The Diels-Alder reactivity of (E)-3-phenylsulfonylprop-2-enenitrile, a cyanoacetylene equivalent

Article abstract of DOI:10.1039/b203391g

(E)-3-Phenylsulfonylprop-2-enenitrile undergoes facile Diels-Alder reactions, moderate regioselectivity being observed with several unsymmetrical dienes. Danishefsky's diene and furfuryl alcohol react regioselectively. The cycloadducts formed with cyclopentadiene and with anthracene undergo base-catalysed elimination of benzenesulfinic acid to yield α,β-unsaturated nitriles.

Full text of DOI:10.1039/b203391g

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The Diels–Alder reactivity of (E )-3-phenylsulfonylprop-2-
enenitrile, a cyanoacetylene equivalent
Pamela J. Bradley and David H. Grayson*
1
University Chemical Laboratory, Trinity College, Dublin 2, Ireland
Received (in Cambridge, UK) 5th April 2002, Accepted 19th June 2002
First published as an Advance Article on the web 8th July 2002
(E)-3-Phenylsulfonylprop-2-enenitrile undergoes facile Diels–Alder reactions, moderate regioselectivity being
observed with several unsymmetrical dienes. Danishefsky’s diene and furfuryl alcohol react regioselectively. The
cycloadducts formed with cyclopentadiene and with anthracene undergo base-catalysed elimination of
benzenesulfinic acid to yield α,β-unsaturated nitriles.
isomer 4, mp 77.5–78 ЊC, is formed as a minor by-product,
Introduction
and we have separated this from 1 by column chromatography
and characterised it.
There has been much interest in synthetic applications of
sulfonyl-activated dienophiles. These comprise both monofunc-
tional systems including, but not limited to, methylsulfonyl-1
and phenylsulfonylethene,2 the 1-nonafluorobutylsulfonylprop-
2-enes,3 phenylsulfonylpropa-1,3-diene,4 p-tolylsulfonylethyne5
and ethenesulfonyl chloride,1 and difunctional systems
exemplified by the (E)-6 and (Z)-1,2-bis(phenylsulfonyl)-
ethenes,6,7 1-phenylsulfonyl-2-trimethylsilylethene,8 1-phenyl-
sulfonyl-2-nitroethene,9 1-benzoyl-2-phenylsulfonylethene,10 the
ethyl (Z)- and (E)-3-phenylsulfonylprop-2-enoates,11 and
1,2-bis(tert-butylsulfonyl)ethyne.12 Within the latter group the
unsymmetrically disubstituted compounds are perhaps of the
greatest potential synthetic utility. However, 1-phenylsulfonyl-
2-trimethylsilylethene is rather unreactive, requiring several
days for its complete addition to cyclopentadiene at room
temperature,8 and 1-phenylsulfonyl-2-benzoylethene does not
give a Diels–Alder adduct with furan.10 The cycloaddition
chemistry of vinylic sulfones has been reviewed.13
It is clear from the literature that there has been no
thorough investigation of the Diels–Alder reactivity of 1. There
is a single report of its cycloaddition to the dimethyl ester of
protoporphyrin IX,17 but no reference is made to either the
source of the dienophile or the stereochemical outcome of
the reaction.
Reaction of 1 with the relatively unreactive diene furan 5
at 30 ЊC led rapidly and quantitatively to a mixture of the
isomeric cycloadducts 6 and 7. These could be separated by
chromatography and were easily identified on the basis of their
1
characteristic H NMR spectra (Experimental). In a process
often noted in this context,18 the kinetic endo-phenylsulfonyl
isomer 6 could be isomerised to the more thermodynamically
stable exo-form 7 together with some of the starting dienophile
1 and furan 5 when it was kept at 37 ЊC in chloroform solution
for several days. Table 1 records the relative proportions of the
cycloadducts 6 and 7 that were formed under different reaction
conditions.
In this paper we describe a simple route to the very reactive
difunctional dienophile (E)-3-phenylsulfonylpropenenitrile 1,
and report on the cycloaddition reactions that it undergoes with
a variety of dienes.
Results and discussion
The sulfonylnitrile 1 has previously been prepared from 2-
chloropropenenitrile by a method somewhat similar to that
which we describe in the present work,14 and also via reaction of
2,3-dibromopropanenitrile with sodium benzenesulfinate in
acetic acid containing sodium acetate.15 The p-tolyl analogue
has been synthesised from 3-chloropropenenitrile via its reac-
tion with sodium toluene-p-sulfinate.16
Exposure of the sulfonylnitrile 1 to the more reactive diene
cyclopentadiene gave, even at Ϫ20 ЊC (although longer reaction
times were required at this temperature), a near-quantitative
yield of the expected adducts 8 and 9 that was separable by
chromatography (Table 2). The major product was again the
endo-phenylsulfonyl isomer 8, and this stereochemistry con-
trasts with that obtained using 1-nitro-2-phenylsulfonylethene
as the dienophile where the nitro group controls the outcome
of the cycloaddition reaction and the phenylsulfonyl group of
the derived cycloadducts is mainly in the exo-position.9 The
stereochemistries of these products were easily inferred from
their NMR spectra.
