Synthesis of cyclic ethers and allylic sulfides by rearrangement of phenylsulfanyl substituted 1,n-diols with toluene-p-sulfonic acid and with toluene-p-sulfonyl chloride

Article abstract of DOI:10.1039/a905498g

Rearrangement of a series of l,n-diols (n = 2 to 12), with a PhS-group adjacent to one OH group, under two sets of conditions gives single compounds in excellent yield drawn for four possible classes of products. The effect of the chain length helps in the understanding of the different cyclisation modes and the mechanism of the rearrangements. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905498g

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Synthesis of cyclic ethers and allylic sulfides by rearrangement of
phenylsulfanyl substituted 1,n-diols with toluene-p-sulfonic acid and
with toluene-p-sulfonyl chloride
Laurent Djakovitch,a Jason Eames,*ab David J. Fox,a Francis H. Sansburya and
Stuart Warren*a
a University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW
b Department of Chemistry, Queen Mary and Westfield College, Mile End Road, London,
UK E1 4NS
Received (in Cambridge, UK) 8th July 1999, Accepted 19th August 1999
Rearrangement of a series of 1,n-diols (n = 2 to 12), with a PhS-group adjacent to one OH group, under two sets of
conditions gives single compounds in excellent yield drawn for four possible classes of products. The effect of the
chain length helps in the understanding of the different cyclisation modes and the mechanism of the rearrangements.
Treatment of a β-hydroxy sulfide, e.g. 1 with acid gives rise to
the formation of an intermediate episulfonium ion e.g. 2, by
stereospecific loss of water.1 This high energy episulfonium ion
cannot be isolated and prefers to decompose by the loss of a
proton to give an allylic sulfide.2 Intramolecular capture of
this episulfonium ion is possible with alcohols,3 esters,4 amides5
and thiols6 to give stereospecifically spirocyclic ethers e.g. 3,
lactones, amines and sulfides. Over the course of these studies
we have elaborated rules for the regio- and stereocontrol
(involving stereochemistry, Baldwin’s rules7 and the Thorpe–
Ingold effect)8 for such rearrangements.9 We have always
observed intramolecular cyclisation at the most substituted end
of the episulfonium ion to give THFs like anti-3, amines anti-5
and THP anti-7. In many cases the capture of an episulfonium
ion does not obey Baldwin’s rules due to the partially dis-
favoured endo-nature of some of these cyclisations. For
example, addition of β-hydroxy sulfide anti-1 with catalytic
toluene-p-sulfonic acid (TsOH) gives the episulfonium ion 2
which is captured intramolecularly to give the spirocyclic
ether anti-3 in essentially quantitative yield via a disfavoured
hybrid 6-endo–5-exo-tet cyclisation (Scheme 1).3,4 This 1,2-PhS
migration occurs stereospecifically with inversion of configur-
ation at the migratory terminus.10 Further studies have revealed
that this rearrangement is under thermodynamic control, how-
ever the observed THF anti-3 is the major kinetic product by
far.11
We were interested in extending this cyclisation procedure to
the synthesis of less common larger ring size cyclic ethers and
now report on our investigation into the different possible
modes of cyclisations observed.12 We comment on the effects of
the chain length n between the two hydroxy groups in the diols
8 during acid-catalysed rearrangement and on an alternative
reaction: the rearrangement of the same diols 8 with toluene-p-
sulfonyl chloride (TsCl) in pyridine which give complementary
products to that observed from the acid-catalysed rearrange-
ment. The acid-catalysed rearrangement of these diols occurs
via episulfonium ion formation, while the TsCl in pyridine reac-
tion proceeds via primary toluene-p-sulfonate 10 as an inter-
mediate, which is not usually isolated. The various products
from the rearrangement of the diol 8, n = 3 are illustrated in
Scheme 2; the rearranged allylic sulfides 13, formed by [1,2]-
PhS shift, the allylic sulfide 14 formed by a less common [1,5]-
PhS shift and the two cyclic ethers 11 formed with [1,2]-PhS
migration by a hybrid 7-endo–6-exo-tet cyclisation and 12
formed without PhS migration by a pure 5-exo-tet cyclisation.
Synthesis and rearrangement of 1,2-diol 8, n ؍ 1
We chose to synthesise the diol 8, n = 1 from the allylic sulfide
16, using our modification of the Sharpless racemic dihydroxyl-
ation to introduce the 1,2-diol functionality.13,14 This sulfide 16
was synthesised using the Wittig reaction; methyl triphenyl-
phosphonium iodide was deprotonated with n-BuLi and
quenched with the aldehyde 15. This reaction had to be carried
out in the absence of light because allylic sulfides like 16 are
well known to rearrange (via the radical mechanism)15 to the
more thermodynamically stable allylic sulfide.16 Treatment of
the diol 8, n = 1 under our usual toluene-p-sulfonic acid condi-
tions4 (TsOH in CH2Cl2) gave the allylic sulfide 19, presumably
via elimination of the episulfonium ion 18 (Scheme 3). In con-
trast, treatment of diol 8, n = 1 with TsCl in pyridine gave the
epoxide 17 in 80% yield by chemoselective tosylation (20) of the
primary OH group in 8, n = 1. The structure of this epoxide was
independently confirmed by synthesis from the aldehyde 15
using sulfonium ylide chemistry.17 However, submission of this
epoxide 17 with TsOH causes rearrangement to give the allylic
sulfide 19 by a [1,2]-SPh shift, presumably via the highly
strained oxaspiro[2.2]cyclopentane transition state 22 and the
Scheme 1 Reagents and conditions: a, TsOH, CH2Cl2, reflux; b,
TMSOTf, CH2Cl2, Ϫ78 ЊC.
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This journal is © The Royal Society of Chemistry 1999
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Scheme 2
Scheme 3 Reagents and conditions: a, Me2S᎐᎐CH2, THF, Ϫ78 ЊC; b, Ph3P᎐CH2, THF, Ϫ78 ЊC; c, cat. OsCl3, quinuclidine, K3Fe(CN)6, t-BuOH–H2O;
᎐
d, TsCl, pyridine; e, TsOH, CH2Cl2, reflux.
Scheme 4 Reagents and conditions: a, LiAlH4, Et2O; b, TsCl, pyridine; c, TsOH, CH2Cl2, reflux.
same episulfonium ion 23 in near quantitative yield. It is worthy
Synthesis and rearrangement of 1,3-diol 8, n ؍ 2
of note that neither of the cyclised products such as an oxetane
or the epoxide 17 have been observed in the acid-catalysed
rearrangement, presumably because neither ring closure can
compete with allylic sulfide formation. Under these reaction
conditions the allylic sulfide 19 must be the thermodynamic
product, but it may also be kinetically preferred.
The homologous 1,3-diol 8, n = 2 was synthesised using our
previously developed aldol methodology.4 Reaction of enolate
24 (derived from ethyl acetate and LDA) with aldehyde 15, fol-
lowed by reduction (LiAlH4, ether, 2 h) gave the 1,3-diol 8, n = 2
in excellent yield (Scheme 4). Acid-catalysed rearrangement of
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Table 1 Yields in the synthesis of 1,n-diols 8; n = 3–6, 8 and 11
Reactions → acetal formation
Addition to
aldehyde 15
Hydrolysis
Organolithium
Alcohols 34
Acetal 35
36
Acetals 37
1,n-Diols 8
n = 3; X = Br
n = 4; X = Cl
n = 5; X = Br
n = 6; X = Br
n = 8; X = Br
n = 11; X = Br
n = 3; X = Br
n = 4; X = Cl
n = 5; X = Br
n = 6; X = Br
n = 8; X = Br
n = 11; X = Br
92%
90%
94%
95%
91%
86%
n = 3
n = 4
n = 5
n = 6
n = 8
n = 12
n = 3; 99%
n = 4; 85%
n = 5; 94%
n = 3;
n = 4;
n = 5;
n = 6;
99%
85%
94%
88%
n = 6
96%
n = 8; 87%
n = 11; 99%
n = 8; 100%
n = 11; 89%
this diol gave the expected THF 26 (99%) via a hybrid 6-endo–5-
exo-tet cyclisation—no oxetane by the competing (pure 5-exo-
tet) pathway was observed. Under the TsCl–pyridine condi-
tions, this 1,3-diol gave an unexpected allylic alcohol 28 (97%)
by a [1,4]-SPh shift via the sulfonium ion 30.12,18 Both [1,2]- and
[1,4]-SPh participation are well documented, and are known to
occur at similar rates.19 Presumably [1,4]-SPh rearrangement in
this case is preferred over [1,2]-SPh participation because the
initial chemoselective tosylation, which gives 29, occurs on the
primary alcohol in 8, n = 2 (Scheme 4).
The structure of the allylic alcohol 28 was confirmed
independently by synthesising the alternative allylic sulfide 33
derived from the alternative [1,2]-SPh shift. Chemoselective
protection of the primary alcohol in diol 8, n = 2 using benzoyl
chloride gave 31, rearrangement with TsOH gave the allylic
sulfide 32 via a known [1,2]-SPh shift1 and deprotection (HCl–
1
EtOH) gave the allylic sulfide 33 (Scheme 5). The H NMR
Scheme 6 Reagents and conditions: a, Cl2CHCO2H, ethyl vinyl ether;
b, Li, 1% Na, Et2O, Ϫ20 ЊC; c, HCl, MeOH–H2O (1:1).
Scheme 5 Reagents and conditions: a, PhCOCl, Et3N, CH2Cl2; b,
TsOH, CH2Cl2, reflux; c, HCl, MeOH.
spectra of both 28 and 33 are clearly different, the allylic H in
28 (adjacent to oxygen) came at a much lower field (δ 4.11 ppm)
than the allylic H in 33 (δ 3.65 ppm) which is next to sulfur,
illustrating the difference in electronegativity (Scheme 5).
Synthesis and rearrangement of homologous 1,n-diols 8, n ؍ 3–6,
8 and 11
These remaining homologous 1,n-diols 8, n = 3–6, 8 and 11 were
synthesised using a methodology developed by Eaton et al.20
The required lithium derivatives 36 were synthesised by protect-
ing the alcohols 34 as an acetal 35, and a subsequent halogen–
lithium exchange with a lithium (1% ϩ Na) metal (Table 1).
Addition of these organolithium reagents to the aldehydes 15
followed by deprotection (HCl–H2O–EtOH) (which was easily
achieved without rearrangement) gave the 1,n-diols 8; n = 3–6,
8 and 11 in excellent yield as shown in Scheme 6 and Table 1.
Acid-catalysed rearrangement of the diols 8, n = 3 gave
exclusively the tetrahydropyrans (THP) 11 in quantitative yield.
Rearrangement must occur via a hybrid 7-endo–6-exo-tet
cyclisation onto the most substituted end of the episulfonium
ion 38 as shown in Scheme 7. The alternative THF 12 from a
pure 5-exo-tet cyclisation was not observed. However, treat-
Scheme 7 Reagents and conditions: a, TsCl, pyridine; b, TsOH,
CH2Cl2, reflux.
ment of the 1,4-diol 8, n = 3 with TsCl in pyridine gave this
alternative THF 12 in excellent yield by simple ether formation.
This THF 12 and THP 11 were easily characterised by both 1H
1
and 13C NMR. In the H NMR, the THP 1121 has a double
doublet for Ha with typical six-membered ring axial–axial (11.2
Hz) and axial–equatorial (4.3 Hz) couplings, however for the
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Table 2 Characterisation of pure-exo and hybrid endo–exo cyclic ethers by 13C NMR and mass spectra
Rearranged heterocycle
hybrid endo–exo-cyclic ethers
Unrearranged heterocycle pure exo-cyclic ethers
δc (ppm) or
mass spectrum
Epoxide 17
THF 12
THP 41
DHP 50
THF 26
THP 11
Quaternary carbon (ppm)
(C–S) 59
(C–O) 74
40%
(C–S) 55
(C–O) 80
100%
(C–S) 57
(C–O) 82
70%
(C–S) 57
(C–O) 80
—
(C–O) 84
(C–S) 55
0%
(C–O) 75
(C–S) 55
0%
Tertiary carbon (ppm)
ϩ
191.1 (PhSC6H10
)
M Ϫ 191.1
136.0 (PhSC2H3
5%
0%
65%
0%
100%
0%
—
—
0%
60%
0%
80%
ϩ
)
THF 12 the Ha resonance overlapped with the other CH2O
protons. The most reliable method came from the 13C NMR
spectra; the THF has a quaternary carbon next to PhS (δ 55)
and a CH group next to oxygen (δ 80), while the THP has a
quaternary carbon next to oxygen (δ 75) and a CH group next
to PhS (δ 55). Additionally, in the mass spectrum, the THF 12
fragments between the ring and the C6H10SPh group and both
fragments (C6H10SPh and C4H7O) are observed. No such frag-
mentation is possible with the THP 11 which gives a PhSC2H3
fragment as the base peak (Table 2).
