Reactions of lithiated (E)-3-halo-1-phenylsulfonylprop-1-enes and (Z)-1-halo-3-phenylsulfonylprop-1-enes with aldehydes

Article abstract of DOI:10.1039/b300925b

(E)-3-Chloro-1-phenylsulfonylprop-1-ene and its iodo- and bromo- analogues, (Z)-1-iodo-3-phenylsulfonylprop-1-ene and (Z)-1-bromo-3-phenylsulfonylprop-1-ene, have each been successfully converted into lithiated carbanions which react regioselectively with aromatic aldehydes to give γ-alkylated products whose nature depends upon the halogen substituent; the chloro-sulfones yield (2Z)-1-aryl-1-chloro-4-phenylsulfonylbut-2-en-1-ols but the bromo- and iodo-derivatives behave differently, yielding (1E)-trans-4-aryl-3,4-epoxy-1-phenylsulfonylbut-1-enes. In sharp contrast, the same lithiated sulfones react with aliphatic aldehydes to give anti-configured β-hydroxysulfones which are formed via diastereoselective α-alkylation reactions.

Full text of DOI:10.1039/b300925b

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Reactions of lithiated (E )-3-halo-1-phenylsulfonylprop-1-enes and
(Z )-1-halo-3-phenylsulfonylprop-1-enes with aldehydes
Eva T. Gallagher and David H. Grayson*
Centre for Synthesis and Chemical Biology, Department of Chemistry, Trinity College,
Dublin 2, Ireland
Received 22nd January 2003, Accepted 27th February 2003
First published as an Advance Article on the web 25th March 2003
(E)-3-Chloro-1-phenylsulfonylprop-1-ene and its iodo- and bromo- analogues, (Z)-1-iodo-3-phenylsulfonylprop-1-
ene and (Z)-1-bromo-3-phenylsulfonylprop-1-ene, have each been successfully converted into lithiated carbanions
which react regioselectively with aromatic aldehydes to give γ-alkylated products whose nature depends upon the
halogen substituent: the chloro-sulfones yield (2Z)-1-aryl-2-chloro-4-phenylsulfonylbut-2-en-1-ols but the bromo-
and iodo-derivatives behave differently, yielding (1E)-trans-4-aryl-3,4-epoxy-1-phenylsulfonylbut-1-enes. In sharp
contrast, the same lithiated sulfones react with aliphatic aldehydes to give anti-configured β-hydroxysulfones which
are formed via diastereoselective α-alkylation reactions.
Introduction
Synthetic applications of heteroatom-substituted carbanions
have attracted considerable attention in recent years. Thus, the
reactions of lithio derivatives of simple allylic sulfones with
aldehydes are well established, and generally proceed in a regio-
specific manner to give α-alkylated products 1.1,2 On the other
hand, lithiation of allyl chloride3,4 followed by reaction of the
derived anion with a variety of aromatic aldehydes affords4
predominantly (Z)-configured γ-substituted products 2. Con-
versely, cinnamyl chloride can be deprotonated5 to give a lithio
derivative which reacts with aromatic ketones and aldehydes to
yield epoxides 3, which must arise via initial alkylation α to the
halogen atom. α-Halosulfones react with base under phase-
transfer6 or other7,8 conditions to give α-anions which undergo
Darzens-like reactions with aldehydes and ketones, giving
trans-α,β-epoxysulfones 4.
The corresponding bromide
8 was most conveniently
obtained11 from 1-phenylsulfonylprop-2-ene 9 via bromination
of its double bond to give the dibromide 10 followed by dehydro-
bromination using triethylamine. Careful control of reaction
conditions was required for this step, since overexposure to tri-
ethylamine gave bromide 8 that was contaminated with some of
the deconjugated sulfone (Z)-1-bromo-3-phenylsulfonylprop-1-
ene 11 from which it could not be separated by chromato-
graphy.
Deliberate treatment of the bromo-compound 8 with tri-
ethylamine with the intention of completely converting it into
the vinylic halide 11 led, at best, to mixtures containing 20% of
8 and 80% of 11.
The chloride 5 could be cleanly deconjugated to give the
(Z)-vinylic chloride 12 when it was treated with triethylamine in
chloroform solution, but the iodide 7 yielded a mixture of
products which apparently included the ammonium salt 13
under these conditions.
The base-mediated deconjugation of (E)-γ-substituted-α,β-
unsaturated allylic sulfones to yield (Z)-γ-substituted-β,γ-
unsaturated sulfones has been explored by Inomata et al.12 who
have invoked a “syn-effect” in order to rationalise their results.
The (Z)-chlorosulfone 12 has been described by Mikhailova
et al.,13 who obtained it from the dichloride 14 by treatment
with base. The same authors report13 that treatment of the
dibromide 10 with bases afforded the conjugated bromosulfone
In this paper we describe the results that we have obtained
when a number of (E)-3-halo-1-phenylsulfonylpropene and
(Z)-1-halo-3-phenylsulfonylpropene derivatives are deproton-
ated to give delocalised 1-halo-3-sulfonylpropenyl carbanions
which are then reacted with either aromatic or aliphatic
aldehydes.
Results and discussion
3-Chloro-1-phenylsulfonylprop-1-ene 5 was prepared from the
readily available9 alcohol 6 via reaction with phosphorus penta-
chloride. The chloride 5 was9 easily converted into the iodide
7 by Finkelstein reaction with sodium iodide in acetone. This is,
as noted by Bordwell et al.,10 a facile process which contrasts
sharply with the poor reactivity of chloromethylphenylsulfone
towards nucleophiles.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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8, but this differs from our experience in that we find that 8
easily isomerises to give mainly the β,γ-compound 11 under
such conditions.
Initial attempts to lithiate the allylic halides 5, 7 or 8 were not
encouraging. Dark red solutions of anions were formed when
they were treated with nBuLi–THF but, even at low temper-
atures, these rapidly became brown, and aqueous work-up after
the addition of an electrophile such as benzaldehyde led to
complex mixtures of what appeared to be homocoupling
products derived from the starting sulfones.
Much more satisfactory results were obtained when lithiation
was carried out in the presence of the electrophile. Thus, addi-
tion of a THF solution containing equimolar amounts of the
chlorosulfone 5 and of benzaldehyde to 1.2 equivalents of
n-BuLi in THF at Ϫ18 ЊC led, after aqueous quenching, to a
reaction mixture which contained one major product 15a
together with a little of the isomerised vinylic chloride 12. These
were easily separated by chromatography.
Oxidation of 15b using chromic acid led to the derived
ketone 16b (82%) together with some of its (E)-isomer 17b
(18%). The (Z)-compound 16b showed δH 6.56 ppm for its
olefinic proton, whereas the olefinic proton trans to the carb-
onyl group in 17b resonated further upfield at δ 6.33 ppm. These
ketones could not be separated by chromatography. Attempts
to further equilibrate 16b and 17b under acidic conditions met
with failure. The related alcohols 15c and 15d were likewise
oxidised using chromic acid to give the derived ketones 16c and
16d which were similarly obtained as inseparable mixtures with
minor amounts of their (E)-isomers 17c and 17d.
