Stereochemically controlled synthesis of 1,8-dioxaspiro[4.5]decanes and 1-oxa-8-thiaspiro[4.5]decanes by phenylsulfanyl migration

Article abstract of DOI:10.1039/b001893g

Single enantiomers and diastereoisomers of 2- and 3-alkyl-3-phenylsulfanyl-1,8-dioxa- and 1-oxa-8-thiaspiro-[4.5]decanes can be prepared in good yield by acid-catalysed phenylsulfanyl (PhS-) migration. Either the syn-or anti-stereochemistry can be controlled by aldol reactions or by reduction of hydroxy-ketones. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b001893g

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Stereochemically controlled synthesis of 1,8-dioxaspiro[4.5]decanes
and 1-oxa-8-thiaspiro[4.5]decanes by phenylsulfanyl migration
Jason Eames,*a,b David J. Fox,a Maria A. de las Herasa and Stuart Warrena
1
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 March 2000, Accepted 2nd May 2000
Published on the Web 30th May 2000
Single enantiomers and diastereoisomers of 2- and 3-alkyl-3-phenylsulfanyl-1,8-dioxa- and 1-oxa-8-thiaspiro-
[4.5]decanes can be prepared in good yield by acid-catalysed phenylsulfanyl (PhS-) migration. Either the syn-
or anti-stereochemistry can be controlled by aldol reactions or by reduction of hydroxy-ketones.
The synthesis of some constitutional isomers of dioxaspiro-
[4.5]decanes is much easier than others. For example, where
there are two oxygen atoms that form an acetal, such as 11 and
2,2 these compounds are well known and easy to synthesise. For
other positional isomers, such as the 1,8-dioxaspiro compounds
like 3, very little is known, especially about the stereochemistry,
though the corresponding lactone such as 4; X = O has been
made (Chart 1).3–5 However, there are some reports that similar
Chart 1
Scheme 1
available ketones as the precursors.7 However, there are a few
examples where piperidine based ketones have been used giving
1,8-diazospiro[4.5]decanes such as anti-13.8
We now report a succinct route to the synthesis of single
diastereoisomers and enantiomers of substituted 1,8-dioxa and
1-oxa-8-thiaspiro[4.5]decanes using a similar strategy to con-
struct the spirocyclic C(1)–O(5) bond. From related chemistry
developed within our laboratory,7 we chose to use the known
ketones 5 and 6 as the starting materials.13–15
substituted 1,7- and 1,8-dioxaspiro compounds have herbicidal
activity.6 By comparison, the 1-oxa-8-thiaspiro[4.5]decane
system is almost unknown, though similar lactones such as 4;
X = S have been reported (Chart 2).3
Results and discussion
Chart 2
The first step was to prepare the 2-PhS-aldehydes 17; X = O
and 18; X = S by the methodology developed by de Groot and
Jansen.16–18 Formation of the lithiated sulfide 14 (by addition
of n-BuLi to methoxymethylphenyl sulfide in THF at Ϫ78 ЊC),
followed by the addition of the ketones 5 and 6 gave the alco-
hols 15; X = O and 16; X = S in excellent yield. Rearrangement
under our modified conditions7 (SOCl2, Et3N in CH2Cl2) gave
the required aldehydes 17; X = O and 18; X = S in high yield
(Scheme 2). This reaction works essentially as well as for the
previously reported hydrocarbon and amine systems (15–18;
where X = CH2 and NMe).7,8
The diol 22 and 23 stereochemistry was controlled by the
reliable anti- and syn-stereoselective aldol reactions developed
by Heathcock et al.19–20 and Masamune and co-workers21
respectively (Scheme 3). Generation of the lithium (E)-enolate
of Heathcock’s ester (2,6-dimethylphenyl propionate)19 and the
boron (Z)-enolate of Masamune’s ester (S-phenyl thiopropion-
We have previously reported the synthesis of spirocyclic
tetrahydrofurans (THFs) like anti-9,7 lactones anti-10,7 pyrrol-
idines syn-118 and thiolane 12 (Scheme 1).9 For example, treat-
ment of the diol anti-7 with catalytic toluene-p-sulfonic acid
(TsOH) in CH2Cl2 gives the episulfonium ion 8 which is cap-
tured intramolecularly at the more substituted end to give the
spirocyclic tetrahydrofuran anti-9 in essentially quantitative
yield.7 We have also shown that enantiomerically pure THFs
and pyrrolidines like anti-9 and syn-11 can be synthesised
efficiently using this procedure.10 This type of 1,2-PhS migration
occurs stereospecifically with no loss of enantiomeric or
diastereoisomeric purity, with inversion of configuration at the
migratory terminus and origin.11 The majority of these spir-
ocycles have one carbocyclic and one heterocyclic ring (O, N
and S),7,12 this was primarily because we used commercially
DOI: 10.1039/b001893g
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914
This journal is © The Royal Society of Chemistry 2000
1903

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ate)20 and addition to the 2-RS aldehydes 17 and 18 gave pre-
dictable syn- and anti-aldols 20, 21, 27 and 28 in excellent yield.
Reduction of these with LiAlH4 gave the syn- and anti-diols 22
and 23. Acid-catalysed rearrangement with TsOH in refluxing
CH2Cl2 proceeded smoothly to give stereospecifically the ethers
anti-24, syn-24, anti-25 and syn-25 in near quantitative yield. It
appears that the presence of the additional oxygen and sulfur
atoms in the six membered rings has little or no effect on the
rearrangement steps to form the 2-PhS aldehyde 17 and 18, nor
in the cyclisation to form the spirocyclic compound 24 and 25.
However, the rearrangement of the thiane-containing diols
such as anti-23 proceeded at least one order of magnitude faster
than that of the tetrahydropyran-containing diols like anti-22,
presumably due to the additional ether linkage in the starting
diol disfavouring episulfonium ion formation. We have
observed similar effects with amine analogues.8
systems (Scheme 4).10 Addition of the boron (Z)-enolate to the
aldehyde 17 gave a single diastereoisomer of the syn-aldol23 syn,
anti-30, and, in the presence of the Lewis acid Et2AlCl (accord-
ing to Heathcock)24,25 gave a single diastereoisomeric anti-aldol
30. Removal of the chiral auxiliary was simply and efficiently
achieved by the addition of LiBH4 with one equivalent of water
in THF (under Pennings conditions),26 giving the diols syn- and
anti-31 respectively in near quantitative yield. Treatment of
these diols syn- and anti-31 under our usual acid-catalysed
conditions gave the enantiomerically pure spirocyclic ethers
syn- and anti-32 in a similar high yield to that obtained in the
racemic series. The rearrangement occurred with no loss of
diastereoisomeric or enantiomeric purity. The enantiomeric
1
excess was near perfect (>98%)—determined by H and 19F
NMR analysis of the corresponding Mosher’s esters (derived
from the syn- and anti-diol 31)27—while those of the THF’s
were determined by 1H NMR in the presence of the chiral shift
reagent Eu(hfc)3 and by comparison with the racemic series syn-
and anti-24.28 The C(2,3) anti- and syn-stereochemistry of the
aldol products 30 was confirmed by subsequent cyclisation to
the THFs (determined by a 500 MHz NOESY spectrum on
anti-24). The absolute stereochemistry at the hydroxy position
(C-3) is assumed from previous work including that on the
carbocyclic compounds in our laboratory under identical
conditions.10
The absolute stereochemistry of similar diols anti- and syn-
31 was controlled by using Evans’ reliable phenylalanine-
derived oxazolinone 29 as the chiral auxiliary,22 primarily
because of our previous experience with related carbocyclic
We next studied the effect of a secondary and tertiary alcohol
as potential nucleophiles for the episulfonium ions like 8. In
previous cases with a primary alcohol as a nucleophile and a
secondary alcohol as a leaving group as in diol anti-7, the reac-
tion may be controlled by preferential loss of the protonated
secondary alcohol to give THF anti-9 (Scheme 1). With two
secondary alcohols, as in syn- and anti-diols 44 and 46, which
protonated secondary alcohol would be lost is uncertain. One
could be lost with [1,2]-SPh participation or the other with
[1,4]-SPh participation, which we believe is possible since
simple data29 have suggested that both [1,2]-SR participation
for an acyclic system was as efficient as [1,4]-SR participation.
Scheme 2
Scheme 3
Scheme 4
1904
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In the case of diols (e.g., 37) with a tertiary alcohol as a potential
nucleophile, preferential loss of the protonated tertiary alcohol
might be expected over the secondary alcohols since such
elimination processes are well known.
We synthesised the tertiary alcohols 35 and 37, which were
simpler to make because of the absence of stereochemistry, by
the addition of MeMgBr to the 1,3-hydroxyketone 34 and 36
(synthesised by the addition of the lithium enolate of acetone
33 to the aldehydes 17 and 18). These reactions occurred cleanly
without enolisation of the ketone (e.g. 34) giving the tertiary
alcohol in excellent yield (Scheme 5).
Scheme 6
sition state, by addition to the bottom face—controlled by the
larger R2CSPh group in the equatorial position. The remaining
anti-diols 44 and 46 were synthesised using Evans and co-
workers’31 reliable intramolecular hydride delivery reagent:
Me4N(AcO)3BH (Scheme 7). Addition of the 1,3-hydroxy-
ketones 34 and 36 to a stirred solution of Me4N(AcO)3BH in
acetic acid at Ϫ30 ЊC for 2 days gave predominately the anti-
diols 44 and 46 in excellent yield. This reduction proceeds via a
chair transition state, where the larger methyl group rather than
Scheme 5
Acid-catalysed rearrangement of these diols 35 and 37 under
our usual conditions (TsOH in CH2Cl2) gave surprisingly the
THFs 41 and 42 in near quantitative yield. By thin layer
chromatography (TLC), no other intermediates were formed
and the rearrangement occurred smoothly and was as efficient
as previous cases with a primary alcohol as a nucleophile. Pre-
sumably, proton transfer between the tertiary and secondary
alcohol in 38 and 39 was rapid, and the stereospecific elimin-
ation of the protonated secondary alcohol 39 by [1,2]-SPh par-
ticipation was evidently preferred. It is even more remarkable
that competing protonation and decomposition of the tertiary
alcohol (e.g. 38) does not occur in refluxing toluene-p-sulfonic
acid in CH2Cl2, instead [1,2]-SPh participation to form the epi-
sulfonium ion and cyclisation 40 occurs efficiently giving the
structurally unusual di-tertiary alkyl ethers such as 41 (Scheme
6). However, under prolonged reflux, the 1,8-dioxaspirodecanes
such as 42 decomposes whereas the 1-oxa-8-thiaspirodecanes
41 are stable. This is presumably the main cause of the lower
yield of 42.
The syn- and anti-1,3-diols 44 and 46 were synthesised using
a stereoselective reduction strategy involving our key inter-
mediate 1,3-hydroxyketones. Access to the syn-diols 44 and 46
were achieved using Prasad and co-workers’30 methodology—
reduction of the ketones 34 and 36 with NaBH4 as an external
reducing agent in the presence of Et2BOMe as a chelating agent
gave predictably the syn-diols as a single diastereoisomer. The
reduction occurs by axial hydride addition to the top face of 43
via a chair transition state rather than a disfavoured boat tran-
the carbonyl (C᎐O) group of the ketone in 45 was in a pseudo-
᎐
equatorial position to avoid the developing 1,3-diaxial inter-
actions. In all cases so far studied,32 Prasad’s syn-stereoselective
reduction was more efficient than Evans’ anti-reduction.
Rearrangement of all four diols syn- and anti-44 and 45 gave
stereospecifically the corresponding spirocyclic ethers (e.g. anti-
50) in excellent yield (Scheme 8). The stereochemistry was
inverted at the migratory terminus and retention was observed
at the nucleophilic centre (by NOE experiments). In no case was
any [1,4]-SPh migration observed. Surprisingly, the secondary
alcohol in anti-48 was sufficiently protonated to give the epi-
sulfonium ion syn-49 via [1,2]-SPh participation and hence the
rearrangement to anti-50. It is difficult to believe that either
secondary alcohol is more basic, so the low concentration of
cation anti-48 must rearrange at least two orders of magnitude
faster than that of anti-47. In all cases so far studied, [1,2]-SPh
participation was much more efficient than [1,4]-SPh partici-
pation, which is clearly different from previous reports that
both [1,2]-SPh and [1,4]-SPh participation occur at the same
rate for simple acyclic systems.29 However, our case is different
since the presence of the nucleophilic tertiary phenylsulfide
(R2CSPh) evidently makes the [1,2]-SPh participation much
more efficient than [1,4]-SPh participation. This is presumably
due to the Thorpe–Ingold effect (both angle and conform-
ational effects)33,34 which is well known to enhance in particular
three-membered ring formation.
This was in sharp contrast to the treatment of diols anti-
and syn-31 with toluene-p-sulfonyl chloride (TsCl) in pyridine
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914
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Scheme 7
Scheme 8
good yield. Migration of the toluene-p-sulfonate group from
the primary alcohol to the secondary alcohol (for THF form-
ation to occur) is evidently much slower than that of proton
transfer.