With this THF 12 now available (Scheme 7), we were able to
demonstrate why we have never observed it in the acid-catalysed
rearrangement of these types of diols such as 8, n = 3. Submis-
sion of this THF under our usual TsOH–CH2Cl2 conditions for
5 min gave the THP 11 in quantitative yield. It is clear the THP
11 is the thermodynamic product from the acid-catalysed
rearrangement. New evidence suggests that the THF 12 is the
major kinetic product of cyclisation onto episulfonium ions
like 38.21
heterocycle (Table 2). However, by 1H NMR the THP 41 has an
unusual double doublet for Ha with axial–axial (10.82 Hz) and
axial–equatorial (1.65 Hz) couplings, which are untypical for a
six membered ring. Resubmission of this THP 41 under pro-
longed heating with TsOH in toluene (12 hours) gave the more
thermodynamic allylic sulfide 42 (92%) and clearly this allylic
sulfide is the thermodynamic product from the cyclisation. In
comparison TsCl–pyridine on diol 8, n = 4 gave the same THP
41 but in 98% yield, by simple ether formation.
We were next interested in improving this 6-exo-tet cyclis-
ation by increasing the effective concentration of the nucleo-
philic OH group in 40 by having a (Z)-alkene in the tethered
chain. The synthesis of diol (Z)-48 was achieved by trimethyl-
silyl protection of the OH group in the ester 25, and DIBAL-H
reduction gave the aldehyde 44 in good yield (Scheme 9). A
Acid-catalysed rearrangement of the homologous 1,5-diol 8,
n = 4 gave for the first time a mixture of products—the THP 41
(59%) and the allylic sulfide 42 (13%)—in a combined yield of
only 72% as illustrated in Scheme 8. Presumably capture of the
Scheme 9 Reagents and conditions: a, Me3SiCl, Et3N, CH2Cl2, 0 ЊC;
b, DiBAL, THF, Ϫ78 ЊC; c, 2 eq. n-BuLi, THF, Ϫ78 ЊC; d, Me3SiCl;
e, 44, THF, Ϫ78 ЊC; e, TBAF, THF.
subsequent Wittig reaction with 46 gave a stereoisomeric mix-
ture (ratio of 1:1) of alkenes (E) and (Z)-47, and deprotection
with TBAF in THF gave a separable mixture of the (E)- and
(Z)-alkene 48 in low yield. In contrast to the long chain diol 8,
n = 4, the rearrangement of the (Z)-alkene 48 gave quantitative
formation of the dihydropyran (DHP) 50, whereas unsurpris-
ingly the (E)-alkene 48 preferred to eliminate to give the allylic
sulfide (E,E)-51. Presumably the cyclisation of (Z)-49 is more
favourable than 40 and elimination cannot compete (Scheme
10).
Rearrangement of the remaining diols 8, n = 5, 6, 8 and 11
under acid catalysed conditions gave the allylic sulfides 53–56
in near quantitative yield (Table 3). For example, cyclisation
of diol 8, n = 5 no longer occurs (the chain length appears to be
Scheme 8 Reagents and conditions: a, TsCl, pyridine; b, TsOH,
CH2Cl2, reflux.
episulfonium ion 40 by a pure 6-exo-tet cyclisation to give the
THP 41 becomes less entropically favoured as the chain length n
increases. Competing elimination of the episulfonium ion 40
gave the allylic sulfide 42 with an overall [1,2]-SPh shift. The
alternative oxepine from a hybrid 8-endo–7-exo-tet in 40 was
not observed. The THP 41 was assigned from the chemical
shifts in the 13C NMR spectrum and the mass fragmentation
pattern, which was characteristic of this type of unrearranged
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too long and formation of the oxepine is disfavoured), and elim-
ination of the episulfonium ion 52 is most preferred to give the
allylic sulfide 53 in 95% yield. The TsCl–pyridine reaction
finally gave the isolable primary toluene-p-sulfonate 10, n = 2
(90%) from diol 8, n = 5 as neither the cyclic ether formation
nor a [1,7]-SPh shift is favourable (Scheme 11).
oxepines (8, n = 3 and 4), and THF’s are favoured only over
oxetanes (8, n = 2). As a consequence of the increase of the
chain length n pure exo-ring closure to give unrearranged cyclic
ethers is favoured—this is purely a thermodynamic con-
sequence. This acid-catalysed rearrangement predictably gives
one compound in near quantitative yield (Table 3).
In the TsCl–pyridine reactions, all diols cyclise by simple
ether formation, except when cyclisation is disfavoured by
either ring strain (e.g., 8, n = 2 where the competitive [1,4]-SPh
occurs) or when the chain length is too long (8, n = 5) and 10,
n = 5 is isolated. Furthermore, cyclisation onto the toluene-p-
sulfonate proceeds under kinetic control. By comparison both
reactions (TsCl–pyridine and TsOH–CH2Cl2) are very sensitive
to ring strain, and disfavour four membered ring formation
(8, n = 2 and 3).
Conclusion
In the acid-catalysed rearrangement of 1,n-diols 8, n = 2, 3, 4, 5,
6, 8 and 11, we have undoubtedly shown that the reaction is
under thermodynamic control. By comparison of the products,
we can deduce that allylic sulfides are formed when the chain
length is too short (8, n = 1) or too long (8, n > 4) for efficient
cyclisation. The rearranged heterocycles are formed only if
the ring size is n = 2 (for THF’s) and n = 3 and 4 (for THP’s) but
not otherwise—THP’s are favoured over both THF’s and
Experimental
All solvents were distilled before use. Tetrahydrofuran (THF)
and ether were freshly distilled from LiAlH4, whilst dichloro-
methane (CH2Cl2) and toluene were freshly distilled from
CaH2. Triphenylmethane was used as the indicator for THF.
n-BuLi was titrated against diphenylacetic acid before use. All
reactions were carried out under nitrogen using oven-dried
glassware. Flash column chromatography was carried out using
Merck Kieselgel 60 (230–400 mesh). Thin layer chromato-
graphy (TLC) was carried out on commercially available
pre-coated plates (Merck Kieselgel 60F254 silica). Proton and
carbon NMR spectra were recorded on a Bruker WM 200, WM
250 or WM400 Fourier transform spectrometers using an
internal deuterium lock. Chemical shifts are quoted in parts
Scheme 10 Reagents and conditions: a, TsOH, CH2Cl2, reflux.
Scheme 11 Reagents and conditions: a, TsCl, pyridine; b, TsOH, CH2Cl2, reflux.
Table 3 Products from the rearrangement of diols 8 and 48 with TsCl–pyridine and with TsOH–CH2Cl2
Product from TsCl–pyridine
Product from TsOH–CH2Cl2
Starting
material
Product type
Yield
Product type
Yield
8; n = 1
8; n = 2
8; n = 3
8; n = 4
Unrearranged heterocycle
[1,4]-SPh Shift
Unrearranged heterocycle
Unrearranged heterocycle
17; 80%
28; 97%
12; 98%
41; 98%
Allylic sulfide
19; 98%
26; 99%
11; 100%
41; 59%
42; 13%
50; 98%
51; 95%
53; 90%
54; 99%
55; 95%
56; 95%
Rearranged heterocycle
Rearranged heterocycle
Unrearranged heterocycle
Allylic sulfide
Unrearranged heterocycle
Allylic sulfide
Allylic sulfide
Allylic sulfide
Allylic sulfide
Allylic sulfide
(Z)-48
(E)-48
8; n = 5
8; n = 6
8; n = 8
8; n = 11
—
—
—
—
Primary tosylate
10; n = 5; 90%
—
—
—
—
—
—
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per milllion downfield from tetramethylsilane. Carbon NMR
spectra were recorded with broad proton decoupling and
Attached Proton Test (ATP). The symbol * after the carbon
shift indicates an even number of attached protons; i.e., CH2
or quaternary carbons. The symbols i-, o-, m- and p- denote
the ipso-, ortho-, meta- and para- positions respectively for the
phenyl ring (PhS group). Mass spectra were recorded on a AEI
Kratos MS30 or MS890 machine using a DS503 data system
for high resolution analysis. All compounds were isolated using
flash column chromatography and were assumed to have a
purity of greater than 98% (determined by NMR).
30.7*, 29.5*, 27.5*, 26.2*, 21.8* and 21.8* (7 × CH2) (Found
Mϩ, 280.1502. C16H24O2S requires M, 280.1496); m/z 280.2
(80%, M), 262.1 (M Ϫ H2O), 191.1 (100, C6H10SPh), 171.1 (25,
M Ϫ SPh), 110.0, (80, PhSH) and 81.1 (90, C6H9).
5-[1Ј-(Phenylsulfanyl)cyclohexyl]pentane-1,5-diol 8, n ؍ 4
In the same way as diol 8, n = 3, the acetal 37, n = 4 (0.68 g, 1.85
mmol) and HCl (5 ml, 3 M) in EtOH–H2O (10 ml, 1:1 ratio)
gave, after flash column chromatography on silica gel eluting
with ether, the diol 8, n = 4 (0.52 g, 96%) as an oil; Rf [ether]
0.45; νmax (film, CDCl3)/cmϪ1 3600–3250 (OH); δH(400 MHz,
CDCl3) 7.54–7.25 (5 H, m, SPh), 3.60 (2 H, t, J 6.2, CH2O), 3.24
(1 H, d, J 9.8, CHOH), 3.19 (1 H, br s, OH) and 2.04–1.13
(16 H, m, 8 × CH2); δC(100 MHz, CDCl3) 137.2 (m-SPh),
130.1* (i-SPh), 129.0 (p-SPh), 128.8 (o-SPh), 74.7 (CHOH),
62.7* (CH2O), 61.8* (CSPh), 32.7*, 30.6*, 30.1*, 29.6*, 26.3*,
23.6*, 21.9* and 21.8* (8 × CH2) (Found Mϩ, 294.1651.
C17H26O2S requires M, 294.1653); m/z 294.1 (40%, M), 191.1
(100, C6H10SPh), 185.2 (20, M Ϫ SPh), 109.0 (20, PhSH) and
81.1 (70, C6H9).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]ethane-1,2-diol 8, n ؍ 1
OsCl3ؒ6H2O (84 µg, 14 mmol) was added to a stirred solution
of allylic sulfide 16 (25 mg, 0.14 mmol), K3Fe(CN)6 (0.11 g,
0.42 mmol), K2CO3 (40 mg, 0.42 mmol), quinuclidine (0.9 mg,
14 µmol) and OsCl3ؒ6H2O (84 µg, 14 mmol) in ButOH–H2O
(1 ml, 1:1). The solution was stirred for 1 hour. The solution
was extracted with ether (3 × 20 ml). The combined organic
layers were dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by flash column chromatography
on silica gel eluting with light petroleum (40–60 ЊC)–ether (1:1)
the diol 8, n = 1 (27 mg, 96%) as an oil; Rf [light petroleum (40–
60 ЊC)–ether (9:1)] 0.2; νmax (film, CDCl3)/cmϪ1 3500–3200
(OH); δH(400 MHz, CDCl3) 7.6–7.3 (5 H, m, SPh), 3.8 (1 H, dd,
J 10.6 and 2.68, CHO), 3.65 (1 H, dd, J 10.8 and 7.8, CHA-
HBO), 3.45 (1 H, dt, J 7.8 and 3.1, CHAHBO), 3.3 (1 H, d, J 2.7
CHOH), 2.19 (1 H, dd, J 8.0 and 3.1, CH2OH) and 2.04–1.20
(10H, m, 5 × CH2); δC(100 MHz, CDCl3) 137.2 (m-SPh), 130.0*
(i-SPh), 129.1 (p-SPh), 128.9 (o-SPh), 75.2 (CHOH), 62.7*
(CH2O), 59.3* (CSPh), 30.9*, 30.7*, 26.0*, 21.7* and 21.6*
(5 × CH2) (Found Mϩ, 252.1181. C14H20O2S requires M,
252.1183); m/z 191.1 (60%, C6H10SPh), 109 (30, SPh), 81.1 (100,
C6H9).
