Concerning the synthesis and enantioselective rearrangements of episulfoxides

Article abstract of DOI:10.1039/a908391j

A novel synthesis of episulfoxides having the norbornane skeleton is possible by use of a rhodium catalyst to effect SO transfer from from-stilbene episulfoxide to norbornene or norbornadiene. Analogous Rh₂(OAc)₄ catalysed sulfur transfer to these alkenes is also possible using propylene sulfide as the sulfur source. These methods did not give useful yields of products with alternative types of alkene substrate. A novel type of chiral lithium amide base reaction, involving the rearrangement of certain types of symmetrical ring-fused episulfoxides, gives alkenyl sulfoxide products in up to 88% ee. The structures of the products, including absolute stereochemistry, were assigned based on X-ray crystal structure determinations. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a908391j

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Concerning the synthesis and enantioselective rearrangements of
episulfoxides
Alexander J. Blake, Paul A. Cooke, Jackie D. Kendall, Nigel S. Simpkins* and
Susan M. Westaway
1
School of Chemistry, The University of Nottingham, University Park, Nottingham,
UK NG7 2RD
Received (in Cambridge, UK) 20th October 1999, Accepted 9th November 1999
A novel synthesis of episulfoxides having the norbornane skeleton is possible by use of a rhodium catalyst to effect
SO transfer from trans-stilbene episulfoxide to norbornene or norbornadiene. Analogous Rh2(OAc)4 catalysed sulfur
transfer to these alkenes is also possible using propylene sulfide as the sulfur source. These methods did not give
useful yields of products with alternative types of alkene substrate.
A novel type of chiral lithium amide base reaction, involving the rearrangement of certain types of symmetrical
ring-fused episulfoxides, gives alkenyl sulfoxide products in up to 88% ee. The structures of the products, including
absolute stereochemistry, were assigned based on X-ray crystal structure determinations.
Introduction
Some time ago we became interested in the possibility of apply-
ing our chiral lithium amide base methodology to the asym-
metric synthesis of cyclic sulfoxides.1 Although initial results
using sulfoxides having 4–6-membered rings gave interest-
ing results, the enantioselectivities in these novel symmetry-
breaking reactions were somewhat modest (<70% ee).2 More
recently we recognised the possibility of employing 3-membered
ring sulfoxides (episulfoxides) in similar asymmetric chemistry,
and were able to attain somewhat better enantioselectivities
for the chiral base mediated rearrangement of such systems.3
Realisation of a novel enantioselective transformation of
episulfoxides highlighted the problems associated with the syn-
thesis of these relatively rare types of heterocycle. We were
prompted to examine new methods for the synthesis of epi-
sulfoxides (and the precursor episulfides) which would be more
direct, and hopefully more efficient, than existing methods. This
study led to the discovery of a new rhodium-catalysed S- and
SO-transfer process, which was applied to the synthesis of
norbornane episulfides and episulfoxides.4
Scheme 1 Reagents and conditions: i, MCPBA, CH2Cl2, RT (86%); ii,
Ph3PS, TFA, PhH (49–60%); iii, Oxone, MeOH, H2O (81%).
Since aspects of the synthesis and asymmetric rearrangement
of episulfoxides are very intimately interrelated, we have chosen
to describe full details of our studies in both of these areas in
one full account.
Results and discussion
(i) Conventional synthesis of episulfoxides
Scheme 2 Reagents and conditions: i, NaH, BnBr (ca. 96%); ii,
MCPBA, CH2Cl2, RT (96%); iii, NH4SCN, CAN; iv, MeSO2Cl, py, then
NaOHaq (60% from 5/6); v, Oxone, MeOH, aq. NaHCO3 (75–78%); vi,
VO(acac)2, TBHP, CH2Cl2 (58%); viii, NaH, BnBr.
For our chiral base studies we required prochiral ring-fused
episulfoxides, which upon treatment with base and then an
alkylating agent would furnish chiral alkenyl sulfoxides, vide
infra. We chose to focus on episulfoxides having the norbornane
skeleton, as well as episulfoxides derived from two different
types of 4-substituted cyclopentene. The latter types were pre-
pared as shown in Schemes 1 and 2 via the intermediacy of the
corresponding epoxides.
Completely stereoselective epoxidation of the cyclopentenyl
sulfone 1 gave the known epoxide 2,5 which was then converted
into the desired episulfoxide 3 by treatment with triphenyl-
phosphine sulfide in the presence of trifluoroacetic acid, and
then oxidation with Oxone.6 In our hands, the use of potas-
sium thiocyanate or thiourea for the conversion of epoxide 2
into the corresponding episulfide was not effective.7,8 Also, a
method which employs ammonium thiocyanate in the presence
of ceric ammonium nitrate (CAN) gave only the product of
epoxide opening by thiocyanate in 92% yield.9 Although this
intermediate could be converted into the desired episulfide by
mesylation and treatment with base, this rather laborious
sequence was barely more effective than the triphenylphosphine
sulfide method (although purification was a little easier).10 This
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163
This journal is © The Royal Society of Chemistry 2000
153

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sulfide 10 using Oxone gave the desired episulfoxide 11 as a
single stereoisomer in good yield.
Although a range of alternative methods were then tested
for the synthesis of episulfides from either norbornene or
norbornadiene, none proved very effective. In the case of
norbornadiene, standard approaches involving the inter-
mediacy of an epoxide are fraught with problems due to neigh-
bouring group participation from the remaining alkene.
The difficulties experienced in securing supplies of ring-fused
episulfoxides prompted us to explore possible new, and more
direct, avenues for their synthesis.
(ii) Synthesis of episulfoxides by rhodium catalysed SO-transfer
If direct transfer of sulfur monoxide to an alkene could be
effected in a straightforward and efficient manner, then a more
direct access to episulfoxides than the methods described above
would clearly be possible. This problem has occupied several
research groups, and although singlet SO has been added to
allene and but-2-yne in an argon matrix at 12 K,14 no practical
and general procedure for episulfoxide preparation has emerged
to date. In one significant report Adam and co-workers have
described reactions employing thiophene endoperoxide 12 to
Fig. 1 A displacement ellipsoid plot of 3 showing the atom numbering
scheme. Ellipsoids are drawn at the 50% probability level. Data were
acquired at 298 K.
method was however adopted in the case of the epoxides shown
in Scheme 2, vide infra.
Although the stereochemistry of the starting epoxide 2 was
not in doubt, we chose to carry out an X-ray structure
determination of the product episulfoxide 3 in order to be abso-
lutely certain of the relative stereochemistry, Fig. 1. As can be
seen, this structure confirmed that the epoxide to episulfide
conversion had proceeded with inversion of configuration, and
also that sulfoxidation had occurred on the less hindered
convex face of the ring-fused episulfide.
In the case of episulfoxides 7 and 8, we were content to
employ a route which provided intermediate epoxides, and
thence episulfides, in a non-stereoselective fashion, so as to
allow screening of two diastereomeric series in subsequent
chiral base reactions. Epoxidation of the benzyl ether derived
from alcohol 4 gave a 3:2 mixture of the epoxides 5:6. These
could not be readily separated, but were best converted into the
corresponding episulfides by the ammonium thiocyanate–CAN
method described earlier. This gave the desired syn and anti
episulfides in a 60% combined yield, and at this stage they were
separated and oxidised to give the pure episulfoxides 7 and 8 as
single stereoisomers.
The stereochemical assignments shown in Scheme 2 were
made following an alternative stereocontrolled synthesis of 6,
which employed the known directed epoxidation of 4 using the
Sharpless VO(acac)2 protocol.11 Conversion of 6 into the
corresponding episulfide (not illustrated) then allowed us to
assign the stereochemistry of the intermediate episulfides and
the derived episulfoxides.
The synthesis of norbornane-derived episulfoxides presented
special problems. We initially adopted a direct, although low-
yielding, synthesis of the episulfide 10, which involved reaction
of norbornadiene 9 with sulfur in a mixture of DMF, NH3 and
pyridine at 100 ЊC, Scheme 3.12 Although the reported yield of
effect sulfur transfer to alkenes, thus resulting in episulfide
formation.15 More recently, the same research group has
demonstrated an alternative thioepoxidation procedure which
relies on photolytic sulfur atom transfer from aromatic sulfines
13.16 Neither of these methods appears to be fully developed as
a general synthetic method and neither offered the convenience
and high yields that we were aiming for.
In contrast to these sulfur transfer reactions, direct SO trans-
fer to an alkene remains problematic because most sources of
SO furnish the triplet ground state, which appears not to give
episulfoxide products with alkenes (vide infra).17 However, the
thermolysis of certain episulfoxides, including 14, can result in
delivery of SO to dienes (resulting in the formation of dihydro-
thiophene S-oxides).18 This type of process appeared to be
worthy of further examination in the context of SO transfer to
alkenes.
Our initial plans involved testing the idea that a thermally
labile episulfoxide might effect SO transfer to an alkene to give
an episulfoxide product. Aromatic episulfoxides are known to
be especially thermally labile, for example trans-stilbene epi-
sulfoxide undergoes loss of SO on gentle heating in CH2Cl2.
Under such conditions the ring-fused episulfoxide 3 illustrated
in Scheme 1 appeared relatively stable. However, warming mix-
tures of (easily available) stilbene episulfoxide with alkene (or
alkyne) substrates, ranging from electron rich vinyl ethers to
electron poor α,β-unsaturated carbonyl compounds, resulted
in no product episulfoxide formation (or any other sulfur-
containing products). This was not too surprising in view of
previous studies, but emphasized the complete failure of SO
transfer, even under very mild conditions. Clearly a radically
different approach to the SO-transfer problem was required.
Further examination of the literature revealed that
transition-metal complexes of SO have been described and, in
the case of (Ph3P)2Pd(SO), have been shown to effect SO trans-
fer to a diene.19 Consequently we repeated our attempts to
transfer SO from stilbene episulfoxide to norbornadiene in the
presence of various transition-metal catalysts. We were
delighted to find that the use of either palladium catalysts, such
as Pd(dba)2 and Pd(MeCN)2Cl2, or rhodium catalysts, includ-
ing (Ph3P)3RhCl and Rh2(OAc)4, in CH2Cl2 resulted in the
Scheme 3
10 by this method is 19%, in our hands the reaction was some-
what less efficient, even in the presence of the free radical
inhibitor 2,6-di-tert-butyl-4-methylphenol.13 Oxidation of epi-
154
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formation of substantial amounts of the desired episulfoxide
product. Optimum reaction conditions involved reaction of
norbornene 15 or norbornadiene 9 with an excess (typically
three equivalents) of stilbene episulfoxide and ca. 2–3 mol%
of Rh2(OAc)4 in CH2Cl2 at room temperature, Scheme 4.
ide and in its delivery to the alkene. One possible reaction
mechanism, in line with findings by Schenk,21 would involve
coordination of the metal to the sulfur lone pair of the starting
episulfoxide (both coordination to sulfur or oxygen appears
possible) and generation of a M᎐SO complex, by loss of
᎐
stilbene, which is then capable of sulfoxidation of a strained
alkene.
During the course of these studies it was also found that
sulfur transfer to norbornene and norbornadiene can also be
catalysed by Rh2(OAc)4, Scheme 6. In this case we used the
Scheme 6 Reagents and conditions: i, propylene sulfide, Rh2(OAc)4
toluene, ∆.
commercially available propylene sulfide as a convenient sulfur
source, the reaction requiring somewhat more vigorous reaction
conditions compared with the SO transfer. Each of the product
episulfides was isolated as a single exo-stereoisomer, the stereo-
chemical assignments being made by comparison with liter-
ature data for 10. Although the yields of episulfides are not high
this new method appears to offer the most practical and oper-
ationally facile route to these compounds to date. As in the case
of SO transfer, we were unable to apply this new process to
other alkenes, and obtained only traces of product in reactions
involving cyclopentadiene dimer.
