Scope and limitation of the [1,2]-phenylsulfanyl (PhS) migration in the synthesis of tetrahydrofurans and tetrahydropyrans from common triol precursors

Article abstract of DOI:10.1039/b208558e

Scope and limitation of the [1,2]-phenylsulfanyl (PhS) migration in the synthesis of tetrahydrofurans and tetrahydropyrans from common triol precursors were discussed. Triols containing three secondary hydroxy groups were rearranged using either toluene-p

Full text of DOI:10.1039/b208558e

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Scope and limitation of the [1,2]-phenylsulfanyl (PhS) migration
in the synthesis of tetrahydrofurans and tetrahydropyrans from
common triol precursors
1
David House,*a Fraser Kerrb and Stuart Warren*c
a Dyson Perrins Laboratory, South Parks Road, Oxford, UK OX1 3QY.
E-mail: sw134@cam.ac.uk
b AstraZeneca, Hurdsfield Industrial Estate, Macclesfield, Cheshire, UK SK10 2NA
c University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 IEW
Received (in Cambridge, UK) 3rd September 2002, Accepted 2nd October 2002
First published as an Advance Article on the web 7th November 2002
Triols containing three secondary hydroxy groups were rearranged using either (i) toluene-p-sulfonic acid or
(ii) trimethyl orthoacetate–pyridinium toluene-p-sulfonate followed by toluene-p-sulfonic acid
In previous papers1 we have demonstrated how enantiomeric-
ally enriched 2,4,5-triols (e.g. 2) could be converted in a single
step to THFs (e.g. 1) (thermodynamic control) or in two-steps
to THPs (e.g. 3) (kinetic control–equilibration sequence)
(Scheme 1). In this final paper on the subject of competition
Scheme 2 Reagents: i, N-bromosuccinimide, CCl4, reflux, 10 h; ii, Mg,
Et2O, 0 ЊC; iii, Ni(dppe)Cl2, vinyl bromide, rt, 48 h; iv, allylsilane 5,
TiCl4, CH2Cl2, rt, 72 h.
Scheme
1
Reagents: i, TsOH, CH2Cl2, 40 ЊC; ii, (MeO)3CMe,
C5H6NϩTsOϪ, CH2Cl2, rt.
experiments between THF and THP formation, we report in
full2 our findings on the effect of replacing the primary hydroxy
at C-5 in triol 2 with a secondary alcohol. Obviously the intro-
duction of a third stereogenic centre increases stereochemical
complexity; for each series of compounds we looked at there
were four possible diastereoisomers to investigate.
Given that we had previously used Sharpless asymmetric
dihydroxylation3 (AD) as a route to enantiomerically enriched
triols we were keen to exploit this reaction further. In particular,
we wished to prepare the styrene 4 (Fig. 1), as styrenes are well
Fig. 1 Styrene target molecule 4.
known to be amongst the best substrates for the AD reaction in
terms of the high levels of enantioselectivity that may be
obtained. Initial attempts to prepare this compound focused on
allylic metal chemistry but were rather unsuccessful (Scheme 2).
Allylsilane 5 was prepared in low yield from benzyltrimethyl-
silane by radical bromination with NBS4 followed by a nickel()
catalysed Kharasch coupling.5 Unfortunately the Lewis acid
conditions needed to promote addition of the allylsilane6 to
aldehyde 6 meant that only tiny amounts of the target styrene
could be isolated and so an alternative route was sought.
Scheme 3 Reagents: i, PhI, 5 mol% Pd(OAc)2, 10 mol% Ph3P, Et3N,
MeCN, 80 ЊC, 24 h; ii, PDC, CH2Cl2, rt; iii, AD-mix-β, MeSO2NH2,
ButOH-H2O, rt; iv, Me4Nϩ BH(OAc)3Ϫ, AcOH-MeCN, Ϫ20 ЊC, 7 days;
v, Et2BOMe, THF–MeOH, Ϫ78 ЊC then NaBH4.
Eventually we settled on preparing styrene 4 from the
homoallylic alcohol 7, reported previously,1 by a Heck reaction
with iodobenzene (Scheme 3). Oxidation of alcohol 4 to give the
homoallylic ketone 8 proved troublesome with PCC, a mixture
of compounds being obtained which were attributed to con-
jugation of the alkene with the carbonyl group. Presumably
this results from the stabilisation of the extended enol by the
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J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b208558e

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Scheme 4 Reagents: i, LDA, THF, Ϫ78 ЊC; ii, aldehyde 16; iii, Et2BOMe, THF–MeOH, Ϫ78 ЊC then NaBH4; iv, Me4Nϩ BH(OAc)3Ϫ, AcOH–
MeCN, Ϫ20 ЊC, 7 days; v, Bun Nϩ FϪ, THF, rt.
4
Table 1 Summary of crystal data, data collection, structure solution
and refinement data for compound 18
benzene ring. We were able to overcome this problem by
switching to the less acidic reagent PDC.7 The styrene 8 was
dihydroxylated using the commercially available AD-mix-β to
give the dihydroxyketone 9 in high yield (92%) and with
excellent enantioselectivity (>98% ee) as predicted. Finally the
triols 10 and 11 were obtained by the same method as used
previously,1 i.e. diastereoselective reduction of the β-hydroxy-
ketone 9 (Scheme 3).8,9
Empirical formula
Formula weight (M)
Crystal system
C20H34O3SSi
382.62 g molϪ1
Triclinic
Unit cell dimensions
a = 10.820(3) Å α = 91.37(3)Њ
b = 13.543(4) Å β = 97.96(2)Њ
c = 7.720(2) Å γ = 87.39(2)Њ
1119.0(5) Å3
Volume
A second series of triols 12–15 were prepared using aldol
chemistry (Scheme 4). A short sequence of reactions starting
from methyl lactate allowed us to prepare the silyl protected
aldehyde 16, a sensitive compound which was generally not
purified before the aldol reaction. Unfortunately the aldol
reaction of ketone 17 with aldehyde 16 gave poor diastereo-
selectivity and a difficult separation of the aldol diastereo-
isomers 18 and 19 by preparative HPLC was necessary.
Similarly, Heathcock observed a low level of Felkin-Anh
control10 in the aldol reaction of the lithium enolate of
pinacolone with 2-methoxypropanal (58:42 selectivity for the
isomer predicted from the Felkin-Anh model).11 The advantage
of this poor selectivity was that it made both diastereoisomers
immediately available and that it was possible to prepare
all four diastereoisomers of the silyl-protected triol target
molecules (20–23) by means of 1,3-stereocontrolled reductions
(Scheme 4). The stereochemistry of the aldol products was
confirmed by means of an X-ray crystal structure† (Fig. 2,
Table 1) since one of the two diastereoisomers (anti-18)
crystallised after the HPLC separation.
Temperature
Space group
Z
Absorption coefficient (µ)
Reflections collected
Independent reflections
Final R indices [I > 2σ(I )]
R indices (all data)
230(2) K
P1
¯
2
0.213 mmϪ1
6366
3924 (Rint = 0.0415)
R1 = 0.0620, wR2 = 0.1102
R1 = 0.1327, wR2 = 0.1359
With the knowledge we had gained from the first set
of substrates that we investigated,1 we used long reaction times
for the toluene-p-sulfonic acid catalysed rearrangement
to ensure equilibrium was established. The triols in the lactic
acid series (i.e. triols 12–15) all rearranged12 to give the
THFs (24–27, respectively) as the major product (Scheme 5).
We were particularly interested to establish the outcome of
rearranging the 2,4anti,4,5anti triol 13, since the THP 28 derived
from this triol would have the maximum number of equatorial
substituents (Fig. 3). Despite this ‘favourable’ arrangement
of substituents in the THP product, the THF was still the
major product, though THP 28 did account for 17% of the
equilibrium.
Fig. 2 X-Ray crystal structure of aldol product anti-18 derived from
methyl lactate.
