Cycloaddition Chemistry of Tetrafluorothiophene S,S-Dioxide

Article abstract of DOI:10.1021/acs.joc.6b00848

Tetrafluorothiophene S,S-dioxide has been found to be a powerful and versatile cycloaddend that undergoes a wide range of reactions as a Diels-Alder diene, dienophile, and [2 + 2] addend. Because it dimerizes only slowly at high temperatures, a broad range of conditions are available for these transformations. Reactions with terminal alkynes yield products of both Diels-Alder and [2 + 2] cycloaddition. Remarkably, the orbital topology-forbidden [2 + 2] process sometimes dominates over the allowed Diels-Alder reaction.

Full text of DOI:10.1021/acs.joc.6b00848

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Cycloaddition Chemistry of Tetrafluorothiophene S,S‑Dioxide
David M. Lemal*
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States
S
* Supporting Information
ABSTRACT: Tetrafluorothiophene S,S-dioxide has been
found to be a powerful and versatile cycloaddend that
undergoes a wide range of reactions as a Diels−Alder diene,
dienophile, and [2 + 2] addend. Because it dimerizes only
slowly at high temperatures, a broad range of conditions are
available for these transformations. Reactions with terminal alkynes yield products of both Diels−Alder and [2 + 2]
cycloaddition. Remarkably, the orbital topology-forbidden [2 + 2] process sometimes dominates over the allowed Diels−Alder
reaction.
Diels−Alder dimerization accompanied by extrusion of SO2. The
minor one (4) was unexpected, a [2 + 2] cycloadduct with 2-fold
symmetry. There are four reasonable possibilities (4a−d) for its
regio- and stereochemistry (highly strained trans 4/5 ring fusions
excluded), of which we strongly favor anti dimer 4a. Presumably,
4a and 4b would form via α,α′ (or β,β′) diradicals, whereas α,β′
diradicals would lead to 4c and 4d.7 To model the energy
difference, radicals 5 and 6 formed by attack of a hydrogen atom
at the α and β positions of TFTDO, respectively, were compared,
and the allylic radical 5 was found to be lower in energy by 13.5
kcal/mol.8 Syn dimer 4b, which twists a bit to relieve O−O
nonbonded repulsion, lies 5.4 kcal/mol above 4a.
INTRODUCTION
■
Anticipating that it would be a highly reactive electrophile and
cycloaddend, we recently synthesized the title compound
tetrafluorothiophene S,S-dioxide (TFTDO) with plans to
explore its chemistry.1 It was expected to prove capable as a
Diels−Alder diene of incorporating a 1,2,3,4-tetrafluorophenyl
and/or -cyclohexadienyl fragment into a wide variety of
molecular architectures. Given the profound effects that
substitution of fluorine for hydrogen has on molecular properties
and behavior,2,3 useful applications could follow, especially in
materials chemistry.4 In the present investigation of TFTDO’s
cycloaddition chemistry, the promise of potent reactivity is
realized, accompanied by surprises.
RESULTS AND DISCUSSION
■
While developing a route to the sulfone TFTDO (1), we
generated the corresponding sulfoxide 2 and found it to be a
highly reactive Diels−Alder diene.1 The downside was that it
Reaction with Alkenes. TFTDO undergoes Diels−Alder
addition to alkenes with extrusion of SO2. In some cases, the
initially formed tetrafluorocyclohexadiene was isolated; in others,
it spontaneously underwent further reaction or was treated with
DDQ to aromatize it (Table 1).
dimerizes quite rapidly in solution at 0 °C, thus greatly limiting its
usefulness as a cycloaddend.5 It was therefore gratifying to find
that the sulfone is a very robust compound. When a 35% (w/v)
solution of TFTDO in 1,2-dichloroethane was heated in a
pressure vessel at 111−112 °C for 55 h, a 5.8:1 mixture of two
dimerization products was obtained in 89% yield.6 It is
noteworthy that 3% of 1 remained unchanged under these
forcing conditions. The principal product (3) was the result of
Styrene adds to TFTDO readily at 50 °C in chloroform with
loss of SO2 to afford 7 (Scheme 1). The calculated reaction
coordinate (Figure 1) reveals that the overall reaction is very
exothermic, the activation enthalpy for addition is quite low, and
the barrier to extrusion of SO2 is tiny.
Received: April 15, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b00848
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Table 1. Cycloadditions of TFTDO with Alkenes
Figure 1. Schematic coordinate for the reaction of TFTDO with
styrene. Relative enthalpies are in kcal/mol (B3LYP/cc-PVDZ+). The
transition-state value for adduct fragmentation is not shown because at
this level of theory, though ΔE⧧ is positive, ΔH⧧ and ΔG⧧ are actually
negative (0.61, −0.40, and −0.96 kcal/mol, respectively). With the 6-
311G**+ basis, the corresponding quantities are all positive: 1.47, 0.38,
and 0.37 kcal/mol, respectively.
ment with DDQ at 80 °C for 3 h gave the 9,10-
dihydrophenanthrene, and conversion to 1,2,3,4-tetrafluorophe-
nanthrene (12) was accomplished with DDQ by prolonged
refluxing in chlorobenzene (bp 125 °C).
The initial product 13 formed when TFTDO was allowed to
react with 1,5-cyclooctadiene underwent internal Diels−Alder
reaction readily at 60 °C to create the cage molecule 14 (Scheme
2). Excess p-benzoquinone (15) added slowly but in good yield
Scheme 2
a
b
By NMR in this and subsequent tables. For the initial product.
Scheme 1
Scheme 3
to TFTDO at 80 °C to give naphthoquinone 17 (Scheme 3).
This product, along with hydroquinone, resulted from oxidation
by benzoquinone of the dihydronaphthoquinone 16 formed
initially. Oxidation occurred either directly or following
tautomerization of 16 to the corresponding hydroquinone.
Because the presence of hydroquinone(s) in the reaction mixture
gave rise to quinhydrone formation, the polar solvent acetonitrile
was needed to keep things in solution, and the workup included
oxidation with persulfate to eliminate the quinhydrones. With its
array of electronegative atoms, TFTDO might have been
Cyclooctene reacted with TFTDO under similar conditions to
give 8 in quantitative NMR yield, and acenaphthylene afforded
dihydrofluoranthene 9 almost quantitatively. The product of 2-
vinylpyridine addition to 1, formed at rt, was aromatized by
heating with DDQ at 80 °C in 1,2-dichloroethane to yield 10.
Indene also added at rt, and the initial product was aromatized
similarly to afford 1,2,3,4-tetrafluorofluorene (11). 1,2-Dihy-
dronaphthalene reacted with TFTDO at 85 °C to give a
tetrahydrophenanthrene that was aromatized in stages. Treat-
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expected to react selectively with electron-rich addends, but its
addition to the highly electron-deficient quinone 15 demon-
strates that it is ambiphilic, capable of reacting across the polarity
spectrum.
With Internal Alkynes. Quite vigorous conditions were
required for cycloaddition of disubstituted acetylenes to
TFTDO, Diels−Alder reactions that yielded tetrafluorobenzenes
upon loss of SO2 (Table 2). Particularly in the case of tolane
arose from [2 + 2] cycloaddition. The identity of 23 was
confirmed with an X-ray crystal structure. Here an orbital
topology-forbidden process out-competed an allowed one.7 The
anatomy of these transformations and possible reasons for
inversion of the usual relationship between allowed and
forbidden processes will be reported elsewhere. A similar result
was found with 1-ethynylcyclohexene as addend (Table 3), with
[2 + 2] cycloaddition to give 25 again dominant over [4 + 2] to
yield 24. In the case of 1-hexyne, the two modes of reaction
competed closely, yielding 26 and 27.