Scheme 4 Reagents and conditions: i, stilbene episulfoxide, Rh2(OAc)4
CH2Cl2, RT.
In both cases only the exo-orientated episulfoxide products
were obtained, although in each case these were formed as
easily separable mixtures of stereoisomers at sulfur. That this
was indeed the case for the unsaturated products 11 and 18 was
demonstrated by their independent oxidation, using the
procedure very recently described by Taylor and co-workers,20
to give the same epoxy-episulfone 19, Scheme 5.
(iii) Asymmetric rearrangement of episulfoxides using chiral
lithium amide bases
Several groups have demonstrated that on treatment with a
suitable base, especially LDA, episulfoxides undergo rearrange-
ment to form intermediate alkenyl sulfenate anions, which can
then be alkylated to give alkenyl sulfoxide products, e.g. Scheme
7.22
Scheme 5 Reagents and conditions: i, Oxone, CF3COCH3.
Unfortunately, this unprecedented sulfoxidation procedure
seems not to be of general utility. Even systems incorporating a
reactive norbornene-type alkene, such as the readily available
Diels–Alder adduct 20, gave none of the desired episulfoxide
Scheme 7
We became interested in the possibility of employing chiral
base reactions for the asymmetric transformation of episulfox-
ides on recognising that such a reaction might lead to synthetic-
ally useful non-racemic alkenyl sulfoxides. The substrates
required are the types of systems described above, i.e. ring-
fused episulfoxide derivatives incorporating at least one
pro-stereogenic centre.
Chiral base reactions of 3, involving treatment with lithium
amide 28, followed by addition of iodomethane, gave the
desired alkenyl sulfoxide 24 in good chemical yield (79%) but in
low ee (ca. 10%), Scheme 8. However, we were delighted to find
that analogous reactions involving the bis-lithium amide 29
gave the sulfoxide 24 as a mixture of diastereomers (epimeric at
sulfur, ca. 2:1 ratio) in 85% yield,23 each of which was formed in
82% ee. As expected, the use of the enantiomeric base (ent-29)
gave the opposite sense of asymmetric induction, leading to the
enantiomer of 24 in similar chemical yield and ee.
adduct. Perhaps in this case the imide functionality inter-
feres with the catalyst. In the case of commercially available
norbornadiene 21 we were able to isolate 16% of a mixture of
products tentatively assigned as the epimeric episulfoxides 22.
A wide range of other alkenes were also tried, but only cis-
cyclooctene and cyclopentadiene dimer gave traces of products,
in quantities too small to fully characterise, but which appeared
to be the desired episulfoxide products on the basis of IR or
mass spectral evidence.
This observation, that only rather strained alkenes react well
in sulfur transfer reactions seems to parallel similar findings of
Adam,16 but at present we have no convincing explanation for
this result.
Although the chiral product 24 was generated in good ee, the
presence of two diastereomeric sulfoxides was an unwanted
complication. Oxidation using Oxone to give the corre-
sponding sulfone 25 facilitated enantiomeric enrichment by
recrystallisation, and also enabled an X-ray crystallographic
Since, in the absence of Rh2(OAc)4, stilbene episulfoxide is
quite stable at room temperature, the metal catalyst must be
involved in both the extrusion of SO from the starting episulfox-
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Table 1 Rearrangement of sulfoxide 11a
Sulfoxide Sulfone Ee(%)([α]D)
Base RX
(%)
(%)
sulfone
Configuration
28
29
29
MeI
MeI
34 (73)
34 (75)
36 (71)
36 (70)
37 (70)
43 (Ϫ19)
62 (ϩ28)
66 (ϩ6)
1R,4S
1S,4R
1S,4R
PhCH2Br 35 (62)
a The absolute configurations shown above are for products obtained
using base 28.
Fig. 2 A displacement ellipsoid plot of 25 showing the atom number-
ing scheme. Ellipsoids are drawn at the 50% probability level. Data were
acquired at 150 K. The absolute configuration shown was established
by refinement of the Flack parameter to a final value of Ϫ0.05(8).
determination, as shown in Fig. 2, which established the
absolute configuration of this series of compounds.
The enantioselective transformation of 3 could also be
carried out using benzyl bromide in place of iodomethane,
which provided alkenyl sulfoxide 26 in 72% yield. Oxidation of
this diastereomeric mixture to the corresponding sulfone 27
again enabled determination of the ee (85%) by HPLC, using
an appropriate chiral stationary phase.
The transformation of episulfoxide 3 into alkenyl sulfoxide
26 proved more reliable if an in situ quench procedure was
employed, involving addition of a mixture of episulfoxide and
alkylating agent to the chiral base. It is possible that this
method minimizes side reactions, or perhaps facilitates smooth
alkylation by avoiding build up of insoluble sulfinate salts. In
any case, we adopted this type of in situ quench procedure
for all subsequent work. The use of chlorotrimethylsilane as
electrophilic quench gave no isolable products, and alternative
alkylating agents also proved unsatisfactory, for example allyl
bromide gave very low yields of impure product.
Scheme 9 Reagents and conditions: i, chiral base 29, THF, Ϫ78 ЊC,
MeI or PhCH2Br; ii, Oxone, MeOH, H2O.
with the earlier results for episulfoxide 3. Notably, the chiral
base selectivity in this reaction results in the conversion of
diastereomeric starting materials into enantiomeric products,
vide infra. Finally, we conducted a study of the chiral base
rearrangement to episulfoxides 11 and 17, having the norbor-
nane skeleton, the results of which are shown in Tables 1 and 2.
In the case of rearrangement of unsaturated episulfoxide 11
we found that the enantiomeric excess was somewhat lower
than for the cyclopentene types, being typically around 65%
using base 29. The immediate sulfoxide products 34 and 35 were
generated as mixtures of diastereomers at the sulfinyl centre (at
most ca. 3:1 ratio) and enantiomeric excess determination was
therefore best carried out after oxidation to the corresponding
alkenyl sulfones. As in the previous examples the simpler base
28 gave inferior results in terms of asymmetric induction.
We then proceeded to examine analogous transformations of
the corresponding saturated episulfoxide, the results of which
are shown in Table 2.
We went on to examine the analogous chiral base transform-
ations of the two diastereomeric episulfoxides 7 and 8, Scheme
9. In each case shown, the starting episulfoxide was converted
Somewhat surprisingly, in this series of reactions the simpler
base 28 gave better levels of enantioselectivity than the bis-
lithium amide 29, the latter base giving very poor results, even
in the presence of added LiCl. As expected, these two bases
gave products of opposite configuration.24 In the reactions
which employed MeI, the sulfoxide products proved difficult to
separate by HPLC, and so again we carried out oxidation to the
corresponding sulfone prior to assay for ee. However, all four
stereoisomers in the mixture resulting from S-benzylation were
separated by HPLC and so the ee assay could be carried out
directly. A sample of the sulfone 40 of 76% ee was recrystallised
from a petroleum ether–EtOAc–Et2O mixture, to furnish crys-
tals which were the subjected to X-ray crystallographic analysis.
Scheme 8 Reagents and conditions: i, chiral base 28 or 29, THF,
Ϫ78 ЊC, MeI or PhCH2Br; ii, Oxone, MeOH, H2O.
into the alkenyl sulfoxide product, 30 or 32 in 85–88% ee, as
determined by HPLC analysis of the derived alkenyl sulfones
31 and 33. It should be noted that the absolute configurations
shown for the products in Scheme 9 are based solely on analogy
156
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Table 2 Rearrangement of sulfoxide 17a
Base
RX
Sulfoxide (%)
Ee(%)([α]D) sulfoxide
Sulfone (%)
Ee(%)([α]D) sulfone
Configuration
29
MeI
MeI
MeI
PhCH2Br
PhCH2Br
PhCH2Br
38 (63)
38 (59)
38 (82)
39 (50)
39 (46)
39 (82)
—
—
—
<5
17 (Ϫ10)
70 (ϩ39)
40 (91)
40 (98)
40 (99)
—
—
—
<5
29 ϩ LiCl
27 (Ϫ24)
76 (ϩ60)
—
—
—
1R,4S
1S,4R
28
29
29 ϩ LiCl
28
1R,4S
1S,4R
a The absolute configurations shown above are for products obtained using base 28 (note the change in bridge priorities gives reveresed Cahn–
Ingold–Prelog stereochemical descriptors compared to Table 1).
the relative effectiveness of the two chiral bases 28 and 29 seen
on swapping between the closely related norbornane episulfox-
ides 11 and 17 is puzzling. Unfortunately, the difficulty in
accessing further episulfoxides, along with the likelihood of
achieving only modest levels of induction, has deterred us from
further study of these systems.
Experimental
General details
Except for the following additions, the general procedures
used were as described previously.25 In the present work all
NMR spectra were run in CDCl3 and all specific rotation
measurements were taken at ambient temperature (20–25 ЊC).
Fig. 3 A displacement ellipsoid plot of 40 showing the atom number-
Enantiomeric excess determinations were carried out using the
columns indicated, and using UV detection at either 254 nm,
for the cyclopentene derivatives, or 210 nm for the norbornane
systems. A Waters 600E System controller was employed, and
the data were processed using an HP-3D DOS Chemstation.
ing scheme. Ellipsoids are drawn at the 50% probability level. Data were
acquired at 150 K. The absolute configuration shown was established
by refinement of the Flack parameter to a final value of 0.0(2).
The result of this structure determination, which establishes the
absolute configuration of 40 (and therefore 38 and 39), is shown
in Fig. 3.
Comparison of the sense of asymmetric induction revealed
by Fig. 2 and 3 shows that the chiral base is consistent in remov-
ing a particular enantiotopic hydrogen for each system—i.e.
compare representations 41 and 42 for the selectivity proven
[(1-Methylcyclopent-3-en-1-yl)sulfonyl]benzene 1
Butyllithium (38.5 ml of a 1.6 M solution in hexanes, 61.7
mmol) was added dropwise to a solution of ethyl phenyl sulfone
(5.00 g, 29.4 mmol) in THF (50 ml) at Ϫ30 ЊC under nitrogen.
The solution was warmed to 0 ЊC and cis-1,4-dichlorobut-2-ene
(3.15 ml, 29.4 mmol) was added. The reaction mixture was
stirred at 0 ЊC for 3 h, poured into water (50 ml) and extracted
with EtOAc (3 × 100 ml). The combined extracts were dried
(MgSO4) and the solvents removed under reduced pressure.
Chromatography (petroleum ether–EtOAc 7:3), followed by
recrystallisation from petroleum ether–EtOAc gave 1 as a white
crystalline solid (5.00 g, 77%), mp 66–67 ЊC; δH (250 MHz) 1.43
(3H, s, CH3), 2.21 (2H, d, J 15.0 Hz, 2 × =CHCHH), 3.29 (2H,
for bis-lithium amide base 29. Unfortunately, we have no
comparison data for this base in reactions with other types of
sulfoxide, which we carried out some time previously, which
were most effective with camphor-derived bases.
d, J 15.0 Hz, 2 × ᎐CHCHH), 5.59 (2H, s, 2 × ᎐CH), 7.53–7.68
᎐
᎐
(3H, m, PhH) and 7.92 (2H, d, J 7.0 Hz, PhH); δC (68 MHz)
23.7 (CH3), 41.5 (CH2), 67.8 (C), 127.5 (CH), 128.8 (CH), 129.9
(CH), 133.5 (CH) and 136.4 (C); m/z (EI) 223 (5%, MHϩ),
143 (7), 125 (9), 82 (16), 81 (100), 80 (76) and 79 (39) (Found
(CI): M ϩ NH4ϩ, 240.1060. C12H14O2S ϩ NH4 requires M,
240.1058).