Preliminary approaches to the 1-oxa-7-thiaspiro[4.4]nonane
system were equally successful except in the important area
of stereochemistry (Scheme 10). The starting point for this
synthesis was the commercially available ketone 55. Conver-
sion to the aldehyde 57 was simply achieved using the
method outlined by de Groot and Jansen.16–18 Addition of the
enolate of ethyl acetate to the aldehyde 57 gave an insepar-
able diastereoisomeric mixture (1:1) of aldol adducts 58 in
excellent yield. Reduction (LiAlH4 in ether) and cyclisation
(TsOH in CH2Cl2) gave the spirocyclic THF 60, with a stereo-
genic centre introduced at the spiro-carbon atom. We were
unable to separate the diastereoisomers 58 to 60 using the
approach outlined in Scheme 10. This is not that important if
the PhS group is removed,10 but it does detract from the
route as a synthetic method.
In conclusion, we have shown the assembly of spirodecanes
with two oxygen atoms not having an acetal relationship, i.e.
being 1,5-related rather than joined to the same carbon atom,
or their thia-analogues, can be efficiently achieved in high yield
by a [1,2]-SPh migration with full control over relative or abso-
lute stereochemistry. Neither oxygen or sulfur interferes with
any of the rearrangements. We have also shown that secondary
and tertiary alcohols can act as nucleophiles in the cyclisation
of 1,3-diols to form THFs with stereospecific PhS migration.
The heterocyclic secondary alcohols react stereospecifically
(with retention of configuration) and the reactions are as
efficient as in the carbocyclic and open-chain systems.
Scheme 9
giving allylic alcohols anti- and syn-54 respectively in excellent
yield, presumably formed via a [1,4]-SPh participation (Scheme
9). In these cases no [1,2]-SPh participation was observed
which must be due to the chemoselective activation of the less
sterically hindered alcohol, to give the primary tosylate 52,
subsequent [1,4]-SPh participation leads to the sulfonium inter-
mediate 53 and decomposition gives the allylic alcohol syn-54 in
1906
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acetate (3:1) to give the alcohol 15; X = O (2.56 g, 78%) as
a colourless oil; Rf [petroleum ether–EtOAc (3:1)] 0.12;
νmax(NaCl)/cmϪ1 3400 (OH) and 1582 (SPh); δH(400 MHz;
CDCl3) 7.49–7.21 (5 H, m, SPh), 4.44 (1 H, s, CHSPh), 3.85–
3.69 (4 H, m, 2 × CH2Oeqϩax), 3.43 (3 H, s, OMe), 2.57 (1 H, s,
OH), 2.05–1.87 (2 H, m, 2 × CHAHBax), 1.59 (1 H, dd, J 13.8
and 2.2, CHAHBeq) and 1.49 (1H, dd, J 13.7 and 2.2, CHAHBeq);
δC(100 MHz; CDCl3) 135.5, 132.9, 129.3, 127.6, 103.0, 72.0,
63.6, 63.4, 57.7, 33.7 and 33.5 (Found Mϩ, 254.0978. C13H18O3S
requires M, 254.0976); m/z (EI) 254 (80%, M), 145 (80,
M Ϫ Ph), 109 (60, SPh) and 83 (100, C5H8S).
4-Hydroxy-4-[methoxy(phenylsulfanyl)methyl]thiane 16; X ؍ S
In the same way as alcohol 15; X = O, methoxymethyl phenyl
sulfide (6.0 g, 6.0 ml, 38.9 mmol), n-BuLi (31.4 ml, 1.3 M in
hexanes, 40.8 mmol) and tetrahydrothiopyran-4(2H)-one 6 (4.3
g, 37.1 mmol) in THF (120 ml) gave, after column chromato-
graphy on silica gel eluting with petroleum ether–ether (9:1),
the alcohol 16; X = S (9.7 g, 97%) as a colourless oil; Rf [petrol-
eum ether–ether (9:1)] 0.1; νmax(film, CDCl3)/cmϪ1 3300 (OH)
and 1550 (SPh); δH(200 MHz; CDCl3) 7.61–7.35 (5 H, m, SPh),
4.41 (1 H, s, CHSPh), 3.45 (3 H, s, OMe), 3.20–2.88 (2 H, m,
ax
2 × SCHAHBeq), 2.50–2.30 (3 H, m, 2 × SCHAHB and OH)
and 2.19–1.69 (4 H, m, 2 × CH2eqϩax); δC(100 MHz; CDCl3)
135.3* (i-SPh), 132.7 (m-SPh), 129.1 (o-SPh), 127.4 (p-SPh),
104.0 (CHOMe), 72.6* (COH), 57.5 (MeO), 34.1* (CH2S),
33.7* (CH2S), 23.8* (CH2) and 23.4* (CH2) (Found Mϩ,
270.0743. C13H18O2S2 requires M, 270.0748); m/z 270.1 (20%,
M), 161.1 (100, M Ϫ SPh), 153.0 (20, PhSCHOMe), 129.0
(M Ϫ SPh Ϫ MeOH), 110.0 (30, PhSH) and 77.0 (5, Ph).
Scheme 10
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. Petroleum ether refers to light petroleum (bp 40–60 ЊC).
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 chromatography
(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 per
million downfield from tetramethylsilane. Carbon NMR spec-
tra 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 qua-
ternary 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. Optical rotation measurements were per-
formed on a Perkin-Elmer 241 Na589 polarimeter and are given
the units 10Ϫ1 deg cm2 gϪ1. All compounds were isolated using
flash chromatography and were assumed to have a purity of
greater than 98% (determined by NMR).
4-(Phenylsulfanyl)-3,4,5,6-tetrahydropyran-4(2H)-carboxalde-
hyde 17; X ؍ O
Thionyl chloride (0.93 g, 0.6 ml, 7.86 mmol) was added drop-
wise to a solution of the alcohol 15; X = O (1 g, 2.93 mmol) and
Et3N (5.5 ml, 3.93 mmol) in CH2Cl2 (40 ml) at 0 ЊC and stirred
for 45 min. This solution was then poured into ice-cold hydro-
chloric acid (28 ml, 3 M) and extracted with CH2Cl2 (3 × 50
ml). The combined extracts were dried (MgSO4) and evapor-
ated under reduced pressure. The residue was purified by flash
column chromatography on silica gel, eluting with petroleum
ether–ethyl acetate (4:1) to give the aldehyde 17; X = O (0.63 g,
74%) as an orange oil; Rf [petroleum ether–ethyl acetate (3:1)]
0.27; νmax(NaCl)/cmϪ1 1714 (CO) and 1582 (SPh); δH(400 MHz;
CDCl3) 9.30 (1 H, s, CHO), 7.51–7.26 (5 H, m, SPh), 3.94 (2 H,
dt, J 11.8 and 4.6, 2 × OCHeq), 3.47 (2 H, ddd, J 11.8, 8.6 and
3.4, 2 × OCHax), 1.90 (2 H, dt, J 13.7 and 4.0, 2 × CHeq) and
1.83 (2 H, ddd, J 13.3, 8.6 and 4.0, 2 × CHax); δC(100 MHz;
CDCl3) 193.6, 137.2, 129.9, 129.1, 127.8, 64.5, 57.2 and 30.3
(Found Mϩ, 222.0708. C13H14O2S requires M, 222.0714); m/z
(EI) 222 (20%, M), 193 (100, M Ϫ CHO), 83 (50, M Ϫ CHO Ϫ
SPh) and 83 (100, C5H8S).
4-(Phenylsulfanyl)thiane-4-carboxaldehyde 18; X ؍ S
In the same way as the aldehyde 17; X = O, the alcohol 16;
X = S (8 g, 29.6 mmol), Et3N (31.9 g, 43.0 ml, 0.316 mol) and
thionyl chloride (5.29 g, 3.30 ml, 44.4 mmol) in CH2Cl2 (300 ml)
gave, after column chromatography on silica gel eluting with
petroleum ether–ether (9:1) the aldehyde 18; X = S (5.92 g,
84%) as an orange oil; Rf [petroleum ether–ether (9:1)] 0.45;
νmax(film, CDCl3)/cmϪ1 1750 (CO); δH(200 MHz; CDCl3) 9.71
(1 H, s, CHO), 7.43–7.25 (5 H, m, SPh), 2.96–2.80 (2 H, m,
2 × SCHeq), 2.61–2.47 (2 H, m, 2 × SCHax) and 2.19–1.90 (4 H,
m, 2 × CH2eqϩax); δC(50 MHz; CDCl3) 193.68 (CHO), 137.09
(m-SPh), 129.78 (p-SPh), 128.97 (o-SPh), 127.47 (i-SPh), 58.92
(CSPh), 31.04 (CH2S) and 24.54 (CH2) (Found Mϩ, 238.0486.
C12H14OS2 requires M, 238.0486); m/z 238.0 (100%, M), 209.0
(90, M Ϫ CHO), 129.0 (30, M Ϫ SPh) and 110.0 (60, PhSH).
4-[Methoxy(phenylsulfanyl)methyl]-3,4,5,6-tetrahydro-(2H)-
pyran-4-ol 15; X ؍ O
n-BuLi (9.4 ml, 14.26 mmol, 1.52 M in hexane) was added
dropwise to a solution of methoxymethyl phenyl sulfide (2 g,
1.91 ml, 12.9 mmol) in THF (50 ml) at –78 ЊC and stirred for 30
min. Tetrahydropyran-4(4H)-one 5 (1.2 ml, 12.9 mmol) in THF
(5 ml) was added dropwise and the solution was stirred for a
further 20 min. A solution of brine (50 ml) was added and the
mixture was allowed to warm to room temperature. The solu-
tion was extracted with ether (3 × 50 ml) and 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 petroleum ether–ethyl
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2,6-Dimethylphenyl (2SR,3RS)-3-hydroxy-2-methyl-3-[4Ј-
(phenylsulfanyl)-3,4,5,6-tetrahydro-(2H)-pyran-4-yl]propionate
anti-20
δH(400 MHz; CDCl3) 7.53–7.30 (5 H, m, SPh), 4.05 (1 H, td,
J 11.5 and 2.3, OCHax), 4.00 (1 H, td, J 11.6 and 2.2, OCHax),
3.84–3.77 (2 H, m, 2 × OCHeq), 3.63–3.57 (3 H, m, CHOH and
ax
CH2OH), 3.02 (1 H, br s, CHOH), 2.21–2.13 (2 H, m, CHAHB
n-BuLi (1.8 ml, 1.5 M in hexanes, 2.66 mmol) was added to a
stirred solution of diisopropylamine (0.35 g, 0.47 ml, 3.45
mmol) in THF (50 ml) at Ϫ78 ЊC and the solution was stirred
for 30 minutes. A solution of Heathcock’s ester 19 (0.43 g, 2.42
mmol) in THF (10 ml) was slowly added and the solution was
stirred for a further 30 minutes. The aldehyde 17 (0.5 g, 2.25
mmol) in THF (10 ml) was slowly added to this solution and
stirred for 30 minutes. Saturated NH4Cl (50 ml) was added and
the solution allowed to warm to room temperature and
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 petroleum ether–ether (9:1) to give the
ester anti-20 (0.76 g, 86%) as white cubes, mp 128–129 ЊC (from
hexane–ether); Rf [ether] 0.4; vmax(NaCl)/cmϪ1 1730 (CO) and
1587 (SPh); δH(400 MHz; CDCl3) 7.55–7.48 (2 H, m, SPh),
7.41–7.29 (3 H, m, SPh), 7.06 (3 H, m, OAr), 4.33 (1 H, d, J 8.5,
OH), 4.13 (1 H, td, J 11.7 and 1.8, OCHax), 4.00 (1 H, td, J 11.7
and 1.8, OCHax), 3.88–3.78 (3 H, m, 2 × OCHeq and CHMe),
3.46 (1 H, dd, J 8.5 and 2.4, CHOH), 2.30 (1 H, ddd, J 15.0,
12.0 and 4.9, CHAHBax), 2.18 (6 H, s, 2 × Me, Ar), 2.11–1.98
(1 H, m, CHAHBax), 1.62 (3 H, d, J 7.4, CHMe) and 1.42–1.36
(2 H, m, 2 × CHAHBeq); δC(100 MHz; CDCl3) 175.1, 147.6,
137.3, 130.1, 129.7, 129.3, 129.1, 128.8, 126.2, 79.5, 63.6, 63.5,
56.8, 37.8, 30.5, 30.4, 18.8 and 16.7 (Found Mϩ, 400.1712.
C23H28O4S requires M, 400.1708); m/z (EI) 400 (20%, M), 193
(50, C11H13OS) and 122 (100, Me2C6H3OH).
and CHMe), 1.91 (1 H, ddd, J 14.3, 11.4 and 4.8, CHAHBax),
1.51 (1H, dd, J 14.6 and 2.2, CHCHDeq), 1.30 (1 H, dd, J 14.3
and 2.2, CHCHDeq) and 1.08 (3 H, d, J 7.0, CHMe); δC(100
MHz; CDCl3) 137.4, 137.3, 129.7, 129.6, 129.4, 129.2, 75.5,
69.2, 64.1, 63.6, 58.8, 35.2, 30.8, 30.4 and 11.7 (Found MHϩ,
282.1268. C15H22O3S requires M, 282.1289); m/z (EI) 283 (40%,
MH), 282 (30, M) and 265 (100, MH Ϫ H2O).
