Lewis acid mediated elimination and rearrangement reactions of α-chlorosulfides derived from phenylthio-substituted 4,5-dihydrofuran-3(2H)-ones

Article abstract of DOI:10.1039/a905169d

Phenylthio-substituted 4,5-dihydrofuran-3(2H)-ones were converted into α-chlorosulfides in a highly diastereo-selective manner with sulfuryl chloride. Treatment of the chlorides with stoichiometric amounts of Lewis acids gave furan-3(2H)-one products resu

Full text of DOI:10.1039/a905169d

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Lewis acid mediated elimination and rearrangement reactions of
ꢀ-chlorosulfides derived from phenylthio-substituted 4,5-dihydro-
furan-3(2H)-ones.
Daniel G. McCarthy,* Cornelius C. Collins, Joan P. O’Driscoll and Simon E. Lawrence†
Chemistry Department, University College, Cork, Ireland
Received (in Cambridge, UK) 28th June 1999, Accepted 27th September 1999
Phenylthio-substituted 4,5-dihydrofuran-3(2H)-ones were converted into α-chlorosulfides in a highly diastereo-
selective manner with sulfuryl chloride. Treatment of the chlorides with stoichiometric amounts of Lewis acids gave
furan-3(2H)-one products resulting from elimination and aryl group migrations. Similar behaviour was observed
with an α-acetoxy sulfide derivative. The X-ray crystal structures of a representative α-chlorosulfide and of a novel,
ring sulfenylated product were determined.
Introduction
Phenylthio substituted-4,5-dihydrofuran-3(2H)-ones 1 and 2
are readily available in a highly stereoselective manner through
silica gel or zinc bromide mediated cyclisations of silyloxyenone–
benzenesulfenyl chloride adducts.1 In the course of developing
the chemistry of the heterocycles 1, we converted the com-
pounds into their α-chlorosulfide2 derivatives 3 and 4, and
investigated Lewis acid catalysed C–C bond forming reactions
of the latter with carbon nucleophiles.3 These reactions were
not successful but some novel chemistry derived from inter-
actions of the chlorides with certain Lewis acids alone emerged
from this work. Details of these studies, together with the single
crystal X-ray structure determination of a furanone derived
α-chlorosulfide and of a novel reaction product resulting from
interaction of the compound with SnCl4 and TiCl4, and related
work are presented in this paper.
Results and discussion
Enones 5 were prepared4 by aldol condensation of the
requisite hydroxyketones with arene carbaldehydes in ethan-
olic KOH and converted into silyloxyenones 6 by standard
methods.5 An alternative route was employed for enone 7:
Horner–Wadsworth–Emmons condensation of 8 with iso-
butyraldehyde under Masamune–Roush conditions6 gave 7.
Phosphonate 8 was prepared by conversion of methyl 2-
hydroxyisobutyrate into its TBS ether using tert-butylchloro-
dimethylsilane (TBSCl), imidazole and a catalytic amount of
4-dimethylaminopyridine (DMAP) under forcing conditions
in dimethylformamide (DMF), followed by condensation of
the silyloxyester with an excess of dimethyl lithiomethylphos-
phonate in tetrahydrofuran (THF).7 Cyclisation of substrates 6
and 7 according to our recently described procedure1 gave the
furanone products as mixtures of diastereomers 1 and 2 (ratio
1:2 >92:8) from which the major isomer 1 could be isolated
acetate–hexane solutions yielded the chlorosulfides as single
diastereomers, assigned structure 4 in each case.
by dry-flash or radial chromatography on silica gel followed,
in certain cases (1d and 1e) by recrystallisation.
The chlorosulfide structures 4a–d were supported by char-
acteristic dihydrofuranone infrared carbonyl absorptions8 in
the 1755–1765 cmϪ1 region and proton NMR chemical shifts in
the range 5.4–5.5 ppm for the methine proton at C-5 in the
heterocyclic ring (3.89 ppm for 4e). With the exception of the
latter where the furanone C-4 and C-5 carbon-13 resonances
were coincidental (88.3 ppm), signals betweeen 81 and 84 ppm
were observed for the furanone C-4 and C-5 ring carbons in
the other chlorosulfides. The relative stereochemistry at these
Reaction of the furanones either as the trans-isomers, i.e. 1,
or as a mixture of isomers in the case of 1a and 2a, with sulfuryl
chloride [chlorinations with N-chlorosuccinimide (NCS) were
problematic for these substrates] in refluxing dichloromethane
produced the α-chlorosulfides as mixtures of diastereomers 3
and 4. Recrystallisation of the individual mixtures from ethyl
† Corresponding author for X-ray crystallography.
J. Chem. Soc., Perkin Trans. 1, 1999, 3667–3675
This journal is © The Royal Society of Chemistry 1999
3667

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Fig. 1 Single crystal X-ray structure of compound 4c showing the
crystallographic numbering scheme.
Fig. 2 Single crystal X-ray structure of compound 13 showing the
crystallographic numbering scheme.
positions in a representative chloride 4c was established by
single crystal X-ray analysis and not surprisingly revealed that
the 3,4-dimethoxyphenyl and phenylthio substituents were
positioned on the same face of the dihydrofuranone ring (Fig.
1) in the thermodynamically more stable chlorosulfide. Since
1
the H NMR chemical shifts of the furanone C-5 ring protons
in the structurally related compounds 4a, 4b and 4d were simi-
lar to that in 4c (5.44 ppm), these chlorides were assigned the
same relative stereochemistry as 4c and, by analogy, 4e also.
Following the precedent of Trost and Massiot, treatment of
furanone 1b with lead tetraacetate9 in CH2Cl2 produced the
acetoxysulfide 9 (νCO = 1760 and 1740 cmϪ1) in 80% yield as
a mixture of diastereomers (ratio ca. 3:2) which were not
separated.
Reaction of 4a with a slight excess of SnCl4 in CH2Cl2 at
room temperature for 12 h resulted in an efficient dehydro-
chlorination reaction to produce the novel phenylthiofuranone
10a in 69% yield. Structure 10a (Mϩ = 296) was supported by a
characteristic furan-3(2H)-one carbonyl group absorption at
1705 cmϪ1 in its infrared spectrum10 and heterocycle 13C NMR
signals at 87.7 (C-2), 102.9 (C-4), 184.3 (C-5) and 204.4 (C-3)
ppm. Similarly, the 5-alkyl furanone 4e gave 11 in high yield
(87%). Interaction of 4b with stannic chloride under the same
conditions produced two compounds: furanone 10b (12%) and
the product of an aryl ring migration, 12b (40%), as the only
isolable reaction products. Acetoxyfuranone 9 which contains a
poor leaving group behaved similarly and gave 10b and 12b in
11 and 30% yield respectively. The spectroscopic properties of
the former were similar to those of 10a and the identity of 12b
was confirmed through independent synthesis via oxidative
cyclisation of hydroxyenone 5b with thallium() nitrate in
methanol according to the procedure of Nogradi and
coworkers.11
Three products, the isomeric pair 10c (7%) and 13 (35%)
together with 14 (15%)—a novel ring chlorinated analogue of
10c, were isolated from the reaction of stannic chloride with 4c.
The molecular structure of 13 was determined by single crystal
X-ray analysis (Fig. 2) and that of 14 from its analytical and
spectroscopic properties. Two one-proton singlets at 6.89 and
1
6.84 ppm in the H NMR spectrum of the compound were
important in establishing the presence of a 1,2,4,5-tetra-
substituted aryl group at the C-5 position in the furanone ring.
The same products were formed from 4c and SnCl4 in toluene
with 10c (44%) predominating; 13 and 14 were isolated in yields
of 10 and 25% respectively. No compounds resulting from
trapping of a chlorosulfide derived cationic intermediate by the
aromatic solvent12 were isolated or detected as products of
these experiments. Further studies involving variation of the
Lewis acid revealed that 4c was unreactive towards TiCl4 at
room temperature over a 24 h period, but produced the same
products 10c (5%), 13 (19%) and 14 (30%) upon heating with
the reagent at reflux. A change in product distribution emerged
from the interaction of 4c with ZnBr2. Furanone 10c (49%)
predominated and compound 13 was not detected in or isolated
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from the reaction product mixture. Surprisingly, the chlorinated
compound 14 rather than its bromo analogue was also a
product of this reaction and was isolated in 11% yield. The
presence of one chlorine substituent in the molecular structure
was established from the mass spectrum of 14 which showed
two ions in the expected ratio at m/z = 392/390 (Mϩ).