6-[1Ј-(Phenylsulfanyl)cyclohexyl]hexane-1,6-diol 8, n ؍ 5
In the same way as diol 8, n = 3, the acetal 37, n = 5 (3.5 g, 9.21
mmol) and HCl (8 ml, 3 M) in EtOH–H2O (40 ml, 1:1) gave,
after flash column chromatography on silica gel eluting with
ether, the diol 8, n = 5 (2.6 g, 94%) as an oil; Rf [ether] 0.5; νmax
(film, CDCl3)/cmϪ1 3600–3300 (OH); δH(400 MHz, CDCl3)
7.49–7.40 (5 H, m, SPh), 3.60 (2 H, t, J 6.6, CH2O), 3.22 (1 H,
dd, J 9.8 and 1.4, CHOH), 3.20 (1 H, br s, OH) and 2.01–1.19
(18 H, m, 8 × CH2); δC(62.5 MHz, CDCl3) 137.2 (m-SPh),
130.1* (i-SPh), 128.9 (p-SPh), 128.8 (o-SPh), 74.6 (CHOH),
62.8* (CH2O), 61.9* (CSPh), 32.6*, 30.5*, 29.6*, 27.1*, 26.3*,
25.9*, 21.9* and 21.8* (8 × CH2) (Found Mϩ, 308.1817.
C18H28O2S requires M, 308.1809); m/z 308.2 (25%, M), 199.1
(25, M Ϫ SPh), 191.1 (90, C6H10SPh), 109.0 (40, PhS), 83.1
(100, C6H11) and 81.0 (90, C6H9).
3-Hydroxy-3-[1Ј-(phenylsulfanyl)cyclohexyl]propanol 8, n ؍ 2
LiAlH4 (0.18 g, 4.7 mmol) was added to a stirred solution of
the ester 37 (0.76 g, 2.36 mmol) in ether (100 ml) at 0 ЊC. The
solution was stirred for 2 hours and poured onto an ice–brine
solution. NaOH (20 ml, 10%) was added and the solution was
extracted with ether (3 × 100 ml). The combined organic layers
were dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by flash column chromatography on
silica gel eluting with ether to give the diol 8, n = 2 (0.56 g, 90%)
as an oil; Rf [ether] 0.40; νmax (film, CDCl3)/cmϪ1 3500–3200
(broad OH); δH(250 MHz, CDCl3) 7.53–7.26 (5 H, m, SPh),
3.88–3.74 (2 H, m, CHOH and OH), 3.54–3.44 (2 H, m,
CH2OH), 2.77 (1 H, s, OH) and 1.96–1.2 (12 H, m, C5H10 and
CH2CH2OH); δC(100 MHz, CDCl3) 137.2 (m-SPh), 130.0*
(i-SPh), 129.1 (p-SPh), 128.9 (o-SPh), 75.1 (CHOH), 62.2*
(CH2O), 61.8* (CSPh), 32.1*, 30.4*, 29.5*, 26.2*, 21.8* and
21.7* (6 × CH2) (Found: Mϩ, 266.1333. C15H22O2S requires M,
266.1340); m/z 157.1 (82%, M Ϫ SPh).
7-[1Ј-(Phenylsulfanyl)cyclohexyl]heptane-1,7-diol 8, n ؍ 6
In the same way as diol 8, n = 3, the acetal 37, n = 6 (74 mg, 0.23
mmol) and HCl (5 ml, 3 M) in EtOH–H2O (10 ml, 1:1 ratio)
gave, after flash column chromatography on silica gel eluting
with ether, the diol 8, n = 6 (67 mg, 88%) as an oil; Rf [ether]
0.45; νmax (film, CDCl3)/cmϪ1 3600–3250 (OH); δH(250 MHz,
CDCl3) 7.52–7.24 (5 H, m, SPh), 3.60 (2 H, t, J 6.6, CH2O), 3.21
(1 H, dd, J 9.4 and 2.0, CHOH) and 1.99–1.09 (21 H, m, 10 ×
CH2 and OH); δC(62.5 MHz, CDCl3) 137.2 (m-SPh), 130.2
(i-SPh), 129.0 (p-SPh), 128.8 (o-SPh), 74.7 (CHOH), 63.0
(CH2O), 62.0 (CSPh), 32.7, 30.6, 30.5, 29.6, 29.5, 27.4, 26.3,
25.6, 21.9 and 21.8 (10 × CH2).
9-[1Ј-(Phenylsulfanyl)cyclohexyl]nonane-1,9-diol 8, n ؍ 8
In the same way as diol 8, n = 3, the acetal 37, n = 8 (80 mg, 0.23
mmol) and HCl (5 ml, 3 M) in EtOH–H2O (10 ml, 1:1 ratio)
gave, after flash column chromatography on silica gel eluting
with ether, the diol 8, n = 8 (78 mg, 100%) as an oil; Rf [ether] 0.4
νmax (film, CDCl3)/cmϪ1 3600–3250 (OH); δH(250 MHz, CDCl3)
7.50–7.25 (5 H, m, SPh), 3.60 (2 H, t, J 6.6, CH2O), 3.22 (1 H, d,
J 9.9 and 1.0, CHOH), 3.07 (1 H, s, OH) and 1.98–1.18 (24 H,
m, 12 × CH2); δC(62.5 MHz, CDCl3) 137.3 (m-SPh), 130.2
(i-SPh), 129.0 (p-SPh), 128.8 (o-SPh), 74.7 (CHOH), 63.0
(CH2O), 62.0 (CSPh), 32.8, 30.6, 29.7, 29.6, 29.5, 29.4, 27.4,
26.3, 25.7 and 21.9 (12 × CH2).
4-[1Ј-(Phenylsulfanyl)cyclohexyl]butane-1,4-diol 8, n ؍ 3
HCl (2 ml, 3 M) was added to a stirred solution of the acetal 37,
n = 3 (0.14 g, 0.39 mmol) in EtOH–water (5 ml, 1:1). The solu-
tion was stirred for 1 hour. Na2CO3 (solid) was added (until the
pH = 7). H2O (50 ml) was added and the solution was extracted
with ether (3 × 100 ml). The combined organic layers were
dried (MgSO4) and evaporated under reduced pressure. The
residue was purified by flash column chromatography on silica
gel eluting with ether to give the diol 8, n = 3 (0.12 g, 99%) as an
oil; Rf [ether] 0.45; νmax (film, CDCl3)/cmϪ1 3600–3200; δH(400
MHz, CDCl3) 7.49–7.25 (5 H, m, SPh), 3.67–3.54 (3 H, m, OH
and CH2OH), 3.27–3.21 (1 H, d, J 10.2, CHOH), 2.96–2.88
(1 H, br s, OH) and 2.00–1.12 (14 H, m, 7 × CH2); δC(100 MHz,
CDCl3) 137.22 (m-SPh), 130.0* (i-SPh), 129.0 (p-SPh), 128.8
(o-SPh), 74.9 (CHO), 62.8* (CH2O), 61.7* (CSPh), 30.8*,
12-[1Ј-(Phenylsulfanyl)cyclohexyl]dodecane-1,12-diol 8, n ؍ 11
In the same way as diol 8, n = 3, the acetal 37, n = 12 (107 mg,
0.23 mmol) and HCl (5 ml, 3 M) in EtOH–H2O (10 ml, 1:1
ratio) gave, after flash column chromatography on silica gel
2776
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782

View Article Online
eluting with ether, the diol 8, n = 8 (80 mg, 89%) as an oil; Rf
[ether] 0.50; νmax (film, CDCl3)/cmϪ1 3600–3250 (OH); δH(250
MHz, CDCl3) 7.54–7.25 (5 H, m, SPh), 3.60 (2 H, t, J 6.6,
CH2O), 3.22 (1 H, dd, J 11.2 and 1.9, CHOH) and 2.39–1.09
(32 H, m, 15 × CH2 and 2 × OH); δC(62.5 MHz, CDCl3) 137.2
(o-SPh), 130.1 (i-SPh), 128.9 (p-SPh), 128.6 (m-SPh), 74.6
(CHOH), 62.9 (CSPh), 61.8 (CH2O), 32.6, 30.4, 29.7, 29.5, 29.3,
27.3, 26.1, 25.6, 21.8 and 21.7 (15 × CH2).
TsOH rearrangement of THF 12 to give the THP 11
In the same way as THP 11, the tetrahydrofuran 12 (50 mg,
0.20 mmol) and toluene-p-sulfonic acid (37 mg, 0.20 mmol)
in CH2Cl2 (3 ml) gave, after flash column chromatography on
silica gel eluting with light petroleum (40–60 ЊC)–ether (9:1),
the tetrahydropyran 11 (49.5 mg, 99%) as an oil; identical
spectroscopically to that obtained previously.
[1-(Phenylsulfanyl)cyclohexyl]ethene 16
6-Hydroxy-6-[1Ј-(phenylsulfanyl)cyclohexyl]hexyl toluene-p-
sulfonate 10, n ؍ 5
n-BuLi (3.63 ml, 1.3 M in hexanes, 4.73 mmol) was added to a
solution of methyltriphenylphosphonium iodide (1.16 g, 4.51
mmol) in THF (50 ml) at Ϫ78 ЊC. The solution was stirred for
5 min. A solution of the aldehyde 15 (1.0 g, 4.51 mmol) in THF
(10 ml) was added. The solution was stirred for 1 h. Saturated
NH4Cl (5 ml) was added and the solution was allowed to warm
to room temperature and extracted with ether (3 × 50 ml). The
combined organic layers were dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by flash col-
umn chromatography on silica gel eluting with light petroleum
(40–60 ЊC)–ether (9:1) to give the allylic sulfide 16 (0.94 g, 95%)
as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.3; νmax
Toluene-p-sulfonyl chloride (72 mg, 3.25 mmol) was added to a
stirred solution of diol 8, n = 5 (0.1 g, 3.25 mmol) in pyridine
(1 ml). The solution was stirred for 12 hours. Ether (20 ml) was
added and the solution was extracted with HCl (10 ml, 3 M)
and evaporated under reduced pressure. The residue was puri-
fied by flash chromatography on a silica gel column with light
petroleum (40–60 ЊC)–ether (1:1) to give the toluene-p-
sulfonate 10, n = 5 (0.135 g, 90%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (1:1)] 0.3; νmax (film, CDCl3)/cmϪ1 3200 (OH);
δH(250 MHz, CDCl3) 7.78 (2 H, d, J 8.3, o-SO2Ar), 7.51–7.28
(7 H, m, SPh and m-SO2Ar), 3.93 (2 H, t, J 6.5, CH2O), 3.18
(1 H, dd, J 9.3 and 2.2, CHOH), 3.08 (1 H, br s, OH), 2.42 (3 H,
s, CH3, Ar) and 2.04–1.10 (20 H, m, 10 × CH2); δC(62.5 MHz,
CDCl3) 144.6* (i-OAr), 137.2 (m-SPh), 133.2 (i-SPh), 130.1*
(i-CCH3, Ar), 129.8 (o-SPh), 129.0 (p-SPh), 128.8 (o-SO2Ar),
127.8 (m-SO2Ar), 74.5 (CHOH), 70.6* (CH2O), 61.8* (CSPh),
30.6*, 30.3*, 29.6*, 28.8*, 26.7*, 26.2*, 25.5*, 21.8* and 21.8*
(10 × CH2) and 21.6 (CH3, Ar) (Found Mϩ, 462.1887. C25H34-
O4S2 requires M, 462.1898); m/z 462.1 (2%, M), 353.2 (40,
M Ϫ SPh), 191.1 (55, C6H10SPh), 91.1 (100, C7H7) and 81.1 (90,
C6H9).
(film, CDCl3)/cmϪ1 1660 (C᎐C); δ (250 MHz, CDCl ) 7.51–
᎐
H
3
7.19 (5 H, m, SPh), 5.74 (1 H, dd, J 17.7 and 10.7, CH), 4.96
(1 H, dd, J 10.7 and 1.0, CHAHB), 4.57 (1 H, dd, J 17.7 and 1.0,
CHAHB) and 1.75–1.20 (10 H, m, 5 × CH2) (Found Mϩ,
218.1132. C14H18S requires M, 218.1129); m/z 218.1 (20%, M),
109.1 (95, PhS and M Ϫ SPh) and 67.1 (100, C5H7).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]epoxyethane 17
In the same way as toluene-p-sulfonate 10, n = 5 the diol 8, n = 1
(0.16 g, 0.62 mmol) and toluene-p-sulfonyl chloride (0.15 g,
0.68 mmol) in pyridine (2 ml) gave, after flash column chrom-
atography on silica gel eluting with light petroleum (40–60 ЊC)–
ether (1:1), the epoxide 17 (0.11 g, 80%) as an oil; Rf [light
petroleum (40–60 ЊC)–ether (1:1)] 0.5; νmax (film, CDCl3)/cmϪ1
1600 (SPh); δH(400 MHz, CDCl3) 7.39–7.19 (5 H, m, SPh), 3.40
(1 H, dd, J 10.5 and 2.3, CHAHBO), 3.32 (1 H, dd, J 13.8 and
2.3, CHAHBO), 2.90 (1 H, dd, J 13.8 and 10.5, CHCH2O)
and 1.72–1.09 (10 H, m, 5 × CH2); δC(100 MHz, CDCl3) 137.2
(m-SPh), 130.6* (i-SPh), 128.7 (p-SPh), 128.7 (o-SPh), 73.6
(CHO), 62.6* (CH2O), 59.1* (CSPh), 36.7*, 30.7*, 30.4*, 25.2*
and 21.7* (5 × CH2) (Found Mϩ, 234.1076. C14H18OS requires
M, 234.1078); m/z 282.1 (15%, M), 191.1 (40, C6H10SPh), 173.1
(5, M Ϫ SPh) and 81.1 (100, C6H9).