We have found (Scheme 1) that Michael addition of benze-
Scheme 1
When a mixture of the cyclopentadiene adducts 8 and 9 was
treated with freshly-sublimed potassium tert-butoxide in tet-
rahydrofuran, benzenesulfinic acid was smoothly eliminated
and the unsaturated bicyclic nitrile 10 was formed. This
unstable compound has previously been prepared19 by reaction
of the difficultly accessible cyanoacetylene 11 with cyclopenta-
nesulfinic acid to 2-chloropropenenitrile 2 yields the tri-
substituted compound 3 which is converted into 1 by treatment
with triethylamine. Overexposure of 3 to triethylamine leads to
the formation of a black tar that is presumably formed via
anionic polymerisation of 1. The previously undescribed (Z)-
1794
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b203391g

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Table 1 Reactions of (E)-3-phenylsulfonylprop-2-enenitrile with furan
Dienophile 1/g
Furan/g
Solvent/cm3
T /ЊC
Time
Ratio 6 : 7
0.09
0.09
0.19
0.14
0.15
0.15
1.4
1.4
2.1
1.4
2.1
2.1
None
None
None
None
None
Benzene (2)
rt
rt
Reflux
0
Ϫ20
rt
25 h
48 h
4 h
5 d
14 d
8 d
2.3
1.9
1.5
6.3
1.8
2.3
Table 2 Reactions of (E)-3-phenylsulfonylprop-2-enenitrile with cyclopentadiene
Dienophile 1/g
Cyclopentadiene/g
Solvent/cm3
T /ЊC
Time
Ratio 8 : 9
0.19
0.19
3.76
3.86
1.94
0.15
0.16
0.16
2.66
2.66
0.83
2.1
Acetone (2)
Benzene (2)
Acetone (35)
Acetone (15)
Acetone (15)
Benzene (2)
Ϫ20
0
rt
rt
0
5 d
5 d
7 h
10 min
24 h
8 d
4.0
4.0
4.5
7.3
4.5
2.3
rt
diene, and our dienophile 1 can thus act as a cyanoacetylene
Use of lithium diisopropylamide as base led to a product
mixture which did not contain any of the diene 15 but which
contained the β,γ-unsaturated nitrile 16 as well as the desired
product 14. Attempted alkylation of 8 using allyl bromide or
allyl chloride as electrophile gave poor yields of mixtures of
products.
equivalent in this [4
ϩ 2π] cycloaddition reaction. 2-
(Methylthio)prop-2-enenitrile 12 is a related synthon,20 but two
steps are required for the transformation of its cycloadducts
into bicyclo[2.2.1]hepta-2,5-dienes.
Attempted conversion of the sulfonyl function of 8 into a
carbonyl group via reaction24 of its anion with bis(trimethyl-
silyl) peroxide was similarly unsuccessful.
2,3-Dimethylbutadiene, cyclohexa-1,3-diene and anthracene
all reacted with 1 to yield, respectively, the expected cycload-
ducts 17, 18 and 19. Only the endo-phenylsulfonyl adduct,
identifiable by the characteristic downfield shift of the proton α
to the sulfonyl group, was obtained from cyclohexa-1,3-diene,
although this diene has been reported25 to react with phenylsul-
fonylethene to give an 81 : 19 mixture of endo- and exo-adducts.
The anthracene adduct 19 could be converted into the unsatur-
ated nitrile 20 via potassium tert-butoxide-catalysed elimination
of benzenesulfinic acid. No Michael adducts analogous to the
tert-butyl ethers 13 were observed in this instance.
When the mixture of cycloadducts 8 and 9 was treated with
an excess of potassium tert-butoxide in tetrahydrofuran com-
pound 10 could not be isolated from the reaction mixture.
Instead, a mixture of the isomeric ethers 13, which could also
be obtained from 10 by its reaction with the alkoxide, was
formed. Addition of the poorly nucleophilic tert-butoxide ion
to strained, reactive Michael acceptors has occasionally been
observed.21
Alkylation of the carbanion derived from the major
cyclopentadiene cycloadduct 8 was next investigated. The pKa
values for methine hydrogens adjacent to nitrile22 and phenyl-
sulfonyl23 substituents are rather similar, but we anticipated
that low-temperature deprotonation of 8 would lead largely to
the α-sulfonyl carbanion due to the relative accessibility of the
relevant exo-proton.
When the sulfone 8 was treated with n-BuLi in THF at Ϫ78
ЊC a dark coloured solution of the anion was formed. Addition
of iodomethane led to discharge of this colour, and work up
gave the methylated product 14 in moderate yield. The NMR
spectrum of 14 was consistent with retention of stereo-
chemistry at the sulfonyl carbon. Accompanying 14 was the
unstable unsaturated nitrile 15 together with a significant
amount of unreacted starting material 8. Since 15 clearly arises
via competing base-catalysed elimination of benzenesulfinic
acid from the primary product 14, the overall yield of the latter
compound is necessarily reduced.
We next investigated the regioselectivity of the Diels–Alder
reaction of 1 with unsymmetrical dienes. Isoprene 21 gave
an unresolvable mixture of products 22 and 23. These had
1
similar H NMR spectra but were clearly differentiated by 13C
NMR spectroscopy. Reaction of the mixture of 22 and 23
with potassium tert-butoxide in DMSO or in THF gave, via
elimination of benzensulfinic acid, the toluonitriles 24 and 25
formed by aerial oxidation or by disproportionation of the
primary elimination products. The regioselectivity of the
Diels–Alder reaction of 1 with isoprene was not improved in
the presence of Lewis acids (ZnCl2, BF3ؒEt2O), indeed, as
others have also noted,26 overall yields were actually reduced.
Similar poor regioselectivity was observed when 1 was
reacted with myrcene 26.
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799
1795

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Cycloaddition of 1 with furfuryl alcohol 38 proceeded in a
regioselective manner to yield the diastereoisomeric adducts 39
and 40 whose structures were elucidated on the basis of their 1H
NMR shifts and coupling patterns.
These results parallel those of Ono,9 who found that 1-nitro-
2-phenylsulfonylethene 27 also reacted with the two dienes 21
and 26 to give mixtures of products in which neither regioi-
somer predominated.
Conclusion
Thus, the unsaturated sulfonylnitrile 1 is an easily prepared
reactive dienophile. The facile base-induced elimination of ben-
zenesulfinic acid from its cycloadducts with cyclopentadiene
and with anthracene demonstrate its application as
a
cyanoacetylene equivalent. Alkylation reactions of the α-
sulfonyl anions of the cycloadducts are of limited value because
of competing elimination of benzenesulfinate ion from the
reaction products. Inadequate regiocontrol is observed in
cycloaddition reactions with simple unsymmetrical dienes, but
excellent results were obtained with Danishefsky’s diene and
with furfuryl alcohol. However, spontaneous crystallisation of
the reaction products from solution may be an important factor
in the latter instance.