Reduction of the ketone 16d using sodium borohydride gave
back the starting alcohol 15d in high yield, confirming their
stereochemical relationship. The fact that only a single geo-
metric isomer of the alcohol was obtained from this reaction is
suggestive of the existence of a rapid equilibrium between the
(Z)- and (E)-isomers of the ketone 16d, with the (Z)-com-
pound undergoing reduction faster than its (E)-isomer.
Using the same lithiation–alkylation protocol, the iodide 7
and the bromide 8 were also successfully deprotonated and
reacted with the same series of aromatic aldehydes. Each of
these allylic halo-derivatives yielded the products 18a–18d
which were entirely different to those that were obtained from
the analogous chloro-compound 5 under the same conditions,
but which are related to the epoxides 4 derivable from simple
α-halosulfones and aldehydes in the presence of base.6–8
In its 1H NMR spectrum, the hydroxy-sulfone 15a exhibits a
2H doublet, J 7.7 Hz, at δ 4.07 ppm that is associated with a
methylene carbon resonance at δ 55.9 ppm. These chemical
shifts, and the vicinal coupling constant, are very similar
to those observed in the NMR spectra of the vinylic chloride
12 whose methylene group appears as a 7.7 Hz doublet at
δ 4.04 ppm, with the corresponding 13C signal at δ 54.6 ppm,
but differ markedly from the data for the allylic chloride
5 where the methylene proton resonance occurs at δ 4.19 ppm
with Jvic 5.2 Hz and the relevant 13C signal appears at
δ 41.2 ppm.
Using the same successful protocol, the chloride 5 was
reacted with a number of other aromatic aldehydes to give the
analogous (Z)-1-aryl-2-chloro-4-phenylsulfonylbut-2-en-1-ols
1
15b–15d. These exhibited H and 13C NMR signals for their
allylic methylene groups that were almost identical to those
given by 15a above.
The stereochemistry of the olefinic double bond of the repre-
sentative sulfone 15b was firmly established by NOE experi-
ments in which irradiation of the –CHOH proton at δ 5.19 ppm
enhanced by 8.5% the signal at δ 6.16 ppm which is due to the
olefinic proton (Fig. 1).
The novel epoxides 18a–18d were readily identified from their
spectroscopic data. Thus, the (E)-configuration of the double
bond, Jtrans ∼ 15 Hz, and the trans-configuration at the oxirane
ring, Jvic ∼ 1.8 Hz, could be assigned on the basis of these
1
coupling constants, and the other features of their H and 13C
NMR spectra (experimental section) were in full agreement
with the structures shown.
Brief treatment of the epoxide 18b with BF3ؒEt2O afforded a
mixture consisting largely of the ketone 19 together with a little
of the aldehyde 20 (ca. 4%). Longer reaction times led to multi-
component product mixtures. The predominant formation of
the ketone 19 from the epoxide 18b is in accord with mech-
anistic expectation in that the Lewis acid-mediated rearrange-
ment proceeds preferentially via the derived stabilised benzylic
carbonium ion 21 rather than the alternative and less stable
sulfonyl-substituted allylic cation 22.
Exactly the same sets of alkylation products 15a–15d or
18a–18d were obtained when either the vinylic chloride 12 or
the vinylic bromide 11 were, respectively, lithiated and then
reacted with aromatic aldehydes (Table 1), supporting the con-
tention that delocalised anions are formed immediately upon
deprotonation.
Fig. 1
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
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Scheme 1
Table 1 Reactions of lithiated halosulfones with aryl aldehydes
Halosulfone
Aldehyde
Product
Yield (%)a
5, 12
C6H5CHO
15a
15b
15c
15d
18a
18b
18c
18d
72, 68
62, 63
72, 71
62, 63
73, 75, 72
n/a, 77, n/a
75, 81, 75
n/a, 80, n/a
5, 12
4-Cl–C6H4CHO
2-MeO–C6H4CHO
3-F–C6H4CHO
C6H5CHO
4-Cl–C6H4CHO
2-MeO–C6H4CHO
3-F–C6H4CHO
5, 12
5, 12
7, 8, 11
7, 8, 11
7, 8, 11
7, 8, 11
a Yields are of purified products.
We rationalise our observed γ-specificity on the basis that
although alkylation α to the phenylsulfonyl group may be the
kinetically favoured reaction pathway, the intermediate thus
formed (path c, Scheme 1) is sterically crowded due to the
presence of the large halogen atom at the terminus of
the (Z)-configured double bond. Accordingly, this alkoxide
collapses to return the carbanion 23 together with the conju-
gated aryl aldehyde, which then reacts at the γ-carbon of 23 to
yield the observed products 15a–15d or 18a–18d.
Supporting this view, we have found that β,γ-unsaturated
sulfones are obtained when aliphatic aldehydes (which do not
possess the benefits of conjugation, making them poorer leav-
ing groups) are reacted with the carbanions derived from either
of the chlorosulfones 5 or 12. These products arise as a result of
alkylation α to the phenylsulfonyl group.
We regard the formation of the hydroxy-sulfones 15a–15d
and of the epoxides 18a–18d as proceeding via the mechanisms
outlined in Scheme 1. Thus, each of the unsaturated halo-
sulfones 5, 7, 8, 11 and 12 is deprotonated to give an anion 23
which then reacts with an aromatic aldehyde to yield an inter-
mediate lithium alkoxide 24. When X = Br or I, the alkoxide 24
undergoes rapid Williamson cyclisation to give the epoxides 18
(path a), but when the poorer leaving group X = Cl is present
allylic rearrangement of 24 to 25 takes precedence and proton-
ation during work-up then leads to the vinylic chlorides 15
(path b).
The γ-regiospecificity involved in reactions of the anion 23
with aromatic aldehydes is in marked contrast to that normally
seen when simple allylic sulfones are the substrates. Thus,
1-toluenesulfonylprop-2-ene 26 affords a lithio-derivative which
reacts14 with benzaldehyde to give a 2 : 1 mixture of both
diastereoisomers of the regioisomeric α-alkylation product 27.
Thus, reaction with isobutyraldehyde of the lithiated anion
derived from 5 afforded 3,4-anti-1-chloro-5-methyl-3-phenyl-
sulfonylhex-1-en-4-ol 28 (75%), together with the deconjugated
chloro-compound 12 (20%). No γ-alkylated compounds were
observable, even in the crude reaction product.