Fig. 3 THP 28, formed from the rearrangement of triol 13, contains
the maximum number of equatorial substituents.
The rearrangement of the triols 10 and 11 required careful
handling (presumably due to the benzylic hydroxy group). The
2,4anti,4,5syn triol 10 rearranged exclusively to THF 29 after
† CCDC reference number 192685. See http://www.rsc.org/suppdata/
p1/b2/b208558e/ for crystallographic files in .cif or other electronic
format.
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662
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Fig. 4 Hypothetical rearrangement products: THF 34 and THP 35
lack a tertiary migration origin.
the leaving hydroxy at C-2 is activated in a single step, leaving
the hydroxy at C-5 free to cyclise.1b Although this led to
mixtures of unrearranged12 THFs and rearranged THPs (a
consequence of kinetic control) these products could be
equilibrated with toluene-p-sulfonic acid in dichloromethane,
converting the unrearranged THFs to THPs.
Reactions of the triols in the lactic acid series turned out to
be very substrate dependent. Rearrangement of the 2,4syn,4,5anti
triol 12 under kinetic conditions gave the unrearranged THF 36
as the major product (Scheme 8). Equilibration with toluene-
Scheme 5 Reagents: i, TsOH, CH2Cl2, 40 ЊC.
Scheme 6 Reagents: i, TsOH, CH2Cl2, 40 ЊC; ii, TsOH, CH2Cl2, rt.
being heated to reflux in dichloromethane for 24 hours
(Scheme 6). The 2,4syn,4,5syn triol 11, however, had to be
rearranged at room temperature (3 days) to avoid decom-
position. Again, the THF 30 was the only isolated product.
These reactions show that for the twelve 2,4,5-triols that have
been investigated, six with a primary hydroxy at C-5 and six
with a secondary hydroxy at C-5, the THF is always more stable
than the alternative THP even when three groups can be
equatorial on the THP. We believe this to be a consequence
of the gem-disubstituted migration origin (the degree of substi-
tution being equal for both ring sizes). In the THPs one of the
C–C bonds must necessarily be axial; presumably the 1,3-
diaxial interactions are too severe and the flatter THF rings are
preferred. It is well known from sugar chemistry that selective
1,2- or 1,3-diol protection can be achieved either by formation
of benzylidene acetals or isopropylidene ketals. For example,
Lavallée showed that selective 1,2-protection of the triol 31
could be achieved by treatment with catalytic toluene-p-sulfonic
acid in acetone.13 The 5-ring ketal 32 was formed in preference
to the 6-ring ketal 33 by a factor of 9:1. In the 6-ring ketal
two methyl groups are forced to adopt axial positions
(Scheme 7).
Scheme
8
Reagents: i, (MeO)3CMe, C5H6NϩؒTsOϪ, CH2Cl2, rt;
ii, TsOH, CH2Cl2, 40 ЊC.
p-sulfonic acid gave only a 74:26 mixture of the rearranged
THP 37 and unrearranged THF 36. The inference here could
be that it is unfavourable for the sulfanyl group to occupy an
axial position, indeed sufficiently unfavourable that it can
partly overcome the driving force for ‘downhill’ migration.15
The 2,4anti,4,5anti-triol 13 behaved quite differently; after
equilibration of an initial THF–THP mixture the only product
identified was the THP 38, with methyl, acetoxy and phenyl-
sulfanyl groups all occupying equatorial positions (Scheme 8).
The 2,4syn,4,5syn-triol 14 gave, after the two-step reaction
sequence, the THP 39 with an axial acetate (the alternative
THF 40 contains an unfavourable 2,3-syn relationship)
(Scheme 8). Finally, in this series of compounds, the
2,4anti,4,5syn-triol 15 gave a single product after treatment with
trimethyl orthoacetate and PPTS: the bicyclic orthoester 41.
Attempts to repeat the reaction at higher temperatures, or with
longer reaction times, led only to decomposition products that
were not characterised. It is interesting to note the stabilising
effect of an exo-methyl group on these compounds. When triol
13 (with 2,4-anti stereochemistry) was reacted with the
same reagent system no bicyclic orthoester intermediate was
observed; presumably an endo-methyl group here destabilises
the orthoester intermediate (if the corresponding orthoester
forms at all).
Scheme 7 Reagents: i, TsOH, acetone, rt.
We have calculated ground state energies for two hypothetical
heterocycles 34 and 35, in which the gem-dimethyl substitution
has been removed (Fig. 4).14 For the anti-THF 34 the energies
were in the range Ϫ93.8 to Ϫ91.2 kcal molϪ1 and for the syn-
THP 35 Ϫ93.5 to Ϫ91.2 kcal molϪ1. The similar energy ranges
for the two heterocycles support the theory that gem-dimethyl
substitution raises the energy of THPs relative to THFs.
We previously published an orthoester-triggered rearrange-
ment in which the C-4 hydroxy nucleophile is protected and
The triols 10 and 11, each containing a benzylic hydroxy
group, behaved similarly to their analogues in the lactic acid
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J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662

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Melting points were measured on a Stuart Scientific SMP1
melting point apparatus and are uncorrected. Infrared spectra
were recorded on Perkin–Elmer 1600 FTIR spectro-
a
photometer. Electron Impact (EI) mass spectra were recorded
on a Kratos double focusing magnetic sector instrument using
a DS503 data system for high-resolution analysis. Fast atom
bombardment (FAB) mass spectra were obtained from a
Kratos MS 890 instrument. Electrospray (ϩES) mass spectra
were recorded using a Brucker Bio-Apex FT-ICR instrument
and LCMS using a Hewlett Packard HPLC system, eluting
with an acetonitrile-water gradient, in conjunction with positive
and negative ion electrospray mass spectrometry.
Scheme
9
Reagents: i, (MeO)3CMe, C5H6NϩؒTsOϪ, CH2Cl2, rt;
ii, TsOH, CH2Cl2, rt.
Optical rotations were recorded on a Perkin–Elmer 241
polarimeter (using the sodium D line; 589 nm) and [α]D are
given in units of 10Ϫ1 deg dm2 gϪ1
.
series. Triol 11 was converted into the THP 43, bearing an axial
acetate, and triol 10 gave only the bicyclic orthoester 42 which
was not successfully transformed into the target heterocycles
(Scheme 9).
(1RS,3E )-1-Hydroxy-4-phenyl-1-[1-(phenylsulfanyl)cyclo-
hexyl]but-3-ene 4
In summary we have demonstrated that for the general
class of 2,4,5-triols under investigation THFs are formed as
thermodynamic products when toluene-p-sulfonic acid is used
as the catalyst for rearrangement regardless of the relative
stereochemistry present in the triol. This is attributed to the
1,3-diaxial interactions which exist in the THPs when one of
the C–C bonds of the tertiary migration origin is forced to enter
an axial environment. The orthoester rearrangement has been
shown to be general apart from triols with 2,4anti,4,5syn stereo-
chemistry in which case the intermediate bicyclic orthoester
is over-stabilised by a 6-exo substituent. The subsequent
equilibration of THF–THP product mixtures gives THPs as
exclusive products in all cases except for triol precursors with
2,4syn,4,5anti stereochemistry where the phenylsulfanyl group
would be forced into an axial position on the THP ring.
A
three-necked round bottomed flask, under an argon
atmosphere, was charged with palladium() acetate (200 mg,
870 µmol, 5 mol%), triphenylphosphine (460 mg, 1.70 mmol,
10 mol%) and acetonitrile (100 cm3). The resulting suspension
was stirred to give a milky-yellow solution. Triethylamine
(50 cm3) was added, followed by iodobenzene (1.95 cm3, 3.55 g,
17.4 mmol) and alkene 7 (5.00 g, 19.1 mmol). After addition of
the alkene the solution became claret red. The solution was
heated to reflux for 6 hours, during which time the solution
turned black, consistent with the generation of palladium().
