.44 (t, 1H, J = 7.4 Hz), 7.21−7.35 (m, 1H), 7.22
(d, 1H, J = 7.6 Hz), 5.53−5.65 (m, 1H), 3.32−3.63 (m, 1H), 2.95−3.11
(m, 2H), 2.59−2.75 (m, 1H), 2.40−2.56 (m, 2H), 1.63−2.17 (m, 4H),
1.28−1.36 (m, 3H), 0.89−0.95 (m, 3H), 0.16 (s, 2.25H), 0.16 (s,
2.25H), 0.13 (s, 2.25H), 0.13 (s, 2.25H). 13C NMR (CDCl3, 100 MHz):
diastereomers = 1/1/1/1; δ 216.8, 200.4, 144.0, 143.7, 133.1, 132.8,
132.5, 128.6, 127.3, 126.4, 83.0, 82.6, 46.1, 45.5, 35.5, 33.7, 32.5, 32.1,
30.6, 29.5, 28.9, 28.5, 18.7, 9.6, −2.8. HRMS (EI+) m/z: calcd for [M]+
C20H30O2S2Si 394.1456, found 394.1464.
O-sec-Butyl S-4-Oxo-4-(thiophen-2-yl)-1-(trimethylsilyl)butyl
Carbonodithioate (2j). Yield: 1.55 g, 83%. Yellow oil. 1H NMR
(CDCl3, 400 MHz): diastereomers = 1/1; δ 7.68 (ddd, 1H, J = 3.6 Hz, J
= 2.3 Hz, J = 1.1 Hz), 7.61 (dd, 1H, J = 4.9 Hz, J = 1.0 Hz), 7.10−7.12 (m,
1H), 5.56−5.64 (m, 1H), 3.25 (dd, 1H, J = 11.1 Hz, J = 3.4 Hz), 3.07−
3.13 (m, 2H), 2.29−2.37 (m, 1H), 1.58−1.90 (m, 3H), 1.33 (d, 1.5H, J =
6.3 Hz), 1.27 (d, 1.5H, J = 6.3 Hz), 0.93 (t, 1.5H, J = 7.5 Hz), 0.90 (t,
1.5H, J = 7.5 Hz), 0.14 (s, 4.5H), 0.13 (s, 4.5H). 13C NMR (CDCl3, 100
MHz): diastereomers = 1/1; δ 215.9, 192.7, 144.2, 133.4, 131.8, 128.0,
83.0, 37.7, 36.2, 28.5, 25.5, 18.7, 9.6, −2.7. HRMS (EI+) m/z: calcd for
[M]+ C16H26O2S3Si 374.0864, found 374.0868.
5-(p-Tolyl)-2-(trimethylsilyl)-2,3-dihydrothiophene 1,1-Diox-
ide (4d). Yield: 393 mg, 70%. White solid, mp 135−140 °C. 1H NMR
(CDCl3, 400 MHz): δ 7.57 (d, 2H, J = 8.2 Hz), 7.20 (d, 2H, J = 7.9 Hz),
6.72 (t, 1H, J = 3.1 Hz), 2.91−3.01 (m, 2H), 2.72−2.86 (m, 1H), 2.36 (s,
3H), 0.30 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 145.1, 139.6, 130.8,
129.6, 126.6, 125.0, 50.2, 27.1, 21.3, −2.7. HRMS (EI+) m/z: calcd for
[M]+ C14H20O2SSi 280.0953, found 280.0952.
5-(4-Methoxyphenyl)-2-(trimethylsilyl)-2,3-dihydrothio-
phene 1,1-Dioxide (4e). Yield: 522 mg, 88%. Yellow solid, mp 117−
122 °C. 1H NMR (CDCl3, 400 MHz): δ 7.59 (d, 2H, J = 8.5 Hz), 6.88
(d, 2H, J = 8.5 Hz), 6.63 (s, 1H), 3.77 (s, 3H), 2.87−2.96 (m, 2H),
2.72−2.79 (m, 1H), 0.26 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ
160.4, 144.4, 129.8, 128.0, 120.2, 114.2, 55.2, 50.0, 26.9, −2.8. HRMS
(EI+) m/z: calcd for [M]+ C14H20O3SSi 296.0902, found 296.0907.