1
The H NMR spectrum of 28 revealed that there was no
apparent vicinal coupling J3,4 between the two methine protons
CHOH–CHSO2Ph. Small vicinal coupling constants (∼1.0–
2.5 Hz) for analogous protons have previously been reported
for a number of simple anti-configured β-hydroxysulfones.15
Notably, the –CHOH proton H-4 of 28 resonates at rather low
field (δ 4.23 ppm), and exhibits a large vicinal coupling constant
of 9.0 Hz to neighbouring H-5, suggesting a strong conform-
ational preference in solution.16 The assignment to H-4 of the
resonance at δ 4.23 ppm rather than a similar 10.5 Hz doublet at
δ 4.33 ppm is based upon the clear coupling of the latter to its
neighbouring olefinic proton. The structure of 28 was fully
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
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1
confirmed by a single-crystal X-ray structure determination17
which revealed (Fig. 2) a dihedral angle of almost 90Њ between
H-3 and H-4.
employed. Nevertheless, the H NMR spectrum of the crude
product mixture indicated that its major component was the
anti-diastereoisomer of the β-hydroxysulfone 32.
When the iodo-sulfone 7 was lithiated in the presence of
isobutyraldehyde, a product mixture was obtained which
contained (NMR) recovered starting material 7, 1-phenyl-
sulfonylprop-2-ene 9 and the anti-β-hydroxysulfone 29 in the
ratio 8 : 6 : 3. We account for the formation of compounds 9
and 29 by assuming that the anion initially formed from the
iodide 7 abstracts iodine from unreacted starting material
to generate the anion of allyl phenyl sulfone together with an
α,α-di-iodo compound which does not survive the work-up
procedure.
Experimental
Unless otherwise stated, H NMR spectra were recorded for
1
solutions in CDCl3 using JEOL PMX-60, Bruker WP-80,
Bruker MSL 300 MHz or Bruker Avance DPX 400 MHz
spectrometers. Coupling constants are given in Hz. Assign-
ments were verified where appropriate by 1H–1H COSY, 1H–13C
COSY and DEPT experiments. IR spectra were recorded for
Nujol mulls (N) or liquid films (L) between sodium chloride
plates using Perkin-Elmer 883 or Paragon 1000 spectrometers.
Mass spectra were obtained at the University of Edinburgh
using a Kratos instrument. Melting points (uncorrected) were
measured in unsealed capillary tubes using a Stuart Scientific
SMP2 digital apparatus or an Electrothermal IA9100 appar-
atus. Thin layer chromatography was carried out using Merck
Kieselgel 60 F254 0.2 mm silica gel plates. Column chromato-
graphy was carried out using Merck Kieselgel 60 (70–230 mesh)
silica gel. All solvents were dried and distilled before use. Ether-
eal extracts of reaction products were dried over anhydrous
magnesium sulfate. Combustion analyses were obtained from
the Microanalytical Laboratory, University College, Dublin.
Fig. 2
The regioselectivity of the reaction between the lithiated
chlorosulfone 5 and isobutyraldehyde to yield 28 contrasts
sharply with that observed when an aromatic aldehyde is
the electrophile, and is quite remarkably diastereoselective,
but the possibility of base-catalysed retro-aldol reactions that
lead to syn–anti interconversion under the conditions that were
employed cannot be ruled out.
However, we have shown that reaction of the lithio derivative
of 1-phenylsulfonylprop-2-ene 9 with isobutyraldehyde under
similar conditions yields both of the possible diastereoisomeric
products of α-alkylation, viz., the anti-compound 29 (54%) and
1
its syn-isomer 30 (9%). The H NMR spectrum of anti-29 is
very similar to that of the analogous chloro-derivative 28. In
particular, the methine protons which are α to the sulfonyl and
hydroxyl groups are not mutually coupled. Contrastingly, the
corresponding methine protons of the syn-diastereoisomer
30 resonate as apparent triplets, exhibiting vicinal coupling
constants J of ca. 9.7 Hz (cf.15).
Crystal data for 28
C13H17Cl1O3S, M = 288.78. Triclinic, a= 8.4685(9), b =
8.7296(9), c = 11.4820(13) Å, V = 712.29(13) Å3, space group
P1, Z = 2, D (calculated) = 1.346 g cmϪ3, crystal dimensions
0.45 × 0.3 × 0.6 mm.
Data collection and processing. Enraf-Nonius CAD-4 dif-
fractometer, temperature 293(2) K, wavelength 0.71073 Å,
absorption coefficient 0.412 mmϪ1, theta range for data collec-
tion 1.85 to 24.98Њ, 2635 reflections collected, index ranges
0 ≤ h ≤ 9; Ϫ9 ≤ k ≤ 9; Ϫ12 ≤ l ≤ 12, 2450 independent reflections
[R(int) = 0.0124].
Structure analysis and refinement. The structure was solved
by direct methods and refined by full matrix least squares
analysis on F 2. Data were corrected for Lorentz and polaris-
ation effects but not for absorption. Hydrogen atoms were
included in calculated positions with thermal parameters 30%
larger than the atom to which they were attached. The non-
hydrogen atoms were refined anisotropically. Final R indices
[I ≥ 2σ(I )] were R1 = 0.0391 and wR2 = 0.0972. The ORTEX
program was used to obtain the drawings.18
The carbanion derived from the chlorosulfone 5 reacted with
isovaleraldehyde to give the anti-configured hydroxy-sulfone 31
(65%), the vinylic chloride 12 (30%) and two very minor prod-
ucts (5%). The 1H NMR spectrum of 31 again revealed that the
methine protons adjacent to the hydroxyl and sulfonyl groups
were not mutually coupled, confirming its anti-stereochemistry.
When the bromo-sulfone 8 was lithiated and reacted with
isobutyraldehyde in the usual way the outcome of the reaction
was not as clean as was the case when the chlorides 5 or 12 were
(E )-3-Chloro-1-phenylsulfonylprop-1-ene 5
This was prepared according to the literature procedure9 and
was obtained as needles, mp 58 ЊC (ethanol–hexane) (lit.9 mp
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
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58.5 ЊC); νmax(N) 1279 and 1144 cmϪ1; δH (300 MHz) 4.19 (2H,
dd, J 5.2 and 1.7, –CH2Cl), 6.66 (1H, dt, J 14.7 and 1.8,
solution of butyllithium. After stirring for 2 h at ca. Ϫ15 ЊC the
reaction was quenched by the addition of water. The products
were extracted with ether in the usual way and the combined
extract was dried and evaporated under reduced pressure.
Products were generally purified by column chromatography
using ether–hexane 2 : 3 as eluant and then, if solids, were
recrystallised from the solvents indicated.
–SO CH᎐CH–), 7.03 (1H, dt, J 14.8 and 5.2, –CH᎐CHCH Cl),
᎐
᎐
2
2
7.55 (2H, m, m-ArH), 7.63 (1H, m, p-ArH) and 7.63 (2H, d,
J 8.0, o-ArH) ppm; δC (75 MHz) 41.25 (–CH2Cl), 127.8
(o-ArC), 129.4 (m-ArC), 133.4 (–SO CH᎐C–), 133.7 (p-ArC),
᎐
2
139.66 (quaternary Ar) and 139.8 (–C᎐CHCH Cl) ppm.