(1RS,2SR)-2-Methyl-1-(4-phenylsulfanyl-3,4,5,6-tetrahydro-
(2H)-pyran-4-yl)propane-1,3-diol anti-22; X ؍ O
In the same way as the diol anti-22; X = O, the ester anti-20;
X = O (0.3 g, 0.74 mmol) and LiAlH4 (85 mg, 2.2 mmol) in
ether (10 ml) gave, after flash column chromatography on silica
gel eluting with petroleum ether–ether (1:1) the diol anti-22;
X = O (0.19 g, 95%) as a colourless oil; Rf [petroleum ether–
ether (1:1)] 0.37; νmax(NaCl)/cmϪ1 3451 (OH) and 1582 (SPh);
δH(400 MHz; CDCl3) 7.51–7.32 (5 H, m, SPh), 4.08 (1 H, td,
J 11.5 and 2.0, OCHax), 3.97 (1 H, td, J 11.7 and 2.3, OCHax),
3.87 (1 H, dd, J 11.6 and 4.2, OCHeq), 3.81–3.67 (3 H, m,
2 × CHAHBOH and OCHeq), 3.32 (1 H, d, J 4.9, CHOH) and
2.96 (1 H, br s, CH2OH), 2.15–2.03 (2 H, m, CHMe and
CHAHBax), 1.78 (1 H, ddd, J 14.3, 11.6 and 4.8, CHAHBax), 1.51
(1 H, dd, J 15.7 and 2.0, CHAHBeq), 1.22 (1 H, dd, J 14.4 and
2.1, CHAHBeq) and 0.88 (3 H, d, J 7.0, CHMe); δC(100 MHz;
CDCl3) 137.4, 129.6, 129.2, 129.0, 79.3, 66.5, 64.0, 63.4, 56.7,
34.6, 29.9, 29.3 and 15.3 (Found Mϩ, 282.1288. C15H22O3S
requires M, 282.1289); m/z (EI) 282 (60%, M), 193 (100,
C11H13OS) and 83 (43, C5H8O).
2,6-Dimethylphenyl (2SR,3RS)-3-hydroxy-2-methyl-3-[4Ј-
(phenylsulfanyl)thianyl]propionate anti-21
(1RS,2SR)-2-Methyl-1-[4Ј-(phenylsulfanyl)thianyl]propane-1,3-
diol anti-23; X ؍ S
In the same way as ester anti-20, diisopropylamine (0.53 g, 0.72
ml, 5.29 mmol), n-BuLi (3.19 ml, 1.3 M in hexanes, 4.15 mmol),
Heathcock’s ester 168 (0.71g, 3.97 mmol) and aldehyde 18;
X = S (0.9 g, 3.78 mmol) in THF (100 ml) gave, after column
chromatography on silica gel eluting with petroleum ether–
ether (9:1), the ester anti-21 (1.3 g, 87%) as a colourless oil; Rf
[petroleum ether–ether (9:1)] 0.1; νmax(film, CDCl3)/cmϪ1 3300
(OH) and 1680 (CO); δH(200 MHz; CDCl3) 7.59–7.28 (5 H, m,
SPh), 7.03 (3 H, s, OAr), 4.42 (1 H, d, J 8.0, CHOH), 3.78 (1 H,
qd, J 7.3 and 2.3, CHMe), 3.56–3.28 (3 H, m, 2 × CHSeq and
CHOH), 2.49–2.31 (3 H, m, 2 × CHSax and CHAHBeq), 2.21
(6 H, s, 2 × Me, Ar), 2.18–2.04 (1 H, m, CHAHBeq), 1.95–1.68 (2
H, m, 2 × CHAHBax) and 1.61 (3 H, d, J 7.3, MeCH); δC(50
MHz; CDCl3) 174.8 (CO), 147.5 (i-OAr), 137.2 (i-SPh), 137.0
(m-OAr), 130.0, 129.3, 129.2, 129.0, 126.0 (o-, m-, p-SPh, p-OAr
and i-CMe), 79.2 (CHOH), 58.6 (CSPh), 37.4 (CHMe), 31.6
(CH2S), 31.5 (CH2S), 23.7 (CH2), 23.5 (CH2), 18.7 (2 × Me, Ar)
and 16.6 (MeCH) (Found Mϩ, 416.1483. C22H28O3S2 requires
M, 416.1479); m/z 416.1 (20%, M), 307.1 (2, M Ϫ SPh), 295.1
(30, M Ϫ OAr), 209.0 (40, C5H8SSPh), 122.1 (100, ArOH) and
110.0 (PhSH).
In the same way as diol anti-22; X = O, the ester anti-21 (0.92 g,
2.21 mmol) and LiAlH4 (0.25 g, 6.63 mmol) in ether (200 ml)
gave, after column chromatography on silica gel eluting with
ether, the diol anti-23; X = S (0.57 g, 87%) as a colourless oil;
Rf [ether] 0.5; νmax(film, CDCl3)/cmϪ1 3500–3300 (OH); δH(200
MHz; CDCl3) 7.50–7.26 (5 H, m, SPh), 3.80–3.15 (5 H, m,
2 × CHSeq, CHOH and CH2O), 3.15–2.85 (1 H, br s, OH),
eq
2.50–2.31 (2 H, m, 2 × CHSax), 2.21–1.95 (3 H, m, 2 × CHAHB
and CHMe), 1.90–1.75 (1 H, m, CHAHBax), 1.61–1.48 (1 H, m,
CHAHBax) and 0.92 (3 H, d, J 7.0, MeCH); δC(50 MHz; CDCl3)
137.0 (m-SPh), 129.5 (p-SPh), 129.1 (o-SPh), 128.4 (i-SPh), 79.2
(CHOH), 66.3 (CH2O), 61.6 (CSPh), 34.4 (CH2S), 31.2 (CH2S),
30.2 (CHMe), 23.9 (CH2), 23.6 (CH2) and 18.4 (MeCH) (Found
Mϩ, 298.1060. C15H22O2S2 requires M, 298.1061); m/z 298.1
(30%, M), 209.0 (100, C5H8SSPh), 189.1 (20, M Ϫ SPh) and
110.0 (60, PhSH).
(1RS,2RS)-2-Methyl-1-[4Ј-(phenylsulfanyl)thianyl]propane-1,3-
diol syn-23; X ؍ S
In the same way as diol anti-22; X = O, the ester syn-28 (0.15
g, 3.7 mmol) and LiAlH4 (41.7 mg, 1.11 mmol) in ether (50
ml) gave, after column chromatography on silica gel eluting
with ether, the diol syn-23; X = S (0.1 g, 93%) as a colourless
oil; Rf [ether] 0.6; νmax(film, CDCl3)/cmϪ1 3500–3300 (OH);
δH(200 MHz; CDCl3) 7.56–7.23 (5 H, m, SPh), 3.58–3.12
(5 H, m, 2 × CHSeq, CHOH and CH2O), 2.49–1.52 (9 H,
m, 2 × CHSax, 2 × CH2, 2 × OH and CHMe) and 1.08 (3 H, d,
J 6.8, MeCH); δC(50 MHz; CDCl3) 137.0 (m-SPh), 129.4
(i-SPh), 129.3 (p-SPh), 129.0 (o-SPh), 75.0 (CHOH), 68.9
(CH2O), 60.9 (CSPh), 35.0 (CHMe), 31.9 (CH2S), 31.7
(CH2S), 24.0 (CH2), 23.7 (CH2) and 11.7 (MeCH); m/z 298.1
(20%, M), 209.0 (100, C5H8SSPh), 189.1 (20, M Ϫ SPh) and
110.0 (30, PhSH).
(1RS,2SR)-2-Methyl-1-(4-phenylsulfanyl-3,4,5,6-tetrahydro-
(2H)pyran-4-yl)propane-1,3-diol syn-22; X ؍ O
Lithium aluminium hydride (0.161 g, 4.2 mmol) was added to a
stirred solution of ester syn-27; X = O (0.55 g, 1.4 mmol) in
ether (80 ml) at 0 ЊC. The solution was stirred for 3 hours and
poured onto an ice–brine mixture. NaOH (20 ml) was added
and the solution extracted with ether (3 × 100 ml). The com-
bined organic layers were dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by flash column
chromatography on silica gel eluting with petroleum ether–
ether (1:1) to give the diol syn-22; X = O (0.24 g, 82%) as white
plates, mp 97–98 ЊC (from ether–hexane); Rf [petroleum ether–
ether (1:1)] 0.37; νmax(NaCl)/cmϪ1 3451 (OH) and 1582 (SPh);
1908
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914

View Article Online
(3RS,4SR)-3-Methyl-4-phenylsulfanyl-1,8-dioxaspiro[4.5]-
decane anti-24; X ؍ O
µmol) in CH2Cl2 (1 ml) gave, after column chromatography on
silica gel eluting with petroleum ether–ether (9:1) the tetra-
hydrofuran syn-25 (18.6 mg, 99%) as a colourless oil; Rf [petrol-
eum ether–ether (9:1)] 0.2; νmax(film, CDCl3)/cmϪ1 1600 and
1550 (SPh); δH(400 MHz; CDCl3) 7.41–7.18 (5 H, m, SPh), 3.98
(1 H, dd, J 8.9 and 6.8, CHAHBO), 3.52 (1 H, dd, J 8.9 and 5.9,
CHAHBO), 3.39 (1 H, d, J 8.3, CHSPh), 3.10–2.94 (2 H, m,
2 × CHSeq), 2.74–2.63 (1 H, m, CHSax), 2.46–2.34 (2 H, m,
CHSax and CHAHBeq), 2.10–2.08 (1 H, m, CHAHBeq), 1.95–1.78
Toluene-p-sulfonic acid (5.3 mg, 28 µmol) was added to a
stirred solution of anti-22; X = O (40 mg, 0.14 mmol) in CH2Cl2
(2 ml). The solution was refluxed for 10 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 petroleum ether–ether (9:1) to give the
tetrahydrofuran anti-24; X = O (35 mg, 94%) as a yellow oil; Rf
[petroleum ether–ether (1:1)] 0.4; νmax(NaCl)/cmϪ1 1583 (SPh);
δH (400 MHz; CDCl3) 7.51–7.21 (5 H, m, SPh), 3.99 (1 H, t,
J 8.3, CHAHBO), 3.85–3.81 (1 H, m, OCHCHDeq), 3.75–3.64
eq
(3 H, m, 2 × CHAHB and CHMe) and 1.12 (3 H, d, J 7.1,
MeCH); δC(100 MHz; CDCl3) 136.6* (i-SPh), 130.5 (m-SPh),
129.0 (o-SPh), 126.4 (p-SPh), 82.1* (CO), 71.9* (CH2O), 61.5
(CHSPh), 38.0* (CH2S), 37.1 (CHMe), 24.2* (CH2S), 25.2*
(CH2), 24.4* (CH2) and 15.7 (MeCH) (Found Mϩ, 280.0956.
C15H20OS2 requires M, 280.0955); m/z 280.1 (50%, M), 164.1
(100, M Ϫ C5H8SO) and 110.0 (59, PhSH).
eq
(3 H, m, OCHCHD and 2 × OCHCHDax), 3.38 (1 H, t, J 8.7,
OCHAHB), 2.81 (1 H, d, J 10.6, CHSPh), 2.30–2.25 (1 H, m,
CHMe), 2.05 (1 H, ddd, J 13.1, 12.8 and 5.1, CHEHFax), 1.75
(1 H, ddd, J 13.3, 12.8 and 5.7, CHEHFax), 1.44 (1 H, dd, J 13.6
and 2.2, CHEHFeq), 1.29 (1 H, dd, J 11.4 and 1.9, CHEHFeq) and
1.15 (3 H, d, J 6.6, Me); δC(100 MHz; CDCl3) 135.6, 132.0,
129.1, 127.2, 81.5, 71.3, 64.7, 64.6, 64.1, 40.1, 36.4, 32.3 and
16.4 (Found Mϩ, 264.1186. C15H20O2S requires M, 264.1183);
m/z (EI) 264 (32%, M) and 164 (100, C11H13OS).