The solution was then cooled to 0 ЊC and hydrochloric acid
(2.0 mol dmϪ3) was added until pH 4 was reached. The solution
was extracted with diethyl ether (4 × 50 cm3), washed with
water (50 cm3) and saturated brine (50 cm3) and dried over
anhydrous magnesium sulfate. The solvent was removed under
reduced pressure to give a dark brown oil. This oil was redis-
solved in [light petroleum (bp 40–60 ЊC)–diethyl ether, 9:1] (30
cm3) and filtered through a plug of silica. This process was
repeated four times to yield a pale yellow solution which was
evaporated under reduced pressure to give the crude product
as an orange liquid. Purification by column chromatography
(silica, isohexane–diethyl ether, 9:1) gave the alcohol 4 (5.20 g,
81%) as an oil which crystallised on standing, mp 85–89 ЊC
(from hexane–ethyl acetate); Rf[light petroleum (bp 40–60 ЊC)–
diethyl ether, 9:1] 0.23; νmax(CH2Cl2)/cmϪ1 3477 (O–H), 3081,
Experimental
All solvents were distilled before use. Tetrahydrofuran and
diethyl ether were freshly distilled from lithium aluminium
hydride whilst dichloromethane and acetonitrile were freshly
distilled from calcium hydride. Triphenylmethane was used as
an indicator for tetrahydrofuran. Diisopropylamine was dried
by distillation from calcium hydride and was stored over 4 Å
molecular sieves. Triethylamine was dried in the same way but
stored over calcium hydride granules. n-Butyllithium was
titrated against diphenylacetic acid before use. All non-aqueous
reactions were carried out under argon using oven-dried
glassware.
2986, 2936, 2856, 1597 (C᎐C) and 1582 (PhS); δ (400 MHz;
CDCl3) 7.60–7.48 (2H, m, PhS), 7.43–7.14 (8 H, m, Ph
and PhS), 6.50 (1 H, d, J 15.9 Hz, CHPh), 6.32 (1 H, dt, J 15.9
᎐
H
and 6.5 Hz, CH᎐CHPh), 3.43 (1 H, dt, J 9.9 and 2.6 Hz, CH–
᎐
Flash column chromatography was carried out using Merck
Kieselgel 60 (230–400 mesh). Thin layer chromatography was
performed on commercially available pre-coated plates (Merck
silica Kieselgel 60F254). Preparative HPLC was performed using
a Zorbax SIL prepacked silica column (21.2 mm id × 25 cm)
with a Gilson model 303 pump and a Cecil Instruments CE
212A UV detection system measuring the absorbance at 254
nm. Analytical HPLC was performed using either a Zorbax
RX-C8 prepacked reverse phase silica column or a Daicel
Chiralpak AD column with a Spectra-Physics SP8800 pump, a
Spectra-Physics SP8450 UV detection system and a ChromJet
single channel integrator.
OH), 2.94* (1H, dd, J 2.8 and 1.0 Hz, OH), 2.58 (1 H, ddt,
J 14.3, 6.5 and 1.1 Hz, CHAHB), 2.38 (1 H, dddd, J 14.3, 9.8,
6.6 and 0.7 Hz, CHAHB) and 2.09–1.13 (10 H, m); δC(62.5
MHz; CDCl3) 137.5Ϫ, 137.3ϩ, 131.8ϩ (CH᎐CHPh), 130.3Ϫ,
᎐
129.1ϩ, 128.9ϩ, 128.5ϩ, 128.3ϩ (CH᎐CHPh), 127.1ϩ, 126.1ϩ,
᎐
74.7ϩ (CHOH), 61.1Ϫ (CSPh), 34.8Ϫ (CH CH᎐CHPh),
᎐
2
30.6Ϫ, 29.9Ϫ, 26.3Ϫ and 21.8Ϫ; m/z (EI) 338 (7%, Mϩ), 320
(3, Mϩ Ϫ H2O), 211 (47), 203 (100), 191 (26, C6H10SPhϩ),
117 (38) and 91 (30); (Found: Mϩ, 338.1706. C22H26OS requires
M, 338.1704).
(3E )-1-[1-(Phenylsulfanyl)cyclohexyl]-4-phenylbut-3-en-1-one 8
Proton and carbon NMR spectra were recorded on Bruker
DPX 250, AM 400, DRX 400 or DRX 500 Fourier transform
spectrometers using an internal deuterium lock. Chemical shifts
are quoted in parts per million (ppm) downfield of tetramethyl-
silane. Coupling constants J are quoted in Hz and are not
rationalised. The symbol * after the proton NMR chemical
shift indicates that the signal disappears after a D2O “shake”.
Carbon NMR spectra were recorded with broad band proton
Alcohol 4 (1.00 g, 2.96 mmol) was added in one portion to a
stirred suspension of pyridinium dichromate7 (1.34 g, 3.55
mmol) in dichloromethane (25 cm3). After stirring for 3 days,
diethyl ether was added and the solution filtered through a
short pad of florisil to give a crude product. Purification by
column chromatography [silica, light petroleum (bp 40–60 ЊC),
9:1] gave the ketone 8 (715 mg, 72%) as a yellow oil; Rf[light
petroleum (bp 40–60 ЊC), 9:1] 0.26; νmax(CH2Cl2)/cmϪ1 3029,
ϩ
Ϫ
decoupling and Attached Proton Test. The symbols and
after the carbon NMR chemical shift indicate odd and even
numbers of attached protons respectively.
2938, 2858, 1697 (C᎐O) and 1599 (C᎐C); δ (400.1 MHz,
᎐ ᎐
H
CDCl3) 7.33–7.22 (10 H, m, Ph and PhS), 6.52 (1 H, d, J 16.0
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662 2655

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Hz, PhCH᎐CH), 6.41 (1 H, dt, J 15.9 and 6.8 Hz, PhCH᎐CH ),
PhCHOH ), 2.05–1.86 (1 H, m), 1.82–1.40 (8 H, m) and 1.31–
1.06 (3 H, m); δC(100.6 MHz; CDCl3) 140.6Ϫ, 137.2ϩ, 129.9Ϫ,
129.2ϩ, 129.0ϩ, 128.5ϩ, 128.0ϩ, 126.9ϩ, 77.0ϩ (CHOH), 74.3ϩ
(CHOH), 71.6ϩ (CHOH), 61.5Ϫ (CSPh), 32.1Ϫ, 31.0Ϫ, 29.4Ϫ,
26.2Ϫ, 21.7Ϫ and 21.7Ϫ; m/z (ϩFAB) 372 (6%, Mϩ), 358 (9), 307
(11), 227 (48), 191 (32, C6H10SPhϩ), 154 (100) and 111 (55);
(Found: MHϩ, 373.1830. C22H29O3S requires M, 373.1838).
᎐
᎐
3.71 (2 H, dd, J 6.6 and 0.9 Hz CH CH᎐CH), 2.04–1.20 (10 H,
᎐
2
m, CH ); δ (100.6 MHz; CDCl ) 204.4Ϫ (C᎐O), 137.2Ϫ, 136.5ϩ,
᎐
2
C
3
133.0ϩ, 130.0Ϫ, 129.3ϩ, 128.8ϩ, 128.5ϩ, 127.4ϩ, 126.3ϩ, 123.7ϩ,
61.3Ϫ (CSPh), 40.3Ϫ (CH C᎐O), 32.6Ϫ (CH2), 25.5Ϫ (CH2)
᎐
2
and 23.1Ϫ (CH2); m/z (EI) 336 (17%, Mϩ), 227 (25), 191 (100,
C6H10SPhϩ), 123 (12), 117 (21) and 105 (37); (Found: Mϩ
336.1561, C22H24OS requires M, 336.1548).