When 1 was reacted with the electronically biased 2-
trimethylsilyloxybuta-1,3-diene 28 a 1 : 2 mixture of the two
regioisomeric cycloadducts 29 and 30 was formed. These were
unstable towards chromatography, and were converted into the
corresponding ketones 31 and 32 by hydrolysis with aqueous
acetic acid. These ketones could be separated by column
chromatography, the minor isomer 31 being eluted first. The
NMR spectra of 31 and 32, although different, did not
permit unambiguous assignment of their structures, and the
ketone 32 was therefore converted into its ethylene acetal which
was treated with potassium tert-butoxide to give the nitrile 33.
An authentic specimen of this nitrile was prepared from
cyclohexane-1,4-dione monoacetal 34 which was converted via
its bisulfite compound into the cyanohydrin 35 using aqueous
potassium cyanide and then dehydrated using thionyl chloride
in pyridine to give 33.
Experimental
1H and 13C NMR spectra were obtained for solutions in CDCl3
unless otherwise stated using JEOL PMX-60, Bruker WP-80 or
Bruker MSL-300 spectrometers. J values are given in Hz. IR
spectra were recorded using Perkin–Elmer 298, Perkin–Elmer
883 or Paragon FT-IR instruments. Melting points were
obtained using a Stuart Scientific SMP2 apparatus and are
uncorrected. GLC analysis was carried out using a Varian
3300–3400 gas chromatograph. TLC was performed using
Merck 60F254 silica-coated plates. Column chromatography was
carried out using Merck Kieselgel 60. All solvents were distilled
before use. Elemental analyses were performed by the Micro-
analytical Laboratory, University College Dublin.
2-Chloro-3-phenylsulfonylpropanenitrile 3
Sodium benzenesulfinate (24.7 g) was dissolved in a mixture of
water (50 cm3) and acetic acid (20 cm3). 2-Chloroprop-2-
enenitrile 2 (13.1 g) was added, followed by methanol (50 cm3).
After 10 min, the solid product 3 (26.16 g; 76%) was collected
by filtration, mp 104 ЊC (lit.13 105–106 ЊC); δH 3.70 (2H, dd, J
14.0 and 6.8, -CH2CH-), 5.01 (1H, t, J 6.8, -CH2CH-) and
7.4–8.15 (5H, m, Ar-) ppm [Found C 47.10, H 3.45, N 6.12.
C9H8ClNO2S requires C 47.06, H 3.48, N 6.10%].
(E )-3-Phenylsulfonylprop-2-enenitrile 1
The crude chloro-compound 3 (24.71 g) was dissolved in
chloroform (175 cm3) and the solution was cooled in an ice–salt
bath. Triethylamine (15 cm3; 0.11 mol) was added dropwise and
the mixture was kept at 0 ЊC during 10 min. It was then washed
sequentially with dilute aqueous hydrochloric acid and with
sodium hydrogen carbonate solution. Evaporation of solvent
after drying over anhydrous magnesium sulfate yielded a solid
which was recrystallised from 70 : 30 ethyl acetate–hexane
(charcoal) to give the unsaturated sulfone 1 (12.5 g; 64%), mp
93–94 ЊC (lit.14 103–104 ЊC from H2O); νmax (Nujol) 3060, 2225,
Reaction of 1 with Danishefsky’s diene 36 gave a mixture of
adducts which could not be separated and which were desi-
lylated using aqueous acetic acid. The resulting crude mixture
of unstable keto-nitriles gave 4-hydroxybenzonitrile 37 as the
sole product when it was treated with potassium tert-butoxide.
1310 and 1150 cmϪ1; δH 6.43 (1H, d, J 15.4, -CH᎐CHCN), 7.15
᎐
(1H, d, J 15.4, -CH᎐CHSO Ph) and 7.3–7.9 (5H, m, Ar-) ppm
᎐
2
[Found C 55.60, H 3.52, N 7.03. C9H7NO2S requires C 55.96, H
3.63, N 7.25%].
1796
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799

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(Z )-3-Phenylsulfonylprop-2-enenitrile 4. This was sometimes
formed as a minor product (ca. 3%), and it could be separated
from 1 by chromatography on silica gel using 40 : 60 ethyl
acetate–hexane as eluant. It crystallised from 70 : 30 ethyl
acetate–hexane as needles, mp 77.5–78 ЊC; νmax (Nujol) 3040,
(0.44 g; 1.3 eq.). After 15 min the yellow reaction mixture was
diluted with water and extracted with ether to give
bicyclo[2.2.1]hepta-2,5-diene-2-carbonitrile 10 as an oil (0.29 g;
75%), δH (80 MHz) 2.06–2.26 (2H, m, 2H-7), 3.63–3.87 (2H, m,
H-1 and H-4), 6.50–6.87 (2H, m, H-5 and H-6) and 7.49
(1H, m, H-3) ppm.
2210, 1300 and 1150 cmϪ1; δH 6.05 (1H, d, J 11.2 Hz, -CH᎐
᎐
CHCN), 7.08 (1H, d, J 11.2 Hz, -CH᎐CHSO Ph) and 7.60–8.23
(5H, m, Ar-) ppm [Found C 55.50, H 3.61, N 7.00. C9H7NO2S
requires C 55.96, H, 3.63, N 7.25%].
᎐
2
3-tert-Butoxybicyclo[2.2.1]hept-5-ene-2-carbonitrile 13
A mixture of the cycloadducts 8 and 9 (0.26 g) was dissolved in
THF (10 cm3) with freshly-sublimed potassium tert-butoxide
(0.47 g; 4.2 eq.). After 20 min the yellow reaction mixture was
diluted with water and extracted with ether to give a mixture of
isomers of 3-tert-butoxybicyclo[2.2.1]hept-5-ene-2-carbonitrile
13 as an oil (0.14 g; 74%), bp 74–75 ЊC/15 mmHg; δH (60 MHz)
1.21 (9H, s, tert-Bu group; both isomers), 1.5–1.9 (2H, m, 2H-7;
both isomers), 2.37 (∼0.5H, dd, J ∼ 3.0, H-2; one isomer), 2.67
(1H, m, H-4; both isomers), 2.8–3.2 (∼2.5H, m, H-1 (both
isomers) and H-2; one isomer), 3.74 (1H, m, H-3; both isomers)
and 5.97–6.35 (2H, m, H-5 and H-6; both isomers) ppm
[Found: C 74.68, H 9.66, N 7.48. C12H19NO requires C 74.61,
H 9.84, N 7.25%].