᎐
2
(Z)-2-Chloro-1-phenyl-4-phenylsulfonylbut-2-en-1-ol
15a.
(E )-3-Iodo-1-phenylsulfonylprop-1-ene 7
15a was obtained from benzaldehyde and either of the lithiated
sulfones 5 (72%) or 12 (68%) as a solid, mp 77 ЊC (ether–
hexane); νmax 3481, 1311 and 1145 cmϪ1; δH (300 MHz) 2.90
(1H, br s, exch. D2O, –OH ), 4.05 (2H, d, J 7.7, –CH2SO2–), 5.19
This was obtained according to the literature9 procedure and
had mp 62 ЊC (lit.9 mp 67–68 ЊC); νmax(N) 1305 and 1146 cmϪ1
;
δH (400 MHz) 3.89 (2H, dd, J 8.0 and 1.0, –CH2I), 6.43 (1H, dd,
J 15.0 and 1.0, –SO CH᎐CH–), 7.07 (1H, dt, J 15.0 and 8.0,
᎐
2
(1H, s, –CHOH), 6.16 (1H, dt, J 7.8 and 1.1, –CH CH᎐C–),
᎐
2
–CH᎐CHCH I), 7.57 (2H, m, m-ArH ), 7.65 (1H, m, p-ArH )
᎐
2
7.27 (5H, m, ArH ), 7.45 (2H, m, m-ArH–SO2), 7.61 (1H, tt,
J 7.6 and 1.3, p-ArH–SO2) and 7.83 (2H, d, J 8.0, o-ArH–SO2)
ppm; δC (75 MHz) 55.86 (–CH2SO2), 76.8 (–CHOH), 113.4
and 7.88 (2H, d, J 7.9, o-ArH ) ppm; δC (100 MHz) Ϫ2.02
(–CH I), 127.7 (o-ArC), 129.3 (m-ArC), 132.2 (–SO CH᎐C–),
᎐
2
2
133.6 (p-ArC), 139.76 (quaternary-ArC) and 141.3 (–CH᎐
᎐
(–CH –C᎐C–), 126.7 (o-ArC), 128.3 (o-ArC–SO –), 128.5
᎐
2
2
CHCH2I) ppm.
(m-ArC and p-ArC), 129.13 (m-ArC–SO2), 133.9 (p-ArC–SO2),
138.24 (quaternary, ArC–SO2), 139.2 (quaternary, ArC) and
(E )-3-Bromo-1-phenylsulfonylprop-1-ene 8
143.8 (quaternary, –CH CH᎐CCl) ppm. [Found: C 59.70, H
᎐
2
4.80. C16H15ClO3S requires: C 59.53, H 4.68%.]
1,2-Dibromo-3-phenylsulfonylpropane 10 was prepared
according to the method of Eisch and Galle11 when it had mp
75 ЊC (lit.11 mp 78–79 ЊC). The dibromide 10 (3.0 g) was dis-
solved in chloroform (30 cm3) with triethylamine (0.89 g; 1 eq.).
After 5 min, the mixture was washed sequentially with dilute
hydrochloric acid and with water, dried and evaporated to give
an oily solid which was recrystallised (ether–hexane) to give the
bromide 8 (1.6 g; 70%), mp 50–51 ЊC (lit.9 mp 34–35 ЊC);
νmax(N) 1303 and 1145 cmϪ1; δH (400 MHz) 4.10 (2H, d,
(Z)-2-Chloro-1-(4Ј-chlorophenyl)-4-phenylsulfonylbut-2-en-
1-ol 15b. 15b was obtained from 4-chlorobenzaldehyde and
either of the lithiated sulfones 5 (62%) or 12 (63%) as a solid,
mp 106 ЊC (ether–hexane); νmax (N) 1338 and 1138 cmϪ1; δH (300
MHz) 2.61 (1H, br s, exch. D2O, –OH ), 4.07 (2H, d, J 7.7,
–CH2SO2–), 5.19 (1H, s, –CHOH), 6.16 (1H, dt, J 7.7 and 1.0,
–CH CH᎐C–), 7.18 (2H, m, o-ArH–Cl), 7.29 (2H, m, m-ArH–
᎐
2
Cl), 7.48 (2H, m, m-ArH–SO2), 7.65 (1H, tt, J 7.5 and 1.3,
p-ArH–SO2) and 7.87 (2H, d, J 8.0, o-ArH–SO2) ppm;
δC (75 MHz) 55.8 (–CH2SO2–), 76.8 (–CHOH), 113.5
J 6.9, –CH Br), 6.68 (1H, dt, J 16.0 and 1.4, –SO CH᎐CH–),
᎐
2
2
7.16 (1H, dt, J 14.9 and 6.9, –CH᎐CHCH Br), 7.56 (2H, m,
᎐
2
m-ArH ), 7.65 (1H, dt, J 7.5 and 1.3, p-ArH ) and 7.89 (2H, d,
J 8.0, o-ArH ) ppm; δC (100 MHz) 26.9 (–CH2), 127.4 (o-ArC),
(–CH CH᎐C–), 128.0 (o-ArC–Cl), 128.3 (o-ArC–SO ), 128.7
᎐
2
2
(m-ArC–Cl), 129.2 (m-ArC–SO2), 134.0 (p-ArC–SO2), 134.3
(quaternary, ArC–Cl), 137.7 (quaternary, ArC–SO2), 138.3
(quaternary, ArC–Cl) and 143.5 (quaternary, –CH᎐CCl) ppm.
129.0 (m-ArC), 133.3 (–SO –CH᎐CH–), 133.6 (p-ArC), 139.1
᎐
2
(–SO –CH᎐CH–) and 139.2 (quaternary ArC) ppm.
᎐
2
᎐
Irradiation of the –CHOH proton at δ 5.19 enhanced the
olefinic proton signal at δ 6.16 by 8.5% and the signal for the
2Ј-protons of the adjacent p-Cl–C6H4 ring by 8.6%. Irradiation
of the olefinic proton signal at δ 6.16 enhanced the methylene
proton resonance at δ 4.07 by 5.5%. Irradiation of the methyl-
ene signal enhanced the resonance due to the o-protons of the
adjacent C6H5 ring by 3.2%. [Found: C 53.97, H 4.03. C16H14-
Cl2O3S requires: C 53.79, H 3.98%.]
(Z )-1-Bromo-3-phenylsulfonylprop-1-ene 11
(E)-3-Bromo-1-phenylsulfonylpropene 8 (1.0 g) was stirred
with triethylamine (0.39 g) in chloroform (10 cm3) for 2 h. The
reaction mixture was then washed with dilute hydrochloric acid
and with water, dried and evaporated to give the bromo-sulfone
11 as a thick brown oil that contained ca. 10% of unchanged
starting material 8 from which it could not be separated; νmax(L)
1338 and 1138 cmϪ1; δH (60 MHz) 4.0 (2H, d, J 7.0, –CH2Br),
6.4 (2H, m, –CH᎐CHBr) and 7.66 (5H, m, ArH ) ppm.