(1R,2R,4S )-4-[1-(Phenylsulfanyl)cyclohexyl]-1-phenylbutane-
1,2,4-triol 11
(1R,2R)-1,2-Dihydroxy-4-[1-(phenylsulfanyl)cyclohexyl]butan-
4-one 9
A 1.0 mol dmϪ3 solution of diethylmethoxyborane9 in tetra-
hydrofuran (140 µl, 0.3 mmol) was added to a solution of
β-hydroxyketone 9 (50 mg, 135 µmol) in tetrahydrofuran–
methanol (4:1) (2.5 cm3) at Ϫ78 ЊC, under an atmosphere of
argon. The mixture was stirred for 5 minutes and then sodium
borohydride (6 mg, 159 µmol) was added and the solution
allowed to stir for 8 hours. Glacial acetic acid (3 cm3) was added
and stirring continued for a further 5 minutes. The solution was
then neutralised with saturated aqueous sodium bicarbonate
solution (30 cm3) and extracted with diethyl ether (3 × 15 cm3).
The organic extracts were dried over anhydrous magnesium sul-
fate and the solvent was removed under reduced pressure to
give a crude product. This product was redissolved in methanol
(5 cm3) and stirred for 5 minutes before removing the methanol
under reduced pressure. This cycle was repeated until TLC
showed no spots with Rf(diethyl ether) > 0.5. Purification by
column chromatography (silica, hexane–ethyl acetate, 2:1) gave
syn,syn-triol11 (37 mg, 74%) as an oil; Rf(hexane–ethyl acetate,
2:1) 0.21; νmax(CH2Cl2)/cmϪ1 3553 (br, O–H), 2936, 2858, 1496,
1476, 1448, 1389 and 1026; [α]D Ϫ38.7 (c. 0.70 in CH2Cl2; >98%
ee); δH(400.1 MHz, CDCl3) 7.37–7.25 (10 H, m, Ph and PhS),
4.47 (1 H, dd, J 6.4 and 4.0 Hz, PhCHOH), 4.16* (1 H, s, OH),
3.8 (1 H, ddt, J 7.8, 6.4 and 1.4 Hz, CHOH), 3.70* (1 H, s, OH),
3.39 (1 H, dt, J 10.4 and 1.6 Hz, PhSCCHOH), 3.15* (1 H, d,
J 3.9 Hz, OH), 1.98–1.45 (9 H, m) and 1.39–1.11 (3 H, m);
δC(100.6 MHz; CDCl3) 141.1Ϫ, 137.2ϩ, 129.8Ϫ, 129.1ϩ, 128.9ϩ,
128.4ϩ, 128.0ϩ, 126.9ϩ, 77.8ϩ (CHOH), 76.5ϩ (CHOH), 75.5ϩ
(CHOH), 60.8Ϫ (CSPh), 32.6Ϫ, 30.0Ϫ, 29.4Ϫ, 26.1Ϫ, 21.7Ϫ and
21.7Ϫ; m/z (ϩFAB) 372 (7%, Mϩ), 245 (40), 227 (54), 191 (65,
C6H10SPhϩ), 154 (21) and 111 (100); (Found: Mϩ 372.1752.
C22H28O3S requires M, 372.1759).
Alkene 8 (500 mg, 1.49 mmol) was added to a vigorously stirred
solution of AD-mix-β (2.08 g) and methanesulfonamide
(142 mg, 1.49 mmol) in a mixture of 2-methylpropan-2-ol
(20 cm3) and water (20 cm3). The reaction was stirred at room
temperature until judged complete by TLC or LCMS. Sodium
sulfite (7.50 g, 59.3 mmol, 12 eq.) was then added and stirring
continued for 30 minutes. The mixture was transferred to a
separating funnel and ethyl acetate (50 cm3) was added. The
solution was extracted a further three times with ethyl acetate
(25 cm3). The combined organic extracts were washed with
water (25 cm3), saturated brine (25 cm3) and dried over
anhydrous magnesium sulfate. The solvent was evaporated
under reduced pressure to give a crude product. Purification by
column chromatography (silica, hexane–ethyl acetate, 2:1) gave
the diol 9 (504 mg, 92%) as plates, mp 102–105 ЊC (from ethyl
acetate); Rf(hexane–ethyl acetate, 2:1) 0.12; retention time/min
(Chiralpak AD column; hexane–ethanol, 9:1) 17.5 (99.4%) and
20.6 (0.6); [α]D Ϫ9.0 (c. 0.26 in CH2Cl2; >98% ee); νmax(CH2Cl2)/
cmϪ1 3597 (O–H), 2938, 2958, 1686 (C=O), 1605, 1454, 1389
and 1333; δH(400.1 MHz, CDCl3) 7.43–7.17 (10 H, m, Ph and
PhS), 4.58 (1 H, dd, J 6.3 and 2.1 Hz, PhCH), 4.22–4.13 (1 H,
m, CHOH), 3.48* (1 H, d, J 2.7 Hz, CHOH ), 3.14 (1 H, d, J 2.9
Hz, PhCHOH ), 2.91 (1 H, dd, J 17.8 and 3.5 Hz, CH H C᎐O),
᎐
B
A
2.83 (1 H, dd, J 17.8 and 8.4 Hz, CH H C᎐O), 1.92–1.55 (6 H,
᎐
B
A
m) and 1.47–1.17 (4 H, m); δC(100.6 MHz; CDCl3) 207.7Ϫ
(C᎐O), 140.8Ϫ, 136.8ϩ, 130.1Ϫ, 129.9ϩ, 129.2ϩ, 129.0ϩ, 128.6ϩ,
᎐
127.3ϩ, 77.2ϩ (PhCHOH), 72.9ϩ (CHOH), 61.3Ϫ (CSPh), 39.2Ϫ
(CH C᎐O), 32.9Ϫ, 25.7Ϫ, 23.4Ϫ and 23.3Ϫ; (Found: MNaϩ
᎐
2
393.1507, C22H26O3NaS requires 393.1500).
(1R,2R,4R)-4-[1-(Phenylsulfanyl)cyclohexyl]-1-phenylbutane-
1,2,4-triol 10
(1RS,2RS,4RS )-4-[1-(Phenylsulfanyl)cyclohexyl]-1-phenyl-
butane-1,2,4-triol 10 and (1RS,2RS,4SR)-4-[1-(Phenylsulfanyl)-
cyclohexyl]-1-phenylbutane-1,2,4-triol 11
Glacial acetic acid (2.5 cm3) was added to a stirred suspension
of tetramethylammonium triacetoxyborohydride8 (569 mg,
2.16 mmol, 8 eq.) in acetonitrile (2.0 cm3) and the resulting
mixture was stirred for 30 minutes at room temperature to give
a colourless solution. This solution was cooled to Ϫ30 ЊC and
a solution of β-hydroxyketone 9 (100 mg, 0.27 mmol) in
acetonitrile (0.5 cm3) was added. The solution was then trans-
ferred to a freezer (Ϫ25 ЊC) for 1 week. The reaction was
quenched by addition of aqueous sodium potassium tartrate
solution (1.0 mol dmϪ3, 10 cm3) and the mixture allowed to
warm slowly to room temperature. The reaction mixture was
then diluted with dichloromethane (10 cm3) and washed with
saturated aqueous sodium bicarbonate solution. The aqueous
layer was extracted with dichloromethane (4 × 10 cm3), the
combined organic layers dried over anhydrous magnesium sul-
fate and the solvent removed under reduced pressure to give a
crude product. Purification by column chromatography (silica,
hexane–ethyl acetate, 2:1) gave anti,syn-triol 10 (75 mg, 75%) as
an oil; Rf(isohexane–ethyl acetate, 2:1) 0.13; [α]D ϩ23.6 (c. 0.25
in CH2Cl2; >98% ee); νmax(CH2Cl2)/cmϪ1 3564 (O–H), 3466
(O–H), 3067, 2936, 2856 and 1422; δH(400.1 MHz, CDCl3)
7.51–7.46 (2 H, m), 7.43–7.31 (3 H, m), 7.31–7.24 (3 H, m),
7.21–7.16 (2 H, m), 4.50 (1 H, dd, J 7.1, 3.1 Hz, PhCHOH),
3.95 (1 H, ddd, J 14.0, 6.5 and 3.4 Hz, CHOH), 3.70 (1 H, dt,
J 10.6 and 2.6 Hz, PhSCCHOH), 3.29* (1 H, br s, PhSCCHOH),
3.19* (1 H, d, J 6.1 Hz, CHOH ), 3.05* (1 H, d, J 3.0 Hz,
Potassium ferricyanide (8.76 g, 26.6 mmol, 3 eq.), potassium
carbonate (3.68 g, 26.6 mmol, 3 eq.), osmium() chloride
(37 mg, 124 µmol, 1.5 mol%), quinuclidine (69 mg, 621 µmol,
7 mol%) and methanesulfonamide (845 mg, 8.88 mmol, 1 eq.)