5-(Phenylsulfanyl)-1-oxaspiro[5.5]undecane 11
Toluene-p-sulfonic acid (3 mg, 17 µmol) was added to a stirred
solution of diol 8, n = 3 (25 mg, 89 µmol) in CH2Cl2 (2 ml). The
solution was refluxed for 5 min. The solution was allowed to
cool to room temperature and filtered through a silica plug. The
solvent was removed under reduced pressure. The residue was
purified by flash column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (9:1) to give the tetra-
hydropyran 11 (23.1 mg, 99%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (9:1)] 0.4; νmax (film, CDCl3)/cmϪ1 1600 (SPh);
δH(400 MHz, CDCl3) 7.49–7.17 (5 H, m, SPh), 3.66–3.56 (2 H,
m, CH2O), 3.03 (1 H, dd, J 11.2 and 4.3, CHSPh) and 2.22–1.05
(14 H, m, 7 × CH2); δC(62.5 MHz, CDCl3) 136.1* (i-SPh), 13.4
(m-SPh), 128.9 (p-SPh), 126.6 (o-SPh), 75.4* (CO), 60.0*
(CH2O), 55.5 (CHSPh), 36.3*, 27.2*, 26.4*, 25.9*, 21.3* and
20.6* (6 × CH2) (Found Mϩ, 262.1395. C16H22OS requires M,
262.1391); m/z 262.1 (25%, M), 165.1 (100, C4H8SPh), 136.0
(80, C2H3SPh) and 109.0 (5, PhS).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]epoxyethane 17
n-BuLi (2.37 ml, 1.3 M in hexanes, 3.28 mmol) was added to a
stirred solution of trimethylsulfonium iodide (0.64 g, 3.13
mmol) in THF (20 ml) at Ϫ30 ЊC. A solution of aldehyde 15
(0.69 g, 3.13 mmol) in THF (1 ml) was added. The solution was
stirred for 1 hour. Saturated NH4Cl (5 ml) was added and the
solution was extracted with ether (3 × 50 ml). The combined
organic layers were dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by flash column
chromatography on silica gel eluting with light petroleum
(40–60 ЊC)–ether (9:1) to give the epoxide 17 (0.64 g, 89%) as an
oil; identical spectroscopically to that obtained previously.
2-[1Ј-(Phenylsulfanyl)cyclohexyl]tetrahydrofuran 12
In the same way as toluene-p-sulfonate 10, n = 5, the diol 8,
n = 3 (70 mg, 0.25 mmol) and toluene-p-sulfonyl chloride (52
mg, 0.25 mmol) gave, after flash column chromatography on
silica gel eluting with light petroleum (40–60 ЊC)–ether (9:1),
the tetrahydrofuran 12 (65 mg, 98%) as an oil; Rf [light petrol-
eum (40–60 ЊC)–ether (9:1)] 0.2; νmax (film, CDCl3)/cmϪ1 1600
(SPh); δH(400 MHz, CDCl3) 7.56–7.24 (5 H, m, SPh), 3.89–3.82
(1 H, dt, J 6.6 and 6.7, OCHAHB), 3.72–3.70 (2 H, m, OCHAHB
and CHO) and 2.08–1.18 (14 H, m, 7 × CH2); δC(100 MHz,
CDCl3) 137.3 (m-SPh), 131.8* (i-SPh), 128.4 (o- and p-SPh),
84.4 (CHO), 68.7* (CH2O), 56.6* (CSPh), 32.1*, 30.2*, 26.6*,
26.3*, 26.0*, 21.8* and 21.7* (7 × CH2) (Found Mϩ, 262.1389.
C16H22OS requires M, 262.1391); m/z 262.1 (30%, M), 191.1
(100, C6H10SPh), 153.1 (90, M Ϫ SPh), 123.0 (20, CH2SPh),
81.1 (65, C6H9) and 71.1 (65, M Ϫ C6H10SPh).
2-Cyclohexenyl-2-(phenylsulfanyl)ethanol 19
In the same way as THP 11, n = 2 the diol 8, n = 1 (59 mg, 59
µmol) and toluene-p-sulfonic acid (2 mg, 11 µmol) in CH2Cl2
(1 ml) gave, after flash column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (1:1), the allylic
sulfide 19 (13.7 mg, 96%) as an oil; Rf [light petroleum (40–
60 ЊC)–ether (1:1)] 0.5; νmax (film, CDCl3)/cmϪ1 3250 (OH);
δH(400 MHz, CDCl3) 7.40–7.22 (5 H, m, SPh), 5.46 (1 H, s,
CH᎐C), 3.78–3.80 (1 H, m, CHSPh), 3.66 (1 H, q, J 6.9, CH -
᎐
A
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782
2777

View Article Online
HBOH), 3.62 (1 H, q, J 6.9, CHAHBOH), 2.15–2.07 (2 H, m,
CH ᎐C), 1.98–1.93 (2 H, m, CH ᎐C), 1.91 (1 H, t, J 6.9, OH)
m, SPh), 5.67 (1H, s, C᎐CH), 4.11 (1 H, t, J 7.0, CHOH), 3.02–
2.92 (2 H, m, CH2SPh), 2.01–1.51 (10 H, m, 5 × CH2) and 1.64
᎐
᎐
᎐
2
2
and 1.87–1.50 (4 H, m, 2 × CH2); δC(100 MHz, CDCl3) 133.1
(1 H, s, OH); δ (100 MHz, CDCl ) 139.3* (C᎐CH), 136.5*
᎐
C 3
(m-SPh), 128.7 (p-SPh), 127.4 (o-SPh), 126.3 (CH᎐C), 62.6*
(i-SPh), 129.1 (m-SPh), 128.9 (o-SPh), 125.8 (p-SPh), 123.4
᎐
(CH2OH), 58.5 (CHSPh), 26.0* and 25.2* (2 × CH2), 22.6* and
22.2* (2 × CH2) (Found Mϩ, 234.1075. C14H18OS requires M,
234.1078); m/z 234.1 (15%, M), 203.1 (30, M Ϫ CH2OH), 109.0
(30, SPh) and 81.1 (100, C6H9).
(CH᎐C), 75.2 (CHOH), 34.2* (CH -SPh), 30.8*, 29.7*, 24.9*,
᎐
2
23.6* and 22.6* (5 × CH2) (Found: Mϩ, 248.1237. C15H20OS
requires M, 248.1235); m/z 248.1 (100%, M), 139 (10, M Ϫ SPh)
and 81 (40, M Ϫ C3H6OSPh).
TsOH rearrangement of epoxide 17 to the allylic sulfide 19
3-Hydroxy-3-[1Ј-(phenylsulfanyl)cyclohexyl]propyl benzoate 31
In the same way as THP 11, n = 2 the epoxide 17 (20 mg, 85
µmol) and toluene-p-sulfonic acid (4 mg, 17 µmol) in CH2Cl2
(1 ml) gave, after flash column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (1:1), the allylic
sulfide 19 (19 mg, 100%) as an oil; identical spectroscopically to
that obtained previously.
Benzoyl chloride (0.4 g, 0.27 ml, 2.88 mmol) was added slowly
to a stirred solution of diol 8, n = 2 (0.9 g, 2.88 mmol), and
Et3N (0.29 g, 0.4 ml, 2.88 mmol) in CH2Cl2 (30 ml). The solu-
tion was stirred for 5 hours. Saturated NH4Cl (10 ml) was added
and the solution was extracted with ether (3 × 100 ml). The
combined organic layers were dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by flash
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1) to give the benzoate 31 (1.02 g,
81%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (1:1)] 0.51;
νmax (film, CDCl3)/cmϪ1 1740 (CO2Ph); δH(400 MHz, CDCl3)
Ethyl 3-hydroxy-3-[1Ј-(phenylsulfanyl)cyclohexyl]propanoate 25
n-BuLi (8.46 ml, 1.3 M in hexanes, 11 mmol) was added to
diisopropylamine (1.41 g, 1.90 ml, 14 mmol) in THF (50 ml) at
Ϫ78 ЊC. The solution was stirred for 30 min. Ethyl acetate (0.88
g, 0.98 ml, 10 mmol) in THF (3 ml) was added slowly to this
solution. The solution was stirred for 30 min. The aldehyde 15
(2 g, 9 mmol) in THF (10 ml) was added slowly. The solution
was stirred for a further 30 min. Saturated NH4Cl (20 ml) was
added and the solution was allowed to warm to room temper-
ature. The solution was extracted with ether (3 × 100 ml). The
combined organic layers were dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by flash col-
umn chromatography on silica gel eluting with light petroleum
(40–60 ЊC)–ether (9:1) to give the ester 25 (3.17 g, 93%) as a
solid, mp 70–71 ЊC (from hexane); Rf [light petroleum (40–
60 ЊC)–ether (1:1)] 0.40; νmax (film, CDCl3)/cmϪ1 1730 (CO2);
δH(250 MHz, CDCl3) 7.53–7.25 (5 H, m, SPh), 4.16 (2H, q,
J 7.1, CH2CH3), 3.87 (1 H, d, J 10.2, OH), 3.08 (1 H, d, J 3.1,
7.95–7.19 (10 H, m, Ph-C᎐O and SPh), 4.55–4.45 (2 H, m,
᎐
CH2O), 3.53–3.45 (1 H, dd, J 10.5 and 1.1, CHOH), 3.30–3.00
(1 H, s, OH), 2.25–1.95 (1 H, ddt, J 15.0, 9.0 and 1.1, CHCHD-
CH2O) and 2.03–1.07 (11 H, m, CHCHDCH2 and 5 × CH2);
δ (100 MHz, CDCl ) 166.6* (C᎐O), 137.3 (m-SPh), 132.9
᎐
C
3
(m-Ph-C᎐O), 130.4* (i-SPh), 130.2* (i-Ph-C᎐O), 129.6 (o-Ph-
᎐
᎐
C᎐O), 129.0 (p-Ph-C᎐O), 128.6 (p-SPh), 128.3 (o-SPh), 71.5
᎐
᎐
(CHOH), 63.0* (CH2O), 60.6* (CSPh), 30.3*, 30.0*, 29.8*,
26.2*, 21.8* and 21.8* (6 × CH2) (Found Mϩ, 370.1594.
C22H26O3S requires M, 370.1602); m/z 370.2 (75%, M), 352.2
(25, M Ϫ H2O), 261.2 (40, M Ϫ SPh), 243.1 (75, M Ϫ SPh Ϫ
H2O), 191.1 (75, C6H11SPh), 139.1 (80, M Ϫ SPh Ϫ OH Ϫ Ph-
C᎐O), 121.1 (80, PhCO ), 105.0 (100, Ph-C᎐O) and 77.0 (75,
᎐
᎐
2
Ph).
OH), 2.90 (1 H, dd, J 15.7 and 2.1, CH H C᎐O), 2.54 (1 H, dd,
᎐
B
A
3-Cyclohexenyl-3-(phenylsulfanyl)propyl benzoate 32
J 15.7 and 10.3, CH H C᎐O), 1.93–1.15 (10 H, m, 5 × CH )
᎐
A
B
2
and 1.27 (3 H, t, J 7.1, CH3); δC(100 MHz, CDCl3) 173.2*
In the same way as THP 11, the benzoate 31 (0.4 g, 1 mmol) and
toluene-p-sulfonic acid (41 mg, 0.2 mmol) in CH2Cl2 (2 ml)
gave, after flash column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (1:1), the allylic sulfide
32 (0.37 g, 97%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(1:1)] 0.5; νmax (film, CDCl3)/cmϪ1 1750 (CO2); δH(200 MHz,
(C᎐O), 137.3 (m-SPh), 131.9* (i-SPh), 129.0 (p-SPh), 128.8
᎐
(m-SPh), 72.7 (CHOH), 60.7 (CH2O), 58.7* (CSPh), 36.4*,
30.3*, 30.1*, 25.9* and 21.7* (5 × CH2) and 14.2 (CH3) (Found
Mϩ, 308.1435. C17H24O3S requires M, 308.1446); m/z 199.1
(18%, M Ϫ SPh).