S-Phenyl (2RS,3RS)-3-hydroxy-2-methyl-3-(4-phenylsulfanyl-
3,4,5,6-tetrahydro-(2H)-pyran-4-yl)propanethioate syn-27; X ؍ O
S-Phenyl thiopropionate (0.38 g, 0.35 ml, 2.31 mmol) and
diisopropylethylamine (0.31 g, 0.42 ml, 2.42 mmol) in ether (6
ml) was added dropwise to a solution of 9-BBN-triflate (8 ml,
2.31 mmol, 0.5 M in ether) at 0 ЊC and stirred for 10 min. The
aldehyde 17 (0.5 g, 2.20 mmol) was added and the solution was
stirred for a further 3 hours. Phosphate buffer (pH = 7, 10 ml),
MeOH (20 ml) and H2O2 (30%, 10 ml) was added and stirred
for 5 min. Saturated NH4Cl (10 ml) was added and the solution
was extracted with ether (3 × 80 ml). The combined organic
extracts were washed (NaHCO3), dried (MgSO4) and evapor-
ated under reduced pressure. The residue was purified by flash
column chromatography on silica gel eluting with petroleum
ether–ether (9:1) to give the ester syn-27; X = O (0.73 g, 86%) as
a yellow oil; Rf [petroleum ether–ether (1:1)] 0.24; νmax(NaCl)/
(3RS,4RS)-3-Methyl-4-phenysulfanyl-1,8-dioxaspiro[4.5]-
decane syn-24; X ؍ O
In the same way as the tetrahydrofuran anti-24; X = O, the diol
syn-22; X = O (50 mg, 0.17 mmol) and toluene-p-sulfonic acid
(6.8 mg, 36 µmol) in CH2Cl2 (1.5 ml) gave, the tetrahydrofuran
syn-24; X = O (45 mg, 99%) as white needles, mp 72–73 ЊC
(from hexane–ether); Rf [petroleum ether–ether (1:1)] 0.37;
νmax(NaCl)/cmϪ1 1581 (SPh); δH(400 MHz; CDCl3) 7.45–7.37
(2 H, m, SPh), 7.31–7.25 (2 H, m, SPh), 7.21–7.17 (1 H, m,
SPh), 4.00 (1 H, dd, J 8.8 and 6.9, CHAHBO), 3.79–3.70 (4 H,
m, 2 × CH2Oeqϩax), 3.55 (1 H, dd, J 8.8 and 6.0, CHAHBO), 3.45
(1 H, d, J 7.8, CHSPh), 2.70 (1 H, sept, J 7.0, CHMe), 1.94
(1 H, ddd, J 13.6, 11.8 and 5.1, CHAHBax), 1.85 (1 H, ddd,
J 13.4, 10.7 and 6.4, CHAHBax), 1.66 (1 H, dd, J 13.6 and 2.4,
CHAHBeq), 1.47 (1 H, dd, J 13.4 and 2.4, CHAHBeq) and 1.13
(3 H, d, J 7.1, Me); δC(100 MHz; CDCl3) 136.6, 130.2, 129.1,
126.4, 81.3, 72.0, 64.8, 64.3, 60.8, 37.2, 36.4, 33.7 and 15.5
(Found Mϩ, 264.1184. C15H22O3S requires M, 264.1183); m/z
(EI) 264 (30%, M), 164 (100, C11H13OS) and 110 (45, PhSH).
cmϪ1 1693 (C᎐O) and 1582 (SPh); δ (400 MHz; CDCl ) 7.54–
᎐
H
3
7.31 (10 H, m, SPh and Ph), 4.04 (1H, td, J 11.5 and 1.8,
OCHax), 4.01 (1H, td, J 11.5 and 2.0, OCHax), 3.90 (1 H, t,
J 4.4, CHOH), 3.82 (1H, ddd, J 11.3, 4.6 and 1.8, OCHeq), 3.79
(1H, ddd, J 11.5, 4.6 and 2.2, OCHeq), 3.49 (1H, qd, J 7.0
and 5.0, CHMe), 2.77 (1 H, d, J 4.2, OH), 2.10 (1 H, ddd,
J 14.6, 11.5 and 4.8, CHAHBax), 1.99 (1H, ddd, J 14.4, 11.4
and 4.7, CHAHBax), 1.47 (1 H, dd, J 14.6 and 2.1, CHAHBeq),
1.47–1.42 (1 H, m, CHAHBeq) and 1.41 (3 H, d, J 7.0,
CHMe); δC(100 MHz; CDCl3) 210.7, 137.4, 137.2, 134.5,
134.3, 129.5, 129.3, 129.2, 129.1, 127.3, 74.6, 63.8, 63.5, 57.8,
48.8, 31.3, 30.6 and 15.0 (Found M Ϫ SPhϩ, 279.1057. C21H24-
O3S2 requires M, 388.1166); m/z (EI) 279 (40, M Ϫ SPh) and
150 (100).
(3SR,4RS)-3-Methyl-4-(phenylsulfanyl)-1-oxa-8-thiaspiro[4.5]-
decane anti-25; X ؍ S
In the same way as THF anti-24; X = O, the diol anti-23; X = S
(88 mg, 0.29 mmol) and toluene-p-sulfonic acid (11.2 mg, 59
µmol) in CH2Cl2 (1 ml) gave, after column chromatography on
silica gel eluting with petroleum ether–ether (9:1) the tetra-
hydrofuran anti-25; X = S (81.5 mg, 99%) as a colourless oil; Rf
[petroleum ether–ether (9:1)] 0.4; νmax(film, CDCl3)/cmϪ1 3300
(OH), 1550 and 1500 (SPh); δH(400 MHz; CDCl3) 7.47–7.20 (5
H, m, SPh), 3.96 (1 H, t, J 8.7, CHAHBO), 3.36 (1 H, t, J 8.7,
CHAHBO), 3.04–2.94 (2 H, m, 2 × CHSeq), 2.74 (1 H, d, J 10.6,
CHSPh), 2.41–2.22 (2 H, m, CHSax), 2.03 (1 H, dt, J 13.4 and
3.4, CHAHBeq), 1.92–1.83 (1 H, m, CHAHBeq), 1.78–1.63 (2 H,
m, 2 × CHAHBax) and 1.13 (3 H, d, J 6.5, MeCH); δC(100 MHz;
CDCl3) 135.6* (i-SPh), 132.1 (m-SPh), 129.1 (o-SPh), 127.2
(p-SPh), 82.3* (CO), 71.3* (CH2O), 65.9 (CHSPh), 40.1
(CHMe), 37.7* (CH2S), 33.5* (CH2S), 25.1* (CH2), 24.2*
(CH2) and 16.3 (MeCH) (Found Mϩ, 280.0950. C15H20OS2
requires M, 280.0956); m/z 280.1 (50%, M), 171.1 (5, M Ϫ
SPh), 164.1 (100, M Ϫ C5H8SO), 116.1 (10, C5H8SO) and 109.0
(20, SPh).
S-Phenyl (2SR,3SR)-3-[(4Ј-phenylsulfanyl)thianyl]-3-hydroxy-
2-methylpropanethioate syn-28; X ؍ S
In the same way as ester syn-27; X = O, 9-BBNOTf (6.6 ml, 0.5
M in toluene, 3.3 mmol), i-Pr2NEt base (0.45 g, 0.61 ml, 3.46
mmol), S-phenyl thiopropionate 26 (0.55 g, 0.50 ml, 3.3 mmol)
and aldehyde 18; X = S (0.75 g, 3.15 mmol) in ether (20 ml)
gave, after column chromatography on silica gel eluting with
petroleum ether–ether (1:1), the ester syn-28; X = S (0.72 g,
58%) as a colourless oil; Rf [petroleum ether–ether (1:1)] 0.5;
νmax(film, CDCl3)/cmϪ1 3300 (OH) and 1700 (CO); δH(200
MHz; CDCl3) 7.60–7.30 (10 H, m, 2 × SPh), 3.90–3.80 (1 H, t,
J 5.0, CHOH), 3.45–3.20 (4 H, m, 2 × CH2Seqϩax), 3.00 (1 H, d,
eqϩax
J 5.0, OH), 2.50–1.90 (5 H, m, 2 × CH2
and CHMe) and
1.45 (3 H, d, J 7.5, MeCH); δC(50 MHz; CDCl3) 201.1 (CO),
137.0 (o-SPha), 137.0 (i-SPha), 134.3 (p-SPha), 134.2 (m-SPha),
129.7 (p-SPhb), 129.4 (m-SPhb), 129.2 (o-SPhb), 128.7 (i-SPhb),
74.0 (CHOH), 60.0 (CSPh), 48.5 (CHMe), 32.3, 31.5, 23.8, 23.7
(4 CH2) and 15.1 (MeCH) (Found Mϩ, 404.0916. C22H24O2S3
requires M, 404.0938); m/z 404.1 (40%, M), 295.1 (40,
M Ϫ SPh), 209.0 (20, C5H8SSPh), 110.0 (100, PhSH) and 77.0
(20, Ph).
(3RS,4RS)-3-Methyl-4-phenylsulfanyl)-1-oxa-8-thiaspiro[4.5]-
decane syn-25; X ؍S
In the same way as THF anti-24; X = O, the diol syn-23; X = S
(20 mg, 67.1 mmol) and toluene-p-sulfonic acid (2.3 mg, 13.4
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914
1909

View Article Online
(2S,3S)-4-Benzyl-3-[3-hydroxy-2-methyl-1-oxo-3-(4-sulfanyl-
3,4,5,6-phenyltetrahydro-(2H)-pyran-4-yl)propionyl]oxazolidin-
2-one syn, anti-30
(2R,3R)-2-Methyl-1-(4-(phenylsulfanyl)-3,4,5,6-tetrahydro-(2H)-
pyran-4-yl)propane-1,3-diol syn-31
LiBH4 (0.40 ml, 2 M in THF, 0.79 mmol) was added dropwise
to a solution of the aldol syn, anti-30 (0.33 g, 0.72 mmol)
and H2O (14 µl, 0.79 mmol) in ether (15 ml) at 0 ЊC and
stirred for 4 hours. NaOH (0.30 ml, 2.5 M) was added and
the mixture was stirred until both layers become clear. Satur-
ated NH4Cl (1 ml) was added and the solution was extracted
with ether (3 × 30 ml). The combined organic extracts were
dried (MgSO4) and evaporated under reduced pressure. The
residue was purified by flash column chromatography on
silica gel eluting with petroleum ether–ether (5:1) to give the
diol syn-31 (0.2 g, 98%) as white cubes, mp 115–116 ЊC (from
ether–hexane); [α]D Ϫ19.25 (c 0.92 in CHCl3); νmax(NaCl)/
cmϪ1 3411 (OH) and 1583 (SPh); δH(400 MHz; CDCl3) 7.53–
7.30 (5 H, m, SPh), 4.05 (1 H, td, J 11.5 and 2.3, OCHax),
4.00 (1 H, td, J 11.6 and 2.2, OCHax), 3.84–3.77 (2 H, m,
2 × OCHeq), 3.63–3.57 (3 H, m, CHOH and CH2OH), 3.02
(1 H, br s, CHOH), 2.21–2.13 (2 H, m, CHAHBax and CHMe),
1.91 (1 H, ddd, J 14.3, 11.4 and 4.8, CHAHBax), 1.51 (1H, dd,
J 14.6 and 2.2, CHCHDeq), 1.30 (1 H, dd, J 14.3 and 2.2,
CHCHDeq), 1.08 (3 H, d, J 7.0, CHMe); δC(100 MHz; CDCl3)
137.4, 137.3, 129.7, 129.6, 129.4, 129.2, 75.5, 69.2, 64.1, 63.6,
58.8, 35.2, 30.8, 30.4 and 11.7 (Found Mϩ, 282.1287.
C15H22O3S requires M, 282.1289); m/z (EI) 283 (40%, MH),
282 (30, M) and 265 (100, MH – H2O).
Diisopropylethylamine (0.36 g, 0.48 ml, 2.77 mmol) was added
to a solution of 4-benzyl-3-propionyloxazolidin-2-one 29 (0.52
g, 2.25 mmol) in CH2Cl2 (10 ml) at 0 ЊC, followed by dropwise
addition of Bu2BOTf (2.47 ml, 1 M in CH2Cl2, 2.47 mmol). The
reaction was stirred for 45 min. A solution of the aldehyde 17
(0.5 g, 2.25 mmol) in CH2Cl2 (10 ml) at –78 ЊC was added
dropwise and the resultant solution stirred for 5 h, after which
MeOH (9 ml) and H2O2 (30%, 1.8 ml) were added. The reaction
mixture was then allowed to warm to 0 ЊC for 1 h. Saturated
NH4Cl (50 ml) was added and the solution allowed to warm to
room temperature and 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 petroleum
ether–ether (1:1) to give the aldol syn, anti-30 (0.76 g, 74%) as
white cubes, mp 54–58 ЊC (from ether–hexane); [α]D ϩ129.8 (c
0.77 in CHCl3); Rf [ether] 0.4; max(NaCl)/cmϪ1 3455 (OH),
1778 (CO) and 1693 (CO); δH(400 MHz; CDCl3) 7.59–7.16
(10 H, m, SPh and Ph), 4.64–4.56 (1 H, m, CHN), 4.38 (1 H,
qd, J 7.0 and 5.3, CHCO), 4.20–4.11 (2 H, m, CH2O), 4.04–
3.94 (3 H, m, 2 × CHOax and CHOH), 3.81–3.74 (2 H, m,
OCHeq), 3.25 (1 H, dd, J 13.2 and 3.0, CHAHBPh), 2.81 (1 H,
d, J 4.3, CHOH), 2.58 (1 H, dd, J 13.1 and 10.3, CHAHBPh),
2.18 (1 H, ddd, J 16.4, 11.8 and 4.8, CHAHBax), 1.94 (1 H,
ddd, J 16.3, 11.6 and 4.7, CHAHBax), 1.54–1.40 (2 H, m,
2 × CHAHBeq) and 1.33 (3 H, d, J 7.0, CHMe); δC(100 MHz;
CDCl3) 177.0, 152.8, 137.0, 136.9, 135.1, 130.1, 129.4, 129.2,
129.1, 129.0, 128.9, 127.4, 74.8, 66.1, 63.7, 63.5, 57.4, 55.3,
38.3, 37.7, 32.3, 30.9 and 14.5 (Found Mϩ, 455.1759.