᎐
(Z)-2-Chloro-1-(2Ј-methoxyphenyl)-4-phenylsulfonylbut-2-
en-1-ol 15c. 15c was obtained from 2-methoxybenzaldehyde
and either of the lithiated sulfones 5 (72%) or 12 (71% after
purification by column chromatography) as an oil, νmax(L) 3489,
1309 and 1145 cmϪ1; δH (300 MHz) 2.25 (1H, br s, exch. D2O,
–OH ), 3.86 (3H, s, –OCH3), 4.03 (2H, dd, J 7.7 and 3.2,
–CH2SO2–), 5.49 (1H, s, –CHOH), 6.08 (1H, dt, J 7.7 and 1.1,
(Z )-1-Chloro-3-phenylsulfonylprop-1-ene 12
The (E)-chloro-sulfone 5 (5.0 g) was stirred with triethylamine
(2.34 g) in chloroform (50 cm3) for 75 min. After this time, the
reaction mixture was washed with dilute hydrochloric acid and
with water, dried and evaporated to yield a solid which was
recrystallised (hexane–benzene) to give the chloride 12 (3.5 g;
70%) as needles, mp 43 ЊC (lit.13 mp 43–44 ЊC); νmax(N) 1338
and 1138 cmϪ1; δH (300 MHz) 4.04 (2H, dd, J 7.7 and 1.2,
–CH CH᎐C–), 6.92 (2H, m, ArH-OMe), 7.15 (1H, dd, J 7.6 and
᎐
2
1.7, ArH-OMe), 7.32 (1H, dt, J 7.9 and 1.8, ArH-OMe), 7.47
(2H, m, m-ArH–SO2), 7.56 (1H, t, J 7.5, p-ArHSO2) and 7.81
(2H, d, J 7.9, o-ArH–SO2) ppm; δC (75 MHz) 55.4 (–OCH3),
55.9 (–CH2SO2–), 72.5 (–CHOH), 110.6 (o-ArC-OMe), 113.2
–CH SO –), 5.88 (1H, q, J 7.7, –CH CH᎐CH–), 6.27 (1H, d,
᎐
2
2
2
J 7.3, –CHCl), 7.53 (2H, m, m-ArH ), 7.63 (1H, m, p-ArH )
and 7.87 (2H, d, J 8.0, o-ArH ) ppm; δC (75 MHz) 54.61
(–CH –C᎐CCl), 120.7 (m-ArC-OMe), 127.1 (quaternary, ArC-
᎐
2
OMe), 128.0 (p-ArC-OMe), 133.7 (p-ArC–SO2), 138.2 (quater-
(–CH SO –), 118.5 (–C᎐CCl), 126.1 (o-ArC), 128.3 (m-ArC),
᎐
2
2
nary, ArC–SO ), 143.1 (quaternary, –CH C᎐CCl) and 156.6
᎐
2
2
129.1 (–CH –CH᎐C–), 133.9 (p-ArC) and 138.1 (quaternary
᎐
2
(quaternary, ArC-OMe) ppm. [Found: C 58.15, H 4.86.
C17H17ClO4S requires: C 57.87, H 4.86%.]
ArC) ppm.
General procedure for reaction of the carbanions derived from the
sulfones 5, 7, 8, 11 or 12 with aldehydes
(Z)-2-Chloro-1-(3Ј-fluorophenyl)-4-phenylsulfonylbut-2-en-
1-ol 15d. 15d was obtained from 3-fluorobenzaldehyde and
either of the lithiated sulfones 5 (62%) or 12 (63% after purifi-
cation by column chromatography) as an oil; νmax (N) 3477,
1308 and 1146 cmϪ1; δH (300 MHz) 3.30 (1H, br s, exch. D2O,
–OH ), 4.05 (2H, d, J 7.7, –CH2SO2–), 5.19 (1H, s, –CHOH),
n-Butyllithium (2.5 M in hexane; 3.6 mmol; 1.2 eq.) was added,
under nitrogen, to dry THF cooled to Ϫ18 ЊC using an ice–salt
bath. A solution of an aldehyde (3 mmol; 1 eq.) and a sulfone
(3 mmol; 1 eq.) in THF (10 cm3 gϪ1 of sulfone) was added to the
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
1378

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6.16 (1H, dt, J 7.67 and 0.9, –CH CH᎐C–), 6.98 (3H, m, o- and
change occurred (TLC). Work-up as described above for the
᎐
2
p-ArH–F), 7.25 (1H, m, m-ArH–F), 7.47 (2H, m, m-ArH–SO2),
7.65 (1H, t, J 7.6, p-ArH–SO2) and 7.87 (2H, d, J 8.0, o-ArH–
SO2) ppm; δC (75 MHz) 55.7 (–CH2SO2–), 76.02 (–CHOH),
oxidation of 15b afforded an oil (0.16 g; 87%) which contained
(NMR) (Z)-2-chloro-1-(3Ј-fluorophenyl)-4-phenylsulfonylbut-
2-en-1-one 16d and (E)-2-chloro-1-(3Ј-fluorophenyl)-4-phenyl-
sulfonylbut-2-en-1-one 17d in 5 : 1 ratio; νmax(L) 1675, 1288 and
1143 cmϪ1; δH (300 MHz) 4.01 (0.33H, d, J 8.2, (E)-CH2SO2–),
4.27 (1.66H, d, J 7.7, (Z)-CH2SO2–), 6.32 (0.17H, t, J 8.2,
113.5 (d, J 21.0, o-ArC–F), 113.7 (–CH CH᎐C–), 115.2 (d,
᎐
2
J 21.0, p-ArC–F), 122.3 (d, J 21.0, o-ArC–F), 128.2 (o-ArC–
SO2), 129.2 (m-ArC–SO2), 129.9 (d, J 7.6, m-ArC–F), 134.0
(p-ArC–SO2), 137.9 (quaternary, ArC–SO2), 141.7 (quaternary,
(E)-CH CH᎐C–), 6.56 (0.83H, t, J 7.7, (Z)-CH CH᎐C–) and
᎐
᎐
2
2
d, J 6.41, ArC–F), 143.4 (quaternary, –CH᎐C–Cl) and 162.6
7.25–7.92 (9H, overlapping ms, ArH ) ppm.
᎐
(quaternary, d, J 244, ArC–F) ppm. [Found: C 56.49, H 4.35.
C16H14ClFO3S requires: C 56.34, H 4.35%.]