CDCl ) 8.15–7.95 (2 H, m, o- to C᎐O, PhCO ), 7.59–7.17 (8 H,
᎐
3
2
4-(Phenylsulfanyl)-1-oxaspiro[4.5]decane 26
m, SPh, p- and m- to C᎐O, PhCO ) 5.45 (1 H, br s, CH᎐C),
᎐
᎐
2
4.99–4.27 (2 H, m, CH2O), 3.76–3.69 (1 H, t, J 3.7, CHSPh) and
2.31–1.42 (10 H, m, 5 CH2); δC(62.5 MHz, CDCl3) 166.4*
In the same way as THP 11, the diol 8, n = 2 (0.1 g, 0.37 mmol)
and toluene-p-sulfonic acid (22 mg, 0.10 mmol) in THF (2 ml)
gave, after flash column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (9:1), the tetrahydro-
furan 26 (92 mg, 99%) as an oil; Rf [light petroleum (40–60 ЊC)–
ether (1:1)] 0.78; νmax (film, CDCl3)/cmϪ1 1600 (SPh); δH(250
MHz, CDCl3) 7.47–7.17 (5 H, m, SPh), 3.97–3.86 (1 H, dt, J 9.0
and 5.0, OCHAHB), 3.86–3.77 (1 H, dt, J 8.8 and 6, OCHAHB),
3.40–3.32 (1 H, t, J 7.7, CHSPh), 2.50–2.36 (1 H, ddt, J 8.0, 7.0
and 2.4, CHCHDCH2O), 2.10–1.96 (1 H, ddt, J 10.0, 9.9 and 8.0,
CHCHDCH2O) and 1.75–1.17 (10 H, m, 5 × CH2) (Found Mϩ,
248.1234. C15H20OS requires M, 248.1236); m/z 150.0 (100%,
M Ϫ C6H10O), 135 (60, C2H2SPh), 117 (95, M Ϫ C2H2SPh) and
109.0 (35, SPh).
(C᎐O), 134.9* (i-PhCO ), 133.2, 132.9, 130.2, 129.5, 128.5,
᎐
2
128.3, 127.2 and 126.0 (Ar, SPh and PhCO2), 130.0* (i-SPh),
125.0* (CH᎐C), 109.0 (CH᎐C), 62.9* (CH O), 53.7 (CHSPh),
᎐
᎐
2
31.6* (CH CH᎐C), 25.1*, 24.2*, 22.6* and 22.5* (4 × CH )
᎐
2
2
(Found Mϩ, 352.1473. C22H24O2S requires M, 352.1496); m/z
352.1 (20%, M), 243.1 (80, M Ϫ SPh), 191.1 (15, C6H10SPh),
121.1 (100, PhCO2), 105.0 (55, PhCO) and 109 (25, SPh).
3-Cyclohexenyl-3-(phenylsulfanyl)propanol 33
NaOH (1 ml, 10%) was added to a stirred solution of benzoate
32 (1 g, 2.83 mmol) in MeOH–H2O (10 ml, 1:1). The solution
was stirred for 1 hour. HCl (2 ml, 3 M) was added (until
pH = 7). H2O (10 ml) was added and the solution was extracted
with ether (3 × 50 ml). The combined organic layers were dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (1:1) to give
the allylic sulfide 33 (0.6 g, 85%) as an oil; Rf [light petroleum
(40–60 ЊC)–ether (1:1)] 0.6; νmax (film, CDCl3)/cmϪ1 3200 (OH);
δH(400 MHz, CDCl3) 7.36–7.18 (5 H, m, SPh), 5.30 (1 H, s,
CH᎐C), 3.76–3.63 (3 H, m, CH O and CHSPh) and 2.21–1.12
1-Cyclohexenyl-3-(phenylsulfanyl)propanol 28
In the same way as the toluene-p-sulfonate 10, n = 5, the diol 8,
n = 2 (0.1 g, 0.36 mmol) and toluene-p-sulfonyl chloride (76 mg,
0.40 mmol) in pyridine (1 ml) gave, after column chrom-
atography on silica eluting with light petroleum (40–60 ЊC)–
ether (6:4) the allylic alcohol 28 (90.5 mg, 97%) as an oil; Rf
[light petroleum (40–60 ЊC)–ether (6:4)] 0.42; νmax (film,
CDCl3)/cmϪ1 3400 (OH); δH(400 MHz, CDCl3) 7.37–7.11 (5 H,
᎐
2
2778
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782

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(10 H, m, 5 × CH2); δC(100 MHz, CDCl3) 135.8* (i-SPh),
135.0* (C᎐CH), 133.2 (m-SPh), 128.5 (p-SPh), 127.1 (o-SPh),
6-Bromo-1-(1Ј-ethoxyethoxy)hexane 35, n ؍ 6, X ؍ Br
᎐
In the same way as acetal 35, n = 3, the bromo alcohol 34, n = 6;
X = Br (2.1 g, 11.6 mmol) and dichloroacetic acid (0.24 g, 0.16
ml, 1.93 mmol) in ethyl vinyl ether (10 ml) gave, after flash
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the acetal 35, n = 6, X = Br (2.7 g,
95%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.36;
δH(250 MHz, CDCl3) 4.65 (1 H, q, J 5.4, OCHO), 3.68–3.34
(4 H, m, 2 × CH2O), 3.39 (2 H, t, J 6.8, CH2Br), 1.85 (2 H, q,
J 6.6, CH2CH2Br), 1.56 (2 H, q, J 6.6, CH2CH2O), 1.52–1.30
(4 H, m, 2 × CH2), 1.28 (3 H, d, J 5.3, CH3CH) and 1.18 (3 H,
t, J 7.1, CH3CH2); δC(62.5 MHz, CDCl3) 99.5 (OCHO),
65.9 and 65.7 (2 × CH2O), 33.8 (CH2Br), 32.7, 29.0, 27.9 and
25.0 (4 × CH2), 19.8 and 15.2 (2 × CH3) (Found (M Ϫ CH3)ϩ,
237.0488. C9H18O2Br requires M Ϫ CH3, 237.0491); m/z 237.0
(85%, M Ϫ CH3), 163.1 (75, M Ϫ OCH(Me)OEt), and 73.1
(100, M Ϫ (CH2)6Br).
125.5 (CH᎐C), 61.0* (CH2OH), 54.0 (CHSPh), 35.3*
᎐
(CH CH᎐C), 25.2*, 24.1*, 22.7* and 22.4* (4 × CH ) (Found
᎐
2
2
Mϩ, 248.1231. C15H20OS requires M, 248.1234); m/z 248.1
(60%, M), 139.1 (75, M Ϫ SPh), 121.1 (100, CHSPh), 109.0 (55,
SPh) and 58 (20, C3H6O).
5-Bromopentanol 34, n ؍ 5, X ؍ Br
In the same way as alcohol 33, the 5-bromopentyl acetate (12 g,
9.56 ml, 57.4 mmol) and NaOH (20 ml, 10%) in EtOH–H2O
(100 ml, 1:1) gave, after flash column chromatography on silica
gel eluting with ether, the bromo alcohol 34, n = 5, X = Br (8.48
g, 89%) as a liquid; Rf [ether] 0.45; νmax (film, CDCl3)/cmϪ1
3400–3200 (OH); δH(250 MHz, CDCl3) 3.63 (2 H, t, J 6.3,
CH2O), 3.39 (2 H, t, J 6.7, CH2Br) and 2.03–1.42 (7 H, m,
3 × CH2 and OH); δC(62.5 MHz, CDCl3) 62.53* (CH2O),
33.73* (CH2Br), 32.48*, 31.73* and 24.42* (3 × CH2).
8-Bromo-1-(1Ј-ethoxyethoxy)octane 35, n ؍ 8, X ؍ Br
3-Bromo-1-(1Ј-ethoxyethoxy)propane 35, n = 3, X ؍ Br
In the same way as acetal 35, n = 3, the bromo alcohol 35, n = 8,
X = Br (2.0 g, 9.6 mmol) and dichloroacetic acid (0.2 g, 0.13 ml,
1.6 mmol) in ethyl vinyl ether (10 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (40–
60 ЊC)–ether (9:1), the acetal 35, n = 8, X = Br (2.43 g, 91%) as
an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.38; δH(250
MHz, CDCl3) 4.66 (1 H, q, J 5.3, OCHO), 3.68–3.30 (4 H, m,
2 × CH2O), 3.39 (2 H, t, J 6.8, CH2Br), 1.84 (2 H, q, J 6.7, CH2-
CH2Br), 1.55 (2 H, q, J 6.7, CH2CH2O), 1.52–1.28 (4 H, m,
2 × CH2), 1.29 (3 H, d, J 5.4, CH3CH) and 1.18 (3 H, t, J 7.1,
CH3CH2); δC(62.5 MHz, CDCl3) 99.7 (OCHO), 65.4 and
60.8 (2 × CH2O), 34.1 (CH2Br), 32.9, 30.0, 29.4, 28.8, 28.2 and
26.3 (6 × CH2), 20.0 and 15.5 (2 × CH3) (Found (M Ϫ CH3)ϩ,
265.0806. C11H20O2Br requires M Ϫ CH3, 265.0806); m/z 291.2
(13%, Mϩ), 237.0 (14, M Ϫ CH3), 191.1 (75, M Ϫ OCH(Me)-
OEt) and 73.1 (100, M Ϫ (CH2)8Br).
The bromo alcohol 34, n = 3 (7.8 g, 5.07 ml, 56.1 mmol) was
added to ethyl vinyl ether (20 ml) at 0 ЊC. Dichloroacetic acid
(0.72 g, 0.46 ml, 5.61 mmol) was added and the solution was
stirred for 12 hours. Na2CO3 (1 g, solid) was added. The solu-
tion was filtered through a cotton wool plug. The solvent was
removed under reduced pressure. The residue was purified by
flash column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1) to give the acetal 35, n = 3
(10.9 g, 92%) as a liquid; Rf [light petroleum (40–60 ЊC)–ether
(9:1)] 0.45; νmax (film, CDCl3)/cmϪ1 3100 (CH); δH(250 MHz,
CDCl3) 4.70 (1 H, m, OCHO), 3.78–3.42 (6 H, m, CH2Br and
2 × CH2O), 2.12–2.00 (2 H, m, CH2), 1.29 (3 H, d, J 5.3,
CH3CH), 1.15 (3 H, t, J 7.3, CH3) and 1.13 (3 H, t, J 7.0, CH3);
δC(62.5 MHz, CDCl3) 99.9 (OCHO), 62.6* (CH2O), 60.5*
(CH2O), 32.8* (CH2Br), 30.6* (CH2), 19.7 and 15.2 (2 × CH3)
(Found Mϩ, 210.0260. C7H15O2Br requires M, 210.0255); m/z
210.0 (100%, M).
11-Bromo-1-(1Ј-ethoxyethoxy)undecane 35, n ؍ 11, X ؍ Br
In the same way as acetal 35, n = 3, the bromo alcohol 35,
n = 11, X = Br (9 g, 36 mmol) and dichloroacetic acid (0.77 g,
0.49 ml, 6.02 mmol) in ethyl vinyl ether (20 ml) gave, after flash
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the acetal 35, n = 11, X = Br (10 g,
86%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.31;
δH(250 MHz, CDCl3) 4.66 (1 H, q, J 5.3, OCHO), 3.70–3.38
(4 H, m, 2 × CH2O), 3.34 (2 H, t, J 6.8, CH2Br), 1.83 (2 H, q,
J 6.8, CH2CH2Br), 1.52 (2 H, q, J 6.7, CH2CH2O), 1.43–1.26
(14 H, m, 7 × CH2), 1.28 (3 H, d, J 5.4, CH3CH) and 1.21 (3 H,
t, J 6.9, CH3CH2); δC(62.5 MHz, CDCl3) 99.6 (OCHO), 65.8
and 65.4 (2 × CH2O), 34.7 (CH2Br), 32.9, 30.0, 29.7, 29.6, 29.5,
28.9, 28.3 and 26.4 (8 × CH2), 20.0 and 15.5 (2 × CH3) (Found
Mϩ, 322.1500. C15H31O2Br requires M, 322.1508); m/z 322.1
(11%, Mϩ), 307.1 (50, M Ϫ CH3), 233.1 (46, M Ϫ OCH(Me)-
OEt), and 73.1 (100, M Ϫ (CH2)11Br).