4-Methyl-5-phenyl-2-(trimethylsilyl)-2,3-dihydrothiophene
1,1-Dioxide (4f). Yield: 511 mg, 91%. White solid, mp 127−128 °C. 1H
NMR (CDCl3, 400 MHz): δ 7.39−7.44 (m, 5H), 2.87−2.90 (m, 2H),
2.67−2.74 (m, 1H), 1.95 (s, 3H), 0.29 (s, 9H). 13C NMR (CDCl3, 100
MHz): δ 143.6, 139.1, 129.4, 128.9, 128.5, 128.0, 49.5, 32.7, 17.2, −2.7.
HRMS (EI+) m/z: calcd for [M]+ C14H20O2SSi 280.0953, found
280.0943.
5-(Naphthalen-2-yl)-2-(trimethylsilyl)-2,3-dihydrothiophene
1,1-Dioxide (4g). Yield: 519 mg, 82%. White solid, mp 132−135 °C.
1H NMR (CDCl3, 400 MHz): δ 8.29 (s, 1H), 7.82−7.88 (m, 3H), 7.66
(dd, 1H, J = 8.6 Hz, J = 1.6 Hz), 7.46−7.52 (m, 2H), 6.90 (t, 1H, J = 3.0
Hz), 2.95−3.01 (m, 2H), 2.77−2.85 (m, 1H), 0.33 (s, 9H). 13C NMR
(CDCl3, 100 MHz): δ 145.2, 133.5, 133.1, 131.9, 128.7, 128.7, 127.6,
126.9, 126.6, 126.2, 125.1, 124.0, 50.3, 27.3, −2.7. HRMS (EI+) m/z:
calcd for [M]+ C17H20O2SSi 316.0953, found 316.0955.
O-sec-Butyl S-6,6-Dimethyl-4-oxo-1-(trimethylsilyl)heptyl
1
Carbonodithioate (2k). Yield: 1.43 g, 79%. Yellow oil. H NMR
(CDCl3, 400 MHz): diastereomers = 1/1; δ 5.55−5.63 (m, 1H), 3.08−
3.12 (m, 1H), 2.50−2.54 (m, 2H), 2.24 (s, 2H), 2.04−2.12 (m, 1H),
1.55−1.81 (m, 3H), 1.31 (d, 1.5H, J = 6.3 Hz), 1.31 (d, 1.5H, J = 6.3 Hz),
0.95 (s, 9H), 0.91 (t, 1.5H, J = 7.4 Hz), 0.90 (t, 1.5H, J = 7.5 Hz), 0.06 (s,
4.5H), 0.06 (s, 4.5H). 13C NMR (CDCl3, 100 MHz): diastereomers =
1/1; δ 216.1, 210.1, 82.7, 55.0, 43.1, 36.0, 30.8, 29.6, 28.5, 24.3, 18.7, 9.5,
−2.7. HRMS (EI+) m/z: calcd for [M]+ C17H34O2S2Si 362.1769, found
362.1774.
General Procedure B for the One-Pot Synthesis of 2-
Sulfolenes 4. TMS xanthate adduct (2 mmol, 1.0 equiv) in Ph2O
(10 mL) under a nitrogen atmosphere was heated to 200−210 °C for 2 h
and then cooled to room temperature. CH2Cl2 (20 mL) was added,
followed by two successive additions of m-CPBA (1.2 equiv, 70−75%)
every 30 min at room temperature (with the exception of substrate 2j),
and then the mixture was quenched with Na2S2O3 and extracted with
CH2Cl2. The combined organic layers were washed with NaHCO3,
dried over anhydrous MgSO4, and concentrated under reduced
pressure, and purification with flash column chromatography (silica
gel, EtOAc-petroleum ether =25/75) gave the title 2-sulfolene.
5-Phenyl-2-(trimethylsilyl)-2,3-dihydrothiophene 1,1-Diox-
ide (4a). Yield: 474 mg, 89%. White solid, mp 113−114 °C. 1H
NMR (CDCl3, 400 MHz): δ 7.66−7.69 (m, 2H), 7.38−7.41 (m, 3H),
2-(Trimethylsilyl)-2,3,4,5,6,7-hexahydrobenzo[b]thiophene
1,1-Dioxide (4h). Yield: 386 mg, 79%. White solid, mp 89−90 °C. 1H
NMR (CDCl3, 400 MHz): δ 2.70−2.74 (m, 2H), 2.50−2.60 (m, 1H),
2.35 (s, 2H), 2.14 (s, 2H), 1.69−1.76 (m, 4H), 0.25 (s, 9H). 13C NMR
(CDCl3, 100 MHz): δ 144.3, 136.6, 48.7, 31.4, 27.1, 21.2, 21.0, 17.9,
−3.0. HRMS (EI+) m/z: calcd for [M]+ C11H20O2SSi 244.0953, found
244.0961.
