Friedel-crafts reactions of a sulfonyl-substituted vinylic epoxide with various aromatics

Article abstract of DOI:10.1039/b103582g

The Friedel-Crafts reactions of a sulfonyl-substituted vinylic epoxide with various aromatic compounds were discussed. A reaction between vinylic epoxide, benzene and BF₃OEt₂ slightly increased the stereoselectivity. Thiophene reacted well without added amine and produced four product isomers. The ¹H NMR signals from C(4)H in these isomers were well separated and indicated the presence of two trans isomers and two cis isomers.

Full text of DOI:10.1039/b103582g

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Friedel–Crafts reactions of a sulfonyl-substituted vinylic epoxide
with various aromatics
Svante Brandänge,* Jan-Erling Bäckvall and Hans Leijonmarck
1
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-l06 91 Stockholm, Sweden
Received (in Cambridge, UK) 23rd April 2001, Accepted 3rd July 2001
First published as an Advance Article on the web 9th August 2001
The phenylsulfonyl-substituted vinylic epoxide 1 was allowed to react with BF3ؒOEt2 and various aromatics. A highly
regioselective but moderately stereoselective mono-Friedel–Crafts reaction occurred which led to products 2
(Table 1). The fluorine-containing compounds 3a–b and 4 were obtained as side products.
A reaction between 1, benzene and BF3ؒOEt2 which was
Introduction
started at Ϫ78 ЊC (DCM–benzene 5 : 1; w : w) and finally
kept at Ϫ16 ЊC for 20 h did not give a higher yield of 2a but
more 3. The stereoselectivity was slightly increased and now the
cis : trans ratio of 2a was 15 : 85 according to HPLC and H
On treatment with a Brønsted acid, or preferably a Lewis acid,
an epoxide can be transformed into a carbonyl compound with
a concomitant 1,2-shift of one of the groups bonded to the
1
epoxide ring carbons.1 With α,β-epoxysulfones a migration of
NMR. The use of less than 1 equiv. of BF3ؒOEt2 also worked
the sulfonyl group can occur.2 On the other hand, in vinylic
well but led to the formation of more of the side products
epoxides (i.e. monoepoxides of 1,3-dienes) the double bond
(TLC). The structure of 2a was confirmed by an independent
could be expected to stabilize an incipient carbocation and thus
synthesis (Scheme 2) which gave a mixture of isomers similar to
govern the regioselectivity of the rearrangement.
Results and discussion
In compound 1, available in two steps from cyclohexa-1,3-
diene,3 the two rearrangement modes are in conflict. To find out
which reaction mode predominates we treated epoxide 1 with
Scheme 2 Reagents: i, Me3SiCl, DBU; ii, PhSOCl, SnCl4; iii, Ac2O,
MeSO3H; iv, LiAlH4; v, MCPBA. The cis : trans ratio of 2a was 30 : 70.
boron trifluoride–diethyl ether (BF3ؒOEt2, 1 equiv., 20 ЊC) in
1
benzene. H NMR analysis of the reaction product mixture
that obtained in the Friedel–Crafts reaction. Compound 2a and
its aryl analogues are air-sensitive compounds.
showed that the major reaction of 1 was not a rearrangement
Analysis of the 1H NMR spectra of the two isomers 2a indi-
but instead a reaction with benzene (Scheme 1). A mixture of cis
cates that the major isomer has the trans and the minor isomer
the cis configuration. The latter shows (after shaking with D2O)
a triplet at δ 4.39 (CHOH, J 2.8 Hz) and a triplet at δ 3.47
(CHPh, J 8.0 Hz). These values are indicative of a dominant
half-chair conformation in which the OH group occupies a
pseudo-axial position and the phenyl group
a pseudo-
equatorial position (thus cis). Electron-attracting allylic sub-
stituents in the cyclohexene ring are known to prefer the
pseudo-axial position.5 In the major isomer the CHOH signal
is at δ 4.46 (t, J 4.4 Hz) and the CHPh signal at δ 3.75 (q, J 4.8
Hz). The values of J for this isomer (trans) indicate that the
two half-chair conformations are more equally represented.