were placed in a round bottom flask and stirred gently. Water
(40 cm3) and 2-methylpropan-2-ol (40 cm3) were added, the
flask was sealed and the solution stirred vigorously. Once the
solids had completely dissolved the alkene 4 (3.00 g, 8.88 mmol)
was added in one portion. Stirring was continued until TLC or
LCMS indicated complete consumption of starting material.
Sodium sulfite (40.2 g, 319 mmol) was then added in one
portion and stirring continued for a further 30 minutes. The
solution was transferred to a separating funnel, diluted with
ethyl acetate (80 cm3) and the aqueous layer separated. The
aqueous layer was then extracted with ethyl acetate (3 × 80
cm3). The combined organic extracts were washed with water
(80 cm3) and brine (80 cm3), dried over anhydrous magnesium
sulfate and finally, the solvent was evaporated under reduced
pressure to give a crude product. Analytical HPLC (isocratic
38:62 MeCN:H2O; 0.1% CF3CO2H, 0.1% Et3N; flow rate 1 cm3
minϪ1) indicated an anti:syn mixture of 46:54 (retention times:
8.02 min, 10.30 min, respectively). Purification by column
chromatography (silica, isohexane–ethyl acetate, 2:1) gave a
white amorphous solid which was crystallised from chloroform
2656
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662

View Article Online
to give anti-triol 10 (1.26 g, 38%) as prisms, mp 115–117 ЊC
(from chloroform); Rf(isohexane–ethyl acetate, 2:1) 0.13,
spectroscopically identical to the enantiomerically enriched
sample and syn-triol 11 (1.61 g, 49%) as an oil; Rf(isohexane–
ethyl acetate, 2:1) 0.21, spectroscopically identical to the
enantiomerically enriched sample.
(3SR,5RS,6RS )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol
14
By the method described for compound 12, silyl ether 22
(384 mg, 1.0 mmol) and tetra-n-butylammonium fluoride
solution (1.0 cm3, 1.0 mmol) in tetrahydrofuran (20 cm3) gave a
crude product as an oil. Purification by column chrom-
atography (silica, diethyl ether) gave the 3,5syn,5,6syn-triol 14 as
an oil (251 mg, 93%); Rf(diethyl ether) 0.24; νmax(CH2Cl2)/cmϪ1
3480 (br, O–H), 2968, 2920, 2873, 1605, 1474, 1459, 1438, 1390,
1368, 1132, 1068 and 852; δH(400 MHz; CDCl3) 7.53–7.48 (2 H,
m, PhS), 7.42–7.32 (3 H, m, PhS), 4.03* (1 H, br s, OH), 3.69*
(1 H, br s, OH), 3.64–3.52 (3 H, m, 3 × CHOH), 2.55 (1 H, br s,
OH), 1.71–1.63 (1 H, m, CHAHB), 1.56 (1 H, ddd, J 14.2, 10.4
and 9.3 Hz, CHAHB), 1.26 (3 H, s, MeA), 1.20 (3 H, s, MeB) and
1.18 (3 H, d, J 6.2 Hz, CHMe); δC(100.6 MHz; CDCl3) 137.4ϩ,
129.9Ϫ (i-Ph), 129.4ϩ, 128.9ϩ, 75.9ϩ (C–O), 75.5ϩ (C–O), 70.8ϩ
(C–O), 55.1Ϫ (CSPh), 33.0Ϫ (CH2), 25.5ϩ (Me), 21.8ϩ (Me) and
19.4ϩ (Me); m/z (ϩFAB) 270 (26%, Mϩ), 253 (88, Mϩ Ϫ OH),
186 (55) and 143 (100); (Found: Mϩ, 270.1296. C14H22O3S
requires M, 270.1290).
(3RS,5SR,6RS )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol
12
Silyl ether 20 (384 mg, 1.0 mmol) was dissolved in tetra-
hydrofuran (20 cm3) and tetra-n-butylammonium fluoride
solution (1.0 cm3, 1.0 mmol of a 1.0 mol dmϪ3 in tetrahydro-
furan, containing 10% water) was added. The reaction was
stirred at room temperature until judged complete by TLC
(generally 1–2 h). Diethyl ether (20 cm3) was added, followed
by water (20 cm3) and the mixture transferred to a separating
funnel. The organic layer was separated and the aqueous layer
extracted with diethyl ether (2 × 20 cm3) and dichloromethane
(2 × 20 cm3). The combined organic layers were dried over
anhydrous magnesium sulfate and the solvent removed under
reduced pressure to give a crude product. Purification by
column chromatography (silica, diethyl ether) gave the
3,5syn,5,6anti-triol 12 as an oil (238 mg, 88%); Rf(diethyl ether)
0.21; νmax(CH2Cl2)/cmϪ1 3685 (O–H), 3598 (O–H), 3482 (br, O–
H), 2972, 2933, 2875, 1605, 1474, 1460, 1390, 1368, 1291, 1129,
1058 and 856; δH(400 MHz; CDCl3) 7.52–7.47 (2 H, m, PhS),
7.43–7.30 (3 H, m, PhS), 4.02* (1 H, s, OH), 3.82–3.73 (1 H, m,
CHMe), 3.67 (1 H, s, OH), 3.68–3.62 (1 H, m, CHOH), 3.53
(1 H, d, J 10.7 Hz, PhSCCHOH) 2.24* (1 H, s, OH), 1.66 (1 H,
br d, J 14.3 Hz, CHAHB), 1.51 (1 H, dt, J 13.9 and 10.2 Hz,
CHAHB), 1.47 (3 H, s, MeA), 1.26 (3 H, s, MeB) and 1.12 (3 H, d,
J 6.4 Hz, CHMe); δC(100.6 MHz; CDCl3) 137.4ϩ, 129.9Ϫ (i-Ph),
129.4ϩ, 128.9ϩ, 75.8ϩ (C–O), 75.6ϩ (C–O), 70.1ϩ (C–O), 55.2Ϫ
(CSPh), 30.1Ϫ (CH2), 25.6ϩ (Me), 21.7ϩ (Me) and 17.7ϩ (Me);
m/z (ϩFAB) 270 (14%, Mϩ), 253 (82, Mϩ Ϫ OH), 186 (100), 154
(61) and 136 (74); (Found: Mϩ, 270.1280. C14H22O3S requires
M, 270.1290).