2-(Trimethylsilyl)-2,3,4,5-tetrahydronaphtho[1,2-b]thio-
phene 1,1-Dioxide (4i). Yield: 369 mg, 63%. Light-yellow solid, mp
1
138−141 °C. H NMR (CDCl3, 400 MHz): δ 7.71−7.73 (m, 1H),
7.16−7.26 (m, 3H), 2.90−2.99 (m, 4H), 2.73−2.80 (m, 1H), 2.49 (t,
2H, J = 8.2 Hz), 0.29 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 145.7,
136.6, 134.5, 128.7, 127.9, 127.0, 125.6, 122.8, 50.8, 31.0, 27.3, 26.3,
−2.7. HRMS (EI+) m/z: calcd for [M]+ C15H20O2SSi 292.0953, found
292.0952.
5-(Trimethylsilyl)-4,5-dihydro[2,2′-bithiophene] 1,1-Dioxide
1
(4j). Yield: 316 mg, 58%. Yellowish-green solid, mp 119−121 °C. H
NMR (CDCl3, 400 MHz): δ 7.55 (d, 1H, J = 3.2 Hz), 7.34 (d, 1H, J = 5.0
Hz), 7.04−7.06 (m, 1H), 6.64 (t, 1H, J = 3.3 Hz), 2.89−3.02 (m, 2H),
2.76−2.82 (m, 1H), 0.29 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ
139.8, 129.8, 129.1, 128.0, 126.9, 126.7, 49.9, 27.5, −2.7. HRMS (EI+)
m/z: calcd for [M]+ C11H16O2S2Si 272.0361, found 272.0357.
E
dx.doi.org/10.1021/jo402169v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
2-(2,2-Dimethylpropylidene)-5-(trimethylsilyl)tetrahydro-
thiophene 1,1-Dioxide (4k). Yield: 406 mg, 78%. White solid, mp
103−105 °C. 1H NMR (CDCl3, 400 MHz): δ 6.33 (s, 1H), 2.77−2.87
(m, 1H), 2.58−2.68 (m, 2H), 2.27, 2.20 (ABq, 2H, JAB = 14.9 Hz), 0.95
(s, 9H), 0.20 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 143.8, 134.0,
48.1, 37.3, 30.9, 29.5, 27.3, −2.9. HRMS (EI+) m/z: calcd for [M]+
C12H24O2SSi 260.1266, found 260.1265.
General Procedure C for the Synthesis of TMS Dienes 6. A
mixture of K2CO3 (5.0 equiv) and DBU (5.0 equiv) in toluene (5 mL)
was refluxed under nitrogen. Trimethylsilyl chloride (5.0 equiv) was
added to the refluxing mixture, followed by 2-sulfolene (0.5 mmol, 1.0
equiv), and the mixture was stirred for 1 h. The crude reaction mixture
was cooled to room temperature and passed through a short silica plug.
After a wash with petroleum ether (60 mL), the filtrate was concentrated
under reduced pressure to afford the titled TMS diene.
Trimethyl((1E,3E)-4-phenylbuta-1,3-dienyl)silane (6a).11
Yield: 84 mg, 83%.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from Nanyang
Technological University and Ecole Polytechnique.
■
REFERENCES
■
(1) For a review of organosilicon in synthesis, see: Chan, T. H.;
Fleming, I. Electrophilic Substitution Reactions of Organosilicon
CompoundsApplications to Organic Synthesis. Synthesis 1979, 761.
(2) Aikawa, K.; Hioki, Y.; Mikami, K. J. Am. Chem. Soc. 2009, 131,
13922.
(3) Yamamoto, K.; Ohta, M.; Tsuji, J. Chem. Lett. 1979, 713.
(4) (a) Stamos, D. P.; Taylor, A. G.; Kishi, Y. Tetrahedron Lett. 1996,
37, 8647. (b) Alimardanov, A.; Negishi, E. Tetrahedron Lett. 1999, 40,
3839.