Support for these stereochemical assignments was obtained
from a reaction between 1 and lithium diphenylcuprate (1.1
equiv., from 0 to 22 ЊC, 1 h, Et2O). The reaction afforded 2a as
an essentially pure stereoisomer (ca. 20% yield) together with
other, unidentified products (full conversion of 1). This stereo-
isomer is identical to the one which had been ascribed the trans
configuration in the 1H NMR analysis. It is the expected stereo-
isomer in the diphenylcuprate reaction since the SN2Ј reaction
of cyclohexa-1,3-diene monoepoxide with lithium diphenyl-
cuprate is known to give trans-4-phenylcyclohex-2-en-1-ol.6 A
palladium-catalysed reaction with a phenylstannane also leads
to this isomer.7
Scheme 1
and trans isomers of compound 2a (Ar = Ph, cis : trans, 20 : 80)
was obtained in an isolated yield of 47%. The main side prod-
ucts were diphenyl sulfone (14%) and the fluoro alcohol 3 (9%;
80 : 20 mixture of stereoisomers; see e.g. ref. 1b for the form-
ation of fluorohydrins from epoxides). A plausible mechanism
involves BF3-induced epoxide ring opening to form a sulfonyl-
substituted allylic cation, or a related polarised complex, which
then reacts in a Friedel–Crafts4 manner with benzene. All three
product types are possibly formed via the same intermediate; a
plausible route to diphenyl sulfone involves deprotonation of
the intermediate to form a sulfonyl-substituted cyclohexadienol
followed by acid-catalysed elimination of water.
The results from reactions between 1 and various aromatic
compounds are given in Table 1. The aromatics used here are
cheap compounds that were used in large excess in order to
favour the 1 : 1 reaction product. Electron-rich aromatics such
DOI: 10.1039/b103582g
J. Chem. Soc., Perkin Trans. 1, 2001, 2051–2054
This journal is © The Royal Society of Chemistry 2001
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Table 1 Products obtained in the Friedel–Crafts reactions of sulfonyl epoxide 1 with BF3ؒOEt2 and various aromatic compounds
Aromatic
compound used
Yield of
2 (%)
1H NMR data
for C(4)H
Isomer
ratiosa
Structure
assignments
Product 2
47
69
δ 3.75; q; J 4.8
δ 3.47; t; J 8.1
80
20
trans-2a
cis-2a
δ 4.11; q; J 4.6
δ 3.89; t; J 8.1
δ 3.70; q; J 4.6
δ 3.42; t; J 8.1
35
25
25
15
ortho-trans-2b
ortho-cis-2b
para-trans-2b
para-cis-2b
65
δ 4.09; q; J 4.9
δ 3.86; t; J 7.1
60
40
trans-2c
cis-2c
55
42
δ 3.84; m; W1/2 ∼9.5 Hz
δ 3.61; t; J 7.5
70
30
2-furyl-trans-2d
2-furyl-cis-2d
δ 4.05; q; J 3.9
δ 3.85; q; J 4.5
δ 3.79; t; J 7.7
δ 3.62; t; J 7.7
55
20
20
5
2-thienyl-trans-2e
3-thienyl-trans-2e
2-thienyl-cis-2e
3-thienyl-cis-2e
a 1H-NMR ratios, except for 2b (HPLC); numbers are given as multiples of 5.
as anisole and 1,4-dimethoxybenzene reacted well with 1 (Table
1); small amounts of diphenyl sulfone (5–6%) were also
obtained. Anisole gave four isomeric products, 2b. Two of these
product was formed as a single stereoisomer (ca. 10%, 1H
NMR). This compound was also detected as a minor product in
some of the Friedel–Crafts reactions. It was never prepared in a
pure form; yet NMR analysis clearly indicated the structure 4.
The two stereoisomers 3a,b were formed in a ratio which varied
strongly between different experiments. In one case an almost
inverted ratio was found: 25 : 75 instead of 80 : 20.
To the best of our knowledge there is only one reported
example of a Friedel–Crafts reaction with a vinylic epoxide.12
After the initial Friedel–Crafts reaction between ethenyloxirane
and toluene, induced by BF3ؒOEt2, there was a fairly easy reac-
tion with a second molecule of toluene forming products of the
1 : 2 composition type. Such 1 : 2 reaction products were
negligible in our reactions with 1 despite the use of a large
excess of aromatic compound.