Table 2. Cycloadditions of TFTDO with Internal Alkynes
With Conjugated Dienes. In Diels−Alder reactions with
dienes, TFTDO could play the role of dienophile instead of
diene. That was found to be the case with a diverse array of
dienes, revealing the sulfone to be an unusually powerful
dienophile (Table 4). With 2,3-dimethylbutadiene, TFTDO
Table 4. Cycloadditions of TFTDO with Conjugated Dienes
(diphenylacetylene) as addend, reaction with TFTDO to give 18
had to compete with dimerization of the sulfone. Obtaining
dimethyl tetrafluorophthalate (19) under conditions comparable
to those for producing 20 and 21 constitutes further evidence for
TFTDO’s ambiphilic nature.
With Terminal Alkynes. Phenylacetylene reacted readily
with TFTDO at 100 °C to afford two products in a 2.8:1 ratio
(Table 3). To our surprise, the expected one, tetrafluorobiphenyl
22, proved to be the minor product; the dominant one (23)
Table 3. Cycloadditions of TFTDO with Terminal Alkynes
a
b
Stereochemistry not assigned. For initial adduct.
afforded 28 in excellent yield at rt. Naphthalene’s challenge to
TFTDO’s dienophilicity was met with the formation of an endo/
exo pair of adducts 29. Like naphthalene, thiophene reacts as a
Diels−Alder diene only with potent dienophiles. It does so with
TFTDO under reflux to give a 3:1 mixture of stereoisomers 30.
Furan added readily at rt to afford a 19:1 mixture of
stereoisomeric adducts 31. Here, the ratio was sufficiently
lopsided that calculations could be expected to reliably allow
assignments of the stereochemistry. The transition state leading
to the exo adduct was calculated to lie 1.1 kcal/mol below that for
C
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the endo isomer and the exo adduct itself to lie 3.1 kcal/mol
below the endo.8 Thus, the major, isolated adduct was the exo
isomer. N-Methylpyrrole added to TFTDO at 0−25 °C, yielding
a 1.5:1 mixture of endo/exo isomers 32. Spin−spin splitting of
the fluorines adjacent to the bridgehead hydrogens was much
greater for the endo than for the exo isomer in both furan and N-
methylpyrrole adducts. On this basis, the major isomer obtained
from the pyrrole has the endo configuration.
When a dilute solution of the pyrrole adducts in deuterio-
chloroform was allowed to stand at rt, 19F NMR signals for
TFTDO slowly appeared. Their identity was confirmed by
addition of furan, which caused them to disappear and peaks for
the furan adduct to develop. The endo isomer was found to be
the principal, if not exclusive, source of the TFTDO. Thus, this
pyrrole adduct undergoes retro-Diels−Alder reaction even at rt, a
reflection of the aromaticity of pyrroles. The facility of retro-
reaction of pyrrole Diels−Alder adducts can be very useful, as
illustrated in the synthesis of the very strained fluoroalkene
octafluorobicyclohex-1(4)-ene.9
where the calculated ratio of diene to triene is 3.2 × 10−6. Thus,
TFTDO eschews reaction with a perfectly adequate dienophile,
choosing instead a diene present at the level of 3 ppm! By this
measure, as with the furan example, the preference at issue is
dramatic.
1,3-Cyclooctadiene was chosen as a strongly twisted diene that
is quite resistant to flattening.12 In reacting with this hydro-
carbon, TFTDO was finally forced to accept the role of diene.
The resulting adduct (−SO2), formed at 80 °C, was aromatized
with DDQ to give benzocyclooctadiene 35.
In 1980, Raasch reported the synthesis of tetrachlorothio-
phene S,S-dioxide (36) and an extensive study of its cyclo-
addition chemistry.13 For the most part, this chemistry closely
parallels that of its perfluoro analogue TFTDO, but there are
exceptions. Particularly notable are the Diels−Alder reactions
with N-methylpyrrole, thiophene, and in a later study,14
naphthalene. Here, the tetrachloro compound served not as
dienophile but as diene to yield 37−39, respectively.
Phenanthrene 39 arose from hydrogen migration in and loss of
HCl from the initially formed dihydrophenanthrene. Further
study will be required to gain an understanding of the strong
tendency of TFTDO to play the dienophile role in its reactions
with conjugated dienes.
To gain a sense of how strongly TFTDO prefers to act as
dienophile rather than diene, energetics for the contrasting
modes of reaction with furan were compared computationally
(Figure 2).8 Surprisingly, both of the adducts obtained
Figure 2. Comparison of possible Diels−Alder adducts of TFTDO and
furan. Energies are in kcal/mol.
experimentally (31n, 31x) were found to lie well above the
two in which TFTDO serves as the diene (33n, 33x). The
transition state leading to 33x lies 8.6 kcal/mol above that for
31x. Even with starting geometries strongly biased toward the
lowest energy adduct 33n, calculations intended to locate a
transition state for its formation evolved to the transition state for
the highest energy adduct 31n, to which it is related by Cope
rearrangement! Clearly, the inherent preference of TFTDO for
the dienophile role can overcome large differences in adduct
stability.
To learn about the energetic price for α-attack on TFTDO to
form an allylic radical, the enthalpy change was calculated for
formation of radical 40: ΔH = −52.8 kcal/mol (Scheme 5).
Scheme 5
Cycloheptatriene offered another test of the dienophile vs
diene preference of TFTDO. Remarkably, the product of its
reaction with the triene had the structrure 34. TFTDO had again
played the dienophile part, not with the triene, but with its
bicyclic valence isomer norcaradiene. The pair exists in a very
mobile equilibrium (Scheme 4).10 In light of the triene’s
nonplanarity,11 its failure to react as a diene was not unexpected,
but it could have served well as a dienophile. No experimental
measurement has been made of the energy difference between
cycloheptatriene and norcaradiene, but the value we calculate is a
full 8.1 kcal/mol at 25 °C.8 The reaction was carried out at 50 °C,
Because a C−C single bond is worth about 85 kcal/mol,15 the
cost of breaking a double bond of TFTDO is roughly (85−53) =
32 kcal/mol. Even allowing for the resulting allylic stabilization,
this is a very low value. It underpins the formation of [2 + 2]
dimer 4 and [2 + 2] cycloaddition with terminal alkynes,
reactions that presumably proceed via diradicals.
CONCLUSION
■
Tetrafluorothiophene S,S-dioxide (TFTDO, 1) has been shown
to be a powerful and versatile electrophilic cycloaddend. It is
perhaps better described as ambiphilic, as it reacts with alkenes
and alkynes of widely varying polarity. With alkenes it undergoes
Diels−Alder reactions with loss of SO2 to afford tetrafluor-
ocyclohexadiene derivatives; those with hydrogens at the ring
juncture can be oxidized with DDQ to tetrafluorobenzenes. With
internal alkynes, tetrafluorobenzenes are formed directly.
Scheme 4
D
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and CDCl3. The tube was immersed in a bath at 50 °C for 3 h and then
allowed to stand at rt for 12 h. Yield of diene 8 was quantitative. Solvent
was replaced with CD2Cl2 for literature comparison, and a bit of CCl3F
was added for calibration. 19F NMR (CD2Cl2): δ −145.3 (m, 2F),
−167.4 (m, 2F) [lit.17 −145.2 (m, 2F), −167.3 (m, 2F)].
Terminal alkynes undergo both the expected Diels−Alder
reaction and [2 + 2] cycloaddition, an orbital topology-forbidden
process that can nonetheless be the dominant reaction pathway.
In reaction with conjugated dienes, TFTDO has invariably
played the role of dienophile except when the diene is badly
twisted. Under sufficiently vigorous conditions, 1 reacts with
itself in both Diels−Alder and [2 + 2] fashion. Attack at an α-
position of TFTDO to form an allylic radical is quite inexpensive
energetically; this fact is important for an understanding of much
of the sulfone’s cycloaddition chemistry.