(3RS,5RS,6RS )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol
15
By the method described for compound 12, silyl ether 23 (384
mg, 1.0 mmol) and tetra-n-butylammonium fluoride (1.0 cm3,
1.0 mmol) in tetrahydrofuran (20 cm3) gave a crude product as
an oil. Purification by column chromatography (silica, diethyl
ether) gave the 3,5anti,5,6syn-triol 15 as an oil (254 mg, 94%);
Rf(diethyl ether) 0.13; νmax(CH2Cl2)/cmϪ1 3864 (O–H), 3603
(O–H), 2971, 2932, 1605, 1474, 1439, 1389, 1126, 1052 and 909;
δH(400 MHz; CDCl3) 7.52–7.48 (2 H, m, PhS), 7.41–7.30 (3 H,
m, PhS), 3.71–3.58 (3 H, m, 3 × CHOH), 3.23* (1 H, s, OH),
2.70* (1 H, d, J 6.0 Hz, OH), 2.38* (1 H, d, J 3.9 Hz, OH), 1.66–
1.53 (2 H, m, CHAHB and CHAHB), 1.25 (3 H, s, MeA), 1.19 (3
H, s, MeB) and 1.15 (3 H, d, J 6.1 Hz, CHMe); δC(100.6 MHz;
CDCl3) 137.4ϩ, 130.2Ϫ (i-Ph), 129.3ϩ, 128.9ϩ, 73.7ϩ (C–O),
71.9ϩ (C–O), 70.5ϩ (C–O), 55.1Ϫ (CSPh), 33.4Ϫ (CH2), 25.7ϩ
(Me), 22.3ϩ (Me) and 19.2ϩ (Me); m/z (ϩFAB) 270 (8%, Mϩ)
253 (75, Mϩ Ϫ OH), 186 (100), 151 (71, Me2CSPhϩ) and 143
(92); (Found: Mϩ, 270.1301. C14H22O3S requires M, 270.1290).
(3SR,5SR,6RS )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol
13
By the method described for compound 12, silyl ether 21
(384 mg, 1.0 mmol) and tetra-n-butylammonium fluoride
(1.0 cm3, 1.0 mmol) in tetrahydrofuran (20 cm3) gave a crude
product as an oil. Purification by column chromatography
(silica, diethyl ether) gave the 3,5anti,5,6anti-triol 13 as an oil
(248 mg, 92%); Rf(diethyl ether) 0.13; νmax(CH2Cl2)/cmϪ1 3610
(O–H), 3489 (O–H), 2971, 2932, 1474, 1460, 1438, 1388,
1368, 1289, 1127, 1053 and 909; δH(400 MHz; CDCl3) 7.55–
7.47 (2 H, m, PhS), 7.42–7.29 (3 H, m, PhS), 3.88–3.77 (2 H,
m, CHOH and MeCHOH), 3.67 (1 H, br d, J 10.4 Hz,
CHOH), 3.16* (1 H, br s, OH), 2.44* (1 H, br s, OH), 2.03*
(1 H, br s, OH), 1.66–1.58 (1 H, m, CHAHB), 1.51 (1 H,
ddd, J 13.2, 10.5 and 2.4 Hz, CHAHB), 1.25 (3 H, s, MeA), 1.20
(3 H, s, MeB), 1.16 (3 H, d, J 6.1 Hz, CHMe); δC(100.6
MHz; CDCl3) 137.4ϩ, 130.2Ϫ (i-Ph), 129.3ϩ, 128.8ϩ, 72.5ϩ
(C–O), 71.8ϩ (C–O), 70.7ϩ (C–O), 55.4Ϫ (CSPh), 31.8Ϫ (CH2),
25.8ϩ (Me), 22.2ϩ (Me) and 17.7ϩ (Me); m/z (ϩFAB) 270 (22%,
Mϩ), 253 (98, Mϩ Ϫ OH), 186 (24), 151 (100, Me2CSPhϩ)
and 143 (91); (Found: Mϩ, 270.1294. C14H22O3S requires M,
270.1290).
(3S,5S,6S )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol 15
By the method described for compound 12, silyl ether 23
(50 mg, 130 µmol) and tetra-n-butylammonium fluoride (130 µl,
130 µmol) in tetrahydrofuran (5 cm3) gave the 3,5anti,5,6syn-triol
(3S,5S,6S)-15 as an oil (33 mg, 95%), spectroscopically
identical to the racemic sample, retention time/min (Chiralpak
AD column; hexane–ethanol, 9:1) 27.1 (1.4%) and 36.8 (98.6);
[α]D Ϫ7.9 (c. 1.0 in CH2Cl2; >97% ee).
(2RS )-2-(tert-Butyldimethylsilyloxy)propanal 16
A modification of a method reported by Kobayashi was used;16
diisobutylaluminium hydride (1.0 mol dmϪ3 in toluene, 12 cm3,
12 mmol) was added under argon, during a 5 minute period,
to a solution of TBDMS-protected methyl lactate (2.18 g,
10 mmol) in diethyl ether (80 cm3) at Ϫ78 ЊC. After stirring for
20 minutes the reaction was quenched at this temperature by
the addition of methanol (1 cm3) followed immediately by a
saturated aqueous solution of potassium sodium tartrate
(15 cm3). Stirring was continued for 30 minutes during which
time the solution was allowed to warm to room temperature.
A further portion of the tartrate solution (50 cm3) was added
and the gelatinous mixture stirred for a further 10 minutes. The
mixture was then filtered under reduced pressure, through a
compacted pad of Celite, into a Buchner flask. The residues
were washed twice with diethyl ether (25 cm3) and filtered. The
resulting biphasic mixture was transferred to a separating
funnel and the organic layer separated. The aqueous layer was
(3R,5R,6S )-2-Methyl-2-phenylsulfanylheptane-3,5,6-triol 13
By the method described for compound 12, silyl ether 21
(73 mg, 191 µmol) and tetra-n-butylammonium fluoride (200 µl,
200 µmol) in tetrahydrofuran (5 cm3) gave the 3,5anti,5,6anti-triol
(3R,5R,6S)-13 as an oil (50 mg, 97%), spectroscopically
identical to the racemic sample, retention time/min (Chiralpak
AD column; hexane–ethanol, 9:1) 22.9 (100%) and 39.4 (0); [α]D
ϩ21.1 (c. 0.47 in CH2Cl2; >99% ee).
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662
2657

View Article Online
extracted with diethyl ether (3 × 30 cm3) and the combined
extracts were dried over anhydrous sodium sulfate. The solvents
were removed under reduced pressure to give a crude product as
a pale yellow liquid. This residue was purified by Kugelröhr
distillation to give the aldehyde 16 (771 mg, 41%) as a liquid, bp
90 ЊC at 20 mmHg (lit.,16 90 ЊC at 20 mmHg); δH(250 MHz;
CDCl3) 9.62 (1 H, d, J 1.2 Hz, CHO), 4.09 (1 H, qd, J 6.9 and
1.2 Hz, CH), 1.28 (3 H, d, J 6.8 Hz, Me), 0.92 (9 H, s, SitBu),
0.11 (3 H, s, SiMeAMeB) and 0.10 (3 H, s, SiMeAMeB); δC(100.6
MHz; CDCl3) 204.1ϩ (CHO), 73.8ϩ (CH–O), 25.7ϩ (SiCMe3),
18.5ϩ (Me), 18.2Ϫ (SiCMe3) and Ϫ4.81ϩ (SiMeAMeB and
the crystals collected by filtration. The crystals were washed
twice with cold hexane (5 cm3) to give the ketone 18 as prisms
(276 mg, 14%), mp 67–68 ЊC (from hexane); νmax(CH2Cl2)/cmϪ1
3598 (O–H), 2956, 2931, 2896, 2857 and 1697 (C᎐O); δ (400
᎐
H
MHz; CDCl3) 7.38–7.25 (5 H, m, PhS), 3.92–3.86 (1 H, m, CH–
t
OH), 3.78 (1 H, qn, J 6.0 Hz, CH–OSiMe2 Bu), 3.11 (1 H, dd,
J 17.4 and 2.7 Hz, CHAHB), 2.97* (1 H, d, J 2.8 Hz, OH), 2.88
(1 H, dd, J 17.4 and 9.3 Hz, CHAHB), 1.42 (3 H, s, Me), 1.40
(3 H, s, Me), 1.18 (3 H, d, J 6.2 Hz, Me), 0.90 (SiCMe3), 0.09
t
t
(SiMeAMeB Bu) and 0.09 (SiMeAMeB Bu); δC(100.6 MHz;
CDCl3) 208.7Ϫ (C᎐O), 136.2ϩ, 131.0Ϫ (i-Ph), 129.4ϩ, 128.9ϩ,
᎐
SiMeAMeB); m/z (EI) 189 (1%, MHϩ), 173 (5), 159 (17, Mϩ
Ϫ
72.6ϩ (C–O), 71.0ϩ (C–O), 56.3Ϫ (CSPh), 38.7Ϫ (CH2), 25.9ϩ
(CMe3), 24.4ϩ (Me), 24.3ϩ (Me), 19.3ϩ (Me), 18.0Ϫ (CMe3),
Ϫ4.30ϩ (SiMeAMeB) and Ϫ4.72ϩ (SiMeAMeB); m/z (ϩES) 405
(100%, MNaϩ) and 383 (28, MHϩ); (Found: MNaϩ, 405.1880.