4-Chloro-1-(1Ј-ethoxyethoxy)butane 35, n ؍ 4, X ؍ Cl
In the same way as acetal 35, n = 3, the chloro alcohol 34, n = 4
(7.8 g, 7.16 ml, 71.8 mmol) and dichloroacetic acid (0.92 g, 0.63
ml, 7.18 mmol) in ethyl vinyl ether (20 ml) gave, after flash
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the acetal 35, n = 4 (11.7 g, 90%) as
a liquid; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.35; νmax
(film, CDCl3)/cmϪ1 3100 (CH); δH(250 MHz, CDCl3) 4.69 (1 H,
m, OCHO), 3.64–3.37 (6 H, m, CH2Cl and 2 × CH2), 1.87–1.66
(4 H, m, 2 × CH2), 1.28 (3 H, d, J 5.4, CH3CH) and 1.18 (3 H, t,
J 7.0, CH3CH2); δC(62.5 MHz, CDCl3) 99.6 (OCHO), 62.5*
(CH2O), 60.8* (CH2O), 32.8* (CH2Cl), 30.5* and 30.5* (2 ×
CH2), 19.8 and 15.4 (2 × CH3) (Found (M Ϫ CH3)ϩ, 165.0679.
C7H14O2Cl requires M, 165.0682); m/z 165.1 (20%, M Ϫ CH3),
91.1 (90, M Ϫ 1-ethoxyethoxy (OEE)) and 73 (100, M Ϫ
C4H8Cl).
4-(1Љ-Ethoxyethoxy)-1-[1Ј-(phenylsulfanyl)cyclohexyl]butanol
37, n ؍ 3
5-Bromo-1-(1Ј-ethoxyethoxy)pentane 35, n ؍ 5, X = Br
In the same way as acetal 35, n = 3, the bromo alcohol 34, n = 5;
X = Br (10 g, 60.2 mmol) and dichloroacetic acid (0.77 g, 0.49
ml, 6.02 mmol) in ethyl vinyl ether (20 ml) gave, after flash
column chromatography on silica gel eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the acetal 35, n = 5, X = Br (13.47 g,
94%) as an oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.4;
δH(250 MHz, CDCl3) 4.65 (1 H, q, J 5.3, OCHO), 3.70–3.35
(4 H, m, 2 × CH2O), 3.26 (2 H, t, J 6.7, CH2Br), 1.87 (2 H, m,
CH2), 1.65–1.43 (4 H, m, 2 × CH2), 1.29 (3 H, d, J 5.4, CH3CH)
and 1.19 (3 H, t, J 7.1, CH3CH2); δC(62.5 MHz, CDCl3) 99.6
(OCHO), 65.8* and 60.7* (2 × CH2O), 33.8* (CH2Br), 32.6*,
29.0* and 25.0* (3 × CH2), 19.8 and 15.3 (2 × CH3).
Lithium (70 mg, lithium ϩ 1% sodium wire, 10 mmol) was
added to a stirred solution of acetal 35, n = 3 (0.63 g, 3 mmol)
in ether (2 ml) at Ϫ20ЊC. The solution was stirred for 3 hours.
A solution of aldehyde 15 (0.22 g, 1 mmol) in ether (1 ml) was
added. The solution was stirred for 1 hour. Saturated NH4Cl
(10 ml) was added and the solution was extracted with ether
(3 × 50 ml). The combined organic layers were dried (MgSO4)
and evaporated under reduced pressure. The residue was puri-
fied by flash column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1) to give the acetal 37;
n = 3 (0.34 g, 99%) as an oil; Rf [light petroleum (40–60 ЊC)–
ether (1:1)] 0.50; νmax (film, CDCl3)/cmϪ1 3200 (OH); δH(250
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782
2779

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MHz, CDCl3) 7.56–7.21 (10 H, m, SPhA and SPhB), 4.64–4.56 (2
H, m, 2 × CHO), 3.62–3.48 (4 H, m, 2 × OCH2CH2), 3.48–3.31
(4 H, m, 2 × OCH2CH3), 3.28–3.22 (2 H, br s, 2 × OH), 2.03–
(1:1)] 0.44; νmax (film, CDCl3)/cmϪ1 3400–3200 (OH); δH(250
MHz, CDCl3) 7.48–7.24 (5 H, m, SPh), 4.64 (1 H, q, J 5.2,
OCHO), 3.70–3.35 (4 H, m, 2 × CH2O), 3.25 (1 H, s, OH), 3.20
(1 H, dt, J 9.2 and 2.5, CHOH), 1.94–1.14 (20 H, m, 13 × CH2),
1.28 (3 H, d, J 5.3, CH3CH) and 1.20 (3 H, d, J 7.1, CH3CH);
δC(62.5 MHz, CDCl3) 137.2 (m-SPh), 130.2 (i-SPh), 129.0
(p-SPh), 128.8 (o-SPh), 99.5 (OCHO), 74.7 (CHOH), 65.2 and
61.9 (2 × CH2O), 60.6 (CSPh), 32.6, 30.5, 29.8, 29.6, 29.5, 27.4,
26.3, 26.2, 21.9 and 21.8 (10 × CH2), 19.8 (CH3CH) and 15.3
(CH3CH) (Found Mϩ, 394.2510. C23H38O3S requires M,
394.2541); m/z 349.2 (68%, M Ϫ OEt) and 73.0 (100, M Ϫ C19-
H29OS).
A
1.30 (24 H, m, 12 × CH2), 1.25–1.23 (3 H, d, J 1.9, CHCH3 ),
B
1.23–1.20 (3 H, d, J 1.9, CHCH3 ) and 1.20–1.10 (1 H, t,
A
B
J 7.0, CH2CH3 and CH2CH3 ); δC(62.5 MHz, CDCl3) 137.4
(m-SPh), 130.5* (i-SPh), 129.0 (p-SPh), 128.6 (o-SPh), 89.5
(OCHO), 74.9 (HCO), 65.0* (CH2O), 60.7* (CH2O), 55.4*
(CSPh), 29.8*, 27.4*, 27.4*, 26.1* and 23.0* (5 × CH2), 25.7,
22.2, 19.8 and 15.2 (2 × MeA and 2 × MeB) (Found Mϩ,
352.2070. C20H32O3S requires M, 352.2072); m/z 352.2 (20%,
M), 335.0 (5, M Ϫ H2O ϩ H), 306.2 (80, M Ϫ CH3CH2OH),
278.2 (10, M Ϫ CH3CHO Ϫ CH3CH2OH), 191.1 (100,
C6H10SPh) and 110 (30, PhSH).
9-(1Љ-Ethoxyethoxy)-1-[(1Ј-phenylsulfanyl)cyclohexyl]nonanol
37, n ؍ 8
5-(1Љ-Ethoxyethoxy)-1-[(1Ј-phenylsulfanyl)cyclohexyl]pentanol
37, n ؍ 4
In the same way as alcohol 37, n = 3, the chloro acetal 35, n = 8
(0.84 g, 3 mmol), lithium (70 mg, lithium ϩ 1% sodium wire, 10
mmol) and aldehyde 15 (0.22 g, 1 mmol) in ether (15 ml) gave,
after flash column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1), the acetal 37, n = 8
(0.37 g, 87%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(1:1)] 0.44; νmax (film, CDCl3)/cmϪ1 3400–3200 (OH); δH(250
MHz, CDCl3) 7.50–7.25 (5 H, m, SPh), 4.65 (1 H, q, J 5.4,
OCHO), 3.71–3.36 (4 H, m, 2 × CH2O), 3.22 (1 H, dd, J 8.7
and 1.1, CHOH), 1.80–1.16 (24 H, m, 12 × CH2), 1.27 (3 H, d,
J 5.1, CH3CH) and 1.18 (3 H, t, J 7.1, CH3CH2); δC(62.5 MHz,
CDCl3) 137.3 (m-SPh), 130.2 (i-SPh), 129.0 (p-SPh), 128.8
(o-SPh), 99.5 (OCHO), 74.7 (CHOH), 65.3 and 62.0 (2 ×
CH2O), 60.6 (CSPh), 32.8, 30.6, 30.0, 29.7, 29.6, 29.5, 29.4,
27.4, 26.3, 26.2, 25.7 and 21.9 (12 × CH2), 19.9 (CH3CH) and
15.3 (CH3CH2) (Found Mϩ, 422.0000. C25H42O3S requires M,
422.2800); m/z 422.0 (4%, M), 377.1 (75, M Ϫ OEt) and 73.0
(92, M Ϫ C21H33OS).
In the same way as alcohol 37, n = 3, the chloro acetal 35, n = 4
(7.38 g, 40.8 mmol), lithium (0.68 g, lithium ϩ 1% sodium wire,
136 mmol) and aldehyde 15 (3 g, 13.6 mmol) in ether (15 ml)
gave, after flash column chromatography on silica gel eluting
with light petroleum (40–60 ЊC)–ether (1:1), the acetal 37, n = 4
(4.26 g, 85%) as an oil, Rf [light petroleum (40–60 ЊC)–ether
(1:1)] 0. νmax (film, CDCl3)/cmϪ1 3400–3200 (OH); δH(400 MHz,
CDCl3) 7.57–7.27 (5 H, m, SPh), 4.66 (1 H, q, J 5.34, OCHO),
3.64 (1 H, t, J 6.3, CHOH), 3.58–3.51 (2 H, m, CH2O), 3.35
(1 H, m, CHAHBO), 3.23 (1 H, m, CHAHBO), 3.04 (1 H, s, OH),
and 1.97–1.19 (16 H, m, 8 × CH2); δC(100 MHz, CDCl3) 137.2
(m-SPh), 130.2* (i-SPh), 128.9 (p-SPh), 128.8 (o-SPh), 99.7
(OCHO), 74.9 (CHOH), 65.3* (CH2O), 62.0* (CSPh), 61.8*
(CH2O), 30.5*, 30.1*, 30.2*, 29.9*, 29.6*, 26.2*, 24.1* and
21.8* (8 × CH2) and 19.8 (CH3CH) (Found (M Ϫ CH2CH3)ϩ,
321.1884. C19H29O2S requires M Ϫ CH2CH3, 321.1888); m/z
321.2 (80%, M Ϫ CH2CH3), 191.1 (100, C6H10SPh), 109 (10,
PhSH) and 81.0 (30, C6H9).
12-(1Љ-Ethoxyethoxy)-1-[(1Ј-phenylsulfanyl)cyclohexyl]-
dodecan-1-ol 37, n ؍ 11
6-(1Љ-Ethoxyethoxy)-1-[(1Ј-phenylsulfanyl)cyclohexyl]hexanol
37, n ؍ 5
In the same way as alcohol 37, n = 3, the bromo acetal 35, n = 11
(0.96 g, 3 mmol), lithium (70 mg, lithium ϩ 1% sodium wire, 10
mmol) and aldehyde 15 (0.22 g, 1 mmol) in ether (15 ml) gave,
after flash column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (9:1), the acetal 37, n = 12
(0.46 g, 99%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(9:1)] 0.14; δH(250 MHz, CDCl3) 7.52–7.25 (5 H, m, SPh), 4.70
(1 H, q, J 5.4, OCHO), 3.67–3.34 (4 H, m, 2 × CH2O), 3.22
(1 H, dt, J 9.3 and 2.1, CHOH), 3.06 (1 H, d, J 2.1, OH), 2.00–
1.05 (32 H, m, 16 × CH2), 1.28 (3 H, d, J 5.3, CH3CH) and 1.18
(3 H, t, J 7.1, CH3CH2); δC(62.5 MHz, CDCl3) 137.4 (m-SPh),
130.0 (i-SPh), 129.1 (p-SPh), 128.9 (o-SPh), 99.7 (OCHO), 74.8
(CHOH), 65.4 and 60.7 (2 × CH2O), 62.2 (CSPh), 32.8, 30.7,
30.0, 29.9, 29.8, 29.7, 27.6, 26.4, 26.2, 22.0, 21.9 (15 × CH2),
20.0 (CH3CH) and 15.5 (CH3CH2) (Found (M Ϫ Me)ϩ,
447.3317. C27H45O3S requires (M Ϫ Me), 447.3296); m/z 447.3
(110%, M Ϫ Me), 419.1 (61, M Ϫ OEt) and 73.0 (92, M Ϫ C24-
H39OS).