1
showed a H NMR signal from the benzylic hydrogen, C(4)H,
which was similar to the corresponding signals from the two
isomers of 2a (Table 1). The signals from C(4)H in the other
two isomers are similar to the corresponding signals from
compound 2c (which has an ortho-methoxylated aryl substitu-
ent). From these similarities (Table 1) it was concluded that the
former two are the para and the latter two the ortho isomers.
There was a preponderance of ortho substitution products
(o : p, 60 : 40), which is typical for kinetically controlled
Friedel–Crafts alkylations of anisole.8
Furan is an acid-sensitive aromatic which cannot be alkyl-
ated using classical Friedel–Crafts conditions.9 Accordingly, a
reaction with furan, performed as above, led to large amounts
of side products. It appeared necessary to neutralise strongly
acidic components. A mixture of 1, N-ethyldiisopropylamine
and BF3ؒOEt2 in the molar ratios 1 : 2.1 : 1.1 proved useful for
the conversion of furan into 2d. Two strongly dominating iso-
mers were obtained; these were assumed to be 2-substituted
furans in analogy with other reactions of furan.
The hypothetical intermediate in our Friedel–Crafts reac-
tions belongs to a class of compounds which has been called
destabilised or electronegatively substituted carbocations.13
A
similar 1-sulfonylated allylic carbocation has shown unusual
features as an intermediate in substitution reactions.14
Experimental
Thiophene reacted well without added amine and gave four
1
product isomers. The H NMR signals from C(4)H in these
Reactions with 13 were performed in flame-dried glassware
under an atmosphere of nitrogen or argon. DCM was distilled
over CaH2 and THF over sodium benzophenone ketyl. Com-
mercial BF3ؒOEt2 (99%, Lancaster) and MCPBA (Aldrich)
were used. Flash chromatography purifications were carried out
using Merck silica gel 60 A (35–70 µ) and TLC using Merck
silica gel 60 F254 plates. Equipment used for analytical HPLC:
Waters 501, Porasil 100–5 column; for preparative HPLC:
Bischoff, Kromasil column (100 SIL, 5 µm, 250 × 20 mm);
isomers were well separated (Table 1) and indicated, as for 2b,
the presence of two trans isomers and two cis isomers. Evidence
regarding the position of substitution in the thiophene rings
was gained from literature 1H NMR data of various 2- or
3-monoalkylated thiophenes.10 These data show a) that the C(5)
hydrogen appears at higher chemical shift than the other hydro-
gens in the thiophene ring irrespective of the substitution
pattern and b) that C(5)H in a 3-monoalkylated thiophene
shows splittings of ca. 5 and 3–3.5 Hz whereas C(5)H in a
2-monoalkylated thiophene shows splittings of ca. 5 and 1–1.5
Hz. From these generalisations it was concluded that the substi-
tution had occurred mainly at the 2-position (ca. 75%). Friedel–
Crafts alkylation of thiophene with 2-chloropropane and AlCl3
yields a ca. 60 : 40 mixture of 2- and 3-isopropylthiophene.11
If no aromatic compound was present one equiv. of BF3ؒ
OEt2 (DCM; 22 ЊC) converted 1 into a roughly 2 : 1 mixture of
3 and diphenyl sulfone. When N-ethyldiisopropylamine was
included the formation of diphenyl sulfone (8%) was sup-
pressed and 3 was isolated in a 51% yield. A third type of
1
refractive index detector in both cases. H NMR (400 MHz),
13C NMR (100 MHz) and 19F NMR spectra (375 MHz) were
recorded on a Varian Mercury spectrometer using CDCl3 as
1
solvent. TMS was used as internal reference for H and 13C
NMR. 19F NMR shifts are relative to external PhCF3 (in C6D6)
set at Ϫ64 ppm. Chemical shifts (δ) are reported in ppm; coup-
ling constants (J) are given in Hz. Multiplicities given as s, d, t,
1
or q should not be taken literally. For many H NMR signals
there are small extra splittings, e.g. for those of C(4)H (Table 1).