Conclusion
Our initial interest in asymmetric transformation of episulfox-
ides, combined with the difficulty in preparing these com-
pounds by existing routes, has led us to explore alternative
methods for their synthesis. Unfortunately, a new transition-
metal catalysed approach for direct SO transfer to alkenes has
proved to be of very narrow application, and this has restricted
the possibilities to explore the chiral base chemistry of a wide
range of episulfoxides. Of the few systems explored, the chiral
lithium amide base rearrangement appears to give only moder-
ate selectivities, mainly in the range 65–85% ee. The change in
(1ꢀ,3ꢀ,5ꢀ)-3-Methyl-3-(phenylsulfonyl)-6-oxabicyclo[3.1.0]-
hexane 2
Solid 3-chloroperoxybenzoic acid (14.4 g, 50 mmol) was added
to a solution of 1 (5.00 g, 22.5 mmol) in CH2Cl2 (50 ml) at 0 ЊC,
and the reaction mixture stirred at room temperature for 18 h.
The reaction mixture was washed with saturated aqueous
Na2SO3 (100 ml), saturated aqueous NaHCO3 (100 ml), dried
(MgSO4) and the solvent removed under reduced pressure.
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163
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Recrystallisation from petroleum ether–EtOAc gave 2 as a
white crystalline solid (4.63 g, 86%), mp 96–98 ЊC (Found: C,
60.50; H, 6.21. C12H14O2S requires C, 60.50; H, 5.88%); δH (400
MHz) 1.39 (3H, s, CH3), 1.92 (2H, d, J 15.0 Hz, 2 × OCH-
CHH), 2.73 (2H, d, J 15.0 Hz, 2 × OCHCHH), 3.63 (2H, s,
2 × OCH), 7.57 (2H, t, J 7.5 Hz, PhH), 7.68 (1H, t, J 7.5 Hz,
PhH) and 7.86 (2H, d, J 7.5 Hz, ArH); δC (68 MHz) 26.4 (CH3),
35.6 (CH2), 57.8 (CH), 66.3 (C), 128.9 (CH), 129.9 (CH), 133.8
(CH) and 135.9 (C); m/z (CI) 239 (6, MHϩ), 183 (2), 143 (13),
125 (9), 97 (100), 79 (30), 77 (27), and 69 (53).
compound and benzyl bromide, used in the next reaction with-
out purification (10.44 g, estimated to contain 6.24 g of the
benzyl ether, 96%). A small portion was purified by chrom-
atography (petroleum ether–Et2O 19:1) and gave the title com-
pound as a colourless oil; νmax (film)/cmϪ1 3053, 2926, 2848,
1615, 1496, 1453, 1362, 1272, 1100, 1028, 735 and 696; δH (400
MHz) 2.12 (2H, m, 3-HH, 5-HH), 2.48 (2H, m, 3-HH, 5-HH),
2.61 (1H, m, 4-H), 3.37 (2H, d, J 7.0 Hz, PhCH2OCH2), 4.52
(2H, s, PhCH ), 5.65 (2H, s, 2 × ᎐CH) and 7.27–7.45 (5H, m,
᎐
2
Ph); δC (100 MHz) 36.0 (CH2), 36.8 (CH), 72.9 (CH2), 74.7
(CH2), 127.4 (CH), 127.6 (CH), 128.3 (CH), 129.5 (CH) and
138.7 (C); m/z (EI) 188 (15, Mϩ), 157 (14), 97 (45), 91 (95), 79
(100) and 67 (71) (Found Mϩ, 188.1209. C13H16O requires M,
188.1201).
(1ꢀ,3ꢁ,5ꢀ)-3-Methyl-3-(phenylsulfonyl)-6-thiabicyclo[3.1.0]-
hexane
Triphenylphosphine sulfide (4.94 g, 16.8 mmol) and trifluoro-
acetic acid (0.64 ml, 8.4 mmol) were added to a solution of 2
(2.00 g, 8.39 mmol) in dry benzene (25 ml) under nitrogen. The
solution was heated to reflux for 3 h and then cooled to room
temperature and the solvent removed under reduced pressure.
The residue was taken up in Et2O (2 × 100 ml), filtered and the
filtrate evaporated under reduced pressure. Chromatography
(petroleum ether–CH2Cl2 4:1) followed by recrystallisation
from petroleum ether–EtOAc gave the title compound as a
white crystalline solid (1.27 g, 60%); mp 114–115 ЊC (Found: C,
56.73; H, 5.61. C12H14O2S2 requires C, 56.66; H, 5.55%); νmax
(CHCl3)/cmϪ1 2942, 2862, 1586, 1462, 1448, 1303, 1152, 1126,
1086, 1069 and 980; δH (250 MHz) 1.51 (3H, s, CH3), 2.23
(2H, dd, J 15.0, 4.0 Hz, 2 × SCHCHH), 2.73 (2H, d, J 15.0
Hz, 2 × SCHCHH), 3.36 (2H, d, J 4.0 Hz, 2 × SCH), 7.52–7.70
(3H, m, PhH) and 7.84 (2H, m, PhH); m/z (EI) 254 (2, Mϩ),
190 (23), 113 (47), 97 (12), 85 (13), 81 (65), 80 (55), 79 (100)
and 77 (38) (Found Mϩ, 254.0432. C12H14O2S2 requires M,
254.0435).
(ii) Epoxidation to give (1ꢀ,3ꢀ,5ꢀ)- and (1ꢀ,3ꢁ,5ꢀ)-3-[(phenyl-
methoxy)methyl]-6-oxabicyclo[3.1.0]hexane 5 and 6. Solid 3-
chloroperoxybenzoic acid (6.34 g, 18.4 mmol) was added to a
solution of 4-[(phenylmethoxy)methyl]cyclopentene (1.73 g, 9.2
mmol) in CH2Cl2 (100 ml). After 40 min, the solution was
washed with saturated aqueous Na2SO3 (50 ml), saturated
aqueous NaHCO3 (2 × 100 ml), dried (MgSO4), and the solvent
removed under reduced pressure. Chromatography (petroleum
ether–EtOAc 9:1) gave a 3:2 (5:6) mixture of diastereoisomers
of the title compound as a colourless liquid (1.81 g, 96%); νmax
(film)/cmϪ1 3027, 2927, 2852, 1496, 1453, 1363, 1205, 1092,
835, 736 and 698; δH (400 MHz) 1.45–2.40 (5H ϩ 5H, m, 2 ×
OCHCH2, 3-H), 3.31 (2H, d, J 8.0 Hz, PhCH2OCH2, minor),
3.39 (2H, d, J 5.5 Hz, PhCH2OCH2, major), 3.46 (2H, s,
2 × OCH, major), 3.47 (2H, s, 2 × OCH, minor), 4.47 (2H, s,
PhCH2, minor), 4.49 (2H, s, PhCH2, major) and 7.26–7.40
(5H ϩ 5H, m, Ph); δC (68 MHz) 30.4 (CH2), 31.0 (CH2), 33.0
(CH), 35.2 (CH), 56.9 (CH), 58.4 (CH), 72.4 (CH2), 72.7 (CH2),
72.8 (CH2), 76.7 (CH2), 127.4 (2 × CH), 127.5 (2 × CH), 128.2
(2 × CH), 138.4 (C) and 138.5 (C); m/z (EI) 204 (1, Mϩ), 186
(2), 113 (22), 92 (35), 91 (100), 77 (13) and 67 (25) (Found Mϩ,
204.1155. C13H16O2 requires M, 204.1150).
Typical episulfide oxidation procedure: preparation of
(1ꢀ,3ꢁ,5ꢀ,6ꢀ)-3-methyl-3-(phenylsulfonyl)-6-thiabicyclo[3.1.0]-
hexane 6-oxide 3
A solution of Oxone (2.20 g, 3.57 mmol) in water (10 ml) was
added to a solution of the episulfide (909 mg, 3.57 mmol) in
methanol (10 ml), and stirred for 5 min. The reaction mixture
was diluted with water (10 ml), extracted with CH2Cl2 (3 × 20
ml), dried (MgSO4) and the solvents removed under reduced
pressure. Chromatography (EtOAc–MeOH 19:1) followed by
recrystallisation from petroleum ether–EtOAc gave 3 as a white
crystalline solid (785 mg, 81%); mp 128–129 ЊC (Found: C,
53.27; H, 5.48. C12H14O3S2 requires C, 53.31; H, 5.22%); νmax
(CHCl3)/cmϪ1 2934, 1586, 1462, 1448, 1306, 1154, 1120, 1084
and 972; δH (400 MHz) 1.36 (3H, s, CH3), 2.26 (2H, m, 2 × SCH-
CHH), 2.40 (2H, d, J 15.5 Hz, 2 × SCHCHH), 3.35 (2H, m,
2 × SCH), 7.58 (2H, t, J 7.5 Hz, PhH), 7.70 (1H, t, J 7.5 Hz,
PhH) and 7.81 (2H, d, J 7.5 Hz, PhH); δC (68 MHz) 23.4 (CH3),
36.0 (CH2), 53.8 (CH), 70.5 (C), 129.3 (CH), 129.8 (CH), 134.3
(CH) and 135.8 (C); m/z (FAB) 271 (70, MHϩ), 270 (4) and 129
(26) (Found MHϩ, 271.0465. C12H14O3S2 ϩ H requires M,
271.0463); m/z (EI) 143 (7), 128 (5), 110 (7), 97 (6), 81 (100), 80
(50) and 77 (29).
Synthesis of episulfoxides 7 and 8
(i) Conversion of epoxides 5 and 6 into the corresponding
episulfides. A solution of the mixture of diastereoisomers 5 and
6 (5.44 g, 26.7 mmol), ammonium thiocyanate (6.09 g, 80.1
mmol) and ammonium cerium() nitrate (2.93 g, 5.35 mmol)
t
in BuOH (70 ml) was heated to reflux for 1.5 h. The solvent
was then removed and CHCl3 (100 ml) was added to the
residue which was then filtered through Kieselguhr and the
solvent removed under reduced pressure to leave a 3:2 mixture
of (1R*,2R*,4R*)- and (1R*,2R*,4S*)-4-[(phenylmethoxy)-
methyl]-2-hydroxycyclopentyl thiocyanate as a yellow oil (6.36
g, 91%); νmax (film)/cmϪ1 3420, 2934, 2861, 2153, 1454, 1364,
1094, 740 and 699; δH (400 MHz) 1.50–2.60 (6H ϩ 6H, m),
3.26–3.57 (3H ϩ3H, m), 4.17 (1H, m, CHOH, minor), 4.26
(1H, m, CHOH, major), 4.50 (2H, s, PhCH2, major), 4.55 (2H,
s, PhCH2, minor) and 7.25–7.40 (5H ϩ 5H, m, Ph); m/z (FAB)
264 (14, MHϩ), 154 (33), 136 (29), 107 (26), 91 (100), 69 (38)
and 55 (51) (Found MHϩ, 264.1060. C14H17NO2S ϩ H requires
M, 264.1058).