With AlCl3 a further change in the behaviour of 4c was
observed: a new furanone, the chlorine containing compound
15, emerged as the only product (28%) of a low yielding reac-
tion. Structure 15 (Mϩ, m/z 284/282) was characterised by its
furanone ring C-5 carbon-13 signal at 174.6 ppm and the
corresponding attached proton resonance at 8.64 ppm, in
particular.
favourable on the basis of the products isolated. Similar reactiv-
ity and compound distribution from the interaction of 4b and 9
with SnCl4 was observed in the present study.
Proton loss from species 18 would generate the phenylthio
compounds 10, 11 and 17 directly. However, intermediate 18
could undergo a 1,2-hydride shift16 to give oxonium ion 19;
proton loss would then yield the phenylthiofuranones. Com-
pounds derived from halide induced loss of the phenyl-
thio group in 19, i.e. 2,2-disubstituted-5-arylfuran-3(2H)-ones
(analogues of the natural product bullatenone) which can be
readily identified by characteristic furanone C-4 proton reson-
ances in the region 6.0–6.4 ppm were not isolated nor detected
as reaction products in our investigations.4,17 An alternative 1,2-
aryl group migration in 18 (R3 = aryl) would generate oxonium
ion 20 via the favourable phenonium ion18 related spiro-dienone
based structure 21 (R3 = H or OMe). Species related to 21
Upon reaction with SnCl4 under the conditions employed for
4c, the related spiro-furanone 4d yielded the isomeric structures
16 and 17 in 48% and 15% yields respectively. The correspond-
ing ring chlorinated analogue of 14 was not detected or isolated
as a reaction product.
Formation of the phenylthiofuranones 10, 11 and 17 can
be rationalised (Scheme 1) through initial Lewis acid mediated
have been cited as intermediates in a range of transformations,
for example the conversion of flavones into isoflavones with
thallium() salts and under enzymatic conditions.19 Loss of
the phenylthio group from 20 would complete formation of the
4-aryl furanones 12. Compounds 12a and 12c were not isolated
as reaction products; the latter however is a potential source of
13, 15 and 16.
Under the reaction conditions employed in this study,
compound 12c could undergo Lewis acid induced electrophilic
substitution with diphenyl disulfide or benzenesulfenyl chlor-
ide20 generated from oxonium ion 20, to produce 13. This
possibility could not be excluded since 12c, prepared from 5c
and thallium() nitrate in methanol,11 reacted slowly with both
sulfur reagents over a 24 h period in the presence of an equi-
molar quantity of stannic chloride and produced 13 in 8 and
11% yields respectively. In contrast, furanone 12c was stable to
AlCl3 in CH2Cl2 for 12 h. Compound 13 could arise by another
mechanism which is outlined in Scheme 2. Thus, intramolecular
electrophilic substitution of the reactive C-5 aryl ring in 22
(E = SnCl4) via a Lewis acid–base adduct of 4c with stannic
chloride leads to the chlorofuranone complex 25. Further reac-
tions of this species via 26 would produce 13 (a concerted
reaction: 25→27, cannot be excluded). The feasibility of 25
as an intermediate could not be tested experimentally since
α-chlorofuranones such as 30 are unknown. Although 26 is a
destabilised carbocation,21 interactions of its cationic site with
the neighbouring furanone ring oxygen atom and sulfur of
the phenylthio group render the structure more favourable as
an intermediate; see structures 28 and 29.
Significant quantities of the aryl ring chlorinated product 14
were isolated from reactions of 4c with SnCl4, TiCl4 and ZnBr2.
Chlorination of the primary reaction product 10c with an
electrophilic chlorine species derived from or contained in the
Lewis acids employed was thought to be a likely source of 14.
Surprisingly, 10c was unreactive towards stannic chloride under
the reaction conditions for 24 h and was recovered in 92% yield.
The mechanism outlined in Scheme 2 for the formation of 13
could accomodate formation of 14 also. Thus, intramolecular
electrophilic chlorination of the 3,4-dimethoxyphenyl ring in
the complex 22 would generate a Lewis acid-base complex of
phenylthio dihydrofuranone 31 (analogous to 24) as a reaction
intermediate. Dehydrogenation of 31, possibly induced by the
Lewis acid, would complete formation of 14. Furanone 1c (a
model for 31) gave a complex mixture of compounds when
treated with SnCl4. Surprisingly, hydroxyenone 5c was the
Scheme 1
loss of chloride ion from the α-chlorosulfides to produce
furanone based acyl thionium ions 18 which can be further
stabilised by a transannular resonance interaction with the
furanone ring oxygen. Acyl thionium ions are commonly
invoked as intermediates in the Pummerer reaction of α-sulfinyl
carbonyl compounds13 and are usually generated by treatment
of these species with acids or their anhydrides.14 Treatment of
α-chlorosulfides with Lewis acids is also an effective source
of acyl thionium ions.12,15 It is interesting to note that reaction
of a mixture of the isomeric chlorides 3c and 4c generated 10c,
13 and 14 in a ratio similar to that observed with 4c alone.
Furthermore, it was found that 4c equilibrated with 3c in the
presence of stannic chloride (ca. 7% after 30 min; the NMR
spectra showed evidence for appearance of the final reaction
products at this stage also) and consequently both isomers are
likely sources of thionium ions 18. Although α-acetoxysulfides
are less effective than α-chlorosulfides as thionium ion pre-
cursors,15c formation of intermediate 18 from 9 is clearly
J. Chem. Soc., Perkin Trans. 1, 1999, 3667–3675
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In summary, interaction of dihydrofuran-3(2H)-ones bearing
α-chlorosulfide functionality, with Lewis acids generates
novel furanone structures resulting from elimination and aryl
group migration reactions. The origin of furanones possessing
phenylthio or chlorine substituted aryl groups at the 4- and
5-positions of the parent heterocycle remains to be established.
Experimental
Melting points were measured on a Thomas Hoover capil-
lary melting point apparatus and are uncorrected. Elemental
analyses were determined in The Microanalysis Laboratory,
University College, Cork, using a Perkin-Elmer 240 elemental
analyser. Infrared spectra were recorded either on a Perkin-
Elmer 682 or a Perkin-Elmer Paragon 1000 FTIR spectrometer.
Solid samples were examined as KBr discs and liquids as thin
films. Mass spectra were measured in electron impact mode
using a Kratos Profile HV4 instrument. 1H NMR spectra were
recorded on JEOL PMX-60 Si (60 MHz) or JEOL JNM GSX-
270 (270 MHz) spectrometers. Proton resonance multiplicities
are documented as broad peaks (br), singlets (s), doublets (d),
triplets (t), quartets (q), and multiplets (m). Proton decoupled
13C NMR spectra were measured at 67.5 MHz on a JEOL JNM
GSX-270 NMR spectrometer. For each carbon resonance, the
number of attached protons was established from experiments
run in the DEPT-90 and DEPT-135 modes. All spectra were
run in CDCl3 with tetramethylsilane (TMS) as an internal
standard unless otherwise specified. Chemical shifts are
expressed in parts per million (ppm), positive shifts being
downfield from TMS; J values are in Hz.
Thin layer chromatography (TLC) analysis was performed
on precoated silica gel-60 HF254 plates (Merck 5554) and
compounds were visualised using ultraviolet light or by iodine
staining. ‘Dry-flash’ chromatography was carried out on silica
gel-60 PF254 (Merck 7747). Preparative radial chromatography
was performed on a Chromatotron (Model 7924, Harrison
Research) using silica gel containing gypsum (Merck 7749) as
the stationary phase, on 4 mm plates.
A Buchi GKR-50 apparatus was employed for bulb-to-bulb
distillations and the oven temperature is quoted as the boiling
point in each case. Organic extracts were dried over anhydrous
magnesium sulfate. Solvents and reagents were dried and
purified by standard methods.24 All experiments involving the
synthesis and reactions of dihydrofuranones including the
Scheme 2
major reaction product and was isolated in 46% yield. Analysis
(TLC and NMR) of the remaining chromatographic fractions
from this reaction failed to reveal any evidence for the presence
of 10c. Consequently the origin of 14 as a reaction product
remains unclear. Isolation of 14 rather than a bromo analogue,
albeit in low yield (12%), from interaction of 4c with ZnBr2
supports an intramolecular chlorination mechanism, however.