(5) Farinola, G. M.; Fiandanese, V.; Mazzone, L.; Naso, F. J. Chem. Soc.,
Chem. Commun. 1995, 2523.
(6) (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780. (b) McNulty, J.;
Das, P. Chem. Commun. 2008, 1244.
((1E,3E)-4-(4-Fluorophenyl)buta-1,3-dienyl)trimethylsilane
(6b).23 Yield: 85 mg, 77%.
((1E,3E)-4-(4-Bromophenyl)buta-1,3-dienyl)trimethylsilane
(6c). Yield: 102 mg, 72%. Yellow oil. 1H NMR (CDCl3, 400 MHz): δ
7.45 (d, 2H, J = 8.4 Hz), 7.27 (d, 2H, J = 8.4 Hz), 6.78 (dd, 1H, J = 15.3
Hz, J = 10.1 Hz), 6.68 (dd, 1H, J = 17.9 Hz, J = 10.1 Hz), 6.51 (d, 1H, J =
15.3 Hz), 6.05 (d, 1H, J = 17.8 Hz), 0.15 (s, 9H). 13C NMR (CDCl3, 100
MHz): δ 143.7, 136.1, 135.9, 132.3, 131.7, 131.4, 127.9, 121.3, −1.3.
HRMS (EI+) m/z: calcd for [M]+ C13H17BrSi 280.0283, found
280.0286.
(7) Lee, B. S.; Gil, J. M.; Oh, D. Y. Tetrahedron Lett. 2001, 42, 2345.
(8) (a) Andreini, B. P.; Carpita, A.; Rossi, R. Tetrahedron Lett. 1988, 29,
2239. (b) Fianese, V.; Marchese, G.; Mascolo, G.; Naso, F.; Ronzini, L.
Tetrahedron Lett. 1988, 29, 3705.
(9) Karabelas, K.; Hallberg, A. J. Org. Chem. 1988, 53, 4909.
(10) Hansen, A. L.; Ebran, J.-P.; Ahlquist, M.; Norrby, P.-O.;
Skrydstrup, T. Angew. Chem., Int. Ed. 2006, 45, 3349.
(11) Ni, Z.-J.; Yang, P.-F. ; Ng, D. K. P.; Tzeng, Y.-L.; Luh, T.-Y. J. Am.
Chem. Soc. 1990, 112, 9356.
Trimethyl((1E,3E)-4-p-tolylbuta-1,3-dienyl)silane (6d).24
Yield: 80 mg, 74%.
(12) Stille, J. K.; Groht, B. L. J. Am. Chem. Soc. 1987, 109, 813.
(13) Matsubara, S.; Otake, Y.; Morikawa, T.; Utimoto, K. Synlett 1998,
1315.
((1E,3E)-4-(4-Methoxyphenyl)buta-1,3-dienyl)trimethyl-
silane (6e).24 Yield: 90 mg, 78%.
Trimethyl((1E,3E)-3-methyl-4-phenylbuta-1,3-dienyl)silane
(6f).11 Yield: 69 mg, 64%.
(14) Petasis, N. A.; Akritopoulou, I. Synlett 1992, 665.
(15) (a) Yang, T.-K.; Chu, H.-Y.; Lee, D.-S.; Jiang, Y.-Z.; Chou, T.-S.
Tetrahedron Lett. 1996, 37, 4537 and references cited therein. (b) Chou,
S.-S. P.; Chao, M.-H. Tetrahedron Lett. 1995, 36, 8825. (c) Tso, H. H.;
Yang, N.-C.; Chang, Y.-M. J. Chem. Soc., Chem. Commun. 1995, 1349.
(d) Tso, H. H.; Chou, T.-S.; Hung, S. C. J. Chem. Soc., Chem. Commun.
1987, 1552. (e) Sengupta, S.; Bhattacharyya, S. Synth. Commun. 1996,
26, 231.
(16) For reviews of the xanthate radical addition transfer reaction, see:
(a) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672. (b) Quiclet-
Sire, B.; Zard, S. Z. Chem.Eur. J. 2006, 12, 6002. (c) Quiclet-Sire, B.;
Zard, S. Z. Top. Curr. Chem. 2006, 264, 201. (d) Zard, S. Z. Aust. J. Chem.