Synthesis of epoxides 5 and 6
Methanesulfonyl chloride (3.15 ml, 40.7 mmol) was added to
a solution of the above thiocyanohydrins (6.36 g, 24.2 mmol) in
pyridine (15 ml) at 0 ЊC. The reaction mixture was quenched
with water (2 ml) after 2.5 h and then diluted with CH2Cl2 (30
ml). The organic layer was washed with 2 M HCl (3 × 50 ml),
saturated aqueous CuSO4 (2 × 50 ml), dried (MgSO4), and the
solvent removed under reduced pressure to leave a 3:2 mixture
of (1R*,2R*,4R*)- and (1R*,2R*,4S*)-2-[(methylsulfonyl)-
oxy]-4-[(phenylmethoxy)methyl]cyclopentyl thiocyanate as a
brown oil (7.44 g, 90%); νmax (film)/cmϪ1 3029, 2937, 2862, 2155,
1453, 1360, 1177, 1095, 969, 884, 742 and 700; δH (400 MHz)
1.60–2.62 (5H ϩ 5H, m), 3.07 (3H, s, CH3, major), 3.08 (3H, s,
(i) Benzylation of 4 to give 4-[(phenylmethoxy)methyl]cyclo-
pentene. A solution of alcohol 4 (3.37 g, 34.4 mmol) in THF (20
ml) was added to a stirred suspension of sodium hydride (2.31
g, 60% dispersion in oil, 58 mmol, washed with petroleum
ether) in THF (80 ml) under nitrogen, followed after 1.5 h by
benzyl bromide (6.2 ml, 52 mmol). After the alcohol had been
consumed by TLC (18 h), the mixture was quenched with
MeOH (1 ml) and diluted with water (50 ml). The layers were
separated and the aqueous layer extracted with CH2Cl2 (50 ml).
The combined extracts were dried (MgSO4) and the solvents
removed under reduced pressure to afford a mixture of the title
158
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CH3, minor), 3.37–3.70 (3H ϩ 3H, m), 4.51 (2H ϩ 2H, s,
PhCH2), 4.93 (1H, app. q, J 7.0 Hz, CHOMs, minor), 5.04 (1H,
app. q, J 5.5 Hz, CHOMs, major) and 7.25–7.40 (5H ϩ 5H, m,
Ph); m/z (FAB) 342 (22, MHϩ), 154 (64), 136 (71), 107 (32), 91
(100), 73 (71) and 57 (57) (Found MHϩ, 342.0829. C15H19NO4S2
ϩ H requires M, 342.0834).
128.4 (CH) and 137.8 (C); m/z (EI) 236 (1, Mϩ), 188 (1), 107 (3),
97 (10), 92 (25), 91 (100), 81 (5), 79 (27), 67 (21) and 65 (14)
(Found MHϩ, 237.0929. C13H16O2S ϩ H requires M, 237.0916).
Alternative stereoselective access to epoxide 611
A solution of tert-butyl hydroperoxide (3.88 mmol) in CH2Cl2
(2.5 ml) was added to a solution of 4 (188 mg, 1.92 mmol) and
VO(acac)2 (20 mg, 0.076 mmol) in CH2Cl2 (5 ml) under nitro-
gen. The reaction mixture was stirred for 19 h and then washed
with saturated aqueous Na2SO3 (2 ml), dried (MgSO4) and
the solvent removed under reduced pressure. Chromatography
(petroleum ether–EtOAc 1:1) gave syn-6-oxabicyclo[3.1.0]-
hexane-3-methanol as a yellow oil (339 mg, 58%); δH (400
MHz) 1.98–2.05 (4H, m, 2-H2, 4-H2), 2.41 (1H, m, CHCH2-
OH), 2.91 (1H, br s, OH), 3.48 (2H, d, J 4.5 Hz, CH2OH) and
3.53 (2H, s, 2 × OCH); m/z (EI) 114 (4, Mϩ), 96 (10), 95 (18), 83
(100), 67 (43), 55 (76) and 41 (61).
A solution of the above epoxide (200 mg, 1.75 mmol) in THF
(2 ml) was added to a stirred suspension of sodium hydride (77
mg, 60% dispersion in mineral oil, 1.93 mmol) in THF (4 ml) at
0 ЊC under nitrogen. The mixture was stirred for 1 h before
benzyl bromide (0.23 ml, 1.93 mmol) was added, then stirred
for a further 22 h at room temperature. The reaction mixture
was quenched with water (10 ml), extracted with EtOAc (3 × 10
ml), dried (MgSO4) and the solvents removed under reduced
pressure. Chromatography (petroleum ether–EtOAc 9:1) gave 6
as a yellow oil (114 mg, 40%).
The above mixture of mesylates (7.44 g, 21.8 mmol) was
stirred with sodium hydroxide (2.16 g, 54.0 mmol) in water
(100 ml) for three days until reaction was complete by TLC
analysis. 2 M HCl (30 ml) was then added, the reaction
extracted with CH2Cl2 (3 × 100 ml), dried (MgSO4), and the
solvent removed under reduced pressure. Chromatography
(petroleum ether–EtOAc 99:1) gave firstly (1α,3α,5α)-3-
[(phenylmethoxy)methyl]-6-thiabicyclo[3.1.0]hexane as a col-
ourless oil (1.48 g, 31%); νmax (film)/cmϪ1 3027, 2949, 2847,
1495, 1453, 1364, 1202, 1126, 1101, 1028, 736 and 697; δH (400
MHz) 1.74 (2H, ddd, J 13.5, 10.5, 2.5 Hz, 2 × SCHCHH),
2.20 (2H, dd, J 13.5, 7.0 Hz, 2 × SCHCHH), 2.36 (1H, m,
3-H), 3.31 (2H, d, J 2.5 Hz, 2 × SCH), 3.43 (2H, d, J 6.0 Hz,
PhCH2OCH2), 4.48 (2H, s, PhCH2) and 7.25–7.37 (5H, m,
Ph); δC (68 MHz) 32.9 (CH2), 33.1 (CH), 41.3 (CH), 72.2
(CH2), 72.9 (CH2), 127.5 (2 × CH), 128.3 (CH) and 138.3 (C);
m/z (EI) 220 (2, Mϩ), 129 (3), 113 (32), 112 (23), 108 (24),
107 (5), 92 (10), 91 (100) and 78 (83) (Found Mϩ, 220.0928.
C13H16OS requires M, 220.0922); followed by (1α,3β,5α)-3-
[(phenylmethoxy)methyl]-6-thiabicyclo[3.1.0]hexane as a pale
yellow oil (2.03 g, 42%); νmax (film)/cmϪ1 3027, 2926, 2852,
1602, 1495, 1452, 1363, 1207, 1097, 1028, 938, 735 and 697;
δH (400 MHz) 2.06 (2H, dd, J 15.0, 1.5 Hz, 2 × SCHCHH),
2.30 (2H, ddd, J 15.0, 10.0, 3.0 Hz, 2 × SCHCHH), 2.50 (1H,
m, 3-H), 3.33 (2H, d, J 3.0 Hz, 2 × SCH), 3.43 (2H, d, J 8.0
Hz, PhCH2OCH2), 4.44 (2H, s, PhCH2) and 7.23–7.38 (5H,
m, Ph); δC (68 MHz) 32.7 (CH2), 37.2 (CH), 42.6 (CH), 72.9
(CH2), 77.5 (CH2), 127.4 (CH), 127.6 (CH), 128.3 (CH) and
138.5 (C); m/z (EI) 220 (1, Mϩ), 188 (2), 187 (6), 129 (13),
113 (30), 107 (8) and 91 (100) (Found Mϩ, 220.0916.
C13H16OS requires M, 220.0922.
(1ꢀ,2ꢁ,4ꢁ,5ꢀ)-3-Thiatricyclo[3.2.1.02,4]oct-6-ene 1012
A solution of diene 9 (11.7 ml, 109 mmol), sulfur (6.95 g, 217
mmol) and 2,6-di-tert-butyl-4-methoxyphenol (5.12 g, 21.7
mmol) in dry DMF (150 ml) was heated at 100 ЊC under nitro-
gen for 3.5 h. After cooling to room temperature, water (150 ml)
was added and the mixture extracted with petroleum ether
(3 × 150 ml). The combined extracts were washed with water
(3 × 150 ml), dried (MgSO4) and the solvent removed under
reduced pressure. Chromatography (petroleum ether) and then
Kugelrohr distillation (oven temperature 100 ЊC, 10 mmHg)
gave 10 as a yellow oil (511 mg, 3.8%); νmax (film)/cmϪ1 2972,
2921, 1633, 1450, 1254, 1218, 1062, 919, 757 and 732; δH (250
MHz) 1.29 (1H, d, J 9.0 Hz, CHH), 1.84 (1H, d, J 9.0 Hz,
(ii) Oxidation of intermediate episulfides to give 7 and 8.
(1α,3β,5α,6α)-3-[(Phenylmethoxy)methyl]-6-thiabicyclo-
[3.1.0]hexane 6-oxide 7. The typical episulfide oxidation pro-
cedure was followed using (1α,3β,5α)-3-[(phenylmethoxy)-
methyl]-6-thiabicyclo[3.1.0]hexane (1.65 g, 7.50 mmol) with the
addition of NaHCO3 (1.94 g, 23.1 mmol) to the reaction
mixture. Purification by chromatography (EtOAc then EtOAc–
MeOH 19:1) gave 7 as a colourless oil (1.34 g, 75%); νmax (film)/
cmϪ1 3029, 2926, 2855, 1453, 1366, 1097, 1029, 969, 742 and
699; δH (400 MHz) 1.87 (2H, dd, J 15.5, 3.0 Hz, 2 × SCHCHH),
2.30–2.47 (3H, m, 2 × SCHCHH, 3-H), 2.83 (2H, d, J 7.5 Hz,
PhCH2OCH2), 3.27 (2H, d, J 5.5 Hz, 2 × SCH), 4.42 (2H,
s, PhCH2) and 7.25–7.38 (5H, m, Ph); δC (68 MHz) 31.1
(CH2), 37.5 (CH), 57.5 (CH), 72.3 (CH2), 72.9 (CH2), 127.5
(CH), 127.7 (CH), 128.3 (CH) and 137.7 (C); m/z (EI) 188 (1),
107 (1), 92 (10), 91 (100), 81 (3), 80 (3), 79 (14), 67 (10) and
65 (7) (Found MHϩ, 237.0956. C13H16O2S ϩ H requires M,
237.0916).
(1α,3α,5α,6α)-3-[(Phenylmethoxy)methyl]-6-thiabicyclo-
[3.1.0]hexane 6-oxide 8. The typical episulfide oxidation pro-
cedure was followed using (1α,3α,5α)-3-[(phenylmethoxy)-
methyl]-6-thiabicyclo[3.1.0]hexane (1.05 g, 4.76 mmol) with the
addition of NaHCO3 (1.94 g, 23.1 mmol) to the reaction mix-
ture. Purification by chromatography (EtOAc then EtOAc–
MeOH 19:1) gave 8 as an unstable colourless oil (875 mg, 78%);
νmax (film)/cmϪ1 3029, 2915, 2853, 1453, 1367, 1093, 1074, 1044,
970, 742 and 699; δH (400 MHz) 1.44 (1H, m, 3-H), 1.89 (2H,
ddd, J 14.5, 11.0, 3.5 Hz, 2 × SCHCHH), 2.36 (2H, dd, J 14.5,
7.5 Hz, 2 × SCHCHH), 3.25 (2H, d, J 6.0 Hz, PhCH2OCH2),
3.31 (2H, d, J 3.5 Hz, 2 × SCH), 4.44 (2H, s, PhCH2) and
7.25–7.38 (5H, m, Ph); δC (68 MHz) 31.7 (CH2), 36.5 (CH),
56.8 (CH), 71.9 (CH2), 73.0 (CH2), 127.5 (CH), 127.7 (CH),
CHH), 2.97 (2H, s, 2 × ᎐CHCH), 3.03 (2H, s, 2 × SCH) and
᎐
6.38 (2H, s, 2 × ᎐CH); m/z (EI) 124 (30 Mϩ), 123 (72), 97 (69),
᎐
91 (100), 79 (52) and 64 (32).