C25H29NO5S requires M, 455.1766); m/z (EI) 455 (20%, M)
and 346 (95, M Ϫ SPh).
(1R,2R)-2-Methyl-1-(4-phenylsulfanyl-3,4,5,6-tetrahydro-(2H)-
pyran-4-yl)propane-1,3-diol anti-31
In the same way as the diol syn-31, the aldol anti, syn-30 (0.19 g,
0.42 mmol), LiBH4 (0.33 ml, 2 M in THF, 0.46 mmol) and H2O
(8 µl, 0.46 mmol) in THF (15 ml) gave, after flash column
chromatography on silica gel eluting with petroleum ether–
ether (1:1), the diol anti-31 (58 mg, 82%) as a colourless oil; Rf
[petroleum ether–ether (1:3)] 0.37; [α]D Ϫ6.9 (c 0.69 in CHCl3);
vmax(NaCl)/cmϪ1 3451 (OH) and 1582 (SPh); δH(400 MHz;
CDCl3) 7.51–7.32 (5 H, m, SPh), 4.08 (1 H, td, J 11.5 and 2.0,
OCHAHBax), 3.97 (1 H, td, J 11.7 and 2.3, OCHAHBax), 3.87
(1 H, dd, J 11.6 and 4.2, OCHAHBeq), 3.81–3.67 (3 H, m,
2 × CH2OH and OCHAHBeq), 3.32 (1 H, d, J 4.9, CHOH), 2.96
(1 H, br s, CH2OH), 2.15–2.03 (2 H, m, CHMe and CHAHBax),
1.78 (1 H, ddd, J 14.3, 11.6 and 4.8, CHAHBax), 1.51 (1 H, dd,
J 15.7 and 2.0, CHAHBeq), 1.22 (1 H, dd, J 14.4 and 2.1, CHA-
HBeq) and 0.88 (3 H, d, J 7.0, CHMe); δC(100 MHz; CDCl3)
137.4, 129.6, 129.2, 129.0, 79.3, 66.5, 64.0, 63.4, 56.7, 34.6, 29.9,
29.3 and 15.3 (Found Mϩ, 282.1288. C15H22O3S requires M,
282.1289); m/z (EI) 282 (60%, M), 193 (100, C11H13OS) and 83
(43, C5H8O).
(2S,3R)-4-Benzyl-3-[3-hydroxy-2-methyl-3-[(4-phenylsulfanyl)-
3,4,5,6-tetrahydro-(2H)-pyran-4-yl]propionyl]oxazolidin-2-one
anti,syn-30
Diisopropylethylamine (0.21 g, 0.28 ml, 1.6 mmol) was added
to a solution of 4-benzyl-3-propionyloxazolidin-2-one 29
(0.32 g, 1.35 mmol) in CH2Cl2 (10 ml) at 0 ЊC, followed by
dropwise addition of Bu2BOTf (0.45 ml, 1 M in CH2Cl2, 1.62
mmol). The reaction was stirred for 45 min. A solution of the
aldehyde 17 (0.6 g, 2.7 mmol) with Et2AlCl (5.4 ml of a
solution 1 M in hexane, 5.4 mmol) in CH2Cl2 (10 ml) at
Ϫ88 ЊC was added dropwise and the resultant solution stirred
for 5 h, after which MeOH (9 ml) and H2O2 (30%, 1.8 ml)
was added. The reaction mixture was then allowed to warm
to 0 ЊC for 1 h. Saturated NH4Cl (50 ml) was added and the
solution allowed to warm to room temperature and 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 petroleum ether–ether (1:1) to give the
aldol anti, syn-30 (0.58 g, 94%) as white cubes, mp 158–
159 ЊC (from ether); Rf [ether] 0.6; νmax(NaCl)/cmϪ1 3452
(OH), 1777 (CO), 1660 (CO) and 1580 (SPh); δH(400 MHz;
CDCl3) 7.56–7.17 (10 H, m, SPh and Ph), 4.93 (1 H, d, J 8.3,
OH), 4.73–4.59 (2 H, m, CHCO and CHN), 4.25–4.15 (2 H,
m, OCH2), 4.08–3.66 (4 H, m, 4 × CHO), 3.54 (1 H, d, J 8.3,
CHOH), 3.42 (1 H, dd, J 13.2 and 2.5, CHAHBPh), 2.56
(1 H, dd, J 13.2 and 11.1, CHAHBPh), 2.03 (1 H, ddd, J 15.0,
11.5 and 4.6, CHAHBax), 1.89 (1 H, ddd, J 15.0, 11.5 and 4.9,
CHAHBax), 1.65–1.35 (2 H, m, 2 × CHAHBeq) and 1.43 (3 H,
d, J 7.1, Me); δC(100 MHz; CDCl3) 179.0, 152.8, 136.9, 135.5,
130.3, 129.9, 129.4, 129.3, 129.0, 129.8, 127.3, 84.0, 66.0,
63.6, 56.0, 55.6, 37.3, 34.3, 32.3, 31.7 and 14.6 (Found Mϩ,
455.1766. C25H29O5S requires M, 455.1766); m/z (EI) 55 (30%,
M) and 346 (M Ϫ SPh).
(3R,4R)-3-Methyl-4-phenysulfanyl-1,8-dioxaspiro[4.5]decane
syn-32
In the same way as the tetrahydrofuran anti-24; X = O, the diol
syn-31 (50 mg, 0.17 mmol) and toluene-p-sulfonic acid (6.8 mg,
36 µmol) in CH2Cl2 (1.5 ml) gave, the tetrahydrofuran syn-32 (43
mg, 96%) as white needles, mp 72–73 ЊC (from hexane–ether);
Rf [petroleum ether–ether (1:1)] 0.37; [α]D Ϫ36.4 (c 1.0 in
CHCl3); vmax(NaCl)/cmϪ1 1581 (SPh); δH (400 MHz; CDCl3)
7.45–7.17 (5 H, m, SPh), 4.00 (1 H, dd, J 8.8 and 6.9, CHA-
HBO), 3.79–3.70 (4 H, m, 2 × CH2Oeqϩax), 3.55 (1 H, dd, J 8.8
and 6.0, CHAHBO), 3.45 (1 H, d, J 7.84, CHSPh), 2.70 (1 H,
heptet, J 7.0, CHMe), 1.94 (1 H, ddd, J 13.6, 11.8 and 5.1,
CHAHBax), 1.85 (1 H, ddd, J 13.4, 10.7 and 6.4, CHAHBax), 1.66
(1 H, dd, J 13.6 and 2.4, CHAHBeq), 1.47 (1 H, dd, J 13.4 and
2.4, CHAHBeq) and 1.13 (3 H, d, J 7.1, Me); δC(100 MHz;
CDCl3) 136.6, 130.2, 129.1, 126.4, 81.3, 72.0, 64.8, 64.3, 60.8,
37.2, 36.4, 33.7 and 15.5 (Found Mϩ, 264.1184. C15H22O3S
requires M, 264.1183); m/z (EI) 264 (30%, M), 164 (100,
C11H13OS) and 110 (45, PhSH).
1910
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914

View Article Online
(3R,4S)-3-Methyl-4-phenylsulfanyl-1,8-dioxaspiro[4.5]decane
anti-32
4-Hydroxy-4-[(4Ј-phenylsulfanyl)thianyl]butan-2-one 36
In the same way as the ketone 34, diisopropylamine (1.66 g,
2.24 ml, 16.5 mmol), n-BuLi (9.92 ml, 1.3 M in hexanes, 12.9
mmol), acetone (0.72 g, 12.3 mmol) and aldehyde 18; X = S (2.8
g, 11.7 mmol) in THF (300 ml) gave, after column chroma-
tography on silica gel eluting with petroleum ether–ether (1:1),
the ketone 36 (3.1 g, 89%) as a colourless oil; Rf [petroleum
ether–ether (1:1)] 0.5; νmax(film, CDCl3)/cmϪ1 3300 (OH) and
1700 (CO); δH(200 MHz, CDCl3) 7.54–7.38 (5 H, m, SPh), 3.92
(1 H, dt, J 10.0 and 2.7, CHOH), 3.41–3.29 (2 H, m, 2 ×
CHSeq), 3.28–2.48 (5 H, m, 2 × CHSax, CH2CO and OH), 2.23
(3 H, s, Me) and 2.20–1.68 (4 H, m, 2 × CH2eqϩax); δC(50 MHz;
CDCl3) 208.5 (CO), 136.9 (m-SPh), 130.1 (i-SPh), 129.2
(p-SPh), 128.9 (o-SPh), 71.4 (CHOH), 57.2 (CSPh), 44.1
(CH2CO), 31.2 (CH2S), 30.9 (CH2S), 23.6 (CH2) and 23.5 (CH2)
(Found Mϩ, 296.0944. C15H20O2S2 requires M, 296.0946); m/z
296.1 (10%, M), 209.0 (40, C5H8SSPh), 110.0 (100, PhSH), 99.0
(40, C5H7S) and 77.0 (45, Ph).
In the same way as for the tetrahydrofuran anti-24; X = O,
the diol anti-31 (10 mg, 34 µmol) and toluene-p-sulfonic acid
(1.5 mg, 8 µmol) in CH2Cl2 (1.5 ml) gave, the tetrahydrofuran
anti-32 (8 mg, 90%) as yellow oil, Rf [petroleum ether–ether
(1:1)] 0.40; [α]D ϩ82.2 (c 0.79 in CHCl3); vmax(NaCl)/cmϪ1
1583 (SPh); δH(400 MHz; CDCl3) 7.51–7.21 (5 H, m, SPh),
3.99 (1 H, t, J 8.3, CHAHBO), 3.85–3.81 (1 H, m, OCHC-
HDeq), 3.75–3.64 (3 H, m, OCHCHDeq and 2 × OCHCHDax), 3.38
(1 H, t, J 8.7, OCHAHB), 2.81 (1 H, d, J 10.6, CHSPh), 2.30–
2.25 (1 H, m, CHMe), 2.05 (1 H, ddd, J 13.1, 12.8 and 5.1,
CHEHFax), 1.75 (1 H, ddd, J 13.3, 12.8 and 5.7, CHEHFax),
1.44 (1 H, dd, J 13.6 and 2.2, CHEHFeq), 1.29 (1 H, dd, J 11.4
and 1.9, CHEHFeq) and 1.15 (3 H, d, J 6.6, Me); δC(100 MHz;
CDCl3) 135.6, 132.0, 129.1, 127.2, 81.5, 71.3, 64.7, 64.6, 64.1,
40.1, 36.4, 32.3 and 16.4 (Found Mϩ, 264.1186. C15H20O2S
requires M, 264.1183); m/z (EI) 264 (32%, M) and 164 (100,
C11H13OS).
2,4-Dihydroxy-2-methyl-4-[(4Ј-phenylsulfanyl)thianyl]butane 37
4-Hydroxy-4-(4-phenylsulfanyl-3,4,5,6-tetrahydro-(2H)-pyran-4-
yl)butan-2-one 34
In the same way as the diol 35, the ketone 36 (0.15 g, 0.56
mmol) and MeMgCl (0.33 ml, 3 M in ether, 1.01 mmol) in ether
(5 ml) gave, after column chromatography on silica gel eluting
with ether, the diol 37 (0.136 g, 90%) as a colourless oil; Rf
[ether] 0.5; νmax(film, CDCl3)/cmϪ1 3400–3300 (OH); δH(200
MHz; CDCl3) 7.54–7.27 (5 H, m, SPh), 3.87 (1 H, s, OH), 3.65
(1 H, dd, J 11.2 and 2.2, CHOH), 3.48 (1 H, s, OH), 3.38–3.18
n-BuLi (2.21 ml, 1.2M in hexanes, 2.66 mmol) was added to a
solution of diisopropylamine (0.35 g, 0.47 ml, 3.45 mmol) in
THF (25 ml) at Ϫ78 ЊC and stirred for 40 min. Acetone 33 (0.14
g, 0.18 ml, 2.42 mmol) was added dropwise and the solution
was stirred for a further 40 min. The aldehyde 17 (0.49 g, 2.2
mmol) in THF (2 ml) was slowly added and the solution was
stirred for a further 20 min. Saturated NH4Cl (1 ml) was added
and the solution was extracted with ether (3 × 30 ml). The
combined organic extracts were dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by flash
column chromatography on silica gel eluting with petroleum
ether–ether (1:3) to give the aldol 34 (0.55 g, 90%) as white
cubes, mp 98–99 ЊC (from ether); Rf [ether] 0.32; νmax(NaCl)/
cmϪ1 3417 (OH), 1712 (CO); δH(400 MHz; CDCl3) 7.48–7.29
(5 H, m, SPh), 4.07–3.92 (3 H, m, CHOH and 2 × CHOax),
3.81–3.77 (2 H, m, 2 × CHOeq), 3.12 (1 H, d, J 3.3, CHOH),
3.05 (1 H, dd, J 17.0 and 1.6, CHAHBCO), 2.74 (1 H, dd, J 17.0
and 10.0, CHAHBCO), 2.24, (3 H, s, Me), 2.03 (1 H, ddd, J 14.8,
11.9 and 4.9, OCHax), 1.90 (1 H, ddd, J 14.5, 11.8 and 4.9,
OCHax) and 1.36–1.32 (2 H, m, 2 × OCHeq); δC(100 MHz;
CDCl3) 209.2, 137.4, 129.7, 129.3, 129.1, 128.6, 71.9, 63.6, 63.5,
55.4, 44.5, 31.1, 30.0 and 29.9 (Found Mϩ, 280.1135. C15H20O3S
requires M, 280.1133); m/z (EI) 280 (40, M), 193 (80) and 69
(100).