C20H34O3NaSSi requires 405.1896). The hexane residue was
concentrated under reduced pressure and the residue purified
by column chromatography [silica, light petroleum (bp 40–60
ЊC)–diethyl ether, 4:1] to give a mixture of ketones 18 and 19 as
an oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.21.
Further purification was carried out by HPLC (hexane, 0.5%
iPrOH) to give a second portion of the ketone 18 (retention
time 13.0 min) as prisms (295 mg, 15%) and the ketone 19
(retention time 14.5 min) as an oil (630 mg, 32%), νmax(CH2Cl2)/
t
CHO), 131 (100, BuMe2SiOϩ), 103 (21), 75 (44) and 73 (58);
(Found: MHϩ, 189.1302. C9H21O2Si requires 189.1311).
(2S )-2-(tert-Butyldimethylsilyloxy)propanal 16
By the same method used for the racemic compound, diisobutyl-
aluminium hydride (1.0 mol dmϪ3 in toluene, 12 cm3, 12 mmol)
and TBDMS-protected (S)-methyl lactate (97% ee) (2.18 g,
10 mmol) in diethyl ether (80 cm3) gave the aldehyde (2S)-16
(1.4 g, 74% crude yield) as a liquid, which was used without
further purification.
2-Methyl-2-phenylsulfanylbutan-3-one 17
cmϪ1 3560 (O–H), 2956, 2931, 2896, 2858 and 1699 (C᎐O);
᎐
Alcohol 44 (5.0 g, 25.5 mmol) was added in one portion, under
argon at 0 ЊC to a stirred solution of pyridinium chloro-
chromate (PCC) (7.86 g, 36.4 mmol) in dichloromethane
(100 cm3). The solution was allowed to warm to room temper-
ature and stirred until the reaction was judged complete by
TLC. Dry diethyl ether (50 cm3) was added and the supernatant
liquor decanted from a black gum. The insoluble residues were
washed 5 times with ether (50 cm3) and the combined ethereal
extracts were filtered through a plug of florisil, which was
washed with more diethyl ether. The solvent was removed under
reduced pressure to give a crude product as a pale yellow–green
oil. Purification was achieved by column chromatography
[silica, light petroleum (bp 40–60 ЊC)–diethyl ether, 9:1] to give
the ketone 17 (4.32 g, 87%) as a pale yellow oil; Rf(light petrol-
eum (bp 40–60 ЊC)–diethyl ether, 9:1) 0.27; νmax(CH2Cl2)/cmϪ1
δH(400 MHz; CDCl3) 7.38–7.25 (5 H, m, PhS), 3.95 (1 H, td,
J 8.5 and 4.1 Hz, CH–OH), 3.86 (1 H, dt, J 10.4 and 6.2 Hz,
CH–OSiMe2 Bu), 2.98 (1 H, dd, J 17.0 and 8.8 Hz, CHAHB),
t
2.90 (1 H, dd, J 17.0 and 3.3 Hz, CHAHB), 2.84* (1 H, d, J 4.9
Hz, OH), 1.42 (3 H, s, Me), 1.41 (3 H, s, Me), 1.17 (3 H, d, J 6.2
t
Hz, Me), 0.91 (SiCMe3), 0.10 (SiMeAMeB Bu) and 0.10 (SiMeA-
MeB Bu); δC(100.6 MHz; CDCl3) 208.1Ϫ (C᎐O), 136.2ϩ, 131.1Ϫ
t
᎐
(i-Ph), 129.3ϩ, 128.8ϩ, 71.9ϩ (C–O), 70.5ϩ (C–O), 56.3Ϫ (CSPh),
38.8Ϫ (CH2), 25.9ϩ (CMe3), 24.3ϩ (Me × 2), 19.0ϩ (Me), 18.1Ϫ
(CMe3), Ϫ4.30ϩ (SiMeAMeB) and Ϫ4.80ϩ (SiMeAMeB); m/z
(ϩFAB) 383 (14%, MHϩ), 365 (9, Mϩ Ϫ H2O), 325 (20),
251 (47, Mϩ Ϫ OSiMe2 Bu), 151 (100, Me2CSPhϩ) and 131 (28,
t
tBuMe2SiOϩ); (Found: MHϩ, 383.2069. C20H35O3SSi requires
383.2076).
3078, 3001, 2971, 2930, 2868, 1698 (C᎐O), 1474, 1462, 1439,
᎐
(5R,6S )-2-Methyl-2-phenylsulfanyl-5-hydroxy-6-(tert-butyl-
dimethylsiloxy)heptan-3-one 18 and (5S,6S )-2-Methyl-2-phenyl-
sulfanyl-5-hydroxy-6-(tert-butyldimethylsiloxy)heptan-3- one 19
1366, 1137 and 1114; δH(400 MHz; CDCl3) 7.37–7.26 (5 H, m,
PhS), 2.39 (3 H, s, Me) and 1.41 (6 H, s); δC(100.6 MHz; CDCl3)
206.4Ϫ (C᎐O), 56.5Ϫ (CSPh) and 24.5ϩ (Me); m/z (EI) 194 (20%,
᎐
Mϩ), 151 (100, Me2CSPhϩ) and 109 (29, PhSϩ); (Found: Mϩ,
By the same method used for the racemic compounds,
n-butyllithium (12.2 cm3 of a 1.4 mol dmϪ3 solution in hexane,
15.5 mmol) and diisopropylamine (1.73 g, 2.41 cm3, 17.1 mmol)
in tetrahydrofuran (100 cm3), ketone 17 (3.00 g, 15.5 mmol) in
tetrahydrofuran (50 cm3) and aldehyde (2S)-16 (ca. 23 mmol) in
tetrahydrofuran (25 cm3) gave the ketone (5R,6S)-18 (768 mg,
13%‡) as an oil, spectroscopically identical to the racemic
sample, [α]D ϩ30.3 (c. 0.6 in CH2Cl2; 97% ee) and the ketone
(5S,6S)-19 (887 mg, 15%†) as an oil, spectroscopically identical
to the racemic sample, [α]D Ϫ18.6 (c. 1.01 in CH2Cl2; 97% ee).