Reduction of (Z )-2-chloro-1-(3Ј-fluorophenyl)-4-phenylsulfonyl-
but-2-en-1-one 16d using sodium borohydride
Oxidation of (Z )-2-chloro-1-(4Ј-chlorophenyl)-4-phenylsulfonyl-
The ketone 16d, containing 20% of the (E)-isomer 17d, (0.2 g),
in methanol–water (90%; 2 cm3), was reacted for 1 h with
sodium borohydride (10 mg). The mixture was quenched with
aqueous acetic acid, extracted with ether, washed with sodium
hydrogen carbonate solution and with water, dried and evapor-
ated to give only (NMR) the alcohol 15d (0.185 g; 92%).
but-2-en-1-ol 15b
The alcohol 15b (0.8 g) was dissolved in ether (8 cm3) and
stirred at 0 ЊC with a solution (3.5 cm3) containing sodium
dichromate dihydrate (245 mg), concentrated sulfuric acid
(0.17 cm3) and water until no further change occurred (TLC).
The mixture was then diluted with ether, washed sequen-
tially with water and with aqueous sodium hydrogen carbonate
solution, dried and evaporated. The crude oil so obtained
(0.66 g) was chromatographed using ether–hexane 3 : 7 as
eluant to separate the product (Z)-2-chloro-1-(4Ј-chloro-
phenyl)-4-phenylsulfonylbut-2-en-1-one 16b (0.56 g; 71%),
contaminated with the isomeric ketone (E)-2-chloro-1-(4Ј-
chlorophenyl)-4-phenylsulfonylbut-2-en-1-one 17b, from un-
reacted starting material (60 mg). The ketones 16b and 17b were
obtained in 82 : 18 ratio as an oil; νmax(L) 1674, 1325 and 1145
cmϪ1; δH (300 MHz) 4.01 (0.33H, d, J 8.3, (E)–CH2SO2–), 4.27
(1.66H, d, J 7.7, (Z)–CH2SO2–), 6.33 (0.18H, t, J 8.3,
(E)-trans-3,4-Epoxy-4-phenyl-1-phenylsulfonylbut-1-ene 18a.
18a was obtained from benzaldehyde and either of the lithiated
sulfones 7 (73%), 8 (75%) or 11 (72%) as a solid, mp 91 ЊC (ethyl
acetate–hexane), which had νmax (N) 1309 and 1149 cmϪ1
;
δH (300 MHz) 3.49 (1H, dd, J 5.7 and 1.7, H-3), 3.82 (1H, br s,
H-4), 6.68 (1H, d, J 14.9, H-1), 6.94 (1H, dd, J 15.0 and 5.7,
H-2), 7.33–7.71 (8H, m, ArH ) and 7.90 (2H, d, J 7.9, o-ArH–
SO2–) ppm; δC (100 MHz) 58.8 (CH), 61.2 (CH), 125.1 (ArC),
127.4 (ArC), 128.3 (ArC), 128.5 (ArC), 129.1 (ArC), 132.4
(–SO –CH᎐C–), 133.3 (ArC), 134.9 (quaternary, ArC), 139.3
᎐
2
(quaternary, ArC) and 141.0 (–SO CH᎐C–) ppm. [Found: C
᎐
2
(E)–CH CH᎐C–), 6.56 (0.82H, t, J 7.7, (Z)–CH CH᎐C–) and
᎐
᎐
2
2
67.07, H 4.92. C16H14O3S requires: C 67.13, H 4.89%.]
7.25–7.95 (9H, overlapping ms, ArH ) ppm. [Found: C 53.75, H
3.69. C16H12Cl2O3S requires: C 54.08, H 3.38%.]
(E)-trans-4-(4Ј-Chlorophenyl)-3,4-epoxy-1-phenylsulfonyl-
but-1-ene 18b. 18b was obtained from 4-chlorobenzaldehyde
and the lithiated sulfone 8 (75%) as a solid, mp 104–105 ЊC
Attempted acid-catalysed isomerisation of the ketones 16b and
17b
(ether–hexane), which had νmax (N) 1343, 1146 and 1242 cmϪ1
;
δH (300 MHz) 3.45 (1H, dd, J 5.7 and 1.8, H-3), 3.79 (1H, d,
J 1.6, H-4), 6.68 (1H, d, J 15.0, H-1), 6.91 (1H, dd, J 15.0 and
5.7, H-2), 7.19 (2H, d, J 8.5, 2H-2Ј), 7.33 (2H, d, J 8.5, 2H-3Ј),
7.61 (3H, m, ArH ) and 7.90 (2H, d, J 8.0, o-ArH–SO2–) ppm;
δC (100 MHz) 58.8 (CH), 60.5 (CH), 126.5 (ArC), 127.4 (ArC),
The 82 : 18 mixture of the isomeric ketones 16b and 17b
described above (0.12 g) was refluxed with methanesulfonic acid
(0.1 g) in benzene (5 cm3) for 2 h and then left at rt overnight.
The mixture was diluted with ether, washed with water and with
sodium hydrogen carbonate solution, dried and evaporated to
return the ketones in unaltered ratio. In another experiment, the
mixture of ketones 16b and 17b was stirred with acetic acid
(80%) containing a small amount of concentrated sulfuric acid.
After the usual work-up, the ratio of (Z) : (E) isomers was
virtually unchanged.
128.5 (ArC), 129.3 (ArC), 132.6 (–SO –CH᎐C–), 133.4 (ArC),
᎐
2
133.5 (quaternary, ArC), 134.2 (quaternary, ArC), 139.2
(quaternary, ArC) and 141.4 (–SO CH᎐C–) ppm. [Found: C
᎐
2
59.91, H 4.32. C16H13ClO3S requires: C 59.85, H 4.08%.]
(E)-trans-3,4-Epoxy-4-(2Ј-methoxyphenyl)-1-phenylsulfonyl-
but-1-ene 18c. 18c was obtained from 2-methoxybenzaldehyde
and either of the lithiated sulfones 7 (75%), 8 (81%) or 11 (75%)
as a solid, mp 120 ЊC (ethyl acetate–hexane), which had νmax (N)
1343, 1147 and 1254 cmϪ1; δH (400 MHz) 3.42 (1H, dd, J 5.5
and 1.5, H-3), 3.80 (3H, s, –OCH3), 4.10 (1H, d, J 1.5, H-4),
6.70 (1H, d, J 15.0, H-1), 6.95 (3H, m, H-2 and ArH ), 7.13 (1H,
dd, J 7.5 and 1.5, ArH ), 7.31 (1H, m, ArH ), 7.63 (3H, m, ArH )
and 7.94 (2H, d, J 8.5, o-ArH–SO2–) ppm; δC (100 MHz) 54.95
(–OCH3), 57.2 (CH), 58.1 (CH), 109.8 (ArC), 120.3 (ArC),
123.5 (quaternary, ArC), 124.5 (ArC), 127.4 (ArC), 128.9
Oxidation of (Z )-2-chloro-1-(2Ј-methoxyphenyl)-4-phenyl-
sulfonylbut-2-en-1-ol 15c
This alcohol (0.2 g) was oxidised in ether (2 cm3) with a solution
(2.0 cm3) containing sodium dichromate dihydrate (140 mg),
concentrated sulfuric acid (0.1 cm3) and water until no
further change occurred (TLC). Work-up as described above
for the oxidation of 15b afforded a thick oil (0.17 g; 85%)
which contained (NMR) (Z)-2-chloro-1-(2Ј-methoxyphenyl)-
4-phenylsulfonylbut-2-en-1-one 16c and (E)-2-chloro-1-(2Ј-
methoxyphenyl)-4-phenylsulfonylbut-2-en-1-one 17c in 8 : 1
ratio; νmax(L) 1678, 1289 and 1145 cmϪ1; δH (300 MHz) 3.78
(0.33H, s, (E)-OCH3), 3.80 (2.66H, s, (Z)-OCH3), 4.21 (2H, d,
J 7.8, (Z)- and (E)-CH2SO2–), 6.25 (0.11H, t, J 8.1, (E)-
(ArC), 129.1 (ArC), 132.0 (–SO –CH᎐C–), 133.2 (ArC), 139.5
᎐
2
(quaternary, ArC), 141.4 (–SO CH᎐C–) and 157.7 (quaternary,
᎐
2
ArC) ppm. [Found: C 65.54, H 5.13. C17H16O4S requires: C
64.54, H 5.10%.]