These often unsymmetrical signals were poorly resolved at 400
MHz; an adequate characterisation in the text was not possible.
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High-resolution MS were run using a JEOL JMS SX/SX102A
instrument (direct inlet, electron impact, 70 eV).
a 50–60% suspension in water; 0.40–0.48 mmol). Work-up with
aq. Na2S2O3 and NaHCO3 gave a mixture of sulfones (cis :
trans = 3 : 7) in more than 90% yield. These sulfones were
indistinguishable (1H NMR) from those (2a) which had been
prepared from 1.
4-Phenyl-2-phenylsulfonylcyclohex-2-enol (2a)
To a stirred solution of epoxide 13 (400 mg, 1.7 mmol) in ben-
zene (3.0 cm3, 20 ЊC, 20 equiv.) was added BF3ؒOEt2 (1.7 mmol)
in small portions. After 3.5 h the reaction mixture was poured
under stirring into half-saturated aqueous NaHCO3 (15 cm3)
and Et2O (20 cm3). The ether phase was separated and the
aqueous phase extracted with another portion of Et2O. The
organic phases were combined, the solvent was evaporated and
DCM (10 cm3) was added. After drying (Na2SO4) and evapor-
ation of the solvent a residue (490 mg) was obtained. The com-
ponents were separated on a silica gel column (2 × 30 cm) using
light petroleum (bp 40–60)–ethyl acetate (5 : 2) as eluant.
Diphenyl sulfone (48 mg) was first eluted, then 2a as a ca.
20 : 80 mixture of isomers (252 mg, 47%) and finally the fluoro
compound 3 (9%). The isomers of 2a were separated by
preparative HPLC; δH for major (trans) isomer of 2a (sample
shaken with D2O): 7.97 (2 H, dd, J 8.1, 1.1, ArH), 7.68 (1 H, tt,
J 7.3, 1.6, ArH), 7.60 (2 H, t, J 7.5, ArH), 7.34–7.22 (3 H, m,
ArH), 7.21 (1 H, d, J 4.0, C(3)H), 6.99 (2 H, d, J 7.0, ArH), 4.46
(1 H, t, J 4.4, C(1)H), 3.75 (1 H, q, J 4.8, C(4)H), 3.21 (1 H, d,
J 1.8, OH, seen only when D2O was omitted), 2.26 (1 H, m,
1 × CH2), 1.82–1.70 (2 H, m, 2 × CH2), 1.68–1.58 (1 H, m,
1 × CH2); δC for major isomer: 143.8, 142.9, 141.6, 139.9, 133.6,
129.3, 128.7, 127.9, 127.7, 127.0, 62.3 (C(1)), 41.2 (C(4)), 27.5
(CH2), 25.9 (CH2); m/z 314 (Mϩ, 10%), 296 (91), 173 (67), 155
(100), 77 (59); m/z 314.0942; C18H18O3S requires 314.0977.
δH for minor (cis) isomer of 2a (sample shaken with D2O):
7.93 (2 H, d, J 8.4, ArH), 7.66 (1 H, t, J 7.3, ArH), 7.57 (2 H, t,
J 7.9, ArH), 7.38–7.16 (6 H, m, 5 × ArH ϩ C(3)H), 4.39 (1 H,
t, J 2.8, C(1)H), 3.47 (1 H, t, J 8.0, C(4)H), 3.16 (1 H, br s,
OH, seen only when D2O was omitted), 2.07 (1 H, dq, J 13.8,
3.2, 1 × CH2), 1.93 (2 H, m, 2 × CH2), 1.67–1.57 (1 H, m,
1 × CH2); δC for minor isomer: 145.2, 142.4, 141.8, 139.3,
128.8, 128.0, 127.6, 127.1, 60.9 (C(1)), 43.8 (C(4)), 30.2 (CH2),
25.7 (CH2); two signals were not detected with certainty (the
13C NMR sample was a mixture of cis and trans isomers).