(1ꢀ,2ꢁ,3ꢁ,4ꢁ,5ꢀ)-3-Thiatricyclo[3.2.1.02,4]oct-6-ene 3-oxide 11
The typical procedure for episulfide oxidation was followed
using episulfide 10 (450 mg, 3.63 mmol), and gave 11 as a
colourless oil (425 mg, 84%); νmax (film)/cmϪ1 2996, 1458, 1311,
1078, 1054 and 708; δH (400 MHz) 1.51 (1H, d, J 9.0 Hz, CHH),
2.35 (2H, s, 2 × SCH), 2.78 (1H, d, J 9.0 Hz, CHH), 3.70 (2H, s,
2 × ᎐CHCH) and 6.83 (2H, s, 2 × ᎐CH); δ (68 MHz) 43.9
᎐
᎐
C
(CH2), 47.1 (CH), 52.4 (CH) and 144.5 (CH); m/z (FAB) 141
(13, MHϩ), 109 (27), 95 (36), 83 (43), 69 (68), 57 (100)
and 55 (87) (Found MHϩ, 141.0369. C7H8OS ϩ H requires M,
141.0374).
Typical procedure for sulfur monoxide transfer to an alkene:
(1ꢀ,2ꢁ,3ꢀ,4ꢁ,5ꢀ)- and (1ꢀ,2ꢁ,3ꢁ,4ꢁ,5ꢀ)-3-thiatricyclo[3.2.1.02,4]-
octane 3-oxide 16 and 17
A solution of trans-2,3-diphenylthiirane 1-oxide (350 mg, 1.54
mmol),26 alkene 15 (51 mg, 0.54 mmol) and rhodium() acetate
(6.5 mg, 0.015 mmol) in CH2Cl2 (5 ml) was stirred for 3 h. The
solvent was removed under reduced pressure, and then chrom-
atography (petroleum ether–EtOAc 1:1, then EtOAc) afforded
firstly 16 as a colourless oil (25 mg, 32%); νmax (film)/cmϪ1 2966,
2872, 1301, 1076, 1041 and 949; δH (250 MHz) 1.06 (1H, dt,
J 10.5, 1.0 Hz, 8-HH), 1.37 (2H, m, 6-HH, 7-HH), 1.76 (2H, m,
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163
159

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6-HH, 7-HH), 2.15 (2H, d, J 1.0 Hz, 1-H, 5-H), 2.41 (1H, dm,
J 10.5 Hz, 8-HH) and 3.27 (2H, br s, 2 × SCH); δC (68 MHz)
29.2 (CH2), 32.8 (CH2), 40.7 (CH) and 47.8 (CH); m/z (FAB)
143 (54, MHϩ), 95 (42), 81 (61), 69 (77), 57 (92) and 55 (100)
(Found MHϩ, 143.0531. C7H10OS ϩ H requires M, 143.0531);
followed by 17 as a colourless oil (20 mg, 26%); νmax (film)/cmϪ1
2967, 2872, 1307, 1064, 1026 and 965; δH (400 MHz) 0.61 (1H,
d, J 11.0 Hz, 8-HH), 0.80 (1H, d, J 11.0 Hz, 8-HH), 1.45–1.65
(4H, m, 6-H2, 7-H2) and 2.86–2.91 (4H, m, 1-H, 2-H, 4-H, 5-H);
δC (68 MHz) 27.7 (CH2), 30.9 (CH2), 38.3 (CH) and 53.6 (CH);
m/z (FAB) 143 (14, MHϩ), 95 (46), 81 (56), 69 (89), 57 (93) and
55 (100) (Found MHϩ, 143.0531. C7H10OS ϩ H requires M,
143.0531).
Typical procedure for sulfur transfer to an alkene: preparation of
(1ꢀ,2ꢁ,4ꢁ,5ꢀ)-3-thiatricyclo[3.2.1.02,4]octane 23
A solution of alkene 15 (53 mg, 0.56 mmol), 2-methylthiirane
(0.10 ml, 1.3 mmol) and rhodium() acetate (2.3 mg, 0.0052
mmol) in toluene (1.5 ml) was heated to reflux for 22 h. After
cooling to room temperature, the solvent was removed under
reduced pressure. Chromatography (petroleum ether) gave 23
as a colourless oil (28 mg, 39%);27 νmax (film)/cmϪ1 2954, 2869,
1448, 1326, 1300, 1138, 1068, 916, 765 and 649; δH (400 MHz)
0.65 (1H, d, J 10.5 Hz, 8-HH), 1.25 (2H, m, 6-HH, 7-HH), 1.53
(1H, dm, J 10.5 Hz, 8-HH), 1.63 (2H, m, 6-HH, 7-HH), 2.45
(2H, br s, 1-H, 5-H) and 2.74 (2H, s, 2 × SCH); δC (125 MHz)
27.6 (2 × CH2), 37.5 (CH) and 37.7 (CH); m/z (EI) 126 (28,
Mϩ), 95 (100), 93 (45) and 66 (35) (Found Mϩ, 126.0498.
C7H10S requires M, 126.0503).
(1ꢀ,2ꢁ,3ꢀ,4ꢁ,5ꢀ)-and(1ꢀ,2ꢁ,3ꢁ,4ꢁ,5ꢀ)-3-Thiatricyclo[3.2.1.02,4]-
oct-6-ene 3-oxide 18 and 11
(1ꢀ,2ꢁ,4ꢁ,5ꢀ)-3-Thiatricyclo[3.2.1.02,4]oct-6-ene 10
The above typical procedure was followed using diene 9 (0.13
ml, 1.2 mmol), and after chromatography (petroleum ether–
EtOAc 1:1, then EtOAc) gave firstly 18 as a colourless oil (30
mg, 20%); νmax (film)/cmϪ1 2996, 1458, 1311, 1078, 1054 and
708; δH (400 MHz) 1.51 (1H, d, J 9.0 Hz, CHH), 2.35 (2H, s,
2 × SCH), 2.78 (1H, d, J 9.0 Hz, CHH), 3.70 (2H, s, 2 ×
The above typical procedure for sulfur transfer was followed
using diene 9 (88 mg, 0.96 mmol), and after chromatography
(petroleum ether) gave 10 as a pale yellow oil (48 mg, 40%); see
above for full analytical data for this compound.
᎐CHCH) and 6.83 (2H, s, 2 × ᎐CH); δ (68 MHz) 43.9 (CH ),
᎐
᎐
C
2
Typical deprotonation procedure using base 29: preparation
of (1S)-{[1-methyl-3-(methylsulfinyl)cyclopent-3-en-1-yl]-
sulfonyl}benzene 24
47.1 (CH), 52.4 (CH) and 144.5 (CH); m/z (FAB) 141 (13,
MHϩ), 109 (27), 95 (36), 83 (43), 69 (68), 57 (100) and 55 (87)
(Found MHϩ, 141.0369. C7H8OS ϩ H requires M, 141.0374);
followed by 11 as a colourless oil (36 mg, 24%); see above for full
analytical data for this compound.
n
A solution of base 29 was prepared by the addition of BuLi
(1.74 ml of a 1.4 M solution in hexanes, 2.44 mmol) to a solu-
tion of the corresponding diamine (555 mg, 1.32 mmol) in THF
(3 ml) at Ϫ78 ЊC followed by warming to room temperature for
10 min. After cooling to Ϫ78 ЊC, a solution of episulfoxide 3
(300 mg, 1.11 mmol) and iodomethane (0.66 ml, 10.6 mmol) in
THF (10 ml) was added. The reaction mixture was stirred for
1 h and then quenched with saturated aqueous NH4Cl (20 ml),
warmed to room temperature and extracted with CH2Cl2
(3 × 20 ml). The combined extracts were dried (MgSO4),
the solvents removed under reduced pressure, and the residue
subjected to chromatography (EtOAc) to give a 2:1 mixture
of diastereomers of 24 as a colourless oil (267 mg, 85%); νmax
(CHCl3)/cmϪ1 2933, 2851, 1621, 1586, 1459, 1378, 1308, 1142,
1122, 1089, 990 and 959; δH (250 MHz) 1.48 (3H, s, CCH3), 1.49
(1ꢀ,2ꢁ,4ꢁ,5ꢀ,6ꢁ,8ꢁ)-7-Oxa-3-thiatetracyclo[3.3.1.02,4.06,8]-
nonane 3,3-dioxide 19
1,1,1-Trifluoroacetone (0.20 ml, 2.2 mmol) was added to a
solution of episulfoxide 18 (25 mg, 0.18 mmol) in MeCN (2.7
ml) and aqueous Na2EDTA (1.8 ml of a 0.4 mM solution,
0.72 µmol) at 0 ЊC. A mixture of Oxone (573 mg, 0.93 mmol)
and NaHCO3 (236 mg, 2.81 mmol) was added in portions
over 30 min. After a further 3 h, the reaction mixture was
diluted with water (2 ml) and extracted with CH2Cl2 (3 × 5 ml)
taking care to keep the temperature of the extracts at 0 ЊC.
The combined organic layers were dried (MgSO4) and the
solvent removed under reduced pressure. Rapid chrom-
atography (petroleum ether–EtOAc 2:1) gave 19 as an unstable
white solid (19 mg, 62%), mp 80–90 ЊC (decomp.); νmax/cmϪ1
3035, 3001, 1293, 1224, 1129, 994, 915, 847, 796 and 754; δH
(250 MHz) 1.47 (1H, d, J 12.0 Hz, 9-HH), 2.22 (1H, d, J 12.0
Hz, 9-HH), 3.20 (2H, br s), 3.31 (2H, br s) and 3.35 (2H, br
s); δC (68 MHz) 17.2 (CH2), 37.8 (CH), 49.4 (CH) and 50.6
(CH); m/z (CI) 173 (9, MHϩ), 108 (25), 107 (22), 91 (18) and
79 (100) (Found MHϩ, 173.0274. C7H8O3S ϩ H requires M,
173.0272).
(3H, s, CCH ), 2.35–2.65 (5H ϩ 5H, m, 2 × ᎐CCHH, SCH ),
᎐
3
3
3.40–3.52 (2H ϩ 2H, m, 2 × ᎐CCHH), 6.24 (1H ϩ 1H, s,
᎐
᎐CH), 7.54–7.75 (3H ϩ 3H, m, PhH) and 7.86–7.95 (2H ϩ 2H,
᎐
m, PhH); m/z (EI) 284 (6, Mϩ), 188 (4), 159 (3), 143 (100), 142
(79), 127 (46), 95 (95), 79 (80) and 77 (80) (Found Mϩ,
284.0534. C13H16O3S2 requires M, 284.0541). The ee was deter-
i
mined as 82% by HPLC (OD column, 20% PrOH in hexane),
the retention times for the major diastereoisomer were 20.1 min
(major) and 23.4 min (minor), and for the minor diastereo-
isomer 27.8 min (minor) and 29.3 min (major).
By the same method, episulfoxide 11 (30 mg, 0.21 mmol) gave
the same product (18 mg, 49%).
Typical sulfoxide oxidation procedure: (1S)-{[1-methyl-3-
(methylsulfonyl)cyclopent-3-en-1-yl]sulfonyl}benzene 25
(1ꢀ,2ꢁ,3ꢀ,4ꢁ,5ꢀ)- and (1ꢀ,2ꢁ,3ꢁ,4ꢁ,5ꢀ)-8-(1,1-Dimethylethoxy)-
3-thiatricyclo[3.2.1.02,4]oct-6-ene 3-oxide 22
A solution of Oxone (521 mg, 0.847 mmol) in water (5 ml) was
added to a solution of sulfoxides 24 (241 mg, 0.847 mmol) in
MeOH (5 ml) and stirred for 1 h. The reaction was diluted with
water (5 ml), extracted with CH2Cl2 (3 × 15 ml), dried (MgSO4)
and the solvent removed under reduced pressure. Purification
by chromatography (petroleum ether–EtOAc 2:3) gave 25 as a
The above typical procedure for sulfur monoxide transfer was
followed using diene 21 (44 mg, 0.27 mmol), and after chrom-
atography (EtOAc) gave a 1:1 mixture of diastereoisomers of
22 as a colourless oil (9 mg, 16%); νmax (film)/cmϪ1 2974, 2931,
1365, 1238, 1194, 1112, 1073, 1033, 884 and 755; δH (400 MHz)
1.05 (9H, s, C(CH3)3), 1.17 (9H, s, C(CH3)3), 2.99 (2H, s),
i
white solid (147 mg, 58%). Recrystallisation from PrOH–
hexane, and then iPrOH gave optically pure material for X-ray
analysis; mp 124–125 ЊC (Found: C, 51.85; H, 5.48; S, 21.12.