CH CH᎐C–), 6.59 (0.88H, t, J 7.8, (Z)-CH CH᎐C–) and 6.66–
᎐
᎐
2
2
6.80 (9H, overlapping ms, ArH ) ppm.
(E)-trans-3,4-Epoxy-4-(3Ј-fluorophenyl)-1-phenylsulfonyl-
but-1-ene 18d. 18d was obtained from 3-fluorobenzaldehyde
and the lithiated sulfone 8 (80%) as a solid, mp 92.5 ЊC (ether–
hexane), which had νmax (N) 1316, 1146 and 1254 cmϪ1; δH (300
MHz) 3.46 (1H, dd, J 5.7 and 1.8, H-3), 3.81 (1H, d, J 1.5, H-4),
6.68 (1H, d, J 15.0, H-1), 6.70–7.07 (4H, overlapping ms, H-2
and ArH ), 7.31 (1H, m, ArH ), 7.57 (2H, m, ArH ), 7.65 (1H,
Oxidation of (Z )-2-chloro-1-(3Ј-fluorophenyl)-4-phenylsulfonyl-
but-2-en-1-ol 15d
This alcohol (0.2 g) was oxidised in ether (2 cm3) with a solution
(2.0 cm3) containing sodium dichromate dihydrate (140 mg),
concentrated sulfuric acid (0.1 cm3) and water until no further
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
1379

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m, ArH ) and 7.90 (2H, d, J 8.4, o-ArH–SO2–) ppm; δC (75
MHz) 59.2 (CH), 60.8 (CH), 112.2 (d, J 22.74, ArC–F), 115.8
(d, J 20.6, ArC–F), 121.4 (d, J 2.91, ArC–F), 127.8 (ArC),
129.4 (ArC), 130.3 (quaternary, d, J 8, ArC–F), 133.2 (ArC),
ArH ), 7.65 (1H, m, ArH ) and 7.85 (2H, d, J 8.6, o-ArH) ppm;
δC (100 MHz) 18.3 (CH3), 19.1 (CH3), 31.9 (–CH(CH3)2), 71.9
(–CHSO –), 73.3 (–CHOH–), 125.4 (–CH᎐CH ), 125.8 (–CH᎐
᎐
᎐
2
2
CH2), 128.9 (ArC), 129.0 (ArC), 133.9 (ArC) and 137.2
(quaternary, ArC) ppm; HRMS: m/z 254.09761. Calculated for
C13H18O3S: 254.09766.
133.7 (–SO –CH᎐C–), 137.0 (quaternary, d, J 8, ArC–F), 139.6
᎐
2
(quaternary, ArC), 140.7 (–SO CH᎐C–) and 163.0 (quaternary,
᎐
2
d, J 244.9, ArC–F) ppm. [Found: C 62.86, H 4.32. C16H13FO3S
requires: C 63.14, H 4.31%.]
3,4-syn-5-Methyl-3-phenylsulfonylhex-1-en-4-ol 30. 30 was
obtained as an oil (9%), which had νmax(L) 3518, 1306 and 1148
cmϪ1; δH (400 MHz) 0.83 (3H, d, J 6.6, –CH3), 1.08 (3H, d,
J 6.8, –CH3), 1.74 (1H, m, –CH(CH3)2), 3.66 (1H, t, J 9.7,
–SO2CH–), 3.96 (1H, s, exch. D2O, –OH ), 4.20 (1H, d, J 9.8,
(E )-4-(4Ј-Chlorophenyl)-1-phenylsulfonylbut-1-en-3-one 19
The epoxide 18b (0.32 g) in dichloromethane (20 cm3) was
treated with boron trifluoride etherate (1 eq.) for 1 h. The mix-
ture was then diluted with ether and the extract was washed
with water, dried and evaporated to give a crude solid product
which (NMR) contained the title compound together with
about 4% of the aldehyde 20 (NMR). The crude product was
triturated with ether to give the ketone 19 as a solid (0.26 g)
which could not be satisfactorily purified by recrystallisation;
νmax(N) 1700, 1338 and 1157 cmϪ1; δH (300 MHz) 3.89 (2H, s,
–CHOH–), 4.97 (1H, d, J 17.0, –CH᎐CH H), 5.26 (1H, d,
᎐
a
J 10.0, –CH᎐CH H), 5.53 (1H, dt, J 17.0, 10.2 and 10.2, –CH᎐
᎐
᎐
b
CH2), 7.57 (2H, m, ArH ), 7.67 (1H, m, ArH ) and 7.86 (2H,
d, J 8.3, o-ArH) ppm; δC (100 MHz) 12.5 (CH3), 19.6 (CH3),
31.1 (–CH(CH3)2), 71.4 (–CHSO2–), 74.2 (–CHOH–), 123.4
(–CH᎐CH ), 127.2 (–CH᎐CH ), 128.4 (ArC), 128.9 (ArC),
᎐
᎐
2
2
133.5 (ArC) and 137.2 (quaternary, ArC) ppm; HRMS: m/z
254.09768. Calculated for C13H18O3S: 254.09766.
–CH C᎐O), 7.11 (1H, d, J 15.1, –SO CH᎐CH–), 7.12 (2H, d,
᎐
᎐
2
2
J 8.5, ArH–Cl), 7.21 (1H, d, J 15.0, –SO CH᎐CH–), 7.32 (2H,
᎐
2
(1Z )-3,4-anti-1-Chloro-6-methyl-3-phenylsulfonylhept-1-en-4-ol
31
d, J 8.5, ArH–Cl), 7.60 (2H, apparent t, J 8.0 and 7.5, ArH–
SO2), 7.71 (2H, t, J 7.5, ArH–SO2) and 7.88 (2H, d, J 8.0, ArH–
SO2) ppm; δC (100 MHz) 48.7 (CH2), 128.3 (ArC), 129.3
(ArC), 129.6 (ArC), 130.9 (ArC), 133.6 (quaternary, ArCSO2–),
This was obtained from the lithiated sulfone 5 (0.64 g) and
isovaleraldehyde (0.26 g) as an oil which was purified by column
chromatography using ether–hexane 2 : 3 as eluant to
give pure material (0.63 g) that had νmax(N) 3521, 1305 and
1149 cm Ϫ1; δH (400 MHz) 0.92 (3H, d, J 6.6, –CH3), 0.95 (3H,
d, J 6.6, –CH3), 1.16 (1H, m, –CHa–CH(CH3)2), 1.50 (1H, m,
–CH(CH3)2), 1.79 (1H, m, –CHb–CH(CH3)2), 3.11 (1H, s, exch.