4-(2-Methoxyphenyl)-2-phenylsulfonylcyclohex-2-enol (2b) and
4-(4-methoxyphenyl)-2-phenylsulfonylcyclohex-2-enol (2b)
To a well-stirred mixture (Ϫ78 ЊC) of 1 (236 mg, 1.00 mmol)
and anisole (1.08 g, 10.0 mmol) in DCM (4 cm3) was slowly
added BF3ؒOEt2 (0.13 cm3, 1.0 mmol). The temperature was
allowed to rise to Ϫ15 ЊC during 2.5 h and the mixture was then
kept at Ϫ17 ЊC for 2 days. Work-up was initiated by pouring the
reaction mixture into a cold (Ϫ17 ЊC) mixture of triethylamine
(1.2 mmol) and MeOH (10 cm3). Conventional extractions gave
a crude product which was purified on a short column of silica
gel (pentane–EtOAc 5 : 2) to obtain a mixture of 2b (69%; four
1
isomers) and 3 (10%). H and 13C NMR spectra were in full
accord with the structures. 1H NMR data for C(4)H in the four
isomers are given in Table 1.
4-(2,5-Dimethoxyphenyl)-2-phenylsulfonylcyclohex-2-enol (2c)
The reaction was performed as for 2a (22 ЊC; 10 equiv.
1
of 1,4-dimethoxybenzene); the H NMR spectrum was in full
accord with the structure; data for C(4)H are given in Table 1.
4-(2-Furyl)-2-phenylsulfonylcyclohex-2-enol (2d)
BF3ؒOEt2 (4.2 mmol) was added to a mixture of 1 (473 mg, 2.00
mmol), furan (5.8 cm3, 40 equiv.) and N-ethyldiisopropylamine
(284 mg, 2.2 mmol). The mixture was stirred in a sealed vessel at
20 ЊC (1 h). Diethyl ether was added and the mixture was
washed with aq. NaHCO3 and then with aq. acid to remove the
amine. After drying (Na2SO4) and evaporation of the solvent, a
residue (534 mg) was obtained. Purification on silica gel gave
the title compound (337 mg, 55%) as a 70 : 30 mixture of stereo-
1
isomers. NMR spectra were run using this mixture. The H
NMR multiplet at 4.34 is most likely due to overlapping signals
from the two isomers. δH for major isomer of 2d: 8.0–7.9 (2 H,
m, ArH), 7.7–7.4 (3 H, m, ArH), 7.33 (1 H, dd, J 1.8, 0.7, furyl-
C(5)H), 7.23 (1 H, d, J 4.4, C(3)H), 6.28 (1 H, dd, J 3.3, 1.8,
furyl-C(4)H), 5.85 (1 H, dd, J 3.3, 0.7, furyl-C(3)H), 4.34 (1 H,
C(1)H), 3.84 (1 H, m, W1/2 ∼ 9.5, C(4)H), 3.10 (1 H, br s, OH),
2.3–1.5 (4 H, m, 4 × CH2); δC for major isomer: 153.1 (furyl-
C(2)), 142.4 (quat. C), 141.7 (CH), 140.4 (CH), 139.0 (quat. C),
133.4 (CH), 129.1 (CH), 127.7 (CH), 109.9 (furyl-CH), 106.0
(furyl-CH), 61.6 (C(1)), 34.9 (C(4)), 27.1 (CH2), 21.8 (CH2).
δH for minor isomer of 2d: 8.0–7.9 (2 H, m, ArH), 7.7–7.4
(3 H, m, ArH), 7.37 (1 H, dd, J 1.8, 0.7, furyl-C(5)H), 7.26 (1 H,
d, J 0.7, C(3)H), 6.33 (1 H, dd, J 3.3, 1.8, furyl-C(4)H), 6.12
(1 H, dd, J 3.3, 0.7, furyl-C(3)H), 4.34 (1 H, C(1)H), 3.61 (1 H,
t, J 7.5, C(4)H), 3.10 (1 H, br s, OH), 2.3–1.5 (4 H, m, 4 × CH2);
δC for minor isomer: 153.8 (furyl-C(2)), 141.8 (CH), 141.5
(CH), 141.4 (quat. C), 138.8 (quat. C), 133.4 (CH), 129.1 (CH),
127.7 (CH), 110.1 (furyl-CH), 105.3 (furyl-CH), 61.0 (C(1)),
36.9 (C(4)), 29.6 (CH2), 21.5 (CH2).