3-endo-Phenylsulfonyl-7-oxabicyclo[2.2.1]hept-5-ene-2-exo-
carbonitrile 6 and 3-exo-phenylsulfonyl-7-oxabicyclo[2.2.1]hept-
5-ene-2-endo-carbonitrile 7
(E)-3-Phenylsulfonylprop-2-enenitrile 1 (0.19 g) was dissolved
in furan 5 (3 cm3) and the solution was heated at 30 ЊC during 4
h. Excess furan was evaporated and the residue was chromato-
graphed on silica gel using 30 : 70 ethyl acetate–hexane as eluant.
First eluted was 3-endo-phenylsulfonyl-7-oxabicyclo[2.2.1]-
hept-5-ene-2-exo-carbonitrile 6 (0.16 g; 60%), which was
recrystallised from 60 : 40 ethyl acetate–hexane to give a solid,
mp 93–94 ЊC; νmax (Nujol) 2240, 1305 and 1150 cmϪ1; δH
(80 MHz) 2.87 (1H, d, J 4.7, H-3), 3.98 (1H, apparent t, J 4.7
and 4.7, H-2), 5.32 (2H, m, H-1 and H-4), 6.66 (2H, m, H-5
and H-6), 7.7 (3H, m, meta- and para-ArH) and 7.9 (2H, m,
ortho-ArH) ppm [Found: C 59.48, H 4.15, N 5.46. C13H11NO3S
requires C 59.77, H 4.21, N 5.36%].
Alkylation of 3-endo-phenylsulfonylbicyclo[2.2.1]hept-5-ene-2-
exo-carbonitrile 8
(a) Using n-BuLi as base:
The sulfone 8 (0.51 g; 1.97 mmol), in THF (15 cm3) at Ϫ78
ЊC, was stirred and treated dropwise with n-BuLi (1.15 M
in hexane; 1.7 cm3; 1 eq.). After 1 h iodomethane (0.3 cm3;
2.5 eq.) was added to the brown solution and the mixture was
allowed to warm to rt over 45 min. After a further 2 h,
aqueous ammonium chloride was added to the yellow solution
which was then extracted with ether to give an oil (0.46 g)
which was chromatographed on silica gel using 30 : 70 ethyl
acetate–hexane as eluant.3-Methylbicyclo[2.2.1]hepta-2,5-
diene-2-carbonitrile 15 (10 mg; 4%) was obtained as an unstable
brown oil, δH (60 MHz) 1.8–2.1 (2H, m, 2H-7), 2.08 (3H, s,
-CH3), 3.5 (1H, m, H-1), 3.7 (1H, m, H-4) and 6.6–6.9 (2H, m,
H-5 and H-6) ppm. This was followed by 3-endo-phenylsulfonyl-
Next eluted was 3-exo-phenylsulfonyl-7-oxabicyclo[2.2.1]-
hept-5-ene-2-endo-carbonitrile
7 (0.1 g; 40%) which was
recrystallised from 50 : 50 ethyl acetate–hexane to give a solid,
mp 103–104 ЊC; νmax (Nujol) 2240, 1297 and 1150 cmϪ1; δH
(80 MHz) 3.38 (2H, m, H-2 and H-3), 5.36 (1H, m, H-4), 5.52
(1H, apparent t, J 0.98 and 0.98, H-1), 6.63 (2H, m, H-5 and
H-6), 7.62 (3H, m, meta- and para-ArH) and 7.9 (2H, m,
ortho-ArH) ppm [Found: C 60.23, H 3.96, N 5.31. C13H11NO3S
requires C 59.77, H 4.21, N 5.36%].
3-endo-Phenylsulfonylbicyclo[2.2.1]hept-5-ene-2-exo-carbonitrile
8 and 3-exo-phenylsulfonylbicyclo[2.2.1]hept-5-ene-2-endo-
carbonitrile 9
3-exo-methylbicyclo[2.2.1]hept-5-ene-2-exo-carbonitrile
14
(0.22 g; 41%), mp 142 ЊC (diethyl ether); νmax (Nujol) 2273 and
1148 cmϪ1; δH (80 MHz) 1.55 (3H, s, -CH3), 1.70 (1H, ddd, J 2, 2
and 10, H-7a), 1.91 (1H, d, J 10, H-7b), 3.0–3.15 (1H, m, H-2),
3.25–3.45 (2H, m, H-1 and H-4), 6.33 (1H, dd, J 5.6 and 3, H-5
or H-6), 6.52 (1H, dd, J 5.6 and 2.7, H-6 or H-5), 7.50–7.73
(3H, m, meta- and para-ArH) and 7.82 (2H, m, ortho-ArH)
ppm [Found: C 65.33, H 5.97, N 5.24. C15H17NO2S requires C
65.45, H 6.18, N 5.09%].
Freshly distilled cyclopentadiene (0.83 g) was added to a solu-
tion of (E)-3-phenylsulfonylprop-2-enenitrile 1 (1.94 g) in acet-
one (15 cm3) and the mixture was kept at 0 ЊC during 24 h.
Solvent and excess cyclopentadiene were evaporated and the
residue (2.64 g) was chromatographed on silica gel using
chloroform–hexane–diethyl ether (30 : 50 : 30) as eluant.
First eluted was 3-exo-phenylsulfonylbicyclo[2.2.1]hept-5-
ene-2-endo-carbonitrile 9 (0.46 g; 18%), which was recrystallised
from 60 : 40 ethyl acetate–hexane to give a solid, mp 137–138
ЊC; νmax (Nujol) 2240, 1580, 1305 and 1150 cmϪ1; δH (80 MHz)
1.61 (1H, dd, J 9.5 and 1.5, H-7a), 2.09 (1H, d, J 9.5, H-7b),
3.06–3.49 (4H, m, H-1, H-2, H-3 and H-4), 6.40 (2H, m, H-5
and H-6), 7.53–7.78 (3H, m, meta- and para-ArH) and 7.92
(2H, m, ortho-ArH) ppm [Found: C 64.46, H 4.86, N 5.26.