We consider it unlikely that 14 arises from contamination of the
starting chlorosulfide 4c with the dichloride 32 since the former
compound was used in an analytically pure state and its spec-
troscopic properties were in full agreement with its molecular
structure. Significant quantities of a related dichloride were
produced upon treatment of the 3,4-methylenedioxyphenyl
analogue of 4c with either N-chlorosuccinimide or sulfuryl
chloride22 and work with this particular substrate was dis-
continued. Halogenation of activated aromatic systems with
N-halosuccinimides is well established.23
Aluminium trichloride induced loss of the phenyl group from
intermediate 31, concomitant with or preceding aryl group
migration, could account for the formation of 15. Upon
reaction with AlCl3, a model compound, furanone 1c, gave a
mixture of products from which 5c was isolated as the only
identifiable material in 39% yield; 12c was not recognisable by
TLC or 1H NMR analysis of the reaction mixture.
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α-chlorosulfides 3 and 4 were conducted in dry solvents under a
nitrogen atmosphere.
Hydroxyenones 5a–d were prepared using literature pro-
cedures4 and converted into their trimethylsilyl ethers with
chlorotrimethylsilane and imidazole in CH2Cl2.5
(1.73 g, 12 mmol) and 5c (3.22 g, 10 mmol) following radial
chromatography using 1:9 ethyl acetate–heptane as eluent; mp
103–104 ЊC (Found: C, 67.1; H, 6.25; S, 8.4. C20H22SO4 requires
C, 67.0; H, 6.2; S, 8.95%); νmax (KBr)/cmϪ1: 2900, 1760, 1590,
1570, 1460, 1260, 1230, 1140, 1086, 1025; δH: 1.05 (3H, s), 1.30
(3H, s), 3.59 (1H, d, J = 9.5), 3.89 (6H, s), 4.81 (1H, d, J = 9.5),
6.87 (1H, d, J = 7.2), 6.99 (1H, br s), 7.07 (1H, m), 7.20–7.30
(3H, m), 7.4–7.43 (2H, m); δC: 21.2, 24.5, 55.9, 56.0, 58.4, 78.6,
81.1, 109.4, 111.1, 119.2, 128.7, 129.05, 131.05, 131.4, 134.45,
149.2, 149.3, 213.3; m/z: 358 (Mϩ), 249, 164 (100%), 110, 91,
77, 43.
(E)-2,6-Dimethyl-2-tert-butyldimethylsilyloxyhept-4-en-3-one
7
Methyl 2-hydroxyisobutyrate (4.73 g, 40 mmol), dry imidazole
(4.35 g, 64 mmol), DMAP (0.5 g, 4 mmol) and TBSCl (7.25 g,
48 mmol) in dry DMF (20 cm3) were heated at 100 ЊC for 16 h.
Dilution of the cooled solution with ethyl acetate (200 cm3),
followed by washing with water (3 × 100 cm3), brine (3 × 50
cm3) and concentration of the dried organic extracts afforded a
light oil. Bulb-to-bulb distillation gave the silyl ether (8.5 g,
90%), bp 80 ЊC at 10 mmHg; νmax(film)/cmϪ1: 1760; δH (60
MHz): 0.10 (6H, s), 0.9 (9H, s), 1.4 (6H, s), 3.73 (3H, s). This
silyl ether (7.42 g, 32 mmol) in dry THF (80 cm3) was added
dropwise to a cold (Ϫ78 ЊC) solution of dimethyl lithio-
methylphosphonate [prepared by addition of dimethyl methyl-
phosphonate (17.34 cm3, 0.16 mol) in dry THF (70 cm3) to
n-butyllithium (100 cm3 of a 1.6  solution in hexane) in dry
THF (100 cm3) at Ϫ78 ЊC]. The mixture was stirred at Ϫ78 ЊC
for 1.5 h, then quenched at this temperature with saturated
ammonium chloride solution (100 cm3). The frozen mixture
was allowed to warm to room temperature and diluted with
ether (3 × 50 cm3). Evaporation of the dried organic layer and
kugelrohr distillation of the residue gave 8 (8.3 g, 80%), bp
100 ЊC at 0.1 mmHg; νmax(film)/cmϪ1: 1720; δH (60 MHz): 0.21
(6H, s), 0.91 (9H, s), 1.42 (6H, s), 3.20 (2H, d, J = 22), 3.65 (6H,
d, J = 11).
trans-3-Phenylthio-2-(3,4-dimethoxyphenyl)-1-oxaspiro[4.5]-
decan-4-one 1d
Isolated as a white crystalline solid (1.64 g, 58%) from PhSCl
(1.23 g, 8.51 mmol) and 5d (2.57 g, 7.1 mmol) following dry-
flash chromatography using 1:9 ethyl acetate–hexane as eluent
and recrystallisation from the same solvent; mp 86–87 ЊC
(Found: C, 68.9; H, 6.5; S, 7.7. C23H26SO4 requires C, 69.3; H,
6.6; S, 8.05%); νmax(KBr)/cmϪ1: 3060, 2930, 1749, 1592, 1513,
1265, 1235, 1082; δH: 1.26–1.75 (10H, m), 3.58 (1H, d, J = 10),
3.88 (3H, s), 3.89 (3H, s), 4.81 (1H, d, J = 10), 6.88 (1H, d,
J = 8.4), 7.01 (1H, s), 7.07 (1H, d, J = 8.1), 7.22–7.44 (5H, m);
δC: 20.75, 21.3, 25.0, 29.1, 33.3, 55.9, 56.0, 58.9, 78.5, 82.5,
109.6, 111.25, 119.1, 128.45, 128.95, 131.1, 134.1, 149.2, 149.3,
212.9; m/z: 398 (Mϩ), 289, 272, 232, 204 (100%), 165, 150, 121,
109, 95, 77, 55.
trans-4-Phenylthio-2,2-dimethyl-5-isopropyl-4,5-dihydrofuran-
3(2H)-one 1e
Dried lithium chloride (0.968 g, 22 mmol) and dry triethyl-
amine (3 cm3, 21 mmol) were added in sequence, under nitrogen,
to a solution of 8 (6.5 g, 20 mmol) in dry acetonitrile (50 cm3).
The resulting milky lithiophosphonate suspension was stirred at
room temperature for 15 min and freshly distilled isobutyr-
aldehyde (1.82 cm3, 20 mmol) was slowly added by syringe. The
mixture was stirred at ambient temperature for 5 days, then
diluted with water (30 cm3) and extracted with ether (5 × 50
cm3). The extracts were washed with brine (3 × 50 cm3), dried
and concentrated in vacuo. Radial chromatography (5% ethyl
acetate in heaxane) of the residue gave 7 (5.13 g, 95%) as a clear
oil; νmax(film)/cmϪ1: 2957, 2873, 1704, 1634 and 1473; δH: 0.20
(6H, s), 0.83 (9H, s), 0.98 (6H, d, J = 6.3), 1.28 (6H, s), 2.40 (1H,
m), 6.68 (1H, d, J = 15.6), 6.86 (1H, dd, J = 5.7 and 15.6);
δC: Ϫ2.3, 21.2, 25.5, 27.0, 34.1, 79.1, 121.1, 154.3, 203.2.