7,8,9,10-Tetrafluoro-6b,10a-dihydrofluoranthene (9). Techni-
cal-grade acenaphthylene was sublimed at atmospheric pressure and
temperature up to 135 °C. The resulting bright yellow flakes contained
about one-third as much acenaphthene as acenaphthylene plus minor
impurities. To a solution of 241 mg of TFTDO (91%, 1.2 mmol) in 3
mL of toluene was added 365 mg of the sublimed acenaphthylene (∼1.8
mmol), and the mixture was heated in a 94 °C bath for 2 h to afford the
Diels−Alder adduct (−SO2) in 97% yield. Toluene was replaced with
CH2Cl2, 2 g of silica gel was added, and solvent was again evaporated.
Residue was poured onto a 10 g column of silica gel and eluted with 5%
EtOAc/hexane. Since separation from acenaphthene was poor, early
fractions were combined and rechromatographed on 12 g of silica gel
with hexane, giving 240 mg of 9 (74% isolated yield). Mp: 131−132 °C.
19F NMR: δ −142.6 (s, 2F), −165.9 (s, 2F). 1H NMR: δ 7.76 (m, 2H),
7.54 (m, 4H), 4.96 (m, 2H). 13C NMR δ 141.6, 139.8 (1JCF = 263 Hz),
136.8, 132.1 (1JCF = 252 Hz), 131.8, 128.3, 124.3, 120.7, 43.2. Anal.
Calcd for C16H8F4: C, 69.57; H, 2.92; F, 27.51. Found: C, 69.56; H, 2.96;
F, 27.41.
EXPERIMENTAL SECTION
■
NMR spectra were measured on 300, 500, and 600 MHz spectrometers,
and, except where noted, all reported here were measured in CDCl3. 19
F
NMR spectra were referenced to internal trichlorofluoromethane via
hexafluorobenzene (δ −162.11 ppm in CDCl3) as internal standard; 1H
and 13C NMR spectra were referenced to TMS via CHCl3 (δ 7.27 and
77.0 ppm, respectively). TFTDO was prepared from its dibromide1 and
assayed by NMR integration versus hexafluorobenzene. For assays,
delay time between pulses was 6 s to take into account differential
relaxation times. NMR product yields were obtained in the same
manner.
2-(2,3,4,5-Tetrafluorophenyl)pyridine (10).18 A solution of 403
mg of TFTDO (90%, 1.9 mmol) and 252 mg of 2-vinylpyridine (2.4
mmol) in 4 mL of 1,2-dichloroethane was allowed to stand at rt for 6 h.
Reaction was complete, and the adduct (−SO2) was present in 95%
yield. From a small-scale reaction in CDCl3, 19F NMR: δ −136.7 (m,
1F), −140.6 (m, 1F), −162.6 (apparent 1:3:3:1 q, Japp = 6.9 Hz, 1F),
−165.1 (apparent 1:4:6:4:1 quin, Japp = 7.1 Hz, 1F). DDQ (500 mg, 2.2
mmol) was added to the 1,2-dichloroethane solution, and the mixture
was stirred in a bath at 80 °C for 2 h to complete the aromatization.
Product was pipetted into a 25 mL round-bottom flask, and the
remaining brown syrup was washed with a little CH2Cl2. To the
combined clear liquid was added 1.5 g of silica gel, solvent was
evaporated, and the tan residue was chromatographed on 12 g of silica
gel with CH2Cl2 as eluent. All but a few late fractions were combined and
recrystallized from hexane at −25 °C. Mp of pyridine 10: 56.5−57.5 °C.
19F NMR: δ −139.3 (m, 1F), −143.4 (m, 1F), −155.1 (m, 1F), −155.8
(m, 1F). 1H NMR: δ 8.73 (dm, J = 4.7 Hz, 1H), 7.81 (m, 2H), 7.77 (m,
1H), 7.33 (m, 1H). 13C NMR: δ 150.3, 150.0, 147.2 (1JCF = 247 Hz),
145.9 (1JCF = 250 Hz), 141.0 (1JCF = 252 Hz), 140.6 (1JCF = 256 Hz),
136.8, 124.3, 123.6, 123.4, 111.6. Anal. Calcd for C11H5F4N: C, 58.16;
H, 2.22; F, 33.46; N, 6.17. Found: C, 58.28; H, 2.13; F, 33.21; N, 6.22.
The isolated yield was rather low, despite the fact that the DDQ
oxidation was quite clean. Presumably some pyridine 10 remained in the
brown residue after the reaction, protonated by or H-bonded to the
DDQ-derived hydroquinone.
2,3,3a,4,5,6,7,7a-Octafluoro-3a,7a-dihydrobenzo[b]-
thiophene 1,1-Dioxide (3) and 2,3,3a,3b,4,5,6a,6b-Octafluoro-
3a,3b,6a,6b-tetrahydrocyclobuta[1,2-b:4,3-b′]dithiophene
1,1,6,6-Tetroxide (4). Into a heavy-walled glass tube with a threaded
Teflon stopper were placed 798 mg of TFTDO (89%, 3.8 mmol) and 2
mL of 1,2-dichloroethane. The pressure vessel was mounted in a vertical
pipe wrapped in heating tape and maintained at 111−112 °C for 55 h.
Two dimerization products were obtained in the ratio 5.8:1 (Diels−
Alder: [2 + 2] dimer). Total yield based on TFTDO consumed was
89%; 3% of the TFTDO was still present. The reaction mixture was
transferred to a 10 mL round-bottom flask and subjected to Kugelrohr
distillation at 10 Torr up to 100 °C. A 317 mg sample of the 598 mg of
distillate was recrystallized from hexane at ∼−25 °C to give the Diels−
Alder product 3 as white needles (195 mg). Mp: 27.5−28.5 °C. 19F
NMR: δ −138.3 (m, 1F), −144.7 (narrow m, 1F), −146.5 (d, J = 10.8
Hz, 1F), −148.3 (narrow m, 1F), −153.4 (m, 1F), −153.6 (m, 1F),
−163.7 (m, 1F), −169.1 (m, 1F). 13C NMR: δ 147.0 (1JCF = 323 Hz),
141.6 (1JCF = 309 Hz), 138.1 (1JCF = ∼274 Hz), 136.7 (1JCF = ∼273 Hz),
136.1 (1JCF = ∼297 Hz), 131.0 (1JCF = 272 Hz), 99.8 (1JCF = 251 Hz),
83.3 (1JCF = 227 Hz). Anal. Calcd for C8F8O2S: C, 30.78; H, 0.0; F,
48.70. Found: C, 30.50; H, 0.0; F, 48.46.
The less volatile [2 + 2] dimer 4 had formed as white crystals on the
walls of the Kugelrohr apparatus between the pot and receiver. It was
washed out with CH2Cl2 and after solvent removal recrystallized from
hexane. Mp: 142.5−143.5 °C. 19F NMR: δ −139.6 (d, J = 5.3 Hz, 2F),
−140.9 (m, 2F), −168.7 (m, 2F), −182.5 (narrow m, 2F). 13C NMR: δ
148.0 (1JCF = 275 Hz), 137.1 (1JCF = 307 Hz), 95.7 (1JCF = 292 Hz), 89.5
(1JCF = ∼268 Hz). Anal. Calcd for C8F8O4S2: C, 25.54; H, 0.0; F, 40.40;
S, 17.05. Found: C, 25.52; H, 0.0; F, 40.66; S, 17.09.