C14H13NO2S requires C 64.85, H 5.05, N 5.40%].
Next eluted was 3-endo-phenylsulfonylbicyclo[2.2.1]hept-5-
ene-2-exo-carbonitrile 8 (2.1 g; 82%), which was recrystallised
from 50 : 50 ethyl acetate–hexane to give a solid, mp 121–123
ЊC; νmax (Nujol) 2240, 1580, 1305 and 1148 cmϪ1; δH (80 MHz)
1.43–1.84 (2H, m, H-7a and H-7b), 2.71 (1H, dd, J 1.7 and 5.4,
H-2), 3.26–3.47 (2H, m, H-1 and H-4), 3.83 (1H, dd, J 5.4 and
3.2, H-3), 6.36 (2H, m, H-5 and H-6), 7.48–7.77 (3H, m, meta-
and para-ArH) and 7.84 (2H, m, ortho-ArH) ppm [Found: C
64.92, H 5.08, N 5.35. C14H13NO2S requires C 64.85, H 5.05, N
5.40%].
(b) Using LDA as base:
A solution of LDA, prepared by adding n-BuLi (1.37 M in
hexane; 6.5 cm3) to diisopropylamine (1.25 cm3) in THF (10
cm3) at Ϫ78 ЊC, was added dropwise to a stirred solution of the
sulfone 8 (1.05 g; 4 mmol) and iodomethane (0.5 cm3; 7.7
mmol) in THF (25 cm3) at Ϫ78 ЊC. After 1.5 h the mixture was
allowed to warm to rt. It was then diluted with water and
extracted with ether to give a brown oil (0.88 g) which was
chromatographed on silica gel using 20 : 50 ethyl acetate–
hexane as eluant. A fraction which was enriched in 3-methyl-
idenebicyclo[2.2.1]hept-5-ene-2-exo-carbonitrile
16
was
obtained and had δH (60 MHz) 1.5–1.75 (2H, m, 2H-7), 2.9 (1H,
m, H-2), 3.25–3.57 (2H, m, H-1 and H-4), 5.10 (2H, d, J 7.0,
-C᎐CH ) and 6.25–6.40 (2H, m, H-5 and H-6) ppm. Attempts
᎐
2
to obtain an analytically pure sample of 16 were unsuccessful.
Another fraction (0.13 g) contained (NMR) a mixture of the
nitriles 10 and 14 in the ratio 9 : 2, and a third fraction (0.47 g)
was identified as being the sulfone 8.
Bicyclo[2.2.1]hepta-2,5-diene-2-carbonitrile 1019
6-Phenylsulfonyl-3,4-dimethylcyclohex-3-enecarbonitrile 17
A mixture of the cycloadducts 8 and 9 (0.86 g) was dissolved in
THF (30 cm3) with freshly-sublimed potassium tert-butoxide
(E)-3-Phenylsulfonylprop-2-enenitrile 1 (2.95 g) was dissolved
in acetone (60 cm3) with 2,3-dimethylbuta-1,3-diene (4.14 g; 3.4
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799
1797

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eq.) and the mixture was refluxed during 23 h. Evaporation of
solvent yielded an oil which soon solidifed. Recrystallisation
from 40 : 60 ethyl acetate–hexane afforded 6-phenylsulfonyl-3,4-
dimethylcyclohex-3-enecarbonitrile 17 (3.98 g; 95%) as a solid,
mp 90–91 ЊC; νmax (Nujol) 2240, 1310 and 1150 cmϪ1; δH
(80 MHz) 1.62 (6H, s, -CH3 groups), 2.35–2.5 (4H, m, -CH2
groups), 2.9–3.23 (2H, m, H-1 and H-2), 7.67 (3H, m, meta- and
para-ArH) and 7.89 (2H, m, ortho-ArH) ppm [Found: C 65.44,
H 6.27, N 5.01. C15H17NO2S requires C 65.45, H 6.18, N
5.09%].
(80 MHz) 1.69 (3H, br s, -CH3 groups), 2.17–2.65 (4H, m,
-CH2 groups), 2.9–3.7 (2H, overlapping ms, -CHCN- and
-CHSO2Ph), 5.2–5.4 (1H, m, vinyl), 7.33–7.65 (3H, m, meta-
and para-ArH) and 7.84 (2H, m, ortho-ArH) ppm; δC (75 MHz)
25.31 and 25.79 (CH3), 24.06 (CH2), 25.31 and 25.79 (CHCN),
28.22, 28.61 and 32.77 (CH2), 59.72 and 60.47 (CHSO2Ph),
117.85 and 118.67 (-CH᎐C), 119.89 (CN), 131.45 and 131.57
᎐
(-CH᎐C-), 129.47, 129.9 and 134.84 (ArCH) and 137.85
᎐
(quaternary) ppm [Found:
C 64.19, H 5.83, N 5.729.
C14H15NO2S requires C 64.37, H 5.75, N 5.36%].
3-endo-Phenylsulfonylbicyclo[2.2.2]oct-5-ene-2-exo-carbonitrile
Elimination of benzenesulfinic acid from 22 and 23
18
A mixture of the cyclohexenes 22 and 23 (0.27 g; 1.03 mmol) in
THF (12 cm3) was treated with potassium tert-butoxide (0.56 g;
4.99 mmol). After 10 min the red solution was diluted with
water and extracted using ether to give an oil (0.1 g) that was
(by NMR comparison with authentic specimens) a mixture of
starting materials and the m- and p-toluonitriles 24 and 25.
(E)-3-Phenylsulfonylprop-2-enenitrile 1 (0.19 g) was dissolved
in acetone (2 cm3) with cyclohexa-1,3-diene (0.24 cm3; 2.5 eq.)
in a small pressure tube. The contents of the tube were frozen
and the tube was sealed and then heated at 80 ЊC during 15 h.