D2O, –OH ), 4.19 (1H, d, J 10.5, –CHSO2–), 4.78 (1H, dd, J 8.8
134.4 (ArC), 134.6 (–SO CH᎐CH–), 138.4 (quaternary,
᎐
2
ArC), 141.4 (–SO CH᎐CH–) and 194.21 (quaternary, C᎐O)
᎐
᎐
2
ppm; HRMS: m/z 320.02740. Calculated for C16H13ClO3S:
320.02739.
(1Z )-3,4-anti-1-Chloro-5-methyl-3-phenylsulfonylhex-1-en-4-ol
28
and 4.1, CHOH), 6.16 (1H, dd, J 10.5 and 7.4, –CH᎐CHCl),
᎐
6.36 (1H, d, J 7.4, –CH᎐CHCl), 7.58 (2H, m, ArH ), 7.71 (1H, t,
᎐
This was obtained from the lithiated sulfone 5 (0.65 g) and
isobutyraldehyde (0.216 g) as a solid (0.62 g; 72%), mp 106 ЊC
J 7.6, ArH ) and 7.91 (2H, d, J 8.6, o-ArH) ppm; δC (75 MHz)
21.9 (CH3), 22.8 (CH3), 24.3 (–CH(CH3)2), 43.3 (CH2), 66.4
(ether–pentane), which had νmax(N) 3493, 1305 and 1146 cm Ϫ1
;
(–CHSO –), 67.4 (–CHOH–), 119.8 (–C᎐CHCl), 127.0 (–CH᎐
᎐
᎐
2
δH (300 MHz) 0.83 (3H, d, J 6.6, –CH3), 1.01 (3H, d, J 6.6,
–CH3), 1.60 (1H, m, J 6.6 and 2.2, –CH(CH3)2), 3.2 (1H, d,
J 1.8, exch. D2O, –OH ), 4.23 (1H, d, J 9.0, –CHOH), 4.33 (1H,
CHCl), 128.4 (ArC), 129.0 (ArC), 134.1 (ArC) and 137.1
(quaternary, ArC) ppm; HRMS: m/z 303.08146. Calculated for
C14H20ClO3S: 303.08217.
d, J 10.5, –CHSO –), 6.14 (1H, dd, J 10.5 and 7.2, –CH᎐CHCl),
᎐
2
6.28 (1H, d, J 7.2, –CH᎐CHCl), 7.54 (2H, m, ArH ), 7.65 (1H, t,
J 7.6, ArH ) and 7.86 (2H, d, J 8.6, ArH ) ppm; δC (75 MHz)
18.5 (CH3), 19.0 (CH3), 32.2 (–CH(CH3)2), 65.5 (–CHSO2–),
Reaction of lithiated (E )-3-bromo-1-phenylsulfonylpropene 8
with isobutyraldehyde
᎐
This was carried out as described above for the reaction of the
lithiated chlorosulfone 5 with isobutyraldehyde and yielded a
product mixture which contained principally (on the basis of
its NMR spectrum) (1Z)-3,4-anti-1-bromo-5-methyl-3-phenyl-
sulfonylhex-1-en-4-ol 32.
73.3 (–CHOH–), 120.2 (–C᎐CHCl), 126.7 (–CH᎐CHCl), 128.9
᎐
᎐
(overlapping signals, ArCatoms), 134.1 (ArC) and 137.2 (qua-
ternary, ArC) ppm; HRMS: m/z 289.06558. Calculated for
C13H18ClO3S: 289.06651.
3,4-anti-5-Methyl-3-phenylsulfonylhex-1-en-4-ol 29 and 3,4-syn-
5-methyl-3-phenylsulfonylhex-1-en-4-ol 30
Reaction of lithiated (E )-3-iodo-1-phenylsulfonylpropene 7 with
isobutyraldehyde
To 1-phenylsulfonylprop-2-ene 9 (0.74 g) in dry THF (5 cm3),
cooled to Ϫ78 ЊC under nitrogen, was added n-butyllithium
(2.5 M in hexane, 1.76 cm3, 1.2 eq.). After 5 min, isobutyralde-
hyde (0.29 g) in THF (1 cm3) was added and the mixture was
stirred for 1 h. It was then brought to rt, quenched with water
and extracted with ether. The ethereal extract was washed with
water, dried and evaporated to give a crude oily product (0.98 g)
which was chromatographed using ethyl acetate–hexane 1 : 9 as
eluant to give recovered starting material 9 (37%) and the
hydroxysulfones 29 and 30.
This was carried out as described above for the reaction of the
lithiated chlorosulfone 5 with isobutyraldehyde and yielded a
product mixture which contained (NMR) unreacted iodide 7
(47%), 1-phenylsulfonylprop-2-ene 9 (35%) and 3,4-anti-4-
hydroxy-5-methyl-3-phenylsulfonylhex-1-ene 29 (18%).
Acknowledgements
We thank Forbairt, the V. K. Krieble Fund and the Trinity
Trust for financial support to E. T. G., Dr Sylvia M. Draper
for carrying out the X-ray crystallographic analysis, Dr John
O’Brien for NMR spectra and Dr Neil Work for some
preliminary experiments.
3,4-anti-5-Methyl-3-phenylsulfonylhex-1-en-4-ol 29. 29 was
obtained as a solid (54%), mp 88–89 ЊC (ether–pentane), which
had νmax(N) 3518, 1307 and 1146 cmϪ1; δH (400 MHz) 0.78 (3H,
d, J 6.8, –CH3), 1.02 (3H, d, J 6.6, –CH3), 1.65 (1H, m,
–CH(CH3)2), 3.05 (1H, s, exch. D2O, –OH ), 3.64 (1H, d, J 10.1,
–SO2CH–), 4.07 (1H, d, J 9.1, –CHOH–), 5.01 (1H, dd, J 17.3
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᎐
᎐
a
b
(1H, dt, J 17.3, 10.1 and 10.1, –CH᎐CH ), 7.52 (2H, m,
᎐
2
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 7 4 – 1 3 8 1
1380

View Article Online
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