1,2,3,4-Tetrafluorofluorene (11). A mixture of TFTDO (297 mg,
88%, 1.4 mmol), 256 mg of distilled indene, and 3 mL of 1,2-
dichloroethane was allowed to stand at rt for 17 h, giving the
dihydrofluorene in 82% yield. A small sample was dissolved in CDCl3 for
19F NMR: δ −142.0 (br d, J = 29 Hz, 1F), −143.1 (dm, J = 20 Hz, 1F),
−165.2 (m, 1F), −165.7 (m, 1F). To the reaction mixture was added 0.5
g (2.2 mmol) of DDQ, and the flask was immersed in a bath at 75 °C for
8 h. Product was deposited on 1.5 g of silica gel, and the brown powder
was placed on a 15 g column of the gel for elution with hexane. Fluorene
11. Mp: 104−105 °C. 19F NMR: δ −143.2 (dd, J = 20, 17 Hz, 1F),
−147.0 (dd J = 20, 17 Hz, 1F), −158.1 (t, J = 20 Hz, 1F), −158.8 (t, J =
20 Hz, 1F). 1H NMR: δ 7.89 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 7.4 Hz, 1H),
7.43 (t, J = 7.3 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 3.94 (s, 2H). 13C NMR:
δ 143.9 (1JCF = 246 Hz), 142.6 (1JCF = 249 Hz), 141.9, 140.1 (1JCF = 250
Hz), 139.3 (1JCF = 252 Hz), 137.1, 127.8, 127.6, 125.3, 124.9, 124.4,
123.4, 34.1. Anal. Calcd for C13H6F4: C, 65.56; H, 2.54; F, 31.91. Found:
C, 65.44; H, 2.42; F, 31.65.
3,4,5,6-Tetrafluoro-1,2-dihydro-1,1′-biphenyl (7). A combina-
tion of 221 mg of TFTDO (91%, 1.1 mmol), 164 mg (1.6 mmol) of
freshly distilled styrene, and 3 mL of chloroform was heated at 50 °C;
reaction was complete after 5.5 h (86% yield). Product was deposited on
2 g of silica gel, then chromatographed on 6 g of the gel with hexane as
eluent. Standing in air at rt, diene 7 degraded rather quickly. 19F NMR: δ
−137.6 (s, 1F), −140.3 (s, 1F), −163.8 (s, 1F), 164.6 (s, 1F). 1H NMR:
δ 7.38 (m, 5H), 3.91 (m, 1H), 3.30 (m, 1H), 2.69, (m, 1H). 13C NMR: δ
141.5 (1JCF = ∼268 Hz), 138.7, 138.2 (1JCF = ∼267 Hz), 134.2 (1JCF
=
253 Hz), 132.2 (1JCF = 253 Hz), 129.2, 128.2, 127.0, 39.4, 31.5.
To confirm the identity of the diene, a 24 mg (0.11 mmol) sample in
CDCl3 was treated with 30 mg (0.13 mmol) of DDQ. Heated in a bath at
∼65 °C for 7 h, the mixture afforded 2,3,4,5-tetrafluorobiphenyl
(22).1,16 Its 19F NMR spectrum was virtually identical with that of 22
reported below.
1,2,3,4-Tetrafluoro-4a,5,6,7,8,9,10,10a-octahydrobenzo[8]-
annulene (8).17 Into an NMR tube were placed 35 mg of TFTDO
(86%, 0.16 mmol), 28 mg (0.25 mmol) of freshly distilled cyclooctene,
1,2,3,4-Tetrafluorophenanthrene (12).19 TFTDO (307 mg,
85%, 1.4 mmol) and 157 mg (1.21 mmol) of 1,2-dihydronaphthalene
were dissolved in 3 mL of 1,2-dichloroethane. Here, the hydrocarbon is
the limiting reagent because if present in excess, separation of the
product from naphthalene formed after aromatization is problematic.
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Mixture was heated in a bath at ∼85 °C for 17 h, with loss of much of the
solvent. The tetrahydrophenanthrene was formed in 83% yield. 19F
NMR: δ −137.7 (s, 1F), −146.4 (s, 1F), −164.3 (unresolved d, J = ∼5.3
Hz, 1F), −165.4 (unresolved d, J = ∼6.0 Hz, 1F). DDQ (304 mg, 1.3
mmol) and 2 mL of 1,2-dichloroethane were added and heating was
resumed for 3 h at 80 °C. The reaction mixture was partitioned between
15 mL of ether and 10 mL of water containing 0.50 g (2.0 mmol) of
Na2S2O3·5H2O. The ether layer was extracted with 10 mL of satd aq
NaHCO3, a little brine, and then dried over Na2SO4. Silica gel (1.5 g)
was added, solvent was evaporated, and the light brown powder was
poured onto a 15 g column of silica gel for elution with hexane. The
DDQ oxidation had produced a little phenanthrene 12 along with the
dihydrophenanthrene. For the dihydro compound, 19F NMR: δ −144.0
(m, 1F), −145.2 (dd, J = 22, 13.0 Hz, 1F), −158.2 (dd, J = 21, 3.2 Hz,
1F), −159.9 (t, J = 20 Hz, 1F). To the combined fractions in 4 mL of
chlorobenzene was added ∼50% excess of DDQ, and the mixture was
refluxed for 22 h. Since a bit of dihydro compound still remained, some
additional DDQ was introduced, and refluxing was continued for
another 6 h. Chlorobenzene was replaced with CH2Cl2, 1.5 g of silica gel
was added, and solvent was evaporated again. The resulting brown
powder was chromatographed on 15 g of silica gel with hexane as eluent,
affording pure phenanthrene 12. Mp: 172.5−173 °C. 19F NMR: δ
−140.0 (unresolved ddm, 1F), −149.3 (dd, J = 21, 14.1 Hz, 1F), −158.6
(unresolved dd, J = 19, 21 Hz, 1F), −158.9 (td, J = 21, 3.8 Hz, 1F). 1H
NMR: δ 8.95 (d, J = 8.1 Hz, 1H), 7.93 (dd, J = 7.4, 1.7 Hz, 1H), 7.89 (dd,
J = 9.1, 1.7 Hz, 1H), 7.80 (d, J = 9.1 Hz, 1H), 7.71 (m 2H). 13C NMR: δ
145.9 (1JCF = ∼261 Hz), 142.4 (1JCF = ∼248 Hz), 139.4 (1JCF = ∼245
Hz), 137.8 (1JCF = ∼245 Hz), 132.3, 129.0, 128.9, 128.0, 127.8, 127.0,
126.9, 118.2, 116.8, 115.8. Anal. Calcd for C14H6F4: C, 67.21; H, 2.42; F,
30.38. Found: C, 66.97; H, 2.56; F, 30.16.
5,6,7,7a-Tetrafluoro-2,3,3a,4,5,7a-hexahydro-1H-1,5,4-
(epipropane[1,1,3]triyl)indene (14). Into an NMR tube were placed
37 mg of TFTDO (89% pure, 0.18 mmol), several drops of 1,5-
cyclooctadiene, and CDCl3. After 5 h in a bath at 60 °C, the tube
contained 14 in 60% yield. An oven-dried 10 mL round-bottom flask was
charged with 297 mg of TFTDO (∼90%, 1.4 mmol), 184 mg (1.7
mmol) of freshly distilled diene, and 3 mL of chloroform. Solution was
refluxed for 3 h, then 1.5 g of silica was added and the solvent was
evaporated. Residue was chromatographed on 9 g of silica gel with
hexane as eluent. Mp of 14: 105.5−106.5 °C. 19F NMR: δ −156.3 (m,
2F), −190.9 (m, 2F). 1H NMR: δ 2.15 (s, 4H), 1.91 (m, 8H). 13C NMR:
δ 131.0 (1JCF = 276 Hz), 96.4 (1JCF = 202 Hz), 44.6, 22.5. Anal. Calcd for
C12H12F4: C, 62.06; H, 5.21. Found: C, 62.07; H, 5.30.