Removal of solvent gave a solid which was a single diastereo-
isomer (NMR). Recrystallisation from diethyl ether gave
3-endo-phenylsulfonylbicyclo[2.2.2]oct-5-ene-2-exo-carbonitrile
18 (0.16 g; 60%), mp 123–125 ЊC; νmax (Nujol) 2235, 1305
and 1145 cmϪ1; δH (80 MHz) 1.23–2.05 (4H, m, -CH2–CH2-),
2.75–3.33 (3H, H-1, H-2 and H-4), 3.38 (1H, dd, J 6.5 and 1.4,
H-3), 6.30 (2H, m, H-5 and H-6), 7.45–7.75 (3H, m, meta- and
para-ArH) and 7.82 (2H, m, ortho-ArH) ppm [Found: C 66.21,
H 5.73, N 5.01. C15H15NO2S requires C 65.91, H 5.53, N
5.12%].
Reaction of (E )-3-phenylsulfonylprop-2-enenitrile 1 with
myrcene 26
A solution of (E)-3-phenylsulfonylprop-2-enenitrile 1 (0.39 g;
2.02 mmol) and freshly distilled myrcene 26 (1.0 cm3; 4.41
mmol) in benzene (7 cm3) was refluxed during 4 h. Solvent
was evaporated and the residue was chromatographed on silica
gel using 50 : 50 ethyl acetate–hexane to yield an oil (0.58 g;
88%), νmax (liquid film) 2240, 1308 and 1148 cmϪ1; δH
(60 MHz) 1.60 (3H, br s, -CH3), 1.67 (3H, br s, -CH3), 1.9–2.1
(4H, m, -CH2 groups), 2.9–3.7 (2H, overlapping ms, -CHCN-
and -CHSO2Ph), 4.8–5.2 (1H, m, vinyl), 5.23–5.45 (1H, m,
vinyl) and 7.3–8.0 (5H, ArH) ppm.
trans-12-Phenylsulfonyl-9,10-ethanoanthracene-11-carbonitrile
19
Anthracene (2.85 g; 16 mmol) and (E)-3-phenylsulfonylprop-2-
enenitrile 1 (1.03 g; 5.3 mmol) in toluene (58 cm3) were refluxed
together during 29 h. The mixture was cooled and excess
anthracene was removed by filtration. After evaporation of
solvent the residue was chromatographed on silica gel using 50 :
50 ethyl acetate–hexane as eluant to give a crude solid (1.96 g),
some of which was purified by sublimation (200 ЊC/0.3 mmHg)
to give trans-12-phenylsulfonyl-9,10-ethanoanthracene-11-carbo-
Reaction of (E )-3-phenylsulfonylprop-2-enenitrile 1 with
2-trimethylsilyloxybuta-1,3-diene 28
2-Trimethylsilyloxybuta-1,3-diene (0.72 g; 5.06 mmol) and (E)-
3-phenylsulfonylprop-2-enenitrile 1 (0.85 g; 4.4 mmol) were
refluxed together in benzene (10.5 cm3) under nitrogen during
26 h. Evaporation of solvent and of excess reagent afforded an
oily mixture (1.46 g; 93%) of the adducts 29 and 30, δH (80
MHz) 0.10 (9H, -SiMe3), 2.13–2.67 (4H, m, -CH2 groups), 4.71
nitrile 19, mp 83–84 ЊC; νmax (Nujol) 2240, 1310 and 1150 cmϪ1
;
δH (80 MHz) 3.34 (1H, dd, J 6.0 and 2.2, H-2), 3.55 (1H, dd,
J, 6.0 and 2.2, H-3), 4.59 (1H, d, J 2.2, H-1), 4.97 (1H, d, J 2.0,
H-4) and 7.12–7.89 (13H, m, ArH) ppm [Found: C 74.51, H
4.64, N 3.79. C23H17NO2S requires C 74.37, H 4.61, N 3.77%].
(1H, m, -CH᎐C-), 7.32–7.68 (3H, m, meta- and para-ArH) and
᎐
7.82 (2H, d, J 8.0, ortho-ArH) ppm.
A mixture of the adducts 29 and 30 (2.02 g) was dissolved in
aqueous acetic acid (80%; 15 cm3). After 1 h at rt the mixture
was diluted with water and extracted using chloroform to give a
crude product mixture which was chromatographed on silica
gel using 7 : 13 ethyl acetate–hexane as eluant.
First eluted was trans-4-phenylsulfonyl-3-cyanocyclo-
hexanone 31 (0.17 g; 10%), mp 149–150 ЊC (ethyl acetate–
hexane); νmax (Nujol) 2235, 1722, 1310 and 1155 cmϪ1; δH
(60 MHz) 2.4–2.67 (8H, m, -CH2 and -CH groups), 7.5–7.77
(3H, m, meta- and para-ArH) and 7.95 (2H, d, J 8.1, ortho-ArH
) ppm [Found: C 59.02, H 4.98, N 5.17. C13H13NO3S requires C
59.30, H 4.98, N 5.32%].
(E )-9,10-Ethenoanthracene-11-carbonitrile 20
The above adduct 19 (0.35 g), in THF (20 cm3), was treated with
potassium tert-butoxide (0.21 g; 2 eq.) at rt After 15 min the
mixture was diluted with water and the product was extracted
using ether to give (E)-9,10-ethenoanthracene-11-carbonitrile
20 (0.13 g; 59%), mp 186–188 ЊC (lit.27 mp 194–196 ЊC); νmax
(Nujol) 2200 cmϪ1; δH (80 MHz) 5.17–5.26 (2H, m, -CHCH᎐
᎐
C(CN)CH-), 6.91–7.37 (8H, m, ArH) and 7.66 (1H, dd, J 6.2
and 1.8, -CH᎐C(CN)-) ppm.
᎐
Next eluted was trans-3-phenylsulfonyl-4-cyanocyclo-
hexanone 32 (0.46 g; 28%), mp 158–159 ЊC (ethyl acetate–
hexane), νmax (Nujol) 2240, 1715, 1305 and 1150 cmϪ1; δH
(80 MHz) 2.35–2.81 (6H, m, -CH2 groups), 3.63–3.86 (2H, m,
H-3 and H-4), 7.51–8.04 (5H, m, ArH) ppm [Found: C 59.41, H
5.00, N 5.12. C13H13NO3S requires C 59.30, H 4.98, N 5.32%].