The furanone was prepared by addition of PhSCl (3.93 g, 28
mmol) in CH2Cl2 (10 cm3) to 7 (7.02 g, 26 mmol) in the same
solvent (40 cm3). Fused zinc bromide (1.46 g, 6.5 mmol) was
added in one portion after 1 h. The resulting black solution was
stirred for 1 h, then filtered through a silica plug and the filtrate
concentrated in vacuo. Radial chromatography of the residue
(2% ethyl acetate in hexanes) gave the furanone (5.1 g, 74%), a
viscous oil, as a mixture of diastereomers (94:6). The oil was
mixed with pentane (5 ml) and stored at Ϫ10 ЊC for 24 h to give
1e as large clear crystals, mp 47–48 ЊC (Found: C, 68.15; H,
7.7; S, 12.4. C15H20SO2 requires C, 68.2; H, 7.6; S, 12.1%);
νmax(KBr)/cmϪ1: 3072, 2974, 2872, 1760, 1582; δH: 0.92 (3H, s),
1.01 (3H, d, J = 6.8), 1.04 (3H, d, J = 6.8), 1.26 (3H, s),
2.01 (1H, septet of doublets, J = 5.7 and 6.8), 3.40 (1H, d,
J = 10.2), 3.76 (1H, dd, J = 5.7 and 10.2), 7.32 (3H, m), 7.50
(2H, m); δC: 17.3, 18.9, 21.8, 24.3, 31.4, 52.5, 81.0, 81.3, 128.4,
128.9, 134.9, 132.2, 214.7; m/z: 264 (Mϩ), 192, 178, 164 (100%),
135, 109, 91, 84, 77, 69.
Synthesis of furanones 1a, 2a and 1b–d
These were prepared using our published general procedure;
analytical and spectroscopic data for 1b is reported therein.1
4-Phenylthio-4-chloro-2,2-dimethyl-5-phenyl-4,5-dihydrofuran-
3(2H)-one 4a
cis- and trans-4-Phenylthio-2,2-dimethyl-5-phenyl-4,5-dihydro-
furan-3(2H)-one 1a and 2a
A solution of SO2Cl2 (0.563 g, 4.17 mmol) in CH2Cl2 (20 cm3)
was added dropwise over 10 min to a stirred mixture of
furanones 1a and 2a, prepared as above (1.13 g, 3.79 mmol), in
the same solvent (20 cm3). The resulting solution was stirred at
room temperature for 3 h, then washed successively with satur-
ated sodium bicarbonate solution (3 × cm3) and water (3 × 10
cm3), dried and concentrated in vacuo. Radial chromatography
of the resulting oil with 95:5 hexane–ethyl acetate as eluent
gave a white solid (1.01 g, 80%) as a mixture of diastereomers.
Recrystallisation of the solid from ethyl acetate–hexane gave a
single diastereomer, mp 91–93 ЊC (Found: C, 65.2; H, 5.2; S,
9.9; Cl, 10.3. C18H17ClSO2. requires C, 65.1; H, 5.1; S, 9.6; Cl,
10.35%); νmax(KBr)/cmϪ1: 2960, 1755, 1595, 15.80; δH: 1.40 (3H,
s), 1.77 (3H, s), 5.49 (1H, s), 7.23–7.50 (8H, m), 7.69 (2H, d,
J = 7.6); δC: 23.0, 26.9, 77.9, 80.6, 84.0, 127.2, 127.3, 128.2,
128.8, 129.2, 130.3, 133.1, 136.8, 202.1; m/z: 332 (35Cl, Mϩ), 296,
246, 226, 198 (100%), 163, 129, 119, 105, 77, 69, 51.
Isolated in the form of a light yellow oil (0.4 g, 70%) as a
mixture of diastereomers 1a and 2a in the ratio 95:5 from
PhSCl25 (0.33 g, 2.3 mmol) and enone 5a (0.5 g, 1.8 mmol)
following radial chromatography using 1:19 ethyl acetate–
heptane as eluent (Found: C, 72.6; H, 6.3; S, 10.7. C18H18SO2
requires C, 72.45; H, 6.1; S, 10.75%); νmax(film)/cmϪ1: 2970,
1750, 1430, 1375, 1160, 1075, 750; δH(1a): 0.99 (3H, s), 1.43
(3H, s), 3.57 (1H, d, J = 10.8), 4.87 (1H, d, J = 10.8), 7.15–7.60
(10H, m); δC(1a): 21.1, 24.4, 58.5, 78.4, 81.1, 126.5, 128.6, 128.8,
128.9, 129.4, 134.7, 131.2, 138.7, 213.2; m/z: 298 (Mϩ), 189, 164
(100%), 121, 102, 77, 51, 43. δH(2a): 1.35 (3H, s), 1.65 (3H, s),
3.90 (1H, d, J = 4.9), 5.52 (1H, d, J = 4.9), 7.20–7.50 (10H, m).
trans-4-Phenylthio-5-(3,4-dimethoxyphenyl)-2,2-dimethyl-4,5-
dihydrofuran-3(2H)-one 1c
Isolated as a white crystalline solid (1.97 g, 55%) from PhSCl
J. Chem. Soc., Perkin Trans. 1, 1999, 3667–3675
3671

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The following compounds were prepared by the same general
method.
4-Acetoxy-4-phenylthio-2,2-dimethyl-5-(4-methoxyphenyl)-4,5-
dihydrofuran-3(2H)-one 9
Lead tetraacetate (0.37 g, 0.83 mmol) in CH2Cl2 (10 cm3) was
added to a solution of 1b (0.21 g, 0.64 mmol) in the same sol-
vent (10 cm3). The resulting mixture was stirred at room tem-
perature under nitrogen until TLC analysis showed that all of
the starting material had been consumed, then filtered and the
solvent evaporated under reduced pressure to leave a yellow oil.
Dry-flash chromatography using 1:19 ethyl acetate–hexane
as eluent yielded 9 (0.198 g, 80%), a white oil, as a mixture
of diastereomers in the ratio 1.4:1 (Found: Mϩ, 386.1189.
C21H22SO5 requires M, 386.1188); νmax (film)/cmϪ1: 2980, 1766,
1740, 1610, 1510, 1220; δH (major isomer): 1.52 (3H, s), 1.68
(3H, s), 2.19 (3H, s), 3.85 (3H, s), 5.85 (1H, s), 6.95 (2H, d,
J = 9), 7.22–7.48 (7H, m); δH (minor isomer): 1.52–1.61 (6H,
br s), 1.57 (3H, s), 3.81 (3H, s), 5.33 (1H, s), 6.86 (2H, d, J = 9),
7.22–7.48 (5H, m), 7.56 (2H, d, J = 9); δC: 19.7, 21.1, 24.3, 24.8,
25.2 (major), 27.0 (major), 55.3 (both isomers), 76.9 (major),
80.5, 80.75 (major), 82.4 (major), 85.2, 90.0 (major), 113.3
(major), 113.6, 126.5 (major), 127.5, 127.6, 128.2, 128.3, 128.7,
128.8, 129.9, 130.2, 136.6 (major), 136.8, 159.45, 160.0 (major),
168.7 (major), 169.3, 202.5, 205.8 (major); m/z: 386 (Mϩ), 326,
179, 141 (100%), 110, 77, 43.
4-Phenylthio-4-chloro-2,2-dimethyl-5-(4-methoxyphenyl)-4,5-
dihydrofuran-3(2H)-one 4b
From SO2Cl2 (0.524 g, 3.88 mmol) in CH2Cl2 (20 cm3) and
furanone 1b (1.16 g, 3.53 mmol) in the same solvent (40 cm3).
Radial chromatography of the resulting white residue using
95:5 hexane–ethyl acetate as eluent gave a white solid (1.05 g,
82%) which was recrystallised from ethyl acetate–hexane, mp
123–124 ЊC (Found: C, 63.0; H, 5.35; Cl, 10.0; S, 8.5. C19H19-
ClSO3 requires C, 62.9; H, 5.2; Cl, 9.8; S, 8.8%); νmax (KBr)/
cmϪ1: 3060, 2975, 2933, 1760, 1613, 1515, 1439, 1257, 1171,
1098, 1031; δH: 1.40 (3H, s), 1.76 (3H, s), 3.86 (3H, s), 5.45 (1H,
s), 7.00 (2H, d, J = 10), 7.26–7.46 (5H, m), 7.64 (2H, d, J = 10);
δC: 23.0, 26.8, 55.3, 78.3, 80.6, 83.9, 113.6, 125.0, 127.3, 128.5,
128.9, 130.35, 136.9, 160.3, 202.3; m/z: 362(35Cl, Mϩ), 326, 253,
226, 198 (100%), 135, 119, 89, 77, 69, 43.
4-Phenylthio-4-chloro-5-(3,4-dimethoxyphenyl)-2,2-dimethyl-
4,5-dihydrofuran-3(2H)-one 4c
From SO2Cl2 (0.83 g, 6.14 mmol) in CH2Cl2 (30 cm3) and
furanone 1c (2.0 g, 5.58 mmol) in the same solvent (30 cm3).