5,6,7,8-Tetrafluoro-1,4-naphthalene-1,4-dione (17). A solu-
tion containing 292 mg of TFTDO (95%, 1.5 mmol), 397 mg of p-
benzoquinone (3.7 mmol), and 3 mL of acetonitrile was refluxed for 49
h. The dominant product was the quinone 17, but some of the initial
adduct (−SO2) was also present. Solvent was evaporated, and the black
residue (color due to quinhydrone formation) was transferred with 20
mL of hot CH2Cl2 to a 50 mL round-bottom flask. Potassium persulfate
(0.50 g, 1.9 mmol) in 10 mL of water was added, and the mixture was
stirred for 1 h at rt, then allowed to stand overnight. The two-phase
mixture was separated, the aqueous layer was washed with 10 mL of
CH2Cl2, and the golden brown combined organic phase was dried over
Na2SO4. The yield of product was 80%, but that included 8% of
unoxidized initial product that had survived the persulfate treatment,
presumably because it had not enolized. Chromatography on 8 g of silica
gel with 20% EtOAc/hexane failed to achieve adequate separation of the
naphthoquinone from the slightly faster eluting benzoquinone. TLC
experimentation with a variety of solvents finally led to benzene, which
was tried in the hope that preferential π-complexation with the
naphthoquinone would cause it to elute significantly faster than
benzoquinone. In benzene, Rf values were 0.22 and 0.16, respectively, so
the combined fractions from above were chromatographed on 10 g of
silica with that eluent. The isolated yield of clean quinone 17 was 220 mg
(65%). Mp was obtained on a sample sublimed at 100 °C and aspirator
pressure: 191−192 °C. 19F NMR: δ −138.1 (narrow m, 2F), −144.0
(narrow m, 2F). 1H NMR: δ 6.92 (s, 2H). 13C NMR: δ 180.5, 147.0 (1JCF
= 273 Hz), 144.6 (1JCF = 266 Hz), 138.7, 116.0. Anal. Calcd for
C10H2F4O2: C, 52.19; H, 0.88; F, 33.03. Found: C, 52.26; H, 0.92; F,
32.93.
3′,4′,5′,6′-Tetrafluoro-1,1′,2′,1″-terphenyl (18).16,20 A mixture
of 402 mg of TFTDO (90%, 1.9 mmol), 1.2 g (6.7 mmol) of tolane, and
4 mL of chlorobenzene was heated in a bath at 105−110 °C for 24 h,
after which ∼2% of the TFTDO remained. The terphenyl (34% yield)
and TFTDO dimers were present in a 3:1 ratio. Solvent was evaporated
and the residue was chromatographed with hexane on 15 g of silica gel.
Separation from unreacted tolane was poor, but two low temperature
recystallizations of selected fractions from hexane gave terphenyl 18, mp
104.5−105.5 °C (lit.20 mp 107−108 °C). 19F NMR: δ −141.5 (m, 2F),
−157.5 (m, 2F) [20.6 (m), 4.6 (m) rel. to hexafluorobenzene; lit.16 (1:1
CDCl3/CCl4) 20.8 (m), 4.7 (m)]. 1H NMR: δ 7.23 (m, 6H), 7.05 (m,
4H) [lit.18 (CCl4) 7.25−6.87 (m)]. 13C NMR: δ 144.9 (1JCF = 245 Hz),
139.9 (1JCF = 255 Hz), 131.4, 130.7, 128.0, 127.9, 125.4.
3,4,5,6-Dimethyl Tetrafluorophthalate (19).21 Into an NMR
tube were placed 43 mg of TFTDO (86%, 0.20 mmol), 147 mg of
dimethyl acetylenedicarboxylate (1.0 mmol), and toluene. The tube was
immersed in a bath at 100 °C for 17 h. The reaction was essentially
complete, giving the phthalate in 53% yield. 19F NMR: δ −137.0 (d, J =
12 Hz, 2F), −149.2 (d, J = 12 Hz, 2F) [lit.21 −137.0 (2F), −149.2 (2F)].
1H NMR: δ 3.91 (6H) [lit.21 3.94 (6H)].
1-Ethyl-2,3,4,5-tetrafluoro-6-methylbenzene (20).17 A solu-
tion of TFTDO (46.0 mg, 86%, 0.21 mmol), 2-pentyne (72 mg, 1.1
mmol), and toluene in an NMR tube was heated at 100 °C for 17 h. The
yield of 20 was ∼35% averaged over two runs. The reaction mixture was
chromatographed on 2 g of silica gel with hexane as eluent. 19F NMR: δ
−143.2 (m, 1F), −146.2 (m, 1F), −161.4 (m, 2F) [lit.17 −143.1 (m, 1F),
−146.1 (m, 1F), −161.4 (m, 2F). 1H NMR: δ 2.70 (m, 2H), 2.24 (m,
3H), 1.17 (m, 3H)] [lit.17 2.67 (m, 2H), 2.21 (m, 3H), 1.14 (m, 3H)].
1,2,3,4-Tetrafluoro-5,6-bis(trimethylsilyl)benzene (21).17 Into
an NMR tube were placed 44 mg of TFTDO (91%, 0.21 mmol), 57 mg
(0.33 mmol) of bis(trimethylsilyl)acetylene, and 1,2-dichloroethane.
After immersion in a bath at ∼80 °C for 28 h, the solution produced 21
in 67% yield. 19F NMR: δ −120.5 (m, 2F), −155.4 (m, 2F) [lit.17 −120.3
(m, 2F), −155.1 (m, 2F)]. 1H NMR: δ 0.42 (s, 18H) [lit.17 0.43 (18H)].
2,3,4,5-Tetrafluorobiphenyl (22)1,16 and 1,3,4,5-Tetrafluoro-
6-phenyl-2-thiabicyclo[3.2.0]hepta-3,6-diene 2,2-Dioxide (23).
A solution of 348 mg of TFTDO (93%, 1.7 mmol) and 193 mg (1.9
mmol) of phenylacetylene in 2 mL of toluene was heated at 100 °C. The
reaction was complete after 2 h, producing in 96% yield a [2 + 2] adduct
and the biphenyl in the ratio 2.8:1. Toluene was evaporated and replaced
with CH2Cl2; silica gel (2 g) was added, and solvent was removed again.
The resulting powder was placed on a 3.5 g column of silica gel and
eluted with hexane to obtain the biphenyl (26% isolated yield). Elution
was then continued with 25% CH2Cl2/hexane to afford the [2 + 2]
adduct (60% isolated yield). For the biphenyl 22, mp 69−69.5 °C (lit.1
65−66 °C). 19F NMR: δ −140.0 (m, 1F), −144.1 (s, 1F), −155.6 (m,
1F), 157.5 (d, J = 18.6 Hz, 1F). 1H NMR: δ 7.48 (m, 5H), 7.08 (m, 1H)
[lit.16 (1:1 CDCl3/CCl4) 7.52 (s, 5H), 7.09 (m, 1H)].
For the [2 + 2] adduct 23, mp 106−107 °C. 19F NMR: δ −137.2 (d, J
= 25 Hz, 1F), −154.6 (s, 1F), −162.3 (s, 1F), −167.7 (d, J = 25 Hz, 1F).