(2 H, m, 2 × CHSeq), 2.52–2.34 (2 H, m, 2 × CHSax), 2.12–1.51
eqϩax
(6 H, m, 2 × CH2
and CH2), 1.27 (3 H, s, Me) and 1.21
(3 H, s, Me); δC(50 MHz; CDCl3) 137.1 (m-SPh), 129.4 (p-SPh),
129.0 (o-SPh), 128.5 (i-SPh), 72.3 (CHOH), 70.8 (COH), 59.5
(CSPh), 40.1 (CH2CO), 31.7 (CH2S), 31.2 (CH2S), 30.7 (CH2),
27.6 (CH2), 23.8 (Me) and 23.7 (Me); m/z 312.1 (20%, M) and
294.1 (100, M Ϫ H2O).
2,2-Dimethyl-4-(phenylsulfanyl)-1-oxa-8-thiaspiro[4.5]decane 41
In the same way as the tetrahydrofuran 24; X = O, the diol 37
(20 mg, 64.1 µmol) and toluene-p-sulfonic acid (2.2 mg, 12.8
µmol) in CH2Cl2 (1 ml) gave, after column chromatography on
silica gel eluting with petroleum ether–ether (9:1), the tetra-
hydrofuran 41 (18 mg, 98%) as a colourless oil; Rf [petroleum
ether–ether (9:1)] 0.5; νmax(film, CDCl3)/cmϪ1 1550 (SPh);
δH(400 MHz; CDCl3) 7.43–7.21 (5 H, m, SPh), 3.36 (3 H, dd,
J 11.6 and 7.1, CHSPh), 3.13–3.01 (2 H, m, 2 × CHSeq), 2.43–
2.29 (2 H, m, 2 × CHSax), 2.24 (1 H, dd, J 12.6 and 7.1, CHA-
HBeq), 2.10 (1 H, t, J 12.0, CHAHBeq), 1.94–1.85 (3 H, m,
ax
2 × CHAHB and CHCHD), 1.68–1.63 (1 H, m, CHCHD), 1.32
3-Methyl-1-(4-phenylsulfanyl-3,4,5,6-tetrahydro-(2H)-pyran-4-
yl)butane-1,3-diol 35
(3 H, s, Me) and 1.18 (3 H, s, Me); δC(100 MHz; CDCl3) 135.5*
(i-SPh), 131.6 (m-SPh), 129.0 (o-SPh), 127.0 (p-SPh), 82.0*
(CO), 78.8* (CO), 57.0 (CHSPh), 45.7* (CH2CO), 39.1*
(CH2S), 34.6* (CH2S), 30.7 (Me), 30.5 (Me), 25.2* (CH2) and
24.1* (CH2) (Found Mϩ, 294.1115. C16H22OS2 requires M,
294.1112); m/z 294.1 (75%, M), 178.1 (100, M Ϫ C5H8SO),
163.1 (50, C5H9SPh) and 110.0 (60, PhSH).
MeMgCl (70 µl, 3 M in ether, 0.22 mmol) was added to a solu-
tion of the ketone 34 (28 mg, 0.1 mmol) in THF (2 ml) at 0 ЊC
and stirred for 30 min. Saturated NH4Cl (10 ml) was added and
the solution was extracted with ether (3 × 30 ml). The com-
bined organic extracts were washed (NaHCO3), dried (MgSO4)
and evaporated under reduced pressure. The residue was puri-
fied by flash column chromatography on silica gel eluting with
CH2Cl2–methanol (1:3) to give the diol 35 (28 mg, 96%) as
a colourless oil; Rf [ether] 0.32; νmax(NaCl)/cmϪ1 3387 (OH);
δH(400 MHz; CDCl3) 7.51–7.48 (2 H, m, SPh), 7.40–7.29 (3 H,
m, SPh), 4.08–3.94 (2 H, m, 2 × CHOax), 3.84–3.75 (3 H, m,
2 × CHOeq and CHOH), 2.02 (1 H, ddd, J 14.6, 11.9 and 5.0,
2,2-Dimethyl-4-phenylsulfanyl-1,8-dioxaspiro[4.5]decane 42
In the same way as the tetrahydrofuran anti-24; X = O, the diol
35 (18 mg, 60 µmol) and toluene-p-sulfonic acid (2.3 mg, 12
µmol) in CH2Cl2 (1.5 ml) gave, the tetrahydrofuran 42 (12 mg,
76%) as white needles, mp 58–59 ЊC (from hexane); Rf [ether]
0.7; vmax(NaCl)/cmϪ1 1560 (SPh); δH(400 MHz; CDCl3) 7.43–
7.21 (5 H, m, SPh), 3.84–3.70 (4 H, m, 2 × CH2Oeqϩax), 3.46
(1 H, dd, J 11.1 and 7.1, CHSPh), 2.27 (1 H, dd, J 12.6 and 7.1,
CH(S)CHAHB), 2.01 (1 H, t, J 12.6, CH(S)CHAHB), 1.97–1.85
(2 H, m, 2 × OCHax), 1.49 (1 H, dd, J 13.3 and 2.2, OCHeq),
1.33 (3 H, s, Me), 1.30 (1 H, dd, J 13.4 and 2.3, OCHeq) and 1.21
(3 H, s, Me); δC(100 MHz; CDCl3) 131.5, 129.1, 127.0, 81.2,
78.8, 64.8, 64.1, 55.8, 45.7, 37.8, 33.6, 30.7 and 30.5.
ax
CHAHBax), 1.85–1.70 (2 H, m, CHAHB and CHCHD), 1.46
(1 H, dd, J 14.6 and 2.1, CHAHBeq), 1.27 (3 H, s, Me), 1.27–1.24
eq
(2 H, m, CHAHB and CHCHD) and 1.24 (3 H, s, Me); δC(100
MHz; CDCl3) 137.4, 129.5, 129.4, 129.1, 128.6, 72.8, 71.0, 63.8,
63.6, 57.6, 41.1, 31.9, 29.9, 29.7 and 27.8 (Found Mϩ, 296.1445.
C16H24O3S requires M, 296.1446); m/z (EI) 296 (M, 60), 280 (30,
M Ϫ OH) and 193 (100, M Ϫ C5H12O2).
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914
1911

View Article Online
(2SR,4RS)-2,4-Dihydroxy-4-[(4Ј-phenylsulfanyl)thian-4Ј-yl]-
butane anti-44
(1SR,3RS)-1-(4-Phenylsulfanyl-3,4,5,6-tetrahydro-(2H)-pyran-
4-yl)butane-1,3-diol anti-46
In the same way as the diol anti-48, ketone 36 (0.1 g, 0.34 mmol)
and tetramethylammonium triacetoxyborohydride (0.71 g, 2.69
mmol) in AcOH–MeCN (4 ml, 1:1) gave, after flash column
chromatography on silica gel eluting with petroleum ether–
ether (1:1) a separable diastereoisomeric mixture (94:6, anti:
syn) of the diol anti-44 (91 mg, 90%) as a colourless oil; Rf
[petroleum ether–ether (1:1)] 0.15; νmax(film, CDCl3)/cmϪ1
3450–3300 (OH); δH(200 MHz; CDCl3) 7.58–7.28 (5 H, m,
SPh), 4.10 (1 H, sext, J 5.4, CHMe), 3.66 (1 H, t, J 6.2, CHOH),
3.48–3.15 (4 H, m, 2 × CH2Seqϩax), 2.71–2.48 (1 H, br s, OH),
2.48–2.32 (2 H, m, 2 × CHAHBeq), 2.08–1.82 (2 H, m, CH2),
1.75–1.52 (2 H, m, 2 × CHAHBax) and 1.18 (3 H, d, J 6.2,
MeCH); δC(50 MHz; CDCl3) 137.0 (m-SPh), 129.4 (p-SPh),
128.9 (o-SPh), 128.8 (i-SPh), 71.2 (CHOH), 65.2 (CHOH),
59.3 (CSPh), 38.1 (CH2CHO), 31.2 (CH2S), 30.9 (CH2S), 23.7
(CH2) and 23.6 (CH2) (Found Mϩ, 298.1056. C15H22O2S2
requires M, 298.1061); m/z 298.1 (100%, M), 209.0 (90, M Ϫ
C4H9S), 123.0 (20, PhSCH2), 110.0 (70, PhSH) and 101.1 (90,
C5H9S).
Me4N(AcO)3BH (0.73 g, 2.8 mmol) was added to a solution of
the ketone 34 (0.1 g, 0.35 mmol) in AcOH–MeCN (4 ml, 1:1) at
Ϫ30 ЊC and stirred for 5 days. Saturated NaHCO3 (50 ml) was
added and the solution was extracted with ether (3 × 30 ml).
The combined organic extracts were washed (NaHCO3), dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel elut-
ing with CH2Cl2–methanol (1:3) to give the diol anti-46 (91 mg,
90%) as a colourless oil; Rf [CH2Cl2–MeOH (50:1)] 0.26;
νmax(NaCl)/cmϪ1 3381 (OH) and 1582 (SPh); δH(400 MHz;
CDCl3) 7.54–7.31 (5 H, m, SPh), 4.20–4.10 (1 H, m, CHOH),
4.08–3.95 (2 H, m, 2 × OCHax), 3.86–3.77 (2 H, m, 2 × OCHeq),
3.74 (1 H, dd, J 9.8 and 2.8, CHOH), 3.17 (1 H, br s, OH), 2.10–
1.96 (1 H, br s, OH), 1.96 (1 H, ddd, J 14.6, 11.8 and 4.9, CHax),
1.79 (1 H, ddd, J 14.6, 11.6 and 4.8, CHax), 1.72–1.63 (2 H, m,
CH2), 1.49 (1 H, dd, J 14.6 and 2.1, CHeq), 1.28 (1 H, dd, J 14.4
and 2.1, CHeq) and 1.23 (3 H, d, J 6.3, CH3); δC(100 MHz;
CDCl3) 137.6, 129.6, 129.3, 129.2, 76.0, 68.8, 63.5, 63.4, 57.7,
38.9, 29.3, 29.2 and 23.4.
(2RS,4RS)-2-Methyl-4-(phenylsulfanyl)-1-oxa-8-thiaspiro[4.5]-
decane anti-50
(2SR,4SR)-2,4-Dihydroxy-4-[(4Ј-phenylsulfanyl)thian-4Ј-yl]-
butane syn-44
In the same way as the tetrahydrofuran anti-24; X = O, the diol
anti-44 (40 mg, 0.13 mmol) and toluene-p-sulfonic acid (4.6 mg,
26.8 µmol) in CH2Cl2 (1 ml) gave, after column chromatography
on silica gel eluting with light petroleum (40–60 ЊC)–ether (9:1)
the tetrahydrofuran anti-50 (37 mg, 99%) as a colourless oil; Rf
[petroleum ether–ether (9:1)] 0.5; νmax(film, CDCl3)/cmϪ1 3500–
3300 (OH); δH(400 MHz; CDCl3) 7.43–7.19 (5 H, m, SPh), 4.19
(1 H, sext, J 6.1, CHCH3), 3.32 (1 H, t, J 8.1, CHO), 3.06–2.95
(2 H, m, 2 × SCHeq), 2.44–2.34 (2 H, m, 2 × OCHax), 2.20–
1.70 (6 H, m, 3 × CH2) and 1.20 (3 H, d, J 6.1, CH3CH);
δC(100MHz, CDCl3) 135.6* (i-SPh), 131.2 (m-SPh), 129.0
(o-SPh), 126.9 (p-SPh), 82.3* (CO), 71.5 (CHO), 55.9
(CHSPh), 40.6* (CH2CO), 38.8* (CH2S), 32.3* (CH2S), 25.3*
(CH2), 24.5* (CH2) and 22.5 (CH3CH) (Found Mϩ, 280.0951.
C15H20OS2 requires M, 280.0955); m/z 280.1 (55%, M), 164.1
(100, M Ϫ C5H8SO) and 110.0 (45, PhSH).