Reaction of (E )-3-phenylsulfonylprop-2-enenitrile 1 with
isoprene 21
A solution of (E)-3-phenylsulfonylprop-2-enenitrile 1 (0.29 g)
with isoprene 21 (0.3 cm3; 2 eq.) in acetone (3 cm3) in a small
pressure tube was frozen and sealed under vacuum and then
heated at 80 ЊC during 14 h. Solvent was evaporated to yield an
oil (0.32 g) which was chromatographed on silica gel using 7 : 13
ethyl acetate–hexane to give a mixture of trans-4-phenyl-
sulfonyl-1-methylcyclohexene-5-carbonitrile 22 and trans-5-
phenylsulfonyl-1-methylcyclohexene-4-carbonitrile 23 as a solid
(0.31 g; 80%) which could not be further separated into its
components. νmax (Nujol) 2240, 1305 and 1150 cmϪ1; δH
1,4-Dioxaspiro[4.5]dec-7-ene-7-carbonitrile 33 from 32
The ketone 32 (80 mg) was refluxed in benzene (10 cm3) with
toluene-p-sulfonic acid (12 mg) and ethylene glycol (0.7 cm3)
during 12 h. The usual work-up followed by chromatography
on silica gel using 20 : 30 ethyl acetate–hexane as eluant
1798
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799

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afforded trans-7-phenylsulfonyl-1,4-dioxaspiro[4.5]decane-8-
carbonitrile (80 mg; 85%) as a solid, mp 76–77 ЊC; δH (80 MHz)
1.26–2.84 (7H, m, -CH2 groups and -CH(CN)-), 3.54 (1H, ddd,
J 12.8, 11.3 and 4.0, -CHSO2Ph), 3.94 (4H, br s, -OCH2CH2-O)
and 7.58–8.03 (5H, m, ArH) ppm. This acetal (80 mg), in THF
(5 cm3), was treated with potassium tert-butoxide (0.1 g) during
15 min at rt. The reaction mixture was diluted with water,
extracted with ether and chromatographed over silica gel,
eluting with 10 : 90 ethyl acetate–hexane, to yield 1,4-
dioxaspiro[4,5]dec-7-ene-7-carbonitrile 33 as an oil (65 mg)
which slowly solidified and which was then sublimed at atmos-
pheric pressure to give crystals, mp 30–31 ЊC; νmax(Nujol) 2210
and 1640 cmϪ1; δH (60 MHz) 1.65–1.95 (2H, m, -CH -C᎐C-),
-CH2OH, -OH and H-3), 5.24 (1H, dd, J 4.3 and 1.3, H-4),
6.63 (2H, m, H-5 and H-6) and 7.7–8.09 (5H, m, ArH) ppm.
Deuterium exchange of the hydroxy proton simplified the
multiplet at δ 4.06–4.54 which became 4.11 (2H, s, -CH2OH)
and 4.36 (1H, dd, J 5.0 and 4.4, H-4) ppm [Found: C 57.30, H
4.15, N 4.35%. C14H13NO4S requires C 57.72, H 4.50, N 4.81%].
The minor product, 3-exo-phenylsulfonyl-1-hydroxymethyl-
7-oxabicyclo[2.2.1]hept-5-ene-2-endo-carbonitrile
40,
was
obtained as a solid, (0.13 g; 16%), mp 122–122.5 ЊC (ethanol);
νmax (Nujol) 3490, 2240, 1300 and 1147 cmϪ1; δH (80 MHz;
[2H6]acetone) 3.16 (1H, br s, exch. D2O, -OH ), 3.52 (1H, d, J
4.6, H-2), 3.78 (1H, d, J 4.6, H-3), 4.09 (2H, s, -CH2OH), 5.43
(1H, d, J 1.8, H-4), 6.60 (1H, d, J 5.7, H-6), 6.77 (1H, dd, J 5.7
and 1.8, H-5), 7.68–7.84 (3H, m, meta- and para-ArH) and 8.04
(2H, d, J 8.0, ortho-ArH) ppm. Deuterium exchange of the
hydroxy proton simplified the multiplet at δ 4.06–4.54 which
became 4.11 (2H, m, -CH2OH) and 4.36 (1H, dd, J 5.0 and 4.4,
H-4) ppm [Found: C 57.71, H 4.58, N 4.33. C14H13NO4S
requires C 57.72, H 4.50, N 4.81%].
᎐
2
2.28–2.65 (4H, m, -CH2 groups), 4.00 (4H, s, -OCH2CH2-O)
and 6.51 (1H, m, H-8) ppm [Found: C 65.67, H 6.87, N 8.34%.
C9H11NO2 requires C 65.45, H 6.66, N 8.48%].
1,4-Dioxaspiro[4.5]dec-7-ene-7-carbonitrile 33 from
cyclohexane-1,4-dione monoethylene acetal 34
Cyclohexane-1,4-dione monoethylene acetal 34 (1.01 g) was
added at rt to water (7.5 cm3) containing sodium metabisulfite
(0.71 g). After 15 min water was evaporated at reduced pressure,
the residue was triturated with ether and the solid bisulfite
compound was collected by filtration. This was dissolved in
water (28 cm3) layered with ether (28 cm3), and the two-phase
mixture was stirred vigorously with potassium cyanide (0.66 g)
during 15 min. Extraction with ether yielded the cyanohydrin
References
1 H. R. Snyder, H. V. Anderson and D. P. Hallada, J. Am. Chem. Soc.,
1951, 73, 3258; J. C. Philips and M. Oku, J. Am. Chem. Soc., 1972,
94, 1012.
2 R. D. Little and L. Brown, Tetrahedron Lett., 1980, 21, 2203;
R. V. C. Carr and L. A. Paquette, J. Am. Chem. Soc., 1980, 102, 853;
R. V. C. Carr, W. A. Kinney, G. D. Crouse and L. A. Paquette,
J. Org. Chem., 1983, 48, 4986.
3 M. Hanack and F. Massa, Tetrahedron Lett., 1977, 18, 661;
K. Laping and M. Hanack, Tetrahedron Lett., 1979, 20, 1309;
R. S. Glass and D. L. Smith, J. Org. Chem., 1974, 39, 3712.
4 K. Hayakawa, H. Nishiyama and K. Kanematsu, J. Org. Chem.,
1985, 50, 512; A. J. Guildford and R. W. Turner, J. Chem. Soc.,
Chem. Commun., 1983, 466.