1H NMR: δ 7.58 (m, 5H), 6.85 (d, J = 3 Hz, 1H). 13C NMR: δ 159.8,
142.6 (1JCF = 321 Hz), 142.3 (1JCF = 305 Hz), 133.0, 129.4, 127.7, 126.9,
126.1, 100.2 (1JCF = 283 Hz), 89.8 (1JCF = 248 Hz). Anal. Calcd for
C12H6F4O2S: C, 49.66; H, 2.08; S, 11.05. Found: C, 49.69; H, 2.12; S,
11.16. A sample allowed to crystallize slowly from methanol/water gave
prisms suitable for X-ray crystal structure analysis.
2′,3′,4′,5′-Tetrafluoro-2,3,4,5-tetrahydro-1,1′-biphenyl
(24)17 and 6-(Cyclohex-1-en-1-yl)-1,3,4,5-tetrafluoro-2-thia-
bicyclo[3.2.0]hepta-3,6-diene 2,2-Dioxide (25). To an NMR
tube were added 46 mg of TFTDO (86%, 0.21 mmol), 25 mg (0.24
mmol) of 1-ethynylcyclohexene, and toluene. The tube was placed in a
bath at 100 °C, and the reaction was complete within 3 h. The [2 + 2]
adduct 25 and Diels−Alder product 24 were obtained in 95% yield in
the ratio 3.2:1. After the reaction had been scaled up by a factor of 7, the
toluene was evaporated and replaced with CH2Cl2. Silica gel (2 g) was
added, solvent was again removed, and the residual powder was placed
on a 4 g column of silica gel. The column was initially eluted with hexane
to afford benzene 24 in 18% isolated yield and then with 25% CH2Cl2/
F
DOI: 10.1021/acs.joc.6b00848
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Featured Article
hexane to obtain [2 + 2] adduct 25 in 64% isolated yield. For benzene
24, 19F NMR: δ −141.1 (m, 1F), −142.6 (m, 1F), −156.8 (1F), 159.4
(m, 1F) [lit.17 −140.9 (m, 1F), −142.3 (m, 1F, −156.6 (m, 1F), −159.3
(m, 1F)]. 1H NMR: δ 6.84 (m, 1H), 6.00 (br s, 1H), 2.30 (s, 2H), 1.72
(m, 4H), 1.20 (m, 2H) [lit.17 6.83 (s, 1H), 5.97 (s, 1H), 2.31−0.88 (m,
8H)].
stereoisomer (endo or exo) of the principal adduct. 19F NMR: δ
−144.9 (d, J = 25 Hz, 1F), −150.6 (d, J = 2.1 Hz, 1F), −156.9 (dm, J =
11.6 Hz, 1F), 158.3 (m, 1F). This isomer was formed in 12% yield
(isomer ratio 5:1).
2,3,3a,7a-Tetrafluoro-3a,4,7,7a-tetrahydro-4,7-epithio-
benzo[b]thiophene 1,1-Dioxide (30). A solution of 238 mg of
TFTDO (95%, 1.2 mmol) in 2.0 mL (25 mmol) of thiophene was boiled
under reflux for 5.3 h, affording a mixture of products that included in
62% yield two 1:1 adducts in the ratio 3:1. Silica gel (1.5 g) was added,
solvent was evaporated, and the residue was chromatographed on 10 g of
silica gel with 20% CH2Cl2/hexane as eluent. The endo and exo adducts
eluted together. 19F NMR: major adduct, δ −143.5 (d, J = 25 Hz, 1F),
−147.7 (s, 1F), −148.8 (s, 1F), −152.6 (d, J = 25 Hz, 1F); minor adduct,
δ −142.7 (d, J = 25 Hz, 1F), −146.5 (s, 1F), −152.0 (s, 1F), −156.1 (d, J
= 25 Hz, 1F). 1H NMR: major adduct, δ 6.82 (dd, J = 5.5, 3.9 Hz, 1H),
6.70 (dd, J = 5.5, 3.9 Hz, 1H), 4.48 (narrow m, 1H), 4.36 (narrow m,
1H); minor adduct, δ 6.72 (m, 1H), 6.53 (m 1H), 4.41 (m, 1H), 4.34
(m, 1H). 13C NMR: major adduct, δ 144.9 (1JCF = ∼322 Hz), 142.9 (1JCF
= 298 Hz), 138.4, 136.0, 105.1 (1JCF = 267 Hz), 94.7 (1JCF = 228 Hz),
51.6, 51.1; minor adduct (CH only), 139.8, 136.7, 55.2, 54.6. Anal. Calcd
for C8H4F4O2S2: C, 35.29; H, 1.48; F, 27.92. Found: C, 35.30; H, 1.36;
F, 28.09.
For [2 + 2] adduct 25, mp 67−69 °C. 19F NMR: δ −136.1 (d, J = 21
Hz, 1F), −155.7 (s, 1F), −161.7 (s, 1F), −167.5 (m, 1F). 1H NMR: δ
6.46 (s, 1H), 6.29 (unresolved m, 1H), 2.29 (s, 2H), 2.17 (s, 2H), 1.69
(m, 4H). 13C NMR: δ 161.1, 142.4 (1JCF = 306 Hz), 142.4 (1JCF = 321
Hz), 140.2, 128.6, 123.3, 100.5 (1JCF = 283 Hz), 89.5 (1JCF = 248 Hz),
26.1, 23.7, 21.3, 21.1. Anal. Calcd for C12H10F4O2S: C, 48.98; H, 3.43; S,
10.90. Found: C, 49.38, H, 3.27; S, 11.12.
1-Butyl-2,3,4,5-tetrafluorobenzene (26)16 and 1,3,4,5-Tetra-
fluoro-6-butyl-2-thiabicyclo[3.2.0]hepta-3,6-diene 2,2-Dioxide
(27). Into a glass pressure tube with threaded Teflon stopper were
placed 296 mg of TFTDO (88%, 1.4 mmol), 281 mg (3.43 mmol) of 1-
hexyne, and 3 mL of chlorobenzene. The vessel was maintained at ∼100
°C for 16 h in a pipe wrapped with heating tape. Two products were
obtained in 80% yield in a ratio of 1.2:1 (Diels−Alder: [2+ 2] adduct).
Solvent was evaporated and replaced with CH2Cl2; silica gel (1.5 g) was
added and solvent was again removed. The resulting tan powder was
chromatographed on 15 g of silica gel with 20% CH2Cl2/hexane as
eluent to obtain the [2 + 2] adduct 27. 19F NMR: δ −140.4 (dd, J = 23,
4.3 Hz, 1F), −154.6 (s, 1F), −163.9 (unresolved m, 1F), −169.1 (ddd, J
= 23, 10.1, 4.1 Hz, 1F). 1H NMR: δ 6.52 (d, J = 4.3 Hz, 1H), 2.42 (m,
2H), 1.61 (m, 2H) 1.42 (sextet, J = 7.3 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H).
13C NMR: δ 166.4, 142.3 (1JCF = 305 Hz), 142.2 (1JCF = ∼324 Hz),
2,3,3a,7a-Tetrafluoro-3a,4,7,7a-tetrahydro-4,7-epoxybenzo-
[b]thiophene 1,1-Dioxide (31). Into an oven-dried 10 mL round-
bottom flask were placed 329 mg of TFTDO (88%, 1.5 mmol) and 3 mL
of CH2Cl2. Flask was cooled in ice and 0.50 mL (470 mg, 6.9 mmol) of
freshly distilled furan was added with stirring through a cotton plug.