2006, 59, 663. (e) Zard, S. Z. Org. Biomol. Chem. 2007, 5, 205.
(f) Quiclet-Sire, B.; Zard, S. Z. Pure Appl. Chem. 2011, 83, 519.
(17) Lusinchi, M.; Stanbury, T. V.; Zard, S. Z. Chem. Commun. 2002,
1532.
Trimethyl((1E,3E)-4-(naphthalen-2-yl)buta-1,3-dienyl)silane
(6g). Yield: 110 mg, 87%. Yellow oil. 1H NMR (CDCl3, 400 MHz): δ
7.78−7.81 (m, 4H), 7.64 (dd, 1H, J = 8.6 Hz, J = 1.5 Hz), 7.42−7.49 (m,
2H), 6.94 (dd, 1H, J = 15.6 Hz, 9.9 Hz), 6.73−6.80 (m, 2H), 6.08 (d, 1H,
J = 18.6 Hz), 0.16 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 144.1, 135.2,
134.7, 133.6, 133.0, 133.0, 132.0, 128.2, 128.0, 127.7, 126.7, 126.3, 125.9,
123.5, −1.2. HRMS (EI+) m/z: calcd for [M]+ C17H20Si 252.1334, found
252.1326.
(E)-(2-(3,4-Dihydronaphthalen-2-yl)vinyl)trimethylsilane (6i).
1
Yield: 100 mg, 88%. Colorless oil. H NMR (CDCl3, 400 MHz): δ
7.10−7.20 (m, 4H), 6.78 (d, 1H, J = 19.0 Hz), 6.52 (s, 1H), 6.06 (d, 1H,
J = 18.9 Hz), 2.89 (t, 1H, J = 8.1 Hz), 2.52 (t, 1H, J = 8.1 Hz), 0.18 (s,
9H). 13C NMR (CDCl3, 100 MHz): δ 145.3, 138.7, 135.8, 134.7, 128.7,
128.2, 127.2, 127.0, 126.6, 126.5, 27.8, 22.4, −1.1. HRMS (EI+) m/z:
calcd for [M]+ C15H20Si 228.1334, found 228.1328.
Trimethyl((1E,3E)-4-(thiophen-2-yl)buta-1,3-dienyl)silane
(6j). Yield: 75 mg, 72%. Yellow oil. 1H NMR (CDCl3, 400 MHz): δ 7.17
(d, 1H, J = 4.3 Hz), 6.97−7.00 (m, 2H), 6.58−6.74 (m, 3H), 5.96−6.03
(m, 1H), 0.13 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 143.5, 142.6,
134.9, 131.4, 127.6, 126.2, 125.6, 124.6, −1.3. HRMS (EI+) m/z: calcd
for [M]+ C11H16SSi 208.0742, found 208.0747.
(18) In practically all of the previous studies, O-ethyl xanthates were
used. The adducts, however, do not undergo the Chugaev elimination at
reasonable temperatures. Hence, the use of O-(2-butyl) xanthates 2 was
required in the present approach.
(19) Trimethylsilyl chloride, TMSCl, should react rapidly with residual
water, and the released HCl can be irreversibly neutralized with excess
anhydrous potassium carbonate. The latter reagent is also a good
dehydrating agent in its own right.
(20) Use of an excess amount of reagents (5 equiv) was required to
drive the reaction to completion within 45 min to 1 h as well as to
safeguard against possible desilylation at prolonged reaction times.
(21) Jones, M. H.; Woodcock, J. T. Int. J. Miner. Process. 1983, 10, 1.
(22) Gheorghe, A.; Quiclet-Sire, B.; Vila, X.; Zard, S. Z. Org. Lett. 2005,
7, 1653.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of the compounds potassium O-sec-
butyl carbonodithioate, 2a−k, 4a−k, 6a−g, 6i, and 6j and the
NOESY spectrum of 6f. This material is available free of charge
via the Internet at http://pubs.acs.org.
(23) Shen, Y.; Wang, T. Tetrahedron Lett. 1990, 31, 543.
(24) Babudri, F.; Farinola, G. M.; Fiandanese, V.; Mazzone, L.; Naso, F.
Tetrahedron 1998, 54, 1085.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: sgkim@ntu.edu.sg.
*E-mail: zard@poly.polytechnique.fr.
Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/jo402169v | J. Org. Chem. XXXX, XXX, XXX−XXX