C13H16O4S2 requires C, 51.98; H, 5.37; S, 21.35%); νmax (CHCl3)/
cmϪ1 2929, 2853, 1629, 1586, 1318, 1140 and 958; δH (400 MHz)
3.18 (3H, m), 3.42 (4H, m), 3.54 (1H, s), 5.45 (2H, m, ᎐CH)
᎐
and 6.29 (2H, br s, ᎐CH); δ (100 MHz) 28.2 (CH3), 28.3
᎐
C
(CH3), 45.6 (CH), 47.9 (CH), 51.0 (CH), 56.4 (CH), 74.4 (C),
74.5 (C), 79.9 (CH), 93.2 (CH), 126.0 (CH) and 134.8 (CH);
m/z (FAB) 213 (4, MHϩ), 107 (24), 95 (29), 81 (35), 69 (57),
57 (100) and 55 (86) (Found MHϩ, 213.0951. C11H16O2S ϩ H
requires M, 213.0949).
1.51 (3H, s, CCH ), 2.52 (1H, d, J 18.5 Hz, ᎐CCHH), 2.63 (1H,
᎐
3
d, J 17.0 Hz, ᎐CCHH), 2.93 (3H, s, SCH ), 3.49–3.61 (2H, m,
᎐
3
2 × ᎐CCHH), 3.57 (1H, d, J 18.0 Hz, HHCCS), 6.60 (1H, s,
᎐
᎐CH), 7.61 (2H, t, J 7.5 Hz, PhH), 7.72 (1H, t, J 7.5 Hz, PhH)
᎐
160
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163

View Article Online
and 7.92 (2H, d, J 7.5 Hz, PhH); m/z (CI) 301 (12, MHϩ), 283
(10), 209 (13), 203 (11), 171 (15), 159 (100), 143 (37), 125 (77),
97 (57) and 79 (71) (Found MHϩ, 301.0578. C13H16O4S2 ϩ H
requires M, 301.0568).
᎐CH) and 7.27–7.47 (5H, m, Ph); δ (100 MHz) 34.5 (CH2),
᎐
C
36.1 (CH2), 38.1 (CH), 41.2 (CH3), 73.0 (CH2), 73.1 (CH2),
127.6 (CH), 127.7 (CH), 128.4 (CH), 138.1 (C), 142.5 (CH),
142.9 (C); m/z (EI) 266 (1, Mϩ), 187 (12), 169 (34), 145 (10), 107
(15), 91 (100), 81 (27), 77 (20) and 65 (23) (Found Mϩ,
266.0982. C14H18O3S requires M, 266.0977). The ee was deter-
(1S)-({1-Methyl-3-[(phenylmethyl)sulfinyl]cyclopent-3-en-1-yl}-
sulfonyl)benzene 26
i
mined as 85% by HPLC (OD column, 10% PrOH in hexane),
the retention times were 26.5 min (major) and 30.4 min (minor).
The above typical deprotonation procedure with base 29 was
followed using episulfoxide 3 (50 mg, 0.19 mmol) with benzyl
bromide as the electrophile. Purification by chromatography
(EtOAc) gave 26 as a mixture of diastereomers (1:1), as a
colourless oil (48 mg, 72%); νmax (CHCl3)/cmϪ1 2935, 2870,
1626, 1584, 1454, 1304, 1151 and 990; δH (400 MHz) 1.42 (3H, s,
CH3, major), 1.43 (3H, s, CH3, minor), 2.25–2.55 (2H ϩ 2H, m,
B. From episulfoxide 8. The typical deprotonation procedure
with base 29 was followed using episulfoxide 8 (56 mg, 0.24
mmol) with iodomethane as the electrophile. Purification as
above gave a 1:1 mixture of diastereoisomers of 30 as a colour-
less oil (20 mg, 34%).
The sulfoxides (6 mg, 0.024 mmol) were oxidised by the
typical oxidation procedure to give 31 as a colourless oil (6 mg,
90%). The ee was determined as 85% by HPLC (OD column,
10% iPrOH in hexane), the retention times are given above, but
the minor enantiomer eluted first.
2 × ᎐CCHH), 3.30–3.44 (2H ϩ 2H, m, 2 × ᎐CCHH), 3.98 (1H,
᎐
᎐
d, HA of AB system, J 13.0 Hz, PhCHH), 4.01–4.05 (1H ϩ 1H,
m, HB of AB and HAЈ of AЈBЈ systems, 2 × PhCHH), 4.11 (1H,
d, HBЈ of AЈBЈ system, J 12.5 Hz, PhCHH), 5.88 (1H, s, ᎐CH,
᎐
major), 6.00 (1H, s, ᎐CH, minor), 7.17–7.37 (5H ϩ 5H, m,
᎐
PhH), 7.56–7.62 (2H ϩ 2H, m, PhH), 7.65–7.72 (1H ϩ 1H, m,
PhH) and 7.86–7.93 (2H ϩ 2H, m, PhH); m/z (FAB) 361 (61,
MHϩ), 219 (53) and 91 (100) (Found MHϩ, 361.0936.
C19H20O3S2 ϩ H requires M, 361.0932).
4-[(Phenylmethoxy)methyl]-1-[(phenylmethyl)sulfinyl]cyclopent-
1-ene 32 and 4-[(phenylmethoxy)methyl]-1-[(phenylmethyl)-
sulfonyl]cyclopent-1-ene 33
The typical deprotonation procedure with base 29 was followed
using episulfoxide 7 (46 mg, 0.19 mmol) with benzyl bromide
as the electrophile. Purification by chromatography (EtOAc–
petroleum ether 1:1 then EtOAc), gave a 1:1 mixture of dia-
stereoisomers of 32 as a colourless oil (41 mg, 65%); νmax (film)/
cmϪ1 3029, 2925, 2851, 1602, 1495, 1453, 1364, 1100, 1074,
1056, 1029, 766, 739 and 699; δH (400 MHz) 2.22–2.85 (5H ϩ
5H, m, 3-H2, 4-H, 5-H2), 3.35–3.44 (2H ϩ 2H, m, PhCH2-
OCH2), 3.92–4.04 (2H ϩ 2H, m, PhCH2), 4.48–4.58 (2H ϩ 2H,
(1S)-({1-Methyl-3-[(phenylmethyl)sulfonyl]cyclopent-3-en-1-yl}-
sulfonyl)benzene 27
The typical oxidation procedure was followed using sulfoxide
26 (20 mg, 0.055 mmol), and gave 27 as a white solid (21 mg,
100%); mp 142–145 ЊC (Found: C, 60.59; H, 5.46; S, 16.86.
C19H20O4S2 requires C, 60.62; H, 5.35; S, 17.03%); νmax (CHCl3)/
cmϪ1 2915, 2849, 1625, 1456, 1317, 1306, 1152, 1121 and 992;
δH (250 MHz) 1.37 (3H, s, CH3), 2.30 (1H, dm, J 16.5 Hz,
m, PhCH ), 6.06 (1H ϩ 1H, m, ᎐CH) and 7.17–7.40 (10H ϩ
᎐
2
᎐CCHH), 2.40 (1H, ddd, J 19.0, 2.5, 2.5 Hz, ᎐CCHH), 3.26
᎐
᎐
10H, m, 2 × Ph); δC (68 MHz) 32.0 (CH2), 32.2 (CH2), 36.0
(2 × CH2), 37.3 (CH), 37.5 (CH), 58.3 (2 × CH2), 73.0 (CH2),
73.1 (CH2), 73.2 (CH2), 73.4 (CH2), 127.7 (CH), 128.2 (CH),
128.4 (CH), 128.6 (CH), 130.0 (CH), 137.2 (CH), 137.5 (CH),
138.2 (2 × C) and 143.6 (2 × C) (the remaining 7 × CH and
2 × C are underneath the other aromatic 13C signals); m/z
(FAB) 327 (99, MHϩ), 235 (4), 181 (9), 123 (10), 107 (18), 92
(11) and 91 (100) (Found MHϩ, 327.1400. C20H22O2S ϩ H
requires M, 327.1419).
The sulfoxides (41 mg, 0.13 mmol) were oxidised by the
typical oxidation procedure to give 33 as a colourless oil (35 mg,
81%); [α]D ϩ1.5 (c, 1.01, CHCl3); νmax (film)/cmϪ1 3030, 2923,
2854, 1619, 1495, 1454, 1309, 1150, 1121, 779, 740, 698 and 637;
δH (400 MHz) 2.26–2.80 (5H, m, 3-H2, 4-H, 5-H2), 3.33 (2H, m,
PhCH2OCH2), 4.19 (2H, s, PhCH2), 4.50 (2H, s, PhCH2), 6.45
(1H, app. dq, J 16.5, 2.5 Hz, ᎐CCHH), 3.43 (1H, app. dq,
᎐
J 19.0, 2.5 Hz, ᎐CCHH), 4.25 (2H, s, PhCH ), 6.39 (1H, s,
᎐
2
᎐CH), 7.35–7.50 (5H, m, PhH), 7.58 (2H, t, J 7.5 Hz, PhH),
᎐
7.70 (1H, t, J 7.5 Hz, PhH) and 7.84 (2H, d, J 7.5 Hz, PhH);
m/z (FAB) 377 (35, MHϩ), 261 (12), 235 (9), 217 (16), 109 (26),
91 (70), 69 (76) and 55 (100) (Found MHϩ, 377.0893.
C19H20O4S2 ϩ H requires M, 377.0881). The ee was determined
i
as 85% by HPLC (OD column, 20% PrOH in hexane), the
retention times were 53.3 min (major) and 68.1 min (minor).
({[3-(Methylsulfinyl)cyclopent-3-en-1-yl]methoxy}methyl)-
benzene 30 and ({[3-(methylsulfonyl)cyclopent-3-en-1-yl]-
methoxy}methyl)benzene 31
A. From episulfoxide 7. The typical deprotonation procedure
with base 29 was followed using episulfoxide 7 (49 mg, 0.21
mmol) with iodomethane as the electrophile. Purification by
chromatography (EtOAc–MeOH 19:1) gave a 1:1 mixture of
diastereoisomers of 30 as a colourless oil (38 mg, 73%); νmax
(film)/cmϪ1 3029, 2932, 2851, 1453, 1364, 1100, 1063, 1028, 958,
741 and 700; δH (400 MHz) 2.28–2.90 (5H ϩ 5H, m, 3-H2, 4-H,
5-H2), 2.60 (3H ϩ 3H, s, CH3), 3.43 (2H ϩ 2H, m, PhCH2-
(1H, dd, J 2.0, 2.0 Hz, ᎐CH) and 7.25–7.48 (10H, m, 2 × Ph);
᎐
δC (100 MHz) 35.0 (CH2), 36.2 (CH2), 38.0 (CH), 60.2 (CH2),
73.0 (CH2), 73.1 (CH2), 127.6 (CH), 127.7 (CH), 128.2 (C),
128.4 (CH), 128.7 (CH), 128.8 (CH), 130.6 (CH), 138.1 (C),
140.9 (C) and 145.6 (CH); m/z (FAB) 343 (10, MHϩ), 341 (6),
253 (4), 235 (4), 181 (17), 154 (15), 137 (13), 107 (13), 91 (100)
and 81 (17) (Found MHϩ, 343.1386. C20H22O3S ϩ H requires
M, 343.1368). The ee was determined as 88% by HPLC (OD
OCH ), 4.52 (2H ϩ 2H, m, PhCH ), 6.33 (1H ϩ 1H, m, ᎐CH)
᎐
i
2
2
column, 10% PrOH in hexane), the retention times were 39.9
and 7.27–7.39 (5H ϩ 5H, m, Ph); δC (68 MHz) 32.2 (CH2), 32.3
(CH2), 36.4 (2 × CH2), 38.0 (CH), 38.1 (CH), 38.9 (2 × CH3),
73.5 (CH2), 73.6 (CH2), 73.7 (CH2), 73.9 (CH2), 128.1 (2 × CH),
128.8 (2 × CH), 135.8 (2 × CH), 136.0 (2 × CH), 138.6 (2 × C)
and 146.6 (2 × C); m/z (EI) 250 (1, Mϩ), 233 (4), 143 (12), 113
(27), 91 (100), 79 (20) and 65 (22) (Found Mϩ, 250.1027.