After 0.5 h, the colorless solution was allowed to warm to rt, and reaction
was complete after 6 h. The product comprised two stereoisomeric
adducts, the major one in 90% and the minor in ∼5% yield. Silica gel (1.5
g) was added to the solution, solvent was removed, and the white residue
was chromatographed on a 15 g column of silica gel with 30% CH2Cl2/
hexane as eluent. All nonempty fractions were colorless and crystalline,
and all contained both isomers (total isolated yield, 91%). To obtain the
major (exo) isomer in pure form, selected fractions were combined and
recrystallized from hexane. Mp: 97.5−98 °C. 19F NMR: major (exo)
isomer, δ −142.3 (dd, J = 25, 3.1 Hz, 1F), −148.0 (unresolved dd, 1F),
−163.6 (s, 1F), −168.6 (d, J = 25 Hz, 1F); minor (endo) isomer, δ
−141.4 (dd, J = 25, 3.2 Hz, 1F), −145.9 (m, 1F), −171.3 (br dd, J = 18.1,
131.9, 100.3 (1JCF = 284 Hz), 90.1 (1JCF = 247 Hz), 28.0, 27.3, 22.2, 13.5.
Anal. Calcd for C10H10F4O2S: C, 44.44; H, 3.73; S, 11.87. Found: C,
44.33; H, 3.72; S, 11.66.
Diels−Alder product 26 obtained in a separate experiment was
dissolved in 1:1 CCl4/CDCl3 for literature comparison. 19F NMR (ppm
relative to hexafluorobenzene): 2.4 (m, 1F), 5.5 (m, 1F), 17.5 (m, 1F),
21.3 (m, 1F) [lit.16 2.5 (td, 1F), 5.7 (m, 1F), 17.6 (m, 1F), 21.6, (m,
1F)].
2,3,3a,7a-Tetrafluoro-5,6-dimethyl-3a,4,7,7a-tetrahydro-
benzo[b]thiophene 1,1-Dioxide (28). A mixture of 102 mg of
TFTDO (95%, 0.51 mmol), 64 mg (0.78 mmol) of 2,3-dimethyl-1,3-
butadiene, and 2 mL of CH2Cl2 was allowed to stand at rt for 17 h.
Reaction was complete, giving the adduct in 93% yield. Silica gel (0.7 g)
was added, solvent was evaporated, and the gel was chromatographed on
a 4 g column of silica gel with 10% CH2Cl2/hexane as eluent. Mp of
adduct 28: 39−40.5 °C. 19F NMR: δ −144.5 (d, J = 25 Hz, 1F), −152.8
(s, 1F), −156.1 (m, 1F), −158.8 (m, 1F). 1H NMR: δ 3.04 (dd, J = 12.9,
5.1 Hz, 1H), 2.80 (m, 3H), 1.78 (s, 3H), 1.76 (s, 3H). 13C NMR: δ 143.4
(1JCF = 321 Hz), 143.2 (1JCF = 298 Hz), 125.1, 124.4, 102.7 (1JCF = 252
Hz), 89.1 (1JCF = 211 Hz), 35.0, 34.9, 18.8, 18.4. HRMS calcd for
C10H10F4O2S: 270.0338, found 270.0336.
2,3,3a,9a-Tetrafluoro-3a,4,9,9a-tetrahydro-4,9-etheno-
naphtho[2,3-b]thiophene 1,1-Dioxide (29). Into a glass pressure
vessel with threaded Teflon stopper were placed 300 mg of TFTDO
(85%, 1.4 mmol), 300 mg of naphthalene (2.3 mmol), and 3 mL of
chlorobenzene. Solution was maintained at 105 °C for 15 h in a vertical
pipe wrapped with heating tape, affording adduct 29 in 62% yield.
Solvent was replaced with a few milliliters of ether, 1.5 g of silica gel was
added, and the ether was evaporated. The off-white residue was
chromatographed on 12 g of silica gel, initially with hexane as eluent to
remove naphthalene. Solvent was then switched to 20% CH2Cl2/
hexane. Selected fractions were combined and recrystallized from
hexane. Adduct 29, mp 134.5−135 °C. 19F NMR: δ −143.9 (d, J = 26
Hz, 1F), −149.6 (s, 1F), −154.5 (dm, J = 13.8 Hz, 1F), −158.0 (ddm, J =
26, 13.8 Hz, 1F). 1H NMR: δ 7.43 (m, 2H), 7.34 (m, 2H), 6.70 (m, 1H),
6.57 (m, 1H), 4.66 (unresolved m, 1H), 4.61 (unresolved m, 1H). 13C
NMR: δ 144.9 (1JCF = 321 Hz), 143.3 (1JCF = 297 Hz), 136.0, 134.9,
134.8, 132.5, 128.1, 128.0, 126.6, 126.5, 102.4 (1JCF = 226 Hz), 90.3 (1JCF
= 222 Hz), 45.2, 45.1. Anal. Calcd for C14H8F4O2S: C, 53.16; H, 2.55; F,
24.03; S, 10.14. Found: C, 53.30; H, 2.57; F, 23.92; S, 10.04. It was clear
from 19F spectra on chromatographic fractions that major “impurity”
peaks eliminated in the recrystallization represented the other
1
∼ 5 Hz, 1F), −173.8 (ddd, J = 25, 18.1, 5.9 Hz, 1F). H NMR: exo
isomer, δ 6.81 (d, J = 5.8 Hz, 1H), 6.73 (d, J = 5.8 Hz, 1H), 5.55 (br s,
1H), 5.28 (br d, J = 1.5 Hz, 1H); endo isomer, δ 6.76 (dd, J = 5.8, 1.4 Hz,
1H), 6.55 (d, J = 5.8 Hz, 1H), 5.38 (d, J = ∼7 Hz, 1H), 5.37 (d, J = 7 Hz,
1H). 13C NMR: exo isomer, δ 143.4 (1JCF = ∼320 Hz), 141.5 (1JCF = 296
Hz), 136.3, 134.2, 101.5 (1JCF = 267 Hz), 90.4 (1JCF = 229 Hz), 79.1,
78.8. Anal. Calcd for C8H4F4O3S: C, 37.51; H, 1.57; S, 12.52. Found: C,
37.47; H, 1.62; S, 12.48.
2,3,3a,7a-Tetrafluoro-8-methyl-3a,4,7,7a-tetrahydro-4,7-
epiminobenzo[b]thiophene 1,1-Dioxide (32). A solution of 340
mg of TFTDO (100%, 1.8 mmol) in 5 mL of CH2Cl2 was cooled in ice,
and 0.20 mL (2.3 mmol) of freshly distilled N-methylpyrrole was added
dropwise with stirring. After 5 min more in the bath, the yellow mixture
was allowed to warm to rt, and 50 min after the addition the reaction was
complete. Two stereoisomeric adducts were present in the ratio 1.5:1
(83% yield). Solvent was evaporated and the oily residue was
chromatographed on 13 g of silica gel with 10% EtOAc/hexane as
eluent. The minor adduct eluted first in fractions that were mostly
yellow or orange. Several were combined and sublimed at ≤1 Torr and
temperatures up to 52 °C to give off-white crystals. Mp: 76.5−77.5 °C.
The major adduct appeared in fractions that were colorless or nearly so,
mp 84.5−85.5 °C. 19F NMR: major (endo) adduct, δ −141.7 (d, J = 26
Hz, 1F), −148.2 (s, 1F), −166.7 (dd, J = 12.3, 4.9 Hz, 1F), −169.7 (ddd,
J = 26, 12.3, 5.4 Hz, 1F); minor (exo) adduct, δ −143.2 (dd, J = 25, 3.7
Hz, 1F), −150.4 (s, 1F), −165.0 (s, 1F), −170.3 (dd, J = 25, 3.5 Hz, 1F).