In the same way as alcohol 37, n = 3, the bromo acetal 35, n = 5,
X = Br (7.69 g, 34.08 mmol), lithium (0.79 g, lithium ϩ 1%
sodium wire, 113 mmol) and aldehyde 15 (2.5 g, 11.36 mmol)
in ether (15 ml) gave, after flash column chromatography on
silica gel eluting with light petroleum (40–60 ЊC)–ether (1:1), an
inseparable diastereomeric mixture (50:50) of the acetal 37,
n = 5 (3.92 g, 94%) as an oil; Rf [light petroleum (40–60 ЊC)–
ether (1:1)] 0.45; νmax (film, CDCl3)/cmϪ1 3300 (OH); δH(250
MHz, CDCl3) 7.53–7.27 (5 H, m, SPh), 4.65 (1 H, q, J 5.3,
OCHO), 3.70–3.08 (4 H, m, 2 × CH2), 3.22 (1 H, dt, J 9.2 and
2.3, CHOH), 3.08 (1 H, d, J 2.4, OH), 2.05–1.21 (18 H, m,
9 × CH2), 1.29 (3 H, d, J 5.3, CH3CH) and 1.19 (3 H, t, J 7.0,
CH3CH2); δC(62.5 MHz, CDCl3) 137.2 (m-SPh), 130.1* (i-SPh),
128.9 (p-SPh), 128.8 (o-SPh), 99.5 (OCHO), 74.6 (CHOH),
65.2* and 60.6* (2 × CH2), 58.0* (CSPh), 30.6*, 30.5*, 29.8*,
29.6*, 27.2*, 26.4*, 26.2*, 25.8* and 21.8* (9 × CH2), 19.8 and
15.3 (2 × CH3) (Found (M Ϫ OCH2CH3)ϩ, 335.2036. C20H31-
O2S requires M Ϫ OCH2CH3, 335.2044); m/z 335.1 (10%, M Ϫ
OCH2CH3), 308.2 (50, M Ϫ EE ϩ H), 291.2 (20, M Ϫ OEE),
191.1 (100, C6H10SPh), 109.0 (25, PhS), 81.1 (85, C6H9) and
73.1 (55, EE).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]tetrahydropyran 41
In the same way as the toluene-p-sulfonate 10, n = 5, the diol 8,
n = 4 (75 mg, 0.26 mmol) and toluene-p-sulfonyl chloride
(57 mg, 0.26 mmol) in pyridine (1 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (40–
60 ЊC)–ether (9:1), the tetrahydropyran 41 (69 mg, 98%) as an
oil; Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.55; νmax (film,
CDCl3)/cmϪ1 1550 (SPh); δH(400 MHz, CDCl3) 7.53–7.26 (5 H,
m, SPh), 4.00 (1 H, dt, J 11.2 and 1.9, CHAHBO), 3.28 (1 H, td,
J 11.2 and 2.7, CHAHBO), 3.07 (1 H, dd, J 10.8 and 1.6,
CHSPh) and 2.04–1.21 (16 H, m, 8 × CH2); δC(100 MHz,
CDCl3) 137.6 (o-SPh), 131.9* (i-SPh), 128.6 (p-SPh), 128.4
(o-SPh), 82.0 (CHOH), 69.1* (CH2O), 57.2 (CSPh), 30.8*,
7-(1Љ-Ethoxyethoxy)-1-[(1Ј-phenylsulfanyl)cyclohexyl]heptanol
37, n ؍ 6
In the same way as alcohol 37, n = 3, the chloro acetal 35, n = 6
(0.76 g, 3 mmol), lithium (70 mg, lithium ϩ 1% sodium wire, 10
mmol) and aldehyde 15 (0.22 g, 1 mmol) in ether (15 ml) gave,
after flash column chromatography on silica gel eluting with
light petroleum (40–60 ЊC)–ether (1:1), the acetal 37, n = 6
(0.37 g, 96%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
2780
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782

View Article Online
30.5*, 25.9*, 25.5*, 24.0*, 23.7*, 21.9* and 21.8* (8 × CH2)
(Found Mϩ, 276.1560. C17H24OS requires M, 276.1548); m/z
276.1 (30%, M), 191.1 (70, C6H10SPh), 167.1 (63, M Ϫ SPh),
110.0 (10, PhSH) and 83.9 (100, M Ϫ C6H10SPh).
slowly to a stirred solution of 3-hydroxyethyl triphenylphos-
phonium bromide 45 (0.18 g, 0.46 mmol) in THF (10 ml) at
0 ЊC. The dark red solution was stirred for 30 min. The solution
was then cooled to Ϫ30 ЊC and Me3SiCl (63 µl, 0.5 mmol) was
added and this solution was stirred for 15 min. A solution of
aldehyde 44 (0.18 g, 0.46 mmol) in THF (10 ml) was slowly
added and allowed to warm to room temperature over 2 hours.
TBAF (0.54 ml, 1 M in THF, 0.54 mmol) was added and solu-
tion was stirred for a further 1 hour. Saturated NH4Cl was
added and the solution was extracted with ether (3 × 25 ml).
The combined organic layers were dried (MgSO4) and evapor-
ated under reduced pressure. The residue was purified by flash
column chromatography on silica gel eluting with ether to give
an separable stereoisomeric mixture of alkenes in a ratio of
1:1 of the (Z)-48 (11.9 mg, 4.7%) as an oil; Rf [ether] 0.38;
δH(250 MHz, CDCl3) 7.51–7.25 (5 H, m, SPh), 5.88 (1 H, m,
5-Cyclohexenyl-5-(phenylsulfanyl)pentan-1-ol 42
In the same way as THP 11, the tetrahydropyran 41 (10 mg,
36.4 µmol) toluene-p-sulfonic acid (6.2 mg, 36.4 µmol) in tolu-
ene (1 ml) gave, after flash column chromatography on silica gel
eluting with light petroleum (40–60 ЊC)–ether (9:1), the allylic
sulfide 42 (9.2 mg, 92%) as an oil; Rf [light petroleum (40–
60 ЊC)–ether (1:1)] 0.4; νmax (film, CDCl3)/cmϪ1 3300–3100 (OH)
and 1600 (SPh); δH(250 MHz, CDCl3) 7.37–7.20 (5 H, m, SPh),
5.25 (1 H, br s, CH᎐C), 3.51 (1 H, t, J 7.6, CHSPh), 3.51 (2 H,
᎐
t, J 7.2, CH2O), 2.50 (1 H, br s, OH) and 2.15–1.20 (14 H, m,
7 × CH2); δC(62.5 MHz, CDCl3) 135.6* (i-SPh), 133.2 (m-SPh),
CH ᎐CH ), 5.63 (1 H, m, CH ᎐CH ), 4.24 (1 H, dd, J 12.0 and
᎐
᎐
A
B
A
B
128.6 (o-SPh), 127.2 (p-SPh), 125.4 (CH᎐C), 57.2 (CHSPh),
᎐
7.9, CHAHBO), 3.97 (1 H, dd, J 12.0 and 6.6, CHAHBO), 3.43 (1
H, s, OH), 3.24 (1 H, dd, J 10.2 and 1.6, CHOH), 2.40 (1 H, dt,
70.7* (CH2O), 31.9*, 27.1*, 25.1*, 24.6*, 23.9*, 22.8* and 22.2*
(7 × CH2); m/z 276.1 (100%, M) and 81.1 (30, C6H9).
J 13.4 and 10.2, CH H CH᎐CH), 2.19 (1 H, dd, J 13.4 and 6.3,
᎐
A
B
CH H CH᎐CH) and 2.01–1.19 (11 H, m, OH and 5 × CH );
᎐
A
B
2
Ethyl 3-trimethylsilyloxy-3-[1-(phenylsulfanyl)cyclohexyl]-
propanoate 43
δ (100 MHz, CDCl ) 137.2 (m-SPh), 131.1 (CH ᎐CH ), 130.1
᎐
C
3
A
B
(CH ᎐CH ), 130.0 (o-SPh), 129.9 (i-SPh), 129.2 (p-SPh), 73.4
᎐
A
B
Me3SiCl (0.21 ml, 3.5 mmol) was added to a stirred solution of
the ester 25, Et3N (0.5 ml, 3.5 mmol) in THF (10 ml) at 0 ЊC.
The solution was stirred for 2 days. Brine (saturated NaCl, 10
ml) was added and the solution was extracted with ether (2 × 10
ml). The combined organic layers were dried (Na2SO4) and
evaporated under reduced pressure. The residue was purified by
flash column chromatography on silica gel eluting with light
petroleum (40–60 ЊC)–ether (9:1) to give the protected ester 43
(0.135 g, 72%) as an oil; Rf [light petroleum (40–60 ЊC)–ether
(9:1)] 0.42; δH(400 MHz, CDCl3) 7.56–7.27 (5 H, m, SPh), 4.17
(2 H, q, J 7.1, CH3CH2O), 4.10 (1 H, dd, J 9.3 and 1.6, CHOSi),
3.43 (1 H, dd, J 15.7 and 1.6, CHAHBCO), 2.52 (1 H, dd, J 15.7
and 9.3, CHAHBCO), 2.16–2.13 (10 H, m, 5 × CH2); δC(100
MHz, CDCl3) 173.2 (CO), 137.5 (o-SPh), 131.2 (i-SPh), 128.7
(p-SPh), 128.4 (m-SPh), 75.6 (CHOH), 60.4 (CH2O), 57.7
(CSPh), 38.6, 31.2, 28.2, 25.9 and 21.8 (5 × CH2), 14.3 (CH3)
and 0.2 (TMS) (Found Mϩ, 380.1864. C20H32O2SSi requires M,
380.1841); m/z 380.2 (24%, M), 291.1 (30, M Ϫ TMSO) and
271.2 (76, M Ϫ SPh).
(CHOH), 61.3 (CSPh), 30.4, 29.5, 28.6, 26.3 and 21.8
(5 × CH2); and the (E)-48 (12.4 mg, 5.3%) as an oil; Rf [ether]
0.28; δH(400 MHz, CDCl3) 7.52–7.28 (5 H, m, SPh), 5.79–5.66
(2 H, m, CHA=CHB), 4.09 (2 H, d, J 4.9, CH2O), 3.45 (1 H, dd,
J 10.2 and 1.6, CHOH), 3.10 (1 H, s, OH), 2.38 (1 H, dd, J 5.1
and 4.9, CH H CH᎐CH), 2.19 (1 H, dd, J 10.3 and 6.0,
᎐
A
B
CH H CH᎐CH) and 2.01–1.17 (11 H, m, OH and 5 × CH );
᎐
A
B
2
δ (100 MHz, CDCl ) 137.3 (m-SPh), 131.2 (CH ᎐CH ), 130.5
᎐
C
3
A
B
(CH ᎐CH ), 130.1 (i-SPh), 129.1 (o-SPh), 128.9 (p-SPh), 74.5
᎐
A
B
(CHOH), 63.6 (CH2O), 61.1 (CSPh), 33.8, 30.6, 29.8, 26.2, 21.9
and 21.8 (6 × CH2).
2-[1Ј-(Phenylsulfanyl)cyclohexyl]-3,6-dihydro-2H-pyran 50
In the same way as THP 11, the (Z)-alkene 48 (11 mg, 37 µmol)
and TsOH (1.4 mg, 7.5 µmol) in CH2Cl2 (5 ml) gave after flash
column chromatography on silica gel, eluting with light petrol-
eum (40–60 ЊC)–ether (9:1), the DHP 50 (11 mg, 99%) as an oil;
Rf [light petroleum (40–60 ЊC)–ether (9:1)] 0.52; δH(400 MHz,
CDCl3) 7.55–7.18 (5 H, m, SPh), 5.85 (1 H, dd, J 10.1 and 1.0,
CH ᎐CH ), 5.47 (1 H, br d, J 10.1, CH ᎐CH ), 4.22 (1 H, d,
᎐
᎐
A
A
B
B
3-Trimethylsilyloxy-3-[1-(phenylsulfanyl)cyclohexyl]propanal 44
J 16.3, CHAHBO), 4.10 (1 H, d, J 16.3, CHAHBO), 3.38 (1 H,
dd, J 10.7 and 3.1, CHSPh), 2.44 (1 H, m, CH H CH᎐CH),
DIBAL-H was slowly added to a stirred solution of ester 43 in
CH2Cl2 at Ϫ78 ЊC. The solution was stirred for 30 min. Ether
(50 ml), NaOH (20 ml, 10%) and K–Na tartrate (20 ml, 15%)
was slowly added and the solution was allowed to stir for a
further 30 min at room temperature. The solution was
extracted with ether (3 × 30ml) and the combined organic
layers were dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by flash column chromatography
on silica gel eluting with light petroleum (40–60 ЊC)–ether (9:1)
to give the aldehyde 44 (2.54 g, 83%) as an oil; Rf [light petrol-
eum (40–60 ЊC)–ether (9:1)] 0.41; δH(400 MHz, CDCl3) 9.91
(1 H, dd, J 2.5 and 0.94, CHO), 7.52–7.26 (5 H, m, SPh), 4.13
(1 H, dd, J 7.8 and 2.7, CHOH), 3.34 (1 H, ddd, J 17.1, 2.7 and
0.9, CHAHBCHO), 2.88 (1 H, ddd, J 17.1, 7.8 and 2.5, CHA-
HBCHO), 2.12–1.10 (10 H, m, 5 × CH2) and Ϫ0.05 (9 H, s,
TMS); δC(100 MHz, CDCl3) 209.9 (CHO), 137.2 (o-SPh), 131.3
(i-SPh), 128.7 (p-SPh), 128.5 (m-SPh), 73.4 (CHOSi), 57.7
(CSPh), 47.8 (CH2CHO), 31.5, 29.8, 25.8, 21.8 and 21.7 (5 CH2)
and 0.3 (TMS) (Found Mϩ, 336.1578. C18H28O2SSi requires M,
336.1655); m/z 336.2 (9%, M), 247.1 (9, M Ϫ TMSO) and 271.2
(25, M Ϫ SPh).