Dry-flash chromatography of the resulting oil using 1:9 ethyl
acetate–hexane as eluent gave a white solid (1.67 g, 76%) as a
mixture of diastereomers (ratio, 1:1.2). Recrystallisation from
ethyl acetate–hexane gave a single diastereomer, mp 126–128 ЊC
(Found: C, 61.35; H, 5.6; S, 8.0, Cl, 9.1. C20H21ClSO4 requires
C, 61.2; H, 5.35; S, 8.2; Cl, 8.9%); νmax(KBr)/cmϪ1: 3056, 2976,
1761, 1593, 1518, 1260, 1163, 1098, 1029; δH 1.43 (3H, s), 1.78
(3H, s), 3.92 (3H, s), 3.97 (3H, s), 5.44 (1H, s), 6.96 (1H, d,
J = 8.4), 7.21–7.45 (7H, m); δC 23.0, 26.8, 55.9, 56.0, 78.3, 80.6,
83.9, 110.5, 110.7, 119.8, 125.4, 127.2, 128.8, 130.4, 136.9,
148.8, 149.8, 202.0; m/z: 392(35Cl, Mϩ), 355, 316, 183, 198, 164,
149, 110, 84, 49 (100%).
Reactions of chlorosulfides 4a–e with SnCl4
Compound 4a. A solution of SnCl4 (0.659 g, 2.53 mmol) in
CH2Cl2 (10 cm3) was added dropwise at ambient temperature to
a solution of 4a (0.765 g, 2.30 mmol) in the same solvent (15
cm3). The mixture was stirred overnight at room temperature,
then washed successively with water (3 × 15 cm3), saturated
sodium bicarbonate solution (3 × 15 cm3) and water (3 × 15
cm3), dried and concentrated under reduced pressure. Radial
chromatography of the resulting brown oil using 95:5 hexane–
ethyl acetate as eluent gave 10a (0.47 g, 69%), mp 88–89 ЊC as a
yellow solid (Found: C, 72.7; H, 5.5; S, 10.4. C18H16SO2 requires
C, 73.1; H, 5.4, S, 10.8%); νmax(KBr)/cmϪ1: 3067, 2980, 1705,
1582, 1546, 1350, 1178, 1072; δH: 1.56 (6H, s), 7.07–7.26 (5H,
m), 7.42–7.58 (3H, m), 8.27 (2H, d, J = 7.5); δC: 23.2, 87.7,
102.9, 125.7, 126.6, 128.5, 128.8, 129.0, 129.2, 132.9, 135.8,
184.3, 204.4; m/z: 296 (Mϩ), 210, 165, 129, 121, 105 (100%),
91, 77, 51, 43.
3-Phenylthio-3-chloro-2-(3,4-dimethoxyphenyl)-1-oxaspiro[4.5]-
decan-4-one 4d
From SO2Cl2 (0.414 g, 3.07 mmol) in CH2Cl2 (20 cm3) and
furanone 1d (1.11 g, 2.79 mmol) in the same solvent (20 cm3).
Radial chromatography of the white reaction residue employ-
ing 95:5 hexane–ethyl acetate as eluent gave a white solid
(0.966 g, 80%) which was recrystallised from ethyl acetate–hex-
ane, mp 114.5–116.5 ЊC (Found: C, 64.1; H, 5.8; Cl, 8.3; S, 7.3.
C23H25ClSO4 requires C, 63.8; H, 5.8; Cl, 8.2; S, 7.45%); νmax
(KBr)/cmϪ1: 2935, 2856, 1760, 1593, 1518, 1439, 1332, 1273,
1026; δH 1.59–2.22 (10H, m), 3.93 (3H, s), 3.97 (3H, s), 5.42
(1H, s), 6.96 (1H, d, J = 8.4), 7.24–7.42 (7H, m); δC: 21.0, 21.4,
24.8, 30.5, 35.6, 55.9, 56.0, 78.8, 82.1, 83.8, 110.6, 110.7, 119.9,
125.8, 127.4, 128.9, 130.3, 136.7, 148.7, 149.7, 201.7; m/z:
432 (35Cl, Mϩ), 396, 306, 266, 238, 165, 121, 109, 77, 69, 55
(100%).
Compounds 4b–e were treated with SnCl4 according to the
same general procedure.
Compound 4b. SnCl4 (0.703 g, 2.70 mmol) in CH2Cl2 (15 cm3)
and 4b (0.89 g, 2.45 mmol) in the same solvent (15 cm3) gave
a dark green solution which was worked up in the usual way.
Radial chromatography of the reaction residue (95:5 hexane–
ethyl acetate) gave 10b (0.098 g, 12%) as a white crystalline
solid, mp 112–113 ЊC (Found: C, 69.65; H, 5.4; S, 9.5. C19H17-
SO3 requires C, 69.9; H, 5.6; S, 9.8%); νmax(KBr)/cmϪ1: 2976,
1693, 1601, 1579, 1542, 1497, 1423, 1266, 1182; δH: 1.56 (6H, s),
3.86 (3H, s), 6.95 (2H, d, J = 8.9), 7.08–7.26 (5H, m), 8.31 (2H,
d, J = 8.9); δC: 22.4, 55.5, 87.5, 100.9, 114.0, 121.8, 125.7, 126.3,
129.1, 131.1, 136.2, 163.5, 183.9, 204.3; m/z: 326 (Mϩ), 283, 240,
197, 159, 149, 135 (100%), 110, 77, 55.
Furanone 12b (0.213 g, 40%) was isolated as a white crystal-
line solid, mp 83–85 ЊC (Found: C, 71.3; H, 6.5. C13H14O3
requires C, 71.5; H, 6.5%); νmax(KBr)/cmϪ1: 3082, 2938, 1680,
1596, 1511, 1466, 1282, 1244; δH: 1.45 (6H, s), 3.84 (3H, s), 6.91
(2H, d, J = 8.9), 7.62 (2H, d, J = 8.9), 8.38 (1H, s); δC: 23.1, 55.3,
88.6, 114.2, 116.3, 121.5, 126.8, 159.0, 170.8, 205.0; m/z: 218
(Mϩ), 175, 148, 132, 117, 105, 89, 77, 63, 51, 43 (100%).
4-Phenylthio-4-chloro-2,2-dimethyl-5-isopropyl-4,5-dihydro-
furan-3(2H)-one 4e
From SO2Cl2 (0.281 g, 2.08 mmol) in CH2Cl2 (10 cm3) and 1e
(0.50 g, 1.89 mmol) in the same solvent (20 cm3) at room tem-
perature, for 14 h. Radial chromatography of the white reaction
residue (eluent hexane) gave a white solid, mp 54–55 ЊC (Found:
C, 59.95; H, 6.3; S, 10.4; Cl, 11.9. C15H19ClSO2 requires C, 60.3;
H, 6.4; S, 10.1; Cl, 11.9%); νmax(KBr)/cmϪ1: 2964, 2872, 1765,
1472, 1180, 1083, 1018; δH: 1.14 (3H, d, J = 6.5), 1.26 (3H, s),
1.30 (3H, d, J = 6.5), 1.60 (3H, s), 2.28 (1H, septet of doublets,
J = 6.5 and 9.7), 3.89 (1H, d, J = 9.7), 7.33–7.51 (5H, m); δC:
19.1, 20.2, 22.9, 26.6, 29.8, 79.7, 88,3, 127.4, 128.6, 128.9, 136.8,
203.0; m/z: 298 (35Cl, Mϩ), 264, 226, 212, 197, 163, 135, 119,
109, 91, 77, 65, 59, 43 (100%).
The compound was identified by comparison of its proper-
ties with those of authentic material, prepared from 5b (0.485 g,
2.20 mmol) and thallium() nitrate11 (1.08 g, 2.42 mmol) in
methanol (20 cm3), at room temperature, for 24 h. Neutralis-
ation of the reaction mixture with 1  NaOMe in MeOH,
evaporation of the solvent in vacuo and dry-flash chromato-
3672
J. Chem. Soc., Perkin Trans. 1, 1999, 3667–3675

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graphy of the residue using 1:9 ethyl acetate–hexane as the
mobile phase gave 12b (0.192 g, 40%) as a white solid.