C14H18O2S requires M, 250.1028).
The sulfoxides (38 mg, 0.15 mmol) were oxidised by the
typical oxidation procedure to give 31 as a colourless oil (40 mg,
98%); [α]D ϩ12 (c, 1.17, CHCl3); νmax (film)/cmϪ1 3027, 2926,
2855, 1622, 1453, 1301, 1141, 1101, 955, 752 and 699; δH (400
MHz) 2.40–2.91 (8H, m, 3-H2, 4-H, 5-H2, CH3), 3.43 (2H, d,
J 5.0 Hz, PhCH2OCH2), 4.52 (2H, s, PhCH2), 6.68 (1H, m,
min (minor) and 42.3 min (major).
2-(Methylsulfinyl)bicyclo[2.2.1]hepta-2,5-diene 34 and 2-(methyl-
sulfonyl)bicyclo[2.2.1]hepta-2,5-diene 36
A. Typical procedure for deprotonation using base 28. A solu-
tion of base 28 was prepared by the addition of nBuLi (0.71 ml
of a 1.60 M solution in hexanes, 1.14 mmol) to a solution of the
corresponding amine hydrochloride (157 mg, 0.60 mmol) in
THF (5 ml) at Ϫ78 ЊC followed by warming to room temper-
ature for 10 min. After cooling to Ϫ78 ЊC, a solution of epi-
sulfoxide 11 (70 mg, 0.50 mmol) and iodomethane (0.31 ml, 5.0
mmol) in THF (1 ml) was added. Work-up as for base 29 and
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163
161

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chromatography (EtOAc) gave a 3:2 mixture of diastereo-
isomers of 34 as a colourless oil (56 mg, 73%); νmax (film)/cmϪ1
2989, 2938, 1548, 1419, 1298, 1037 and 708; δH (400 MHz)
2.13–2.26 (2H ϩ 2H, m, CH2), 2.54 (3H, s, CH3, minor), 2.61
(3H, s, CH3, major), 3.81 (1H ϩ 1H, br s), 3.87 (1H, br s,
major), 4.02 (1H, br s, minor), 6.79 (1H ϩ 1H, m), 6.89 (1H ϩ
1H, m) and 7.22 (1H ϩ 1H, m, 3-H); δC (68 MHz) 37.2 (CH3),
37.9 (CH3), 47.8 (CH), 48.9 (CH), 51.2 (CH), 51.3 (CH), 73.9
(CH2), 74.0 (CH2), 142.2 (CH), 142.5 (2 × CH), 142.7 (CH),
147.3 (CH), 147.9 (CH) and 159.8 (2 × C); m/z (EI) 154 (23,
Mϩ), 138 (8), 123 (13), 107 (43), 106 (54), 91 (100), 79 (65), 77
(52), 66 (96) and 65 (77) (Found Mϩ, 154.0450. C8H10OS
requires M, 154.0452).
1-H or 4-H), 3.74 (1H, br s, 1-H or 4-H), 4.18 (1H, d, JAB 14.0
Hz, PhCHH), 4.24 (1H, d, JAB 14.0 Hz, PhCHH), 6.72 (1H, dd,
J 5.0, 3.0 Hz, 5-H or 6-H), 6.81 (1H, dd, J 5.0, 3.0 Hz, 5-H or
6-H), 7.28–7.45 (5H, m, Ph) and 7.47 (1H, d, J 3.0 Hz, 3-H);
δC (100 MHz) 51.5 (CH), 51.9 (CH), 60.7 (CH2), 74.7 (CH2),
127.8 (C), 128.6 (CH), 128.8 (CH), 130.9 (CH), 141.8 (CH),
142.7 (CH), 155.4 (C) and 157.9 (CH); m/z (FAB) 247 (16,
MHϩ), 176 (13), 154 (100), 137 (69), 136 (72), 107 (25), 91 (44),
69 (29) and 57 (39) (Found MHϩ, 247.0796. C14H14O2S ϩ H
requires M, 247.0793). The ee was determined as 66% by HPLC
i
(OD column, 3% PrOH in hexane), the retention times were
46.8 min (minor) and 51.3 min (major).
The sulfoxides (52 mg, 0.34 mmol) were oxidised by the
typical oxidation procedure, and chromatography (petroleum
ether–EtOAc 1:1) gave 36 as a colourless oil (41 mg, 71%); [α]D
Ϫ19 (c, 1.46, CHCl3); νmax (film)/cmϪ1 2997, 2940, 1551, 1299,
1162, 1134 and 762; δH (400 MHz) 2.22 (1H, d, J 6.5 Hz,
7-HH), 2.31 (1H, dt, J 6.5, 1.5 Hz, 7-HH), 2.88 (3H, s, CH3),
3.86 (1H, br s, 1-H or 4-H), 3.91 (1H, br s, 1-H or 4-H), 6.81
(1H, dd, J 5.0, 3.0 Hz, 5-H or 6-H), 7.01 (1H, dd, J 5.0, 3.0 Hz,
5-H or 6-H) and 7.59 (1H, d, J 3.0 Hz, 3-H); δC (100 MHz) 41.2
(CH3), 50.8 (CH), 51.7 (CH), 74.9 (CH2), 142.1 (CH), 142.4
(CH), 154.5 (CH) and 157.1 (C); m/z (EI) 170 (12, Mϩ), 107 (6),
91 (100), 90 (24), 78 (4), 77 (9) and 65 (11) (Found Mϩ,
170.0397. C8H10O2S requires M, 170.0402). The ee was deter-
mined as 43% by HPLC (OD column, 2% iPrOH in hexane), the
retention times were 33.4 min (major) and 35.3 min (minor).
2-(Methylsulfinyl)bicyclo[2.2.1]hept-2-ene 38 and 2-(methyl-
sulfonyl)bicyclo[2.2.1]hept-2-ene 40
A. Deprotonation using base 29. The typical deprotonation
procedure with base 29 was followed using episulfoxide 17 (59
mg, 0.42 mmol), with iodomethane as the electrophile. Purifi-
cation by chromatography (Et2O–MeOH 49:1) gave a 3:1 mix-
ture of diastereoisomers of 38 as a colourless oil (41 mg, 63%);
νmax (film)/cmϪ1 2970, 2871, 1574, 1419, 1307, 1125, 1056, 1027,
952, 875 and 656; δH (400 MHz) 1.10–1.90 (6H ϩ 6H, m,
3 × CH2), 2.66 and 2.67 (3H ϩ 3H, 2 × s, CH3), 3.11 (1H ϩ 1H,
br s), 3.19 (1H, br s, major), 3.35 (1H, br s, minor), 6.57 (1H, d,
J 3.0 Hz, ᎐CH, minor) and 6.61 (1H, d, J 3.0 Hz, ᎐CH, major);
᎐
᎐
δC (100 MHz) 24.8 (CH2), 24.9 (CH2), 25.4 (CH2), 25.5 (CH2),
38.5 (CH3), 39.3 (CH3), 41.0 (CH), 41.1 (CH), 42.9 (CH), 43.5
(CH), 48.9 (CH2), 49.4 (CH2), 139.3 (CH), 139.9 (CH), 150.7
(C) and 151.5 (C); m/z (EI) 156 (16, Mϩ), 128 (46), 113 (43), 85
(63), 83 (100), 81 (63) and 65 (33) (Found Mϩ, 156.0611.
C8H12OS requires M, 156.0609).
The sulfoxides (36 mg, 0.23 mmol) were oxidised by the
typical oxidation procedure and gave 40 as a white solid (36 mg,
91%) (Found: C, 55.69; H, 7.26. C8H12O2S requires C, 55.79; H,
7.02%); νmax (film)/cmϪ1 2976, 2875, 1581, 1294, 1174, 1136,
1060, 964 and 758; δH (400 MHz) 1.18–1.92 (6H, m, 3 × CH2),
2.96 (3H, s, CH3), 3.15 (1H, br s, 4-H), 3.32 (1H, br s, 1-H) and
B. Deprotonation using base 29. The typical deprotonation
procedure with base 29 was followed using episulfoxide 11 (47
mg, 0.34 mmol) with iodomethane as the electrophile. Purifi-
cation by chromatography (EtOAc) gave a 3:2 mixture of
diastereoisomers of 34 as a colourless oil (39 mg, 75%).
The sulfoxides (36 mg, 0.23 mmol) were oxidised by the
typical oxidation procedure, and chromatography (petroleum
ether–EtOAc 1:1) gave 36 as a colourless oil (28 mg, 70%); [α]D
ϩ28 (c, 1.20, CHCl3). The ee was determined as 62% by HPLC
6.95 (1H, d, J 3.0 Hz, ᎐CH); δ (100 MHz) 24.3 (CH2), 25.0
᎐
C
i
(OD column, 3% PrOH in hexane), the retention times are
(CH2), 42.1 (CH3), 43.0 (CH), 43.6 (CH), 49.4 (CH2), 146.3
(CH) and 147.4 (C); m/z (EI) 172 (11, Mϩ), 144 (36), 91 (12), 81
(100), 65 (29) and 53 (20) (Found Mϩ, 172.0565. C8H12O2S
requires M, 172.0558). The sample was racemic by HPLC (OD
column, 2.5% iPrOH in hexane).
given above but the minor enantiomer eluted first.
2-[(Phenylmethyl)sulfinyl]bicyclo[2.2.1]hepta-2,5-diene 35 and
2-[(phenylmethyl)sulfonyl]bicyclo[2.2.1]hepta-2,5-diene 37
The typical deprotonation procedure with base 29 was followed
using episulfoxide 11 (50 mg, 0.36 mmol) with benzyl bromide
as the electrophile. Purification by chromatography (EtOAc)
gave a 3:1 mixture of diastereoisomers of 35 as a colourless oil
(51 mg, 62%); [α]D Ϫ19 (c, 0.96, CHCl3); νmax (film)/cmϪ1 3062,
2980, 2938, 1547, 1495, 1454, 1297, 1072, 1043, 766 and 700;
δH (400 MHz) 2.07–2.18 (2H ϩ 2H, m, 7-H2), 3.72 (1H, br s,
minor), 3.76 (1H, br s, major), 3.85 (1H, br s, minor), 3.88–4.06
(3H ϩ 2H, m), 6.75 (1H, dd, J 5.0, 3.0 Hz, minor), 6.78 (1H,
dd, J 5.0, 3.0 Hz, major), 6.86–6.92 (1H ϩ 1H, m), 7.05 (1H, d,
J 3.0 Hz, 3-H, major), 7.11 (1H, d, J 3.0 Hz, 3-H, minor), and
7.20–7.37 (5H ϩ 5H, m, Ph); δC (100 MHz) 48.4 (CH), 49.1
(CH), 51.4 (CH), 51.5 (CH), 58.2 (CH2), 58.7 (CH2), 73.5
(CH2), 74.0 (CH2), 128.1 (CH), 128.5 (CH), 128.6 (CH), 130.1
(CH), 130.2 (CH), 142.2 (CH), 142.4 (CH), 142.7 (CH), 142.9
(CH), 148.8 (CH), 150.1 (CH), 157.6 (C) and 158.1 (C) (the
additional quaternary and two methine carbon signals are
coincident with the other signals); m/z (EI) 230 (1, Mϩ), 164 (3),
123 (2), 91 (100), 85 (19) and 83 (29) (Found Mϩ, 230.0756.