Synthesis of 4-phenyl-2-phenylsulfonylcyclohex-2-enol (2a) from
4-phenylcyclohexanone
4-Phenylcyclohexanone was transformed into the correspond-
ing TMS enol ether as described for cyclohexanone;15 the crude
enol ether was converted into 4-phenyl-2-(phenylsulfinyl)cyclo-
hexanone (cis ϩ trans) as described for 2-(phenylsulfinyl)-
cyclohexanone.16 The sulfoxide was subjected to a Pummerer
reaction using the technique applied to 2-(phenylsulfinyl)cyclo-
hexanone.17 The crude product was purified (silica gel, toluene)
to give 4-phenyl-2-phenylthiocyclohex-2-enone in an 85% yield;
mp (uncorr.) 110–111 ЊC (from Et2O); δH: 7.48 (2 H, d, J 7.0,
ArH), 7.38–7.22 (6 H, m, ArH), 7.10 (2 H, d, J 7.0, ArH), 6.39
(1 H, dd, J 3.3, 1.1, C(3)H), 3.72 (1 H, m, C(4)H), 2.69 (1 H,
ddd, J 16.5, 5.5, 4.7, 1 × C(6)H), 2.58 (1 H, ddd, J 16.5, 11.7,
4.7, 1 × C(6)H), 2.35 (1 H, m, 1 × C(5)H), 2.02 (1 H, m,
1 × C(5)H); δC(relative to CDCl3 at 77.2): 195.2 (CO), 146.1
C(3), 143.1 (quat. C), 138.9 (quat. C), 134.6, 131.6 (quat. C),
129.8, 129.1, 128.9, 127.7, 127.3, 44.1, 37.4, 32.8. This ketone
(140 mg, 0.50 mmol), dissolved in THF (3 cm3), was reduced
(0 ЊC then 22 ЊC for 2 h) with LiAlH4 (19 mg, 0.50 mmol).
Work-up gave 4-phenyl-2-phenylthiocyclohex-2-enol as an oil
(81%); 1H NMR showed a 3 : 7 mixture of stereoisomers which
were not separated; δH of major isomer (salient signals only):
6.20 (1 H, d, J 3.7, C(3)H), 4.21 (1 H, t, J 5.1, C(1)H), 3.57 (1 H,
m, C(4)H), 2.42 (1 H, br s, OH); δH of minor isomer (salient
signals only): 6.21 (1 H, d, J 3.7, C(3)H), 4.11 (1 H, s with
shoulders, C(1)H), 3.48 (1 H, m, C(4)H), 2.28 (1 H, br s,
OH). The mixture (57 mg, 0.20 mmol) in DCM (2 cm3) was
S-oxidised selectively18 (0 ЊC, 90 min) with MCPBA (138 mg of
4-(2-Thienyl)-2-phenylsulfonylcyclohex-2-enol (2e) and 4-(3-
thienyl)-2-phenylsulfonylcyclohex-2-enol (2e)
Compound 2e was prepared (0 ЊC, 1 h) analogously to 2a from
1 (118 mg, 0.50 mmol), thiophene (420 mg, 5.00 mmol) and
BF3ؒOEt2 (71 mg, 0.50 mmol) in DCM (2.5 cm3). The 1H NMR
spectrum of the concentrated reaction product mixture (147
mg) indicated a yield of ca. 60% for 2e and ca. 15% for 3.
Purification on a silica gel column (30 × 2 cm; pentane–EtOAc
5 : 2) gave a fraction (84 mg) consisting of 2e (42% yield) and 3.