(1H, s); δC: 22.9, 56.1, 87.7, 112.5, 113.0, 114.1, 119.5, 123.4,
147.8, 148.6, 174.6, 204.8; m/z: 282 (35Cl, Mϩ, 100%), 247, 219,
196, 181, 149, 135, 91, 77, 55, 43.
Compound 4c. Method 1. SnCl4 (0.373 g, 1.43 mmol) in
CH2Cl2 (10 cm3) and 4c (0.511 g, 1.3 mmol) in the same solvent
(10 cm3) gave a dark green coloured mixture which was worked
up as for 4a to give a brown oil. Repeated radial chrom-
atography (eluent, 3% ethyl acetate in hexane) gave 13 (0.162 g,
35%) as a white solid, mp 99–100 ЊC (Found: C, 67.6; H, 5.7;
S, 8.6. C20H20SO4 requires C, 67.4; H, 5.7; S, 9.0%); νmax (KBr)/
cmϪ1: 2984, 2928, 2846, 1699, 1591, 1508, 1374, 1253, 1142,
1038; δH: 1.32 (6H, s), 3.84 (3H, s), 3.92 (3H, s), 6.98–7.28 (7H,
m), 8.52 (1H, s); δC: 22.8, 56.0, 87.7, 113.0, 115.0, 119.2, 121.4,
125.4, 126.0, 126.6, 129.0, 138.2, 148.5, 149.8, 174.5, 204.8; m/z
356 (Mϩ), 247, 225, 176, 121, 97, 81, 69, 55, 41 (100%).
The second product (0.032 g, 7%), a yellow oil, was identified
as 10c (Found: C, 67.4; H, 5.9; S, 8.55. C20H20SO4 requires C,
67.4; H, 5.7; S, 9.0%); νmax(film)/cmϪ1: 2962, 1700, 1580, 1498,
1439, 1363, 1262, 1235, 1182, 1138, 1084; δH: 1.50 (6H, s), 3.70
(3H, s), 3.85 (3H, s), 6.84 (1H, d, J = 8.6), 7.02–7.19 (5H, m),
7.81 (1H, d, J = 2.0), 7.9 (1H, dd, J = 2.0, 8.6); δC: 23.3, 55.8,
55.9, 87.6, 100.7, 110.6, 111.4, 121.6, 123.2, 125.6, 126.1, 128.6,
136.1, 148.6, 153.2, 183.8, 204.3; m/z: 356 (Mϩ), 270, 207, 179,
165, 149, 109, 77, 69, 51, 43.
The third product (0.075 g, 15%) isolated as a white solid,
was identified as 14, mp 75–77 ЊC (Found: C, 61.8; H, 4.9; S,
8.3; Cl, 8.8. C20H19SClO4 requires C, 61.5; H, 4.9; S, 8.2; Cl,
9.1%); νmax(KBr)/cmϪ1: 3060, 2977, 2933, 1710, 1603, 1582,
1500, 1439, 1403, 1217, 1182; δH: 1.61 (6H, s), 3.59 (3H, s), 3.90
(3H, s), 6.89 (1H, s), 6.94 (1H, s), 7.08–7.27 (5H, m); δC: 23.2,
55.9, 56.3, 89.4, 105.6, 113.2, 113.4, 120.3, 125.2, 125.8, 126.6,
129.0, 136.3, 147.5, 151.9, 186.9, 204.0; m/z: 390 (35Cl, Mϩ), 355,
327, 304, 278, 223, 213, 199, 149, 139, 121, 109, 91, 77, 69, 51,
41 (100%).
Method 6. A mixture of 4c (0.588 g, 1.5 mmol) and ZnBr2
(0.372 g, 1.65 mmol) in CH2Cl2 (15 cm3) was stirred at room
temperature for 24 h. Reaction work-up as in Method 1 and
radial chromatography using 3% ethyl acetate in hexane gave
10c (0.264 g, 49%) and 14 (0.063 g, 11%).
Compound 4d. SnCl4 (0.628 g, 2.41 mmol) in CH2Cl2 (30 cm3)
and 4d (0.95 g, 2.19 mmol) in the same solvent (30 cm3), at
room temperature, for 12 h gave a brown oil after the usual
work-up. Radial chromatography (eluent, 5% ethyl acetate in
hexanes) produced 16 (0.417 g, 48%) as a white solid, mp 155–
157 ЊC (Found: C, 69.5; H, 6.35; S, 7.7. C23H24SO4 requires C,
69.7, H, 6.1, S, 8.1%); νmax(KBr)/cmϪ1: 2936, 2854, 1687, 1613,
1589, 1502, 1440, 1244, 1211, 1180, 1036; δH: 1.36–1.76 (10H,
m), 3.84 (3H, s), 3.95 (3H, s), 6.99–7.26 (7H, m) and 8.53 (1H,
s); δC: 22.3, 24.7, 31.9, 56.3, 56.5, 90.0, 113.5, 115.9, 119.4,
121.5, 125.9, 126.5, 126.7, 129.3, 138.7, 148.7, 150.0, 175.1,
205.0; m/z: 396 (Mϩ), 307, 277, 262, 201, 183, 134, 123, 101, 77
(100%), 51, 41.
Also isolated was 17 (0.166 g, 13%), mp 105–107 ЊC (Found:
C, 69.6; H, 6.4, S, 7.7. C23H24SO4 requires C, 69.7; H, 6.1; S,
8.1%); νmax(KBr)/cmϪ1: 2937, 1696, 1599, 1542, 1493, 1422,
1274, 1024; δH: 1.33–1.87 (10H, m), 3.69 (3H, s), 3.91 (3H, s),
6.86 (1H, d, J = 8.9), 7.00–7.20 (5H, m), 7.86–7.90 (2H, m);
δC: 21.8, 24.5, 32.1, 55.8, 56.1, 89.5, 101.3, 110.7, 111.9, 121.9,
123.0, 125.6, 126.2, 129.1, 136.3, 148.7, 153.15, 183.9, 204.2;
m/z: 396 (Mϩ), 341, 279, 253, 225, 179, 165, 149, 137, 107, 91
(100%), 73, 63, 43.
Compound 4e. SnCl4 (0.344 g, 1.32 mmol) in CH2Cl2 (15 cm3)
and 4e (0.359 g, 1.20 mmol) in the same solvent (15 cm3) gave a
dark brown oil. Radial chromatography using 5% ethyl acetate
in hexane as eluent yielded 11 (0.274 g, 87%) as a white crystal-
line solid, mp 90–91 ЊC (Found: C, 68.7; H, 6.8; S, 12.0.
Method 2. SnCl4 (0.073 g, 0.28 mmol) in CH2Cl2 (5 cm3) was
added to a mixture (diastereomeric ratio 1:1.2) of 3c and 4c
(0.1 g, 0.25 mmol) in the same solvent (5 cm3). The solution was
stirred at room temperature for 12 h and worked-up as above.
1H NMR analysis of the residue involving integration of the
methyl group resonances at 1.32, 1.50 and 1.61 ppm established
the presence of 13, 10c and 14 in the ratio 7:2:6.
C15H18SO2 requires C, 68.7; H, 6.9; S, 12.2%); νmax(KBr)/cmϪ1
:
2971, 2932, 2874, 1709, 1566, 1465; δH: 1.12 (6H, d, J = 7), 1.38
(6H, s), 3.36 (1H, septet, J = 7), 7.00–7.19 (5H, m); δC: 19.1,
23.0, 28.8, 88.6, 102.1, 125.6, 126.6, 128.9, 136.5, 199.4, 203.9;
m/z: 262 (Mϩ), 247, 191, 163, 121, 99, 71, 51, 43 (100%).
A second experiment on the same scale using isomerically
1
pure 4c was stopped after 30 min. H NMR analysis showed
that the product mixture contained 7% of the isomer 3c (H-5 at
5.94 ppm).
Reaction of 9 with SnCl4
A solution of SnCl4 (0.373 g, 1.43 mmol) in CH2Cl2 (10 cm3)
was added dropwise to 9 (0.502 g, 1.3 mmol) in the same solvent
(10 cm3). The resulting mixture, which developed a dark green
colour, was stirred at room temperature for 12 h and worked up
as for 4a to produce a brown oil. Radial chromatography using
5% ethyl acetate in hexane as eluent gave 10b (0.047 g, 11%) and
12b (0.085 g, 30%).