35 as a solid (1.0 g; 95%), νmax (Nujol) 3370 and 2240 cmϪ1
;
δH (60 MHz) 1.6–2.4 (8H, m, -CH2 groups), 3.75 (1H, br s,
exch. D2O, -OH ) and 4.13 (4H, s, -OCH2CH2-O) ppm. This
cyanohydrin 35 (1.94 g) was dissolved in pyridine (40 cm3) at
0 ЊC and treated with thionyl chloride (0.8 cm3). After 12 h
the mixture was worked up in the usual way to give 1,4-
dioxaspiro[4.5]dec-7-ene-7-carbonitrile 33, identical in every
respect with material obtained from the ketone 32 as described
above.
5 A. P. Davis and G. H. Whitham, J. Chem. Soc., Chem. Commun.,
1980, 639.
6 O. de Lucchi and G. Modena, Tetrahedron Lett., 1983, 24, 1653.
7 O. de Lucchi, V. Lucchini, L. Pasquato and G. Modena, J. Org.
Chem., 1984, 49, 596.
8 L. A. Paquette and R. V. Williams, Tetrahedron Lett., 1981, 22, 4643.
9 N. Ono, A. Kamimura and A. Kaji, Tetrahedron Lett., 1986, 27,
1595.
10 H. R. Snyder and D. P. Hallada, J. Am. Chem. Soc., 1952, 74, 5595;
J. Sauer, H. Wiest and A. Mielert, Chem. Ber., 1964, 97, 3183.
11 A. D. Buss, G. C. Hirst and P. J. Parsons, J. Chem. Soc., Chem.
Commun., 1987, 1836.
12 A. Riera, M. Marti, A. Moyano, M. A. Pericas and J. Santamaria,
Tetrahedron Lett., 1990, 31, 2173.
13 N. S. Simpkins, Sulphones in Organic Synthesis, Pergamon Press,
Oxford, 1993.
14 I. L. Knunyants, M. G. Lin’Kova and N. L. Weller, Izv. Akad. Nauk
SSSR, Ser. Khim., 1966, 6, 1075.
15 E. A. Berdnikov, F. K. MuKhitova, F. R. Tantasheva and
E. G. Kataev, Zh. Org. Khim., 1977, 13, 1418.
16 F. Scotti and E. J. Fraza, J. Org. Chem., 1964, 29, 1800.
17 A. R. Morgan, V. S. Pangka and D. Dolphin, J. Chem. Soc., Chem.
Commun., 1984, 1047.
18 R. W. Sweger and A. W. Czarnik, in Comprehensive Organic
Synthesis, eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford,
1991 5, 551.
Reaction of (E )-3-phenylsulfonylprop-2-enenitrile 1 with
Danishefsky’s diene 36
1-Methoxy-3-trimethylsilyloxybuta-1,3-diene 36 (2.0 cm3; 1.05
mmol) was added to a solution of (E)-3-phenylsulfonylprop-2-
enenitrile 1 (1.76 g; 9.1 mmol) in benzene (35 cm3) under an
atmosphere of nitrogen and the mixture was refluxed during 23
h. Evaporation of solvent yielded a solid (3.84 g). This (2.38 g)
was treated with aqueous acetic acid (80%; 25 cm3) during 24 h
at rt after which time extraction using ethyl acetate afforded an
oil (1.9 g) which contained (NMR) 4-hydroxybenzonitrile
together with a mixture of diastereoisomers of 3-phenyl-
sulfonyl-4-cyano-5-methoxycyclohexanone. This oil, in THF
(17 cm3), was treated with potassium tert-butoxide (0.32 g)
during 2 h and then worked up to give 4-hydroxybenzonitrile 37
(0.94 g; 90% from 1), spectroscopically identical with authentic
material.
Reaction of (E )-3-phenylsulfonylprop-2-enenitrile 1 with furfuryl
alcohol 38
19 W. Adam, O. de Lucchi, L. Pasquato and B. Will, Chem. Ber., 1987,
120, 531.
20 J.-L. Boucher and L. Stella, Tetrahedron, 1986, 42, 3871.
21 S. Mirsadegi and B. Rickborn, J. Org. Chem., 1985, 50, 4340.
22 R. G. Pearson and R. L. Dillon, J. Am. Chem. Soc., 1953, 75, 2439.
23 P. D. Magnus, Tetrahedron, 1977, 33, 2019 and references therein.
24 P. G. Cookson, A. G. Davies and N. Fazal, J. Organomet. Chem.,
1975, 99, C31.
25 R. V. C. Carr, R. V. Williams and L. A. Paquette, J. Org. Chem.,
1983, 48, 4976.
26 B. M. Trost and A. J. Bridges, J. Am. Chem. Soc., 1976, 98, 5017.
27 C. F. Hueber, US Pat. 3707515, 1973 ( (Chem. Abstr., 1973, 78,
58150a)); . See also: E. Ciganek, DE 2236579, 1973, who reports mp
127–128 ЊC ( (Chem. Abstr., 1973, 78, 159321)).
Furfuryl alcohol 38 (1.4 cm3; 1.62 mmol) was added to a
solution of (E)-3-phenylsulfonylprop-2-enenitrile 1 (0.54 g; 2.8
mmol) in benzene (7 cm3) at rt After 6 h, the reaction products
were collected by filtration and separated by fractional crystal-
lisation from ethanol.
The major product, 3-endo-phenylsulfonyl-1-hydroxymethyl-
7-oxabicyclo[2.2.1]hept-5-ene-2-exo-carbonitrile
39,
was
obtained as a solid (0.49 g; 60%), mp 113–114 ЊC (ethanol);
νmax (Nujol) 3450, 2240, 1300 and 1150 cmϪ1; δH (80 MHz;
[2H6]acetone) 3.12 (1H, d, J 5.1, H-2), 4.06–4.54 (4H, m,
J. Chem. Soc., Perkin Trans. 1, 2002, 1794–1799
1799