C14H14OS requires M, 230.0765).
B. Deprotonation with base 29 in the presence of LiCl. The
typical deprotonation procedure with base 29 was followed
using episulfoxide 17 (31 mg, 0.22 mmol) with iodomethane as
the electrophile, except for the addition of a solution of lithium
chloride (7.8 mg, 0.18 mmol) in THF (1 ml) to the solution of
base 29 before 17 was added. Work-up and chromatography as
before gave a 3:1 mixture of diastereoisomers of 38 as a colour-
less oil (20 mg, 59%).
The sulfoxides (20 mg, 0.13 mmol) were oxidised by the
typical oxidation procedure and gave 40 as a white solid (21.5
mg, 98%); [α]D Ϫ24 (c, 1.20, CHCl3). The ee was determined as
27% by HPLC (OD column, 2.5% iPrOH in hexane), the reten-
tion times were 26.6 min (minor) and 38.8 min (major).
C. Deprotonation with base 28. The typical deprotonation
procedure with base 28 was followed using episulfoxide 17 (50
mg, 0.35 mmol), with iodomethane as the electrophile. Work-up
and chromatography as before gave a 3:1 mixture of diastereo-
isomers of 38 as a colourless oil (45 mg, 82%).
The sulfoxides (48 mg, 0.21 mmol) were oxidised by the
typical oxidation procedure, and chromatography (petroleum
ether–EtOAc 3:1) gave 37 as a colourless oil (36 mg, 70%); [α]D
ϩ6 (c, 1.56, CHCl3); νmax (film)/cmϪ1 2978, 2941, 1583, 1550,
1456, 1307, 1163, 1119, 778 and 698; δH (400 MHz) 2.09 (1H, d,
J 6.5 Hz, 7-HH), 2.15 (1H, d, J 6.5 Hz, 7-HH), 3.57 (1H, br s,
The sulfoxides (45 mg, 0.29 mmol) were oxidised by the typ-
ical oxidation procedure and gave 40 as a white solid (49 mg,
99%); [α]D ϩ60 (c, 1.13, CHCl3). The ee was determined as 76%
by HPLC (OD column, 2.5% PrOH in hexane), the retention
times were as above but the major enantiomer eluted first.
Recrystallisation from petroleum ether–EtOAc–Et2O afforded
i
162
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163

View Article Online
colourless crystals for X-ray crystallographic analysis, mp
49–51 ЊC.
unique reflections measured and used in all calculations. Final
R1 [2334 F > 4σ(F)] = 0.0264 and wR(all F2) was 0.0641. The
Flack parameter refined to Ϫ0.05(8), thereby establishing the
absolute configuration.28
2-[(Phenylmethyl)sulfinyl]bicyclo[2.2.1]hept-2-ene 39
A. Deprotonation using base 29. The typical deprotonation
procedure with base 29 was followed using episulfoxide 17 (53
mg, 0.37 mmol) with benzyl bromide as the electrophile. Purifi-
cation by chromatography (EtOAc) gave a 9:1 mixture of
diastereoisomers of 39 as a white solid (43 mg, 50%). A small
portion was recrystallised from petroleum ether–CH2Cl2 to give
colourless crystals; mp 91–93 ЊC (Found: C, 72.13; H, 7.01.
C14H16OS requires C, 72.37; H, 6.94%); νmax (film)/cmϪ1 2967,
2870, 1602, 1495, 1454, 1305, 1072, 1054, 1029, 764 and 699;
δH (400 MHz) 1.05–1.84 (6H, m, 5-H2, 6-H2, 7-H2), 2.77 (1H, br
s, 1-H), 3.05 (1H, br s, 4-H), 4.02 (1H, d, JAB 12.5 Hz,
PhCHH), 4.10 (1H, d, JAB 12.5 Hz, PhCHH), 6.49 (1H, d, J 3.0
Compound 40. The crystal was handled as for that of com-
pound 25. Crystal data. C8H12O2S, M = 172.24, monoclinic,
a = 6.101(2), b = 8.826(4), c = 7.894(3) Å, β = 98.54(3)Њ, U =
420.3(3) Å3, T = 150(2) K, space group P21 (No. 4), Z = 2,
Dc = 1.361 g cmϪ3, µ(Mo-Kα) = 0.331 mmϪ1, 1468 unique
reflections measured and used in all calculations. Final R1 [1359
F > 4σ(F)] = 0.0522 and wR(all F2) was 0.142. The Flack par-
ameter refined to 0.0(2), thereby establishing the absolute
configuration.28
Acknowledgements
Hz, ᎐CH) and 7.25–7.43 (5H, m, Ph); δ (68 MHz) (major
᎐
C
We are grateful to The Nuffield Foundation for support of
S. M. W. and to the University of Nottingham and the ORS
Awards Scheme for support of J. D. K. We also acknowledge
the Engineering and Physical Sciences Research Council
(EPSRC) for funding for a diffractometer. We thank Dr W.-S.
Li for experimental assistance with one of the X-ray structure
determinations.
diastereoisomer) 24.9 (CH2), 25.1 (CH2), 42.1 (CH), 43.0 (CH),
47.8 (CH2), 59.9 (CH2), 128.2 (CH), 128.5 (CH), 130.1 (CH),
140.1 (CH) and 149.7 (C) (the additional quaternary carbon
signal is coincident with one of the signals); m/z (EI) 232 (2,
Mϩ), 183 (4), 125 (5), 91 (100) and 65 (8) (Found Mϩ, 232.0921.
C14H16OS requires M, 232.0922). The sample was racemic by
HPLC (OD column, 2% iPrOH in hexane).
B. Deprotonation using base 29 in the presence of LiCl. The
typical deprotonation procedure with base 29 was followed
using episulfoxide 17 (29 mg, 0.20 mmol) with benzyl bromide
as the electrophile, except for the addition of a solution of lith-
ium chloride (5.8 mg, 0.14 mmol) in THF (1 ml) to the solution
of base 29 before 17 was added. Work-up and chromatography
as before gave a 9:1 mixture of diastereoisomers of 39 as a
white solid (22 mg, 46%); [α]D Ϫ10 (c, 1.16, CHCl3). The ee was
References
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2 R. Armer, PhD Thesis, University of Nottingham, 1994.
3 A. J. Blake, S. M. Westaway and N. S. Simpkins, Synlett, 1997, 919.
4 J. D. Kendall and N. S. Simpkins, Synlett, 1998, 391.
5 G. M. P. Giblin, S. H. Ramcharitar and N. S. Simpkins, Tetrahedron
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6 T. H. Chan and J. R. Finkenbine, J. Am. Chem. Soc., 1972, 94, 2880.
7 E. E. van Tamelen, J. Am. Chem. Soc., 1951, 73, 3444.
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9 N. Iranpoor and F. Kazemi, Synthesis, 1996, 821.
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11 D. M. Hodgson, J. Witherington and B. A. Moloney, J. Chem. Soc.,
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i
determined as 17% by HPLC (OD column, 2% PrOH in
hexane), the retention times for the major diastereoisomer
were 38.4 min (minor) and 45.8 min (major), and for the minor
diastereoisomer 28.2 min (major) and 50.0 min (minor).
C. Deprotonation using base 28. The typical deprotonation
procedure with base 28 was followed using episulfoxide 17 (49
mg, 0.35 mmol) with benzyl bromide as the electrophile (0.41
ml, 3.4 mmol). Purification as before gave the title compound as
a white solid (65 mg, 82%); [α]D ϩ39 (c, 0.70, CHCl3). The ee
12 J. Emsley, D. W. Griffiths and G. J. J. Jayne, J. Chem. Soc., Perkin
Trans. 1, 1979, 228.
13 P. D. Bartlett and T. Ghosh, J. Org. Chem., 1987, 52, 4937.
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15 W. Adam and S. Weinkötz, Chem. Commun., 1996, 177.
16 W. Adam, O. Deeg and S. Weinkötz, J. Org. Chem., 1997, 62, 7084.
17 SO is thermodynamically unstable and decomposes to give S2O and
SO2, see P. W. Schenk andR. Steudel, Angew. Chem., Int. Ed. Engl.,
1965, 4, 402.
i
was determined as 70% by HPLC (OD column, 2% PrOH in
hexane), the retention times are given above, and although the
diastereoselectivity was the same, the opposite enantiomer was
favoured.
18 I. A. Abu-Yousef and D. N. Harpp, J. Org. Chem., 1997, 62, 8366.
19 (a) O. Heyke, A. Neher and I.-P. Lorenz, Z. Anorg. Allg. Chem.,
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20 P. Johnson and R. J. K. Taylor, Tetrahedron Lett., 1997, 38, 5873.
21 W. A. Schenk, J. Leißner and C. Burschka, Z. Naturforsch., 1985,
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22 See M. D. Refvik, R. D. J. Froese, J. D. Goddard, H. H. Pham, M. F.
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references therein.
23 K. Bambridge, M. J. Begley and N. S. Simpkins, Tetrahedron Lett.,
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Data for crystal structure determinations†
Compound 3. A crystal was attached to a glass fibre before
transfer to the diffractometer. Crystal data. C12H14O3S2, M =
270.35, monoclinic, a = 6.2928(9), b = 19.505(3), c = 10.367(2)
Å, β = 96.581(14)Њ, U = 1264.1(3) Å3, T = 298(2) K, space group
P21/n (No. 14), Z = 4, Dc = 1.421 g cmϪ3, µ(Mo-Kα) = 0.414
mmϪ1, 2221 unique reflections measured and used in all
calculations. Final R1 [1779 F > 4σ (F)] = 0.0447 and wR(all F2)
was 0.110.
24 For previous examples, see R. A. Ewin, D. A. Price, N. S. Simpkins,
A. M. MacLeod and Alan P. Watt, J. Chem. Soc., Perkin Trans. 1,
1997, 401.
25 A. D. Hughes, D. A. Price and N. S. Simpkins, J. Chem. Soc., Perkin
Trans. 1, 1999, 1295.
26 B. F. Bonini, G. Maccagnani, G. Mazzanti and P. Zani, Gazz. Chim.
Ital., 1990, 120, 115.
27 M. U. Bombala and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 1979,
3013.
Compound 25. A crystal was encapsulated in a film of
RS3000 perfluoropolyether oil attached to a glass fibre before
transfer into the cold stream of the low temperature device on
the diffractometer. Crystal data. C13H16O4S2, M = 300.38,
monoclinic, a = 9.907(7), b = 5.888(4), c = 12.317(6) Å, β =
103.06(5)Њ, U = 699.8(6) Å3, T = 150(2) K, space group P21 (No.
4), Z = 2, Dc = 1.425 g cmϪ3, µ(Mo-Kα) = 0.387 mmϪ1, 2458
28 H. D. Flack, Acta Crystallogr., Sect. A, 1983, 39, 876.
† CCDC reference number 207/383. See http://www.rsc.org/suppdata/
p1/a9/a908391j/ for crystallographic files in .cif format.
Paper a908391j
J. Chem. Soc., Perkin Trans. 1, 2000, 153–163
163