Method 3. Repetition of the reaction on the same scale as in
Method 1, in toluene at room temperature, overnight produced
a yellow precipitate. This was isolated by filtration, washed with
toluene (2 × 10 cm3), dissolved in ethyl acetate (30 cm3), washed
with water (3 × 15 cm3) and saturated sodium bicarbonate
solution (3 × 15 cm3), dried and concentrated in vacuo to yield
a brown oil. The filtrate was treated in the same manner,
combined with the oil and evaporated. Repeated radial
chromatography of the residue using 5% ethyl acetate in hex-
anes as eluent gave 10c (0.203 g, 44%), 13 (0.046 g, 10%) and 14
(0.129 g, 25%).
Method 4. A solution of 4c (0.98 g, 2.5 mmol) and TiCl4
(0.522 g, 2.75 mmol) in CH2Cl2 (20 cm3) was refluxed under
nitrogen for 24 h. The reaction mixture was worked-up and the
products isolated and purified as in Method 1 to produce 10c
(0.045 g, 5%), 13 (0.17 g, 19%) and 14 (0.289 g, 30%).
Reaction of 10c with SnCl4
A solution of 10c (0.25 g, 0.70 mmol) and SnCl4 (0.20 g, 0.77
mmol) in CH2Cl2 (15 cm3) was stirred at room temperature for
24 h, during which time a yellow precipitate formed; the mix-
ture was then heated at reflux for 48 h. The starting material
(0.23 g, 92%) was isolated following work-up of the reaction
using the procedure employed for 4a.
Method 5. A mixture of 4c (0.589 g, 1.50 mmol) and AlCl3
(0.22 g, 1.65 mmol) in CH2Cl2 (10 cm3) was stirred at room
temperature for 12 h. The reaction was worked-up as in Method
1 and radial chromatography of the residue with 3% ethyl
acetate in hexane as eluent gave 15 (0.12 g, 28%) as a white
solid, mp 120–122 ЊC (Found: C, 59.6; H, 5.4; Cl, 13.0.
C14H15ClO4 requires C, 59.5; H, 5.35; Cl, 12.5%); νmax(KBr)/
cmϪ1: 3082, 3000, 1685, 1593, 1516, 1383, 1250, 1205; δH: 1.41
(6H, s), 3.76 (3H, s), 3.84 (3H, s), 6.83 (1H, s), 7.20 (1H, s), 8.64
Reaction of 12c with diphenyl disulfide
Furanone 12c was isolated as a white solid (0.153 g, 28%) from
5c (0.551 g, 2.20 mmol) and thallium() nitrate11 (1.08 g, 2.42
mmol) in methanol (20 cm3) using the procedure employed
for 12b; mp 132–135 ЊC (Found: C, 67.2; H, 6.7. C14H16O4
requires C, 67.7; H, 6.5%); νmax(KBr)/cmϪ1: 3061, 2968, 1680,
1614, 1594, 1517, 1358, 1258, 1136, 1026; δH: 1.46 (6H, s),
3.89 (3H, s), 3.92 (3H, s), 6.87 (1H, d, J = 8.2), 7.20 (1H, dd,
J. Chem. Soc., Perkin Trans. 1, 1999, 3667–3675
3673

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J = 8.2 and 2.0), 7.34 (1H, d, J = 2.0), 8.41 (1H, s); δC: 23.1,
55.6, 88.7, 109.2, 111.6, 116.3, 117.9, 121.95, 148.6, 149.2,
171.0, 205.0; m/z: 248 (Mϩ), 233, 205, 189, 178, 162, 147, 102,
91, 77.
A solution of 12c (0.198 g, 0.8 mmol), diphenyl disulfide
(0.174 g, 0.8 mmol) and SnCl4 (0.260 g, 1 mmol) in CH2Cl2 (15
cm3) was stirred at room temperature for 24 h and worked up as
for 4a. 1H NMR analysis of the product mixture (0.155 g)
involving integration of the characteristic furanone C-5 proton
resonances at 8.41 and 8.52 ppm, for 12c and 13 respectively,
showed that the latter had been formed in 8% yield.
observed reflections [I > 2σ(I)]. The data were corrected for
decay (1.8%) during processing.
Structure analysis and refinement. Both structures were
solved by Direct Methods and refined by full-matrix least-
squares on F2 with all non-H atoms anisotropic and hydrogen
atoms allowed to ride on their parent atom. For 4c, convergence
was achieved with R = 0.036, wR2 = 0.089. For 13, convergence
was achieved with R = 0.061, wR2 = 0.104. Calculations were
performed on a PC with the SHELXL,26 PLATON27 and
maXus28 suite of programs.‡
Reaction of 12c with benzenesulfenyl chloride
Acknowledgements
A solution of 12c (0.094 g, 0.4 mmol), PhSCl (0.058 g, 0.4
mmol) and SnCl4 (0.13 g, 0.44 mmol) in dry CH2Cl2 (5 cm3) was
stirred at room temperature for 24 h and worked up as for 4a. 1H
NMR analysis of the product mixture (0.076 g) showed that 13
had been formed in 12% yield.
We are grateful to University College Cork for postgraduate
scholarships to C. C. C. and J. P. O’D, to The Federation of
Irish Chemical Industries for a bursary to C. C. C. and to Cork
County Council for a Higher Education Grant to J. P. O’D. We
thank Ms Maureen Kelly for preliminary experiments, Dr
Michael Cronin for developing the synthesis of compound 4e
from 8 and Cork University Foundation for the purchase of an
X-ray diffractometer. Gifts of research materials from Eli Lilly,
S. A.-Irish Branch, Irotec Laboratories, Hickson Pharmachem,
Plaistow Ltd and Pfizer Pharmaceuticals are acknowledged.
Reaction of 12c with AlCl3
A solution of 12c (9 mg, 0.036 mmol) in dry CH2Cl2 (2 cm3) was
added to a suspension of AlCl3 (5.3 mg, 0.04 mmol) in the same
solvent (2 cm3). The mixture was stirred overnight and then
filtered. Work-up of the organic filtrate as above gave a white
solid (8 mg) identified as 12c.
‡ CCDC reference number 207/366. See http://www.rsc.org/suppdata/
p1/1999/3667 for crystallographic files in .cif format.
Reaction of 1c with SnCl4 and AlCl3
A solution of 1c (0.15 g, 0.42 mmol) in dry CH2Cl2 (5 cm3) was
added to SnCl4 (0.12 g, 0.46 mmol) in the same solvent (5 cm3).
The mixture was stirred overnight at ambient temperature,
under nitrogen and worked up in the usual way. Dry-flash
chromatography using 1:19 ethyl acetate–hexane as eluent gave
two fractions. The first (61 mg) was a complex mixture of com-
pounds and no evidence for the presence of 10c either by TLC
analysis with an authentic sample in various solvent systems or
by comparison of its 1HNMR spectrum with those of the mix-
ture could be obtained. The second fraction contained a single
compound identified as 5c (62 mg, 46%) by comparison of its
spectra with those of an authentic sample.
Similarly, reaction of 1c with a suspension of AlCl3 (0.061 g,
0.46 mmol) on the same scale gave a mixture of products from
which 5c (52 mg, 39%) was the only identifiable compound
isolated. 1H NMR examination of the reaction residue failed to
reveal any evidence for the presence of 12c (furanone H-5, 8.41
ppm).
References
1 C. C. Collins, M. F. Cronin, H. A. Moynihan and D. G. McCarthy,
J. Chem. Soc., Perkin Trans. 1, 1997, 1267.
2 For leading references on α-chlorosulfide chemistry, see: B. M.
Dilworth and M. A. McKervey, Tetrahedron, 1986, 42, 3731;
M. A. McKervey and M. Kennedy, Comprehensive Organic
Synthesis, ed. S. V. Ley (Series eds. B. M. Trost and I. Fleming),
Pergamon, Oxford, 1991, vol. 7, pp. 206–214; N. W. A. Geraghty,
Comprehensive Organic Functional Group Transformations, ed. G. W.
Kirby (Series eds. A. R. Katritzky, O. Meth-Cohn and C. W. Rees),
Elsevier, Oxford, 1995, vol. 4, pp. 61–73; P. Magnus and J. D.