In the same way as the diol syn-48, the ketone 36 (0.1 g, 0.34
mmol), diethylmethoxyborane (0.34 ml, 1 M in THF, 0.34
mmol) and NaBH4 (25.3 mg, 0.67 mmol) in ether (50 ml) gave,
after flash column chromatography on silica gel eluting with
petroleum ether–ether (1:1) a separable diastereomeric mixture
(3:97, anti:syn) of the diol syn-44 (96 mg, 96%) as a colourless
oil; Rf [petroleum ether–ether (1:1)] 0.25; νmax(film, CDCl3)/
cmϪ1 3500–3300 (OH); δH(200 MHz; CDCl3) 7.53–7.30 (5 H, m,
SPh), 3.99–3.75 (3 H, m, CHOH and CHOH), 3.53–3.14 (3 H,
m, 2 × CHSeq and OH), 2.46–2.31 (2 H, m, 2 × CHSax), 2.12–
1.48 (6 H, m, 3 × CH2) and 1.18 (3 H, d, J 6.3, MeCH); δC(50
MHz; CDCl3) 137.1 (m-SPh), 129.3 (p-SPh), 129.0 (o-SPh),
128.6 (i-SPh), 75.6 (CHOH), 66.4 (CHOH), 59.2 (CSPh), 37.6
(CH2CHO), 31.0 (CH2S), 30.5 (CH2S), 23.7 (CH2) and
23.6 (CH2) (Found Mϩ, 298.1065. C15H22O2S2 requires M,
298.1061); m/z 298.1 (50%, M), 209.0 (85, M Ϫ C4H9S), 122.0
(20, PhSCH), 109.0 (65, SPh) and 101.1 (100, C5H9S).
(2RS,4SR)-2-Methyl-4-(phenylsulfanyl)-1-oxa-8-thiaspiro[4.5]-
decane syn-50
(1SR,3SR)-1-(4-Phenylsulfanyl-3,4,5,6-tetrahydro-(2H)-pyran-4-
yl)butane-1,3-diol syn-46
In the same way as the tetrahydrofuran anti-24; X = O, the diol
syn-44 (40 mg, 0.13 mmol) and toluene-p-sulfonic acid (4.6 mg,
26.8 µmol) in CH2Cl2 (1 ml) gave, after column chromatography
on silica gel eluting with petroleum ether–ether (9:1), the tetra-
hydrofuran syn-50 (37 mg, 99%) as a colourless oil; Rf [petrol-
eum ether–ether (9:1)] 0.4; νmax(film, CDCl3)/cmϪ1 1550 (SPh);
δH(400 MHz; CDCl3) 7.42–7.20 (5 H, m, SPh), 4.08 (1 H,
double quintet, J 9.6 and 5.9, CHMe), 3.32 (1 H, dd, J 10.7 and
6.7, CHSPh), 3.10–2.98 (2 H, m, 2 × SCHeq), 2.49–2.39 (3 H,
m, 2 × SCHax and CHAHBeq), 1.93 (2 H, dd, J 7.9 and 3.7,
Et2BOMe (0.29 ml, 1 M in THF, 0.29 mmol) was added to a
solution of the aldol 34 (80 mg, 0.29 mmol) in THF–MeOH
(4 ml, 3:1) at Ϫ78 ЊC and stirred for 5 min. NaBH4 (22 mg, 0.58
mmol) was added and the solution was stirred for a further 2 h.
Acetic acid (1 ml) was then added and the mixture was allowed
to warm to room temperature. Saturated NH4Cl (10 ml) was
added and the solution was extracted with ether (3 × 30 ml).
The combined organic extracts were washed (NaHCO3), dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel elut-
ing with CH2Cl2–methanol (1:3) to give the diol syn-46 (78 mg,
96%) as white plates, mp 102–103 ЊC (from ether–hexane); Rf
[CH2Cl2–MeOH (50:1)] 0.34; νmax(NaCl)/cmϪ1 3381 (OH) and
1582 (SPh); δH(400 MHz; CDCl3) 7.49–7.31 (5 H, m, SPh),
4.10–3.96 (3 H, m, CHOH and 2 × OCHax), 3.85–3.78 (2 H, m,
2 × OCHeq), 3.74 (1 H, br s, CHOH), 3.59 (1 H, dd, J 10.5 and
1.8, CHOH), 3.52 (1 H, br s, CHOH), 2.00 (1 H, ddd, J 14.6,
11.9 and 5.0, CHAHBax), 1.82–1.74 (2 H, m, CHCHD and
CHAHBeq), 1.64–1.55 (1 H, m, CHCHD), 1.47 (1 H, dd, J 14.6
and 2.0, CHAHBax), 1.27–1.20 (1 H, m, CHAHBeq) and 1.19 (3 H,
d, J 6.3, Me); δC(100 MHz; CDCl3) 137.5, 129.5, 129.3, 129.2,
75.9, 68.7, 63.8, 63.5, 57.8, 38.1, 29.8, 29.4 and 23.9 (Found
M Ϫ C4H9O2ϩ, 193.0696. C11H13OS requires M, 193.0687);
m/z (EI) 193 (90, M Ϫ C4H9O2) and 110 (100, SPh).
eq
2 × CH2), 1.87–1.65 (3 H, m, CHAHB and 2 × CHAHBax) and
1.25 (3 H, d, J 6.0, MeCH); δC(100 MHz; CDCl3) 135.5*
(i-SPh), 131.4 (m-SPh), 129.0 (o-SPh), 127.0 (p-SPh), 81.4*
(CO), 72.5 (CHO), 57.4 (CHSPh), 41.5* (CH2CO), 37.5*
(CH2S), 35.7* (CH2S), 25.1* (CH2), 24.4* (CH2) and 22.2
(MeCH) (Found Mϩ, 280.0955. C15H20OS2 requires M,
280.0955); m/z 280.1 (40%, M), 164.1 (100, M Ϫ C5H8SO) and
110.0 (40, PhSH).
(2RS,4SR)-2-Methyl-4-phenylsulfanyl-1,8-dioxaspiro[4.5]-
decane syn-51
In the same way as the tetrahydrofuran anti-24; X = O, the diol
syn-46 (50 mg, 0.18 mmol) and toluene-p-sulfonic acid (6.8 mg,
36 µmol) in CH2Cl2 (2.5 ml) gave, the tetrahydrofuran syn-51 (43
mg, 94%) as a colourless oil; Rf [ether] 0.68; νmax(NaCl)/cmϪ1
1912
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914

View Article Online
1583 (SPh); δH(400 MHz; CDCl3) 7.42–7.37 (2 H, m, SPh),
7.31–7.20 (3 H, m, SPh), 4.10–4.03 (1 H, double quintet, J 9.4
and 6.4, OCHMe), 3.82–3.72 (4 H, m, 2 × OCH2eqϩax), 3.41
(1 H, dd, J 10.1 and 7.1, CHSPh), 2.49 (1 H, ddd, J 12.8, 7.0
and 6.0, CHAHB), 1.96 (1 H, ddd, J 13.3, 11.6 and 5.2, CHC-
HDax), 1.8 (1 H, ddd, J 14.7, 11.6 and 4.5, CHCHDax), 1.71 (1 H,
dt, J 12.8 and 10.1, CHAHB), 1.56 (1 H, qd, J 13.3 and 2.4,
CHCHDeq), 1.43 (1 H, qd, J 13.4 and 2.3, CHCHDeq) and 1.28
(3 H, d, J 6.1, Me); δC(100 MHz; CDCl3) 135.6, 131.3, 129.1,
126.9, 80.7, 72.4, 64.7, 64.4, 56.1, 41.4, 36.4, 34.6 and 22.2.
M, 264.1189); m/z (EI) 264 (65%, M), 155 (100, M Ϫ SPh), 110
(90, SPh) and 83 (40, C5H7O).
3-Hydroxy-3-[methoxy(phenylsulfanyl)methyl]thiolane 56
In the same way as alcohol 15; X = O, methoxymethyl phenyl
sulfide (4.75 g, 4.55 ml, 30.9 mmol), n-BuLi (24.9 ml, 1.3 M in
hexanes, 32.4 mmol) and tetrahydrothiophen-3-one 55 (3.0 g,
2.51 ml, 29.4 mmol) in THF (150 ml) gave, after column
chromatography on silica gel eluting with petroleum ether–
ether (9:1), an inseparable diastereomeric mixture (54:46) of
the alcohol 56 (7.1 g, 95%) as a colourless oil; Rf [petroleum
ether–ether (9:1)] 0.1; νmax(film, CDCl3)/cmϪ1 3300 (OH) and
1550 (SPh); δH(200 MHz; CDCl3) 7.55–7.23 (10 H, m, SPhmaj
and SPhmin), 7.75 (1 H, s, CHSPhmaj), 4.74 (1 H, s, CHSPhmin),
3.49 (6 H, s, OMemaj and OMemin), 3.23–2.65 (8 H, m, 2 ×
(2RS,4RS)-2-Methyl-4-phenylsulfanyl-1,8-dioxaspiro[4.5]-
decane anti-51
In the same way as the tetrahydrofuran anti-24; X = O, the diol
anti-46 (50 mg, 0.18 mmol) and toluene-p-sulfonic acid (6.8 mg,
36 µmol) in CH2Cl2 (2.5 ml) gave, the tetrahydrofuran anti-51
(45 mg, 96%) as a colourless oil; Rf [ether] 0.7; νmax(NaCl)/cmϪ1
1583 (SPh); δH(400 MHz; CDCl3) 7.42–7.38 (2 H, m, SPh),
7.31–7.20 (3 H, m, SPh), 4.24 (1 H, sext, J 6.3, OCHMe), 3.82–
3.70 (4 H, m, 2 CH2Oeqϩax), 3.42 (1 H, t, J 7.5, CHSPh), 2.16
(1 H, dt, J 13.0 and 7.2, CHAHB), 2.06 (1 H, ddd, J 13.1, 7.9 and
6.4, CHAHB), 1.94–1.81 (2 H, m, 2 × CHCHDax), 1.60 (1 H, dq,
J 12.5 and 2.5, CHCHDeq), 1.40 (1 H, dq, J 13.3 and 2.5, CHC-
HDeq) and 1.23 (3 H, d, J 6.2, Me); δC(100 MHz; CDCl3)
135.6, 131.3, 131.2, 129.1, 126.8, 81.4, 71.8, 64.8, 64.4, 55.5,
40.5, 37.8, 31.6 and 22.5 (Found Mϩ, 264.1184. C15H20O2S
requires M, 264.1183); m/z (EI) 264 (20%, M), 164 (100) and
110 (60, SPh).
maj
maj
CH2 and 2 × CH2min) and 2.20–2.08 (4 H, m, CH2 and
CH2min); δC(50 MHz; CDCl3) 134.9 (i-SPhmin), 134.8 (i-SPhmaj),
132.9 (m-SPhmaj and i-SPhmin), 129.4 (o-SPhmaj and o-SPhmin),
127.7 (p-SPhmaj and p-SPhmin), 99.0 (CHSPhmaj and CHSPhmin),
86.2 (COHmin), 86.0 (COHmaj), 57.5 (MeOmaj and MeOmin),
39.8, 39.6, 39.5 and 39.2 (2 × CH2Smaj and 2 × CH2Smin), 29.2
(CH2min) and 29.0 (CH2maj) (Found Mϩ, 256.0588. C12H16O2S2
requires M, 256.0591); m/z 256.1 (40%, M), 147.1 (35,
M Ϫ SPh) and 115.0 (100, M Ϫ SPh Ϫ MeOH).
3-(Phenylsulfanyl)thiolane-3-carboxaldehyde 57
In the same way as aldehyde 17; X=O, the alcohol 56 (6.0 g, 23.4
mmol), Et3N (25.2 g, 34.0 ml, 0.25 mol) and thionyl chloride
(8.36 g, 5.23 ml, 70.3 mmol) in CH2Cl2 (350 ml) gave, after
column chromatography on silica gel eluting with petroleum
ether–ether (9:1), the aldehyde 57 (3.66 g, 70%) as a colourless
oil; Rf [petroleum ether–ether (9:1)] 0.35; νmax(film, CDCl3)/
cmϪ1 1750 (CO) and 1550 (SPh); δH(200 MHz; CDCl3) 9.31
(1 H, s, CHO), 7.49–7.25 (5 H, m, SPh), 3.12 (1 H, AB quartet,
CHAHBS), 3.05–2.97 (1 H, m, CHCHDS), 2.94 (1 H, AB quartet,
CHAHBS), 2.83–2.70 (1 H, m, CHCHDS), 2.55–2.42 (1 H, m,
CHEHF) and 2.15–1.99 (CHEHF); δC(50 MHz; CDCl3) 191.9
(CHO), 136.3 (m-SPh), 129.8 (p-SPh), 129.2 (i-SPh), 129.1
(o-SPh), 66.3 (CSPh), 35.5 (CH2S), 35.3 (CH2S) and 29.0 (CH2)
(Found Mϩ, 224.0327. C11H12OS2 requires M, 224.0329); m/z
224.0 (50%, M), 195.0 (20, M Ϫ CHO), 115.1 (40, M Ϫ SPh),
109.0 (45, SPh) and 87.0 (100, C4H6S ϩ H).