1H NMR: endo adduct, δ 6.51 (d, J = 5.4 Hz, 1H), 6.30 (d, J = 5.4 Hz,
1H), 4.33 (m, 2H), 2.37 (s, 3H); exo adduct, δ 6.57 (d, J = 5.2 Hz, 1H),
6.45 (d, J = 5.2 Hz, 1H), 4.45 (s, 1H), 4.26 (s, 1H), 2.19 (s, 3H). 13
C
NMR: endo adduct, δ 144.2 (1JCF = 321 Hz), 142.4 (1JCF = 299 Hz),
134.5, 132.0, 103.9 (1JCF = ∼270 Hz), 92.7 (1JCF = 231 Hz), 72.1, 71.8,
33.7; exo adduct, δ 143.4 (1JCF = ∼320 Hz), 142.3 (1JCF = 296 Hz),
G
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134.2, 131.4, 102.5 (1JCF = 259 Hz), 91.8 (1JCF = 221 Hz), 69.1, 68.9,
32.5. Anal. Calcd for C9H7F4NO2S: C, 40.15; H, 2.62; N, 5.20; S, 11.91.
Found: C, 40.38; H, 2.67; N, 5.32; S, 11.87.
Hughes. The crystal structure of 23 was provided by Victor G.
Young, Jr., Department of Chemistry, University of Minnesota.
19F NMR signals for TFTDO slowly appear at rt in CDCl3 solutions
of the endo adduct, signifying retro-Diels−Alder reaction. This was
confirmed by addition of furan, which resulted in disappearance of the
TFTDO signals, appearance of those of the furan adduct, and further
slow growth of the latter over time. The exo adduct dissociates much
more slowly, if at all, at rt.
REFERENCES
■
(1) Lemal, D. M.; Akashi, M.; Lou, Y.; Kumar, V. J. Org. Chem. 2013,
78, 12330.
(2) (a) Chambers, R. D. Fluorine in Organic Chemistry; Blackwell
Publishing Ltd.: Oxford, 2004; Chapter 4. (b) Lemal, D. M. J. Org. Chem.
2004, 69, 1.
2,3,3a,6a-Tetrafluoro-3a,4a,5,5a,6,6a-hexahydro-4H-4,6-
ethenocyclopropa[4,5]benzo[1,2-b]thiophene 1,1-Dioxide
(34). A solution of 270 mg of TFTDO (87%, 1.2 mmol) and 209 mg
(2.3 mmol) of distilled 90% cycloheptatriene in 3 mL of 1,2-
dichloroethane was heated for 7 h at 50 °C, giving an adduct in 78%
yield. Solvent was evaporated and the residue mostly dissolved in a little
20% CH2Cl2/hexane, leaving behind brown insoluble material. The
solution was chromatographed on a 10 g column of silica gel with that
solvent as eluent. Most of the nonempty fractions were combined and
recrystallized from hexane, affording the adduct 34 as small prisms. Mp:
83.5−85 °C. 19F NMR: δ −143.8 (dd, J = 26, 2.3 Hz, 1F), −153.3 (s,
1F), −162.9 (dm, J = 18.5 Hz, 1F), −167.8 (dd, J = 26, 18.5 Hz, 1F). 1H
NMR: δ 5.91 (m, 1H), 5.77 (m, 1H), 3.71 (m, 1H), 3.65 (m, 1H), 1.53
(m, 1H), 1.44 (m, 1H), 0.61 (m, 1H), 0.44 (m, 1H). 13C NMR: δ 144.5
(1JCF = 314 Hz), 143.6 (1JCF = 297 Hz), 128.3, 125.5, 103.2 (1JCF = 263
Hz), 89.7 (1JCF = 218 Hz), 37.3, 37.1, 4.5, 4.0, 3.9. Anal. Calcd for
C11H8F4O2S: C, 47.14; H, 2.88. Found: C, 47.08; H, 2.64.
(Z)-1,2,3,4-Tetrafluoro-5,6,7,8-tetrahydrobenzo[8]annulene
(35). A combination of 569 mg of TFTDO (90%, 2.7 mmol), 419 mg
(3.9 mmol) of distilled 1,3-cyclooctadiene, and 5 mL of 1,2-
dichloroethane was heated at 80 °C for 10 h to produce an adduct
(−SO2) in 55% yield. For a sample in CDCl3, 19F NMR: δ −139.9 (m,
1F), −147.6 (m, 1F), −164.7 (m, 1F), −165.8 (m, 1F). DDQ (700 mg,
3.1 mmol) was added to the reaction mixture, which was then heated at
∼80 °C for 21 h. Solvent was evaporated from the resulting thick, dark
brown slurry, and the residue was slurried with a few mL of CH2Cl2.
Silica gel (2.0 g) was added and solvent was again evaporated, leaving a
brown powder that was placed on a 15 g column of silica gel for elution
with hexane. All fractions were colorless, viscous oils. 19F NMR of 35: δ
−142.0 (dd, J = 21.7, 12.3 Hz, 1F), −145.6 (dd, J = 21, 12.3 Hz, 1F),
−159.3 (t, J = 21 Hz, 1F); −161.4 (t, J = 21 Hz, 1H). 1H NMR: δ 6.28 (d,
J = 11.9 Hz, 1H), 6.10 (dt, J = 11.9, 6.1 Hz, 1H), 2.80 (br s, 2H), 2.20 (br
s, 2H), 1.69 (br s, 2H), 1.52 (m, 2H). 13C NMR: δ 145.2 (1JCF = 241
Hz), 144.5 (1JCF = 244 Hz), 139.5 (1JCF = 252 Hz), 138.3 (1JCF = 250
Hz), 137.4, 123.9, 121.8, 117.8, 29.9, 27.0, 24.1, 21.7. Anal. Calcd for
C12H10F4: C, 62.61; H, 4.38; F, 33.01. Found: C, 62.42;, H, 4.42; F,
32.89.
(3) For a diverse selection of examples, see: (a) Liao, K. C.; Bowers, C.
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P.; Gentles, I. R.; Hankamar, B. Langmuir 2010, 26, 18868. (f) Stensrud,
K. F.; Heger, D.; Sebej, P.; Wirz, J.; Givens, R. S. Photochem. Photobiol.
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J. Am. Chem. Soc. 2006, 128, 12020. (h) Banks, H. D. J. Org. Chem. 2006,
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(4) For a review of the chemistry of thiophene S,S-dioxides, see:
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2006, 75, 1015.
(5) Cycloadditions of 2 with acetylenes yield stable products after
spontaneous SO2 extrusion, but adducts with alkenes readily
decompose, further limiting its utility.
(6) Except where described as isolated, reported yields were
determined by NMR.
(7) [2 + 2] cycloadditions are orbital topology-forbidden to occur
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cc-PVDZ+ level of theory except where indicated otherwise. Wherever
unspecified, all energy values reported are free energies. All transition
states had a single negative frequency. Jaguar, version 2014-4;
Schrodinger, LLC, New York, 2014.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00848.
X-ray data for 23 (CIF)
1H, 19F, and 13C NMR spectra; total energies and
Cartesian coordinates for calculated structures; X-ray
crystal data plus ORTEP for 23 (PDF)
(18) He, Y.; Chen, Z.; He, C.-Y.; Zhang, X. Chin. J. Chem. 2013, 31,
873.
(19) Li, Z.; Twieg, R. J. Chem. - Eur. J. 2015, 21, 15534.
(20) Brewer, J. P. N.; Eckhard, I. F.; Heaney, H.; Marples, B. A.; Ward,
T. J. J. Chem. Soc. C 1970, 2569.
(21) Lemal, D. M.; Ramanathan, S.; Shellito, J. J. Org. Chem. 2008, 73,
3392.
AUTHOR INFORMATION
Corresponding Author
*E-mail: david.m.lemal@dartmouth.edu.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The author thanks the National Science Foundation for support
of this work (Grant No. CHE-0653935). He is pleased to
acknowledge helpful discussions with his colleague Russell
H
DOI: 10.1021/acs.joc.6b00848
J. Org. Chem. XXXX, XXX, XXX−XXX