᎐
A
B
2.22 (1 H, br d, J 17.3, CH H CH᎐CH) and 1.87–1.21 (10 H,
᎐
A
B
m, 5 × CH2); δc(100 MHz, CDCl3) 135.5 (m-SPh), 131.9
(i-SPh), 128.4 (o-SPh), 128.1 (p-SPh), 126.1 (CH ᎐CH ), 124.8
᎐
A
B
(CH ᎐CH ), 77.9 (CHO), 66.9 (CH OH), 56.9 (CSPh), 31.1,
᎐
A
B
2
30.8, 25.9, 25.4, 21.9 and 21.8 (6 × CH2).
(E,E)-5-(Cyclohex-1-enyl)-5-phenylsulfanylpent-2-en-1-ol 51
In the same way as THP 11, the (E)-alkene 48 (12 mg, 41 µmol)
and TsOH (1.5 mg, 8.2 mmol) in CH2Cl2 (5 ml) gave after flash
column chromatography eluting with ether, the allylic sulfide
(E,E)-51 (12 mg, 99%) as an oil; Rf [ether] 0.5 δH(400 MHz,
CDCl ) 7.38–7.18 (5 H, m, SPh), 5.66 (2 H, m, CH᎐CH), 5.27
᎐
3
(1 H, s, CH᎐C), 4.08 (2 H, t, J, 4.5, CH OH), 3.53 (1 H, t, J 7.6,
᎐
2
CHSPh), 2.40 (2 H, t, J 5.8, CH CH᎐CH), 21.6 (1 H, d, J 16.4,
᎐
2
CH H CH᎐C) and 1.99–1.24 (8 H, m, 3 × CH , CH H CH᎐C
᎐
᎐
A
B
2
A
B
and OH); δC(100 MHz, CDCl3) 135.3 and 135.2 (i-SPh and
C᎐CH), 133.3 (m-SPh), 131.0, 129.9 and 125.7 (CH᎐CH and
᎐
᎐
CH᎐C), 128.5 (o-SPh), 127.1 (m-SPh), 63.6 (CH OH), 56.7
᎐
2
(CHSPh), 35.6, 25.2, 24.3, 22.7 and 22.4 (5 × CH2).
(E)- and (Z)-1-[1-(Phenylsulfanyl)cyclohexyl]pent-3-ene-1,5-diol
6-Cyclohexenyl-6-(phenylsulfanyl)hexan-1-ol 53
48
In the same way as THP 11, the alcohol 8, n = 5 (62 mg, 0.2
mmol) toluene-p-sulfonic acid (10 mg, 50 µmol) in CH2Cl2
n-BuLi (0.18 ml, 1.25 M in hexanes, 1.01 mmol) was added
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782
2781

View Article Online
(1 ml) gave, after flash column chromatography on silica gel
eluting with ether, the allylic sulfide 53 (55 mg, 95%) as an oil; Rf
[ether] 0.51; δH(250 MHz, CDCl3) 7.35–7.17 (5 H, m, SPh), 5.25
26.3, 25.8, 23.9, 22.8 and 22.7 (14 × CH2) (Found Mϩ,
374.2632. C24H38OS requires M, 374.2643); m/z 374.2 (24%, M)
and 265.1 (100, M Ϫ SPh).
(1 H, br s, CH᎐C), 3.62 (2 H, t, J 6.6, CH O), 3.50 (1 H, t, J 7.6,
᎐
2
CHSPh) and 2.17–1.33 (17 H, m, 8 × CH2 and OH); δC(62.5
Acknowledgements
MHz, CDCl ) 135.8 and 135.6 (i-SPh and CH᎐C), 133.2
᎐
3
We thank the EPSRC for a grant (to J. E.), Ray V. H. Jones
(Zeneca Process Technology Department, Grangemouth) for a
CASE award (to J. E.) and Rhône-Poulenc Industrialisation
(CRIT) Saint-Fons for a grant (to L. D.).
(o-SPh), 128.4 (m-SPh), 126.9 (p-SPh), 125.4 (CH᎐C), 62.9
(CH2O), 57.3 (CHSPh), 32.6, 32.5, 27.4, 25.5, 23.8, 22.7 and
22.5 (8 × CH2).
᎐
7-Cyclohexenyl-7-(phenylsulfanyl)heptan-1-ol 54
References
In the same way as THP 11, the alcohol 8, n = 6 (65 mg, 0.2
mmol) toluene-p-sulfonic acid (10 mg, 50 µmol) in CH2Cl2 (1
ml) gave, after flash column chromatography on silica gel elut-
ing with ether, the allylic sulfide 54 (60 mg, 99%) as an oil; Rf
[ether] 0.50; δH(250 MHz, CDCl3) 7.40–7.17 (5 H, m, SPh), 5.24
1 P. Brownbridge and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1977,
2272.
2 V. K. Aggarwal and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1987,
2579.
3 V. K. Aggarwal and S. Warren, Tetrahedron Lett. 1986, 27, 101.
4 V. K. Aggarwal, I. Coldham, S. McIntye and S. Warren, J. Chem.
Soc., Perkin Trans. 1, 1991, 451.
5 I. Coldham and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1993,
1637.
(1 H, br s, CH᎐C), 3.61 (2 H, t, J 6.6, CH O), 3.61 (1 H, t,
᎐
2
J 7.6, CHSPh) and 2.16–1.24 (19 H, m, 9 × CH2 and OH);
δ (62.5 MHz, CDCl ) 135.7 and 135.5 (i-SPh and CH᎐C), 133.1
᎐
C
3
(m-SPh), 128.4 (o-SPh), 126.8 (p-SPh), 125.4 (CH᎐C), 62.9
᎐
(CH2O), 57.33 (CHSPh), 32.7, 32.4, 29.1, 27.6, 25.6, 25.2, 23.7,
22.7 and 22.5 (9 × CH2) (Found Mϩ, 304.1860. C19H28OS
requires M, 304.1816); m/z 304.1 (79%, M) and 195.1 (42,
M Ϫ SPh).
6 (a) J. Eames, R. V. H. Jones and S. Warren, Tetrahedron Lett., 1996,
37, 707; (b) J. Eames and S. Warren, J. Chem. Soc., Perkin Trans. 1,
1999, 2783.
7 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734.
8 (a) A. J. Kirby, Adv. Phys. Org. Chem., 1981, 17, 183; (b) L.
Mandolini, Adv. Phys. Org. Chem., 1986, 22, 1.
9 (a) F. H. Sansbury and S. Warren, Tetrahedron Lett., 1991, 32, 3425;
(b) S. McIntyre, F. H. Sansbury and S. Warren, Tetrahedron Lett.,
1991, 32, 5409; (c) F. H. Sansbury and S. Warren, Tetrahedron Lett.,
1992, 33, 539.
10 Inversion also occurs at the migratory origin, see V. K. Aggarwal,
I. Coldham, S. McIntye, F. H. Sansbury, M.-J. Villa and S. Warren,
Tetrahedron Lett., 1988, 29, 4885.
11 J. Eames and S. Warren, Tetrahedron Lett., 1996, 37, 3525.
12 Preliminary communication: L. Djakovitch, J. Eames, R. V. H.
Jones, S. McIntyre and S. Warren, Tetrahedron Lett., 1995, 36, 1723.
13 J. Eames, H. J. Mitchell, A. Nelson, P. O’Brien, S. Warren and
P. Wyatt, Tetrahedron Lett., 1995, 36, 1719.
9-Cyclohexenyl-9-(phenylsulfanyl)nonan-1-ol 55
In the same way as THP 11, the alcohol 8, n = 8 (70 mg,
0.2 mmol) toluene-p-sulfonic acid (10 mg, 50 µmol) in CH2Cl2
(1 ml) gave, after flash column chromatography on silica gel
eluting with ether, the allylic sulfide 55 (65 mg, 95%) as an oil;
Rf [ether] 0.56; δH(250 MHz, CDCl3) 7.47–7.16 (5 H, m, SPh),
5.24 (1 H, br s, CH᎐C), 3.62 (2 H, t, J 6.6, CH O), 3.49 (1 H, t,
᎐
2
J 7.6, CHSPh) and 2.28–1.24 (23 H, m, 11 × CH2 and OH);
δ (62.5 MHz, CDCl ) 135.8 and 135.7 (i-SPh and CH᎐C),
᎐
C
3
133.1 (m-SPh), 128.3 (o-SPh), 126.7 (p-SPh), 125.4 (CH᎐C),
᎐
14 J. Eames, H. J. Mitchell, A. Nelson, P. OBrien, S. Warren and
P. Wyatt, J. Chem. Soc., Perkin. Trans. 1, 1999, 1095.
15 P. Brownbridge and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1977,
1131.
16 J. Eames, Ph.D. Thesis, University of Cambridge, 1996.
17 E. J. Corey and M. J. Chaykovsky, J. Am. Chem. Soc., 1965, 87,
1353.
63.0 (CH2O), 57.4 (CHSPh), 32.8, 32.5, 29.5, 29.4, 29.3, 27.6,
25.7, 25.2, 23.7, 22.7 and 22.5 (11 × CH2) (Found Mϩ,
322.2171. C21H32OS requires M, 332.2174); m/z 332.2 (40%, M)
and 233.1 (100, M Ϫ SPh).
13-Cyclohexenyl-13-(phenylsulfanyl)tridecan-1-ol 56
18 J. Eames, M. A. de las Heras, R. V. H. Jones and S. Warren,
Tetrahedron Lett., 1996, 37, 1117.
19 E. L. Eliel, W. H. Pearson, L. M. Jewell, A. G. Abatjoglou and
W. R. Kenan, Tetrahedron Lett., 1980, 21, 331.
20 P. C. Eaton, G. F. Cooper, R. C. Johnson and R. H. Muellur, J. Org.
Chem., 1972, 37, 1947.
21 J. Eames, N. Kuhnert, F. H. Sansbury and S. Warren, Synlett, 1999,
1211.
In the same way as THP 11, the alcohol 8, n = 12 (80 mg, 0.2
mmol) toluene-p-sulfonic acid (10 mg, 50 µmol) in CH2Cl2
(1 ml) gave, after flash column chromatography on silica gel
eluting with ether, the allylic sulfide 56 (68 mg, 95%) as an oil;
Rf [ether] 0.56; δH(250 MHz, CDCl3) 7.35–7.17 (5 H, m, SPh),
5.24 (1 H, br s, CH᎐C), 3.62 (2 H, t, J 4.2, CH O), 3.50 (1 H, t,
᎐
2
J 4.8, CHSPh) and 2.16–1.65 (29 H, m, 14 × CH2 and OH);
δ (62.5 MHz, CDCl ) 136.0 and 135.9 (i-SPh and CH᎐C), 133.2
᎐
C
3
(o-SPh), 128.5 (o-SPh), 126.9 (p-SPh), 125.4 (CH᎐C), 63.2
᎐
(CH2O), 57.5 (CHSPh), 32.9, 32.6, 29.6, 29.6, 29.5, 29.4, 27.7,
Paper 9/05498G
2782
J. Chem. Soc., Perkin Trans. 1, 1999, 2771–2782