Kreisberg, Tetrahedron Lett., 1999, 40, 451. For applications of
α-chlorosulfide chemistry involving other furanone systems, see: N.
De Kimpe, A. Georgieva, M. Boeykens and L. Lazar, J. Org Chem.,
1995, 60, 5262; A. M. E. Richecoeur and J. B. Sweeney, Tetrahedron
Lett., 1998, 39, 8901.
3 T. V. Lee and J. O. Okonkwo, Tetrahedron Lett., 1983, 24, 327;
I. Fleming and J. Igbal, Tetrahedron Lett., 1983, 24, 327; G. C.
Kulkarni, S. N. Karmakar, S. L. Kelkar and M. S. Wadia,
Tetrahedron, 1988, 44, 5189.
4 T. Sakai, A. Yamawaki, H. Ito, M. Utaka and A. Takeda,
J. Heterocycl. Chem., 1986, 23, 2119.
X-Ray crystallographic analysis of 4c and 13
5 E. J. Corey and A. Venkateswarlu, J. Am. Chem. Soc., 1972, 94,
6190; T. H. Greene and P. G. M. Wutts, Protective Groups in Organic
Synthesis, Wiley, New York, 2nd edn., 1991, pp. 68–73.
6 M. A. Blanchette, W. Choy, J. T. Davis, A. P. Essenfield,
S. Masamune, W. R. Roush and T. Sakai, Tetrahedron Lett., 1984,
25, 2183.
7 For typical procedures, see: H. Nemoto, H. Ishibashi, M. Mori,
S. Fujita and K. Fukumoto, J. Chem. Soc., Perkin Trans. 1, 1990,
2835; D. S. Karanewsky, M. F. Malley and J. Z. Gougoutas, J. Org.
Chem., 1991, 56, 3744.
8 T. H. Eberlain, F. G. West and R. W. Tester, J. Org. Chem., 1992, 57,
3479; S. Hormuth and H.-U. Reissig, J. Org. Chem., 1994, 59, 67.
9 B. M. Trost and G. S. Massiot, J. Am. Chem. Soc., 1977, 99, 4405.
10 A. B. Smith III, P. A. Levenberg, P. J. Jerris, R. M. Scarborough Jr.
and P. M. Wovulich, J. Am. Chem. Soc., 1981, 103, 1501.
11 S. Antus, L. Farkas, M. Nogradi and F. Boross, J. Chem. Soc.,
Perkin Trans. 1, 1977, 948.
Crystal data. Compound 4c. C20H21O4SCl, M = 392.88,
Monoclinic, a = 12.291(4), b = 11.696(2), c = 13.693(3) Å,
β = 96.52(2)Њ, U = 1954.1(8) Å3, P2/n (alt. P2/c No. 13), Z = 4,
Dx = 1.335 g cmϪ3. Colourless needles. Crystal dimensions
0.60 × 0.55 × 0.50 mm, µ(Mo-Kα) = 3.24 cmϪ1
.
Compound 13. C20H21O4S, M = 357.43, Monoclinic, a =
5.920(2), b = 16.419(5), c = 18.436(5) Å, β = 93.33(3)Њ, U =
1788.9(9)Å3, P21/n (alt. P21/c No. 14), Z = 4, Dx = 1.327 g cmϪ3
.
Colourless blocks. Crystal dimensions 0.70 × 0.60 × 0.40 mm,
µ(Mo-Kα) = 2.02 cmϪ1
.
Both unit cells were obtained by least-squares refinement on
diffractometer angles for 25 automatically centred reflections,
Mo-Kα graphite monochromated radiation, λ = 0.71069 Å.
Data collection and processing. MACH-3 diffractometer,
ω/2θ mode.
12 M. A. McKervey and P. Ratananukul, Tetrahedron Lett., 1983, 24,
117; D. Fletcher, F. J. Ablenas, A. C. Hopkinson and E. Lee-Ruff,
Tetrahedron Lett., 1986, 27, 4835.
13 A. Padwa, D. E. Gunn and M. H. Osterhout, Synthesis, 1997, 1353;
O. D. Lucchi, U. Miotti and G. Modena, Org. React., 1991, 40, 157.
14 G. A. Russell and G. I. Mikol, in Mechanisms of Molecular
Migrations, ed. B. S. Thyagaragan, Wiley-Interscience, New York,
1968, vol. 1, pp. 157–176.
For 4c, 7280 reflections were measured up to θ = 25Њ, 3445
unique reflections (Rint = 0.044) giving 2362 observed reflections
[I > 2σ(I)]. The data were corrected for decay (7.6%) during
processing. For 13, 6389 reflections were measured up to
θ = 27.5Њ, 4044 unique reflections (Rint = 0.027) giving 1665
3674
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15 (a) T. Iwama, H. Matsumoto, H. Shimizu, T. Kataoka, O. Muraoka
and G. Tanabe, J. Chem. Soc., Perkin Trans. 1, 1998, 1569; (b) T.
Kataoka, Y. Nakamura, H. Matsumoto, T. Iwama, H. Kondo,
H. Shimizu, O. Muraoka and G. Tanabe, J. Chem. Soc., Perkin
Trans. 1, 1997, 309; (c) H. Kosugi, Y. Watanabe and H. Uda, Chem.
Lett., 1989, 1865.
16 For a recent study, see: D. Craig, R. M. Lawrence and D. J.
Tapolczay, Synlett, 1997, 1001.
17 W. Parker, R. A. Raphael and D. I. Wilkinson, J. Chem. Soc., 1958,
3871; R. F. W. Jackson and R. A. Raphael, J. Chem. Soc., Perkin
Trans. 1, 1984, 535; H. J. Bestmann, W. Frank, C. Moll, A.
Pohlschmidt, T. Clarke and A. Goller, Angew. Chem., Int. Ed., 1998,
37, 338.
18 For leading references, see: S. Nagumo, T. Hisano, Y. Kakimoto,
N. Kawahara, M. Ono, T. Furukawa, S. Takeda and H. Akita,
Tetrahedron Lett., 1998, 39, 8109; G. A. Olah, N. J. Head, G. Rasul
and G. K. Surya Prakask, J. Am. Chem. Soc., 1995, 117, 875;
T. H. Lowry and K. S. Richardson, Mechanism and Theory in
Organic Chemistry, Harper and Row, New York, 3rd edn., 1987,
pp. 434–448.
19 O. V. Singh, C. P. Garg and R. S. Kapoor, Tetrahedron Lett., 1990,
31, 2747; T. Kinoshita, K. Ichinose and U. Sankawa, Tetrahedron
Lett., 1990, 31, 7355; L. Crombie and D. A. Whiting, Tetrahedron
Lett., 1992, 33, 3663.
20 G. Capozzi, G. Modena and L. Pasquato, The Chemistry of Sulfenic
Acids and their Derivatives, ed. S. Patai, Wiley, New York, 1990,
ch. 10, pp. 421–423.
21 X. Creary, Chem. Rev., 1991, 91, 1625; N. P. Schepp and J. Wirz,
J. Am. Chem. Soc., 1994, 116, 11749.
22 D. G. McCarthy and J. P. O’Driscoll, unpublished results.
23 M. C. Carreno, J. L. Garcia Ruano, G. Sanz, M. A. Toledo and
A. Urbano, Synlett, 1997, 1241; M. C. Carreno, J. L. Garcia Ruano,
G. Sanz, M. A. Toledo and A. Urbano, Tetrahedron Lett., 1996, 37,
4081.
24 B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell,
Vogel’s Textbook of Practical Organic Chemistry, Longman
Scientific and Technical, Harlow, 5th edn., 1989; D. D. Perrin,
W. L. F. Armarego and D. R. Perrin, Purification of Laboratory
Chemicals, Pergamon, Oxford, 2nd edn., 1980.
25 A. G. M. Barrett, D. Dhanak, G. G. Graboski and S. J. Taylor, Org.
Synth., 1989, 68, 8.
26 G. M. Sheldrick, SHELXL-97, University of Göttingen, Germany,
1998.
27 A. L. Spek, PLATON, University of Utrecht, Holland, 1998.
28 C. J. Gilmore, maXus, University of Glasgow, 1997.
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