Preparative HPLC showed three peaks from 2e and two peaks
from 3. First eluted (peak 1) was a 7 : 3 mixture of 2-thienyl-
trans-2e (major isomer of 2e) and 2-thienyl-cis-2e; δH: 7.97–7.90
J. Chem. Soc., Perkin Trans. 1, 2001, 2051–2054
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(2 H, m, ArH), 7.70–7.54 (3 H, m, ArH), 7.27–7.24 (0.7 H, m,
C(3)H, partly obscured by solvent peak), 7.21 (0.3 H, dd, J 5.1,
1.5, C(3)H), 7.18 (1 H, dd, J 5.1, 1.1, thienyl-C(5)H), 6.98 (0.3
H, dd, J 5.1, 3.7, thienyl-C(4)H), 6.94 (0.7 H, dd, J 5.1, 3.7,
thienyl-C(4)H), 6.90 (0.3 H, dt, J 3.7, 1.1, thienyl-C(3)H),
6.68 (0.7 H, dt, J 3.3, 1.1, thienyl-C(3)H), 4.40 (0.3 H, m,
C(1)H), 4.34 (0.7 H, m, C(1)H), 4.05 (0.7 H, q, J 3.9, C(4)H),
3.79 (0.3 H, t, J 7.7, C(4)H), 3.23 (0.7 H, s, OH), 3.09 (0.3 H, s,
OH), 2.36–2.25 (0.7 H, m, CH2), 2.10–2.00 (1 H, m, CH2), 1.86–
1.69 (2.3 H, m, CH2); peak 2 (3-thienyl-cis-2e, contaminated
with a small amount of 4): δH 7.94–7.90 (2 H, m, ArH), 7.68–
7.54 (3 H, m, ArH), 7.33 (1 H, dd, J 4.8, 2.9, thienyl-C(5)H),
7.20 (1 H, d, J 1.8, C(3)H), 7.06 (1 H, ddd, J 2.9, 1.5, 0.7,
thienyl-C(2)H), 6.98 (1 H, dd, J 5.1, 1.5, thienyl-C(4)H), 4.37
(1 H, ddd, J 4.0, 2.6, 1.1, C(1)H), 3.62 (1 H, t, J 7.7, C(4)H),
2.28 (br s, OH), 2.05 (1 H, dq, J 13.9, 3.3, CH2), 2.00–1.91 (3 H,
m, CH2), 1.60 (1 H, m, CH2); peak 3 (3-thienyl-trans-2e):
δH 7.98–7.92 (2 H, m, ArH), 7.70–7.56 (3 H, m, ArH), 7.30
(1 H, dd, J 4.8, 2.9, thienyl-C(5)H), 7.25 (1 H, d, J 4.4, C(3)H),
6.86 (1 H, dd, J 4.9, 1.3, thienyl-C(4)H), 6.73 (1 H, m, thienyl-
C(2)H), 4.39 (1 H, t, J 4.0, C(1)H), 3.85 (1 H, q, J 4.5, C(4)H),
2.50 (1 H, br s, OH), 2.23 (1 H, m, CH2), 1.84–1.75 (1 H, m,
CH2), 1.72–1.61 (2 H, m, CH2); peaks 4 and 5: 3a and 3b
respectively.
gave a crude product mixture (100 mg). Separation on a silica
gel column (pentane–EtOAc 1 : 1) first gave diphenyl sulfone
1
(8%), then a pool (78 mg) of 3 and 4 (82 : 18, H NMR). This
corresponds to a 51% yield of 3 and an 11% yield of 4. The
retention times in analytical HPLC (pentane–EtOAc 5 : 1) were
24.0 (4), 34.0 (3a) and 36.8 min (3b); the ratio 3a : 3b was
44 : 56.
2-Fluoro-2-phenylsulfonylcyclohex-3-enol (4)
δH (salient signals only): 7.97 (2 H, d, J 8.1, ArH), 6.41 (1 H,
ddt, J 10.2, 4.2, 2.9, olefinic H), 5.50 (1 H, ddt, J 9.8, 4.6, 2.2,
olefinic H), 4.56 (1 H, ddd, J 12.6, 9.5, 3.3, C(1)H), 2.75 (1 H,
br s, OH); δC (JC–F): 142.1 (J 8.4), 134.8, 134.5 ?, 130.6 (J 1.5),
129.1, 117.7 (J 19.8, C(3)), 103.7 (J 219.7, C(2)), 66.1 (J 17.5,
C(1)), 26.4, 23.4 (J 3.0); δF: Ϫ152.3 (m)
Acknowledgements
We thank Ms Charlotte Mattsson for aid in the preparation of
2a (Scheme 2) and Mr Suresh Gohil (SLU, Uppsala) for
running mass spectra.