(1SR,2SR)-1-(3,6-Dihydro-(2H)-pyran-4-yl)-2-methyl-3-
phenylsulfanylpropan-1-ol anti-54
Toluene-p-sulfonyl chloride (80 mg, 0.39 mmol) was added to a
stirred solution of the diol anti-31 (0.1 g, 0.35 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 silica gel eluting with petrol-
eum ether–ether (1:1) to give the allylic alcohol anti-54 (33 mg,
64%) as a colourless oil; Rf [ether] 0.6; [α]D Ϫ7.5 (c 0.2 in
CHCl3); νmax(NaCl)/cmϪ1 3426 (OH) and 1580 (SPh); δH(400
MHz; CDCl3) 7.37–7.31 (2 H, m, Ph), 7.27–7.24 (2 H, m, Ph),
7.16–7.13 (1 H, m, Ph), 5.68 (1 H, s, CH᎐C), 4.16–4.14 (2 H, m,
᎐
OCH CH᎐), 3.88 (1 H, d, J 7.6, CHOH), 3.80 (1 H, dt, J 10.9
᎐
2
Ethyl 3-[(3Ј-phenylsulfanyl)thiolanyl]propionate 58
and 5.4, CHAHBO), 3.71 (1 H, ddd, J 11.3, 6.9 and 4.5, CHA-
HBO), 3.32 (1 H, dd, J 12.9 and 3.6, CHAHBS), 2.75 (1 H, dd,
J 12.9 and 8.4, CHAHBS), 2.14–2.09 (1 H, m, CHCHD), 1.99–
1.91 (2H, m, CHCHD and CHMe) and 0.98 (3 H, d, J 6.8, Me);
δC(100 MHz; CDCl3) 137.0, 136.7, 129.5, 128.9, 128.8, 125.7,
123.2, 79.3, 65.2, 64.2, 36.7, 36.0, 24.0 and 16.4 (Found Mϩ,
264.1183. C15H22O3S requires M, 264.1183); m/z (EI) 264 (20%,
M), 143 (100) and 109 (30, SPh).
In the same way as ester anti-20; X = O, diisopropylamine (0.94
g, 1.26 ml, 9.29 mmol), n-BuLi (5.61 ml, 1.3 M in hexanes, 7.3
mmol), ethyl acetate (0.61 g, 0.68 ml, 6.97 mmol) and aldehyde
57 (1.5 g, 6.63 mmol) in THF (150 ml) gave, after HPLC eluting
with petroleum ether–ether (1:1), an inseparable diastereo-
meric mixture (50:50) of the ester 58 (1.88 g, 90%) as a colour-
less oil; Rf [petroleum ether–ether (1:1)] 0.35; νmax(film, CDCl3)/
cmϪ1 3300 (OH) and 1700 (CO); δH(200 MHz; CDCl3) 7.68–
7.31 (10 H, m, 2 × SPh), 4.35–4.11 (6 H, m, 2 × CH2 and
2 × OH), 3.31–3.05 (8 H, m, 4 × CH2S), 2.99–2.85 (4 H, m,
2 × CH2CO2), 2.42–1.89 (4 H, m, 2 × CH2) and 1.29 (6 H, t,
J 7.2, 2 × Me); δC(50 MHz; CDCl3) 172.5 and 172.4 (2 × CO),
138.9 (2 × o-SPh), 138.4 (2 × o-SPh), 131.3 and 131.3 (2 ×
i-SPh), 129.7 (2 × p-SPh), 71.0 and 71.0 (2 × CHOH), 67.8 and
67.8 (2 × CH2O), 61.0 (2 × CSPh), 38.9 and 38.9 (2 × CH2CO2),
37.3, 37.2 and 37.1 (4 × CH2S), 29.6 and 29.5 (2 × CH2) and
14.2 (2 × Me) (Found Mϩ, 312.0846. C15H20O3S2 requires M,
312.0853); m/z 312.1 (30, M), 267.0 (20, M Ϫ OEt), 202.1 (65,
M Ϫ PhSH), 185.1 (100, M Ϫ SPh Ϫ H2O), 110.0 (55, PhSH),
87.0 (70, C4H7S) and 77.0 (20, Ph).
(1SR,2SR)-1-(3,6-Dihydro-(2H)-pyran-4-yl)-2-methyl-3-phenyl-
sulfanylpropan-1-ol syn-54
In the same way as the allylic alcohol anti-54, the diol syn-31
(100 mg, 0.35 mmol) and toluene-p-sulfonyl chloride (80 mg,
0.39 mmol) in pyridine (1 ml) gave, after flash column chroma-
tography on silica gel eluting with petroleum ether–ether (3:1)
the allylic alcohol syn-54 (76 mg, 82%), as a colourless oil; Rf
[ether] 0.6; [α]D Ϫ10.2 (c 0.82 in CHCl3); νmax(NaCl)/cmϪ1 3426
(OH) and 1580 (SPh); δH(400 MHz; CDCl3) 7.36–7.15 (5 H, m,
Ph), 5.69 (1 H, br s, CH᎐C), 4.16–4.15 (3 H, m, OCH CH᎐C
᎐
᎐
2
and CHOH), 3.80–3.70 (2 H, m, CH2O), 3.05 (1 H, dd, J 13.0
and 6.7, CHAHBS), 2.79 (1 H, dd, J 13.0 and 6.9, CHAHBS),
2.06–1.99 (1 H, m, CHCHD), 1.94–1.80 (2 H, m, CHCHD and
CHMe) and 0.99 (3 H, d, J 6.7, Me); δC(100 MHz; CDCl3)
136.6, 136.5, 129.0, 129.7, 126.1, 121.3, 76.1, 65.4, 64.1, 38.0,
35.6, 25.1 and 13.5 (Found Mϩ, 264.1184. C15H20O2S requires
3-[(3Ј-Phenylsulfanyl)thiolanyl]propan-1,3-diol 59
In the same way as diol anti-22, the ester 58 (1.8 g, 5.76 mmol)
and LiAlH4 (0.65 g, 17.3 mmol) in ether (20 ml) gave, after
J. Chem. Soc., Perkin Trans. 1, 2000, 1903–1914
1913

View Article Online
3 N. Satyamurthy, K. D. Berlin, D. R. Powell and D. Vanderhelm,
Phosphorus Sulfur, 1984, 19, 137.
4 R. A. Kuroyan, S. A. Pogosyan, N. P. Grigoryan, M. Aleksanyan,
A. A. Karapetyan, S. V. Lindeman and Y. T. Struchklov, Arm. Khim.
Zh., 1991, 44, 152.
5 M. S. Sargsyan, K. A. Petrosyan and A. A. Gevorkyan, Arm. Khim.
Zh., 1990, 43, 132.
6 K. G. R. Sudelin, J. E. Powell and W. D. Kollmeyer, USP 4 410
335/1983; Chem. Abstr., 1984, 100, 103178.
7 V. K. Aggarwal, I. Coldham, S. McIntyre and S. Warren, J. Chem.
Soc., Perkin Trans. 1, 1991, 451.
8 I. Coldham and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1993,
1637.
9 J. Eames, R. V. H. Jones and S. Warren, Tetrahedron Lett., 1996, 37,
707.
10 K. Chibale and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1995,
2411.
11 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.
12 J. Eames, R. V. H. Jones and S. Warren, Tetrahedron Lett., 1996, 27,
4823.
13 K. Kondo, A. Negishi, K. Matsui, D. Tunemoto and S. Masamune,
J. Chem. Soc., Chem. Commun., 1972, 1311.
14 G. R. Owen and C. B. Reese, J. Chem. Soc. (C), 1970, 2401.
15 R. Arentzen, Y. T. Y. Kui and C. B. Reese, Synthesis, 1975, 509.
16 J. Otera, Synthesis, 1988, 95.
17 A. de Groot and B. J. M. Jansen, Synthesis, 1985, 434.
18 A. de Groot and B. J. M. Jansen, Tetrahedron Lett., 1981, 22, 887.
19 C. H. Heathcock, C. T. Buse, W. A. Kleschick, M. C. Pirrung,
J. E. Sohn and J. Lampe, J. Org. Chem., 1980, 45, 1066.
20 C. H. Heathcock, M. C. Pirrung, S. H. Montgomery and J. Lample,
Tetrahedron, 1981, 37, 4087.
column chromatography on silica gel eluting with ether, an
inseparable diastereoisomeric mixture (50:50) of diol 59 (1.4 g,
90%) as a colourless oil; Rf [ether] 0.55; νmax(film, CDCl3)/cmϪ1
3500–3300 (OH); δH(200 MHz; CDCl3) 7.65–7.28 (10 H, m,
2 × SPh), 3.95–3.73 (6 H, m, 2 × CH2O and 2 × CHOH), 3.21–
2.61 (12 H, m, 4 × CH2S and 4 × OH) and 2.29–1.70 (8 H, m,
4 × CH2); δC(50 MHz; CDCl3) 137.2 (2 × m-SPh), 130.2 (2 ×
i-SPh), 129.4 (2 × p-SPh), 128.9 (2 × o-SPh), 74.2 and 73.8
(2 × CHOH), 69.0 and 69.0 (2 × CH2O), 61.7 and 61.6
(2 × CSPh), 37.4, 36.7 and 36.6 (4 × CH2S), 33.8, 33.7 and 29.8
(4 × CH2) (Found Mϩ, 270.0741. C13H18O2S2 requires M,
270.0748); m/z 270.1 (60%, M), 252.1 (5, M Ϫ H2O), 109.0
(30, SPh) and 87.0 (100, C4H6S ϩ H).
4-(Phenylsulfanyl)-1-oxa-6-thiaspiro[4.4]nonane 60
In the same way as tetrahydrofuran anti-24; X = O, the diol 59
(0.1 g, 0.33 mmol) and toluene-p-sulfonic acid (12.6 mg, 66
µmol) in CH2Cl2 (1 ml) gave, after column chromatography on
silica gel eluting with petroleum ether–ether (9:1), an insepar-
able diastereomeric mixture (50:50) of the syn- and anti-
tetrahydrofuran 60 (93 mg, 99%) as a colourless oil; Rf [petrol-
eum ether–ether (9:1)] 0.3; νmax(film, CDCl3)/cmϪ1 1550 (SPh);
δH(400 MHz; CDCl3) 7.57–7.21 (10 H, m, SPha and SPhb),
4.04–3.93 (2 H, m, CHAHBOa and CHAHBOb), 3.89–3.83 (1 H,
m, CHAHBOa and CHAHBOb), 3.74–3.67 (2 H, m, CHAHBSa and
CHAHBSb), 3.22 (1 H, d, J 11.4, CHSPh), 3.04–2.78 (7 H, m,
CHAHBSa, CHAHBSb, CH2Sa, CH2Sb and CHSPh), 2.52–2.43
a
b
a
(2 H, m, CHAHB and CHAHB ) and 2.19–1.86 (6 H, m, CH2 ,
21 M. Hirama, D. S. Garvey, L. D. L. Lu and S. Masamune,
Tetrahedron Lett., 1979, 20, 3937.
22 R. Gage and D. A. Evans, Org. Synth., 1990, 68, 83.
23 D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981, 103,
2127.
24 M. A. Walker and C. H. Heathcock, J. Org. Chem., 1991, 56, 5747.
25 H. Danda, M. M. Hansen and C. H. Heathcock, J. Org. Chem.,
1990, 55, 173.
b
a
b
CH2 , CHAHB and CHAHB ); δC(100 MHz, CDCl3) 135.1*
(i-SPh), 131.3 (m-SPh), 129.2 (o-SPh), 127.2 (p-SPh), 93.9*
(CO), 65.0* (CH2O), 51.7 (CHSPh), 40.3* (CH2S), 36.5*
ϩ
(CH2S), 34.5* (CH2) and 29.1* (CH2) (Found M Ϫ C2H4
,
252.0641. C13H16OS2 requires M Ϫ C2H4, 252.0642); m/z 252.1
(100%, M Ϫ C2H4).
26 T. D. Penning, S. W. Djuric, R. A. Haack, V. J. Kalish, J. M.
Miyashiro, B. W. Rowell and S. S. Yu, Synth. Commun., 1990, 20,
307.
Acknowledgements
27 J. A. Dale, D. L. Dull and H. S. Mosher, J. Org. Chem., 1969, 34,
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 the Spanish Ministerio de
Educación y Ciencia and Comisión Interministerial de Ciencia
y Technología (CICYT) for support (to M. A. H.).
2543.
28 K. Chibale, Ph.D. Thesis, University of Cambridge, 1992.
29 E. L. Eliel, W. H. Pearson, L. M. Jewell, A. G. Abatjoglou and
W. R. Kenan, Tetrahedron Lett., 1980, 21, 331.
30 K.-M. Chen, G. E. Hardtmann, K. Prasad, O. Repic and M. J.
Shapiro, Chem. Lett., 1987, 10, 1923.
31 K. T. Chapman, D. A. Evans and E. M. Carreira, J. Am. Chem. Soc.,
1988, 110, 3560.
32 J. Eames, M. A. de las Heras, R. V. H. Jones and S. Warren,
Tetrahedron Lett., 1996, 37, 1117.
33 A. J. Kirby, Adv. Phys. Org. Chem., 1981, 17, 183.
34 P. G. Sammes and D. J. Weller, Synthesis, 1995, 1205.
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