References
1 (a) B. Rickborn, in Comprehensive Organic Chemistry, eds. B. M.
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4-Fluoro-2-phenylsulfonylcyclohex-2-enol (3a and 3b)
Compounds 3a and 3b were obtained (9% yield) as a 4 : 1 mix-
ture of stereoisomers in the synthesis of 2a from 1; this mixture
was used to obtain 13C NMR data. The isomers were separated
by preparative HPLC; δH for 3a (major isomer): 7.92 (2 H, d,
J 7.5, ArH), 7.68 (1 H, tt, J 7.5, 1.8, ArH), 7.58 (2 H, t, J 7.7,
ArH), 7.03 (1 H, ddd, J 10.6, 2.2, 1.1, C(3)H), 5.12 (1 H, dddd,
J 46.9, 9.9, 5.5, 2.2, C(4)H), 4.36 (1 H, m, C(1)H), 3.10 (1 H, t,
J 2.0, OH), 2.18–1.98 (3 H, m, CH2), 1.67–1.55 (1 H, m, CH2);
δC for 3a (JC–F): 144.1 (J 8.4, C(2)), 138.1 (J 23.7, C(3)), 138.1
(ArC), 133.8 (ArC), 129.2 (ArC), 128.0 (ArC), 86.9 (J 171.7,
C(4)), 61.1 (J 1.5, C(1)), 27.9 (J 9.9, C(6)), 23.2 (J 18.3, C(5));
δF for 3a: Ϫ47.5 (dm, J 45.8); retention time in analytical HPLC
(pentane–EtOAc 5 : 1), 34.0 min; m/z 256 (Mϩ, 7%), 210 (24),
125 (33), 115 (100), 77 (43); m/z 256.0532; C12H13O3FS requires
256.0569.
7 D. R. Tueting, A. M. Echavarren and J. K. Stille, Tetrahedron, 1989,
45, 979.
8 G. A. Olah, J. A. Olah and T. Ohyama, J. Am. Chem. Soc., 1984, 106,
5284.
δH for 3b (minor isomer): 7.92 (2 H, d, J 8.2, ArH), 7.68 (1 H,
tt, J 7.7, 1.6, ArH), 7.59 (2 H, t, J 7.7, ArH), 7.05 (1 H, t, J 4.6,
C(3)H), 5.17 (1 H, dq, J 46.3, 4.1, C(4)H), 4.37 (1 H, quintet,
J 3.4, C(1)H), 3.11 (1 H, dd, J 2.2, 1.5, OH), 2.16 (1 H,
dm, J 33.0, C(5)H), 1.98–1.77 (3 H, m, CH2); δC for 3b (JC–F):
146.0 (J 9.9, C(2)), 137.9 (ArC), 134.7 (J 19.1, C(3)), 133.8
(ArC), 129.2 (ArC), 128.0 (ArC), 83.3 (J 168.6, C(4)), 61.6
(J 2.3, C(1)), 25.8 (J 1.5, C(6)), 23.8 (J 20.3, C(5)); δF for 3b:
Ϫ44.3 (dddt, J 45.8, 33.6, 16.8, 3.8); retention time in analytical
HPLC (pentane–EtOAc 5 : 1), 36.8 min.
9 C. C. Price, Org. React. (N. Y.), 1946, 3, 1.
10 For a recent example, see W. Pan, M. Balci and P. B. Shevlin, J. Am.
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18 L. A. Paquette and R. V. C. Carr, Org. Synth., 1986, 64, 157, and
references therein.
4-Fluoro-2-phenylsulfonylcyclohex-2-enol (3)
Compound 3 was more efficiently prepared when 1 (118 mg,
0.50 mmol) in DCM (1 cm3) was added to a mixture of BF3ؒ
OEt2 (0.09 cm3, 0.75 mmol) and N-ethyldiisopropylamine
(32 mg, 0.25 mmol) in DCM (1 cm3, 22 ЊC). Work-up after 18 h
2054
J. Chem. Soc., Perkin Trans. 1, 2001, 2051–2054