194.0765. C11H14OS requires M, 194.0765).
(5SR,6RS )-2-Methyl-2-phenylsulfanyl-5-hydroxy-6-(tert-butyl-
dimethylsiloxy)heptan-3-one 18 and (5RS,6RS )-2-Methyl-2-
phenylsulfanyl-5-hydroxy-6-(tert-butyldimethylsiloxy)heptan-3-
one 19
n-Butyllithium (3.8 cm3 of a 1.5 mol dmϪ3 solution in hexane,
5.67 mmol) was added to a solution of diisopropylamine
(547 mg, 0.80 cm3, 5.67 mmol) in tetrahydrofuran (40 cm3),
under argon, at 0 ЊC. After stirring for 10 minutes the solution
was cooled to Ϫ78 ЊC and the ketone 17 (1.00 g, 5.15 mmol) in
tetrahydrofuran (5 cm3) added over a 10 minute period. Stirring
was continued for 1 hour and the aldehyde 16 (1.10 g, 5.85
mmol) in tetrahydrofuran (5 cm3) was added over a 5 minute
period. The reaction was quenched after 2 hours at Ϫ78 ЊC,
by the addition of saturated ammonium chloride solution
(30 cm3), and the reaction allowed to warm to room temper-
ature. The resulting slurry was transferred to a separating
funnel and the residue washed in with water (10 cm3) followed
by diethyl ether (30 cm3). The organic layer was separated and
the aqueous layer extracted with diethyl ether (3 × 30 cm3). The
combined organic extracts were dried over magnesium sulfate
and concentrated under reduced pressure to give a crude
product as a pale yellow oil which, on standing, partly crystal-
lised. The semi-crystalline slurry was diluted with hexane and
(3RS,5SR,6RS )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldi-
methylsiloxy)heptane-3,5-diol 20
Using the method described for compound 11, ketone 18
(500 mg, 1.31 mmol), diethylmethoxyborane (1.6 cm3, 1.6
mmol) and sodium borohydride (59 mg, 1.56 mmol) in 4:1
tetrahydrofuran–methanol (12.5 cm3) gave a crude product as
an oil. Purification by column chromatography [silica, light pet-
roleum (bp 40–60 ЊC)–diethyl ether, 4:1] gave the 3,5syn,5,6anti-
diol 20 as an oil (305 mg, 61%); Rf[light petroleum (bp 40–
60 ЊC)–diethyl ether, 4:1] 0.09; νmax(CH2Cl2)/cmϪ1 3497 (O–H),
2956, 2929, 2856, 1463 and 1438; δH(400 MHz; CDCl3) 7.52–
7.49 (2 H, m, PhS), 7.40–7.30 (3 H, m, PhS), 3.71* (1 H, s, OH),
‡ Only part of the crude material was separated by HPLC.
2658
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662

View Article Online
3.65 (1 H, dt, J 11.7 and 6.0 Hz, CHMe), 3.61–3.52 (2 H, m,
CHOH and CHOH), 3.43 (1 H, s, OH), 1.96 (1 H, br d, J 14.2
Hz, CHAHB), 1.38 (1 H, dt, J 14.3 and 10.2 Hz CHAHB), 1.26 (3
H, s, Me), 1.19 (3 H, s, Me), 1.14 (3 H, d, J 6.1 Hz, CHMe), 0.86
(9 H, s, SitBu), 0.06 (SiMeAMeB) and 0.05 (SiMeAMeB);
δC(100.6 MHz; CDCl3) 137.5ϩ, 130.5Ϫ (i-Ph), 129.2ϩ, 128.8ϩ,
76.9ϩ (C–O), 76.5ϩ (C–O), 71.6ϩ (C–O), 54.5Ϫ (CSPh), 32.6Ϫ
(CH2), 25.8ϩ (CMe3), 25.0ϩ (Me), 23.0ϩ (Me), 18.8ϩ (Me), 18.0Ϫ
(CMe3), Ϫ4.32ϩ (SiMeAMeB) and Ϫ4.78ϩ (SiMeAMeB); m/z
(ϩFAB) 385 (13%, MHϩ), 367 (43, Mϩ – OH), 309 (27), 235
(96), 151 (73, Me2CSPhϩ) and 131 (100, tBuMe2SiOϩ); (Found:
MHϩ, 385.2214. C20H37O3SSi requires 385.2233).
Ϫ4.83ϩ (SiMeAMeB); m/z (ϩFAB) 385 (2%, MHϩ), 367 (23,
Mϩ Ϫ OH), 309 (9), 235 (100), 151 (37, Me2CSPhϩ) and 131
(48, tBuMe2SiOϩ); (Found: MHϩ, 385.2232. C20H37O3SSi
requires 385.2233).
(3RS,5RS,6RS )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldi-
methylsiloxy)heptane-3,5-diol 23
Using the method described for compound 10, ketone 19
(500 mg, 1.31 mmol) and tetramethylammonium triacetoxy-
borohydride (4.14 g, 15.7 mmol) in 1:1 MeCN:AcOH (20 cm3)
gave a crude product as an oil. Purification by column chroma-
tography [silica, light petroleum (bp 40–60 ЊC)–diethyl ether,
4:1] gave the 3,5anti,5,6syn-diol 23 as an oil (441 mg, 88%);
Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.09;
νmax(CH2Cl2)/cmϪ1 3562 (O–H), 2958, 2931, 2887, 2858, 1472,
1463 and 1438; δH(400 MHz; CDCl3) 7.55–7.49 (2 H, m, PhS),
7.39–7.28 (3 H, m, PhS), 3.73–3.60 (3 H, m, CHMe, CHOH and
PhSCCHOH), 3.07* (1 H, s, PhSCCHOH ), 2.29* (1 H, d, J 5.8
Hz, OH), 1.59 (1 H, dd, J 13.6 and 9.4 Hz, CHAHB), 1.45 (1 H,
dd, J 13.2, 10.6 and 2.3 Hz, CHAHB), 1.23 (3 H, s, Me), 1.19
(3 H, s, Me), 1.16 (3 H, d, J 6.0 Hz, CHMe), 0.87 (9 H, s, SitBu),
0.07 (SiMeAMeB) and 0.06 (SiMeAMeB); δC(100.6 MHz; CDCl3)
137.5ϩ, 130.6Ϫ (i-Ph), 129.1ϩ, 128.8ϩ, 73.0ϩ (C–O), 72.0ϩ (C–O),
71.8ϩ (C–O), 55.1Ϫ (CSPh), 34.9Ϫ (CH2), 25.8ϩ (CMe3), 25.6ϩ
(Me), 22.7ϩ (Me), 20.3ϩ (Me), 18.0Ϫ (CMe3), Ϫ4.15ϩ (SiMeA-
MeB) and Ϫ4.83ϩ (SiMeAMeB); m/z (ϩFAB) 385 (9%, MHϩ),
367 (66, Mϩ Ϫ OH), 309 (24), 235 (84), 151 (72, Me2CSPhϩ),
143 (100) and 131 (89, tBuMe2SiOϩ); (Found: MHϩ, 385.2230.
C20H37O3SSi requires 385.2233).
(3SR,5SR,6RS )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldi-
methylsiloxy)heptane-3,5-diol 21
Using the method described for compound 10, ketone 18
(500 mg, 1.31 mmol) and tetramethylammonium triacetoxy-
borohydride (4.14 g, 15.7 mmol) in 1:1 MeCN:AcOH (20 cm3)
gave a crude product as an oil. Purification by column chrom-
atography [silica, light petroleum (bp 40–60 ЊC)–diethyl ether,
4:1] gave the 3,5anti,5,6anti-diol 21 as an oil (372 mg, 74%);
Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.07;
νmax(CH2Cl2)/cmϪ1 3568 (O–H), 2957, 2931, 2886, 2857, 1472,
1463 and 1438; δH(400 MHz; CDCl3) 7.54–7.49 (2 H, m, PhS),
7.40–7.28 (3 H, m, PhS), 3.82–3.78 (2 H, m, CHOH and
CHMe), 3.67 (1 H, d, J 10.3 Hz, PhSCCHOH), 3.01* (1 H, s,
PhSCCHOH ), 2.35* (1 H, d, J 3.9 Hz, CHOH ), 1.53 (1 H, dd,
J 13.6 and 8.7 Hz, CHAHB), 1.44 (1 H, ddd, J 13.0, 10.5 and 2.4
Hz, CHAHB), 1.24 (3 H, s, Me), 1.20 (3 H, s, Me), 1.09 (3 H, d,
J 5.9 Hz, CHMe), 0.86 (9 H, s, SitBu), 0.06 (3 H, s, SiMeAMeB)
and 0.02 (3 H, s, SiMeAMeB); δC(100.6 MHz; CDCl3) 137.5ϩ,
130.4Ϫ (i-Ph), 129.2ϩ, 128.8ϩ, 72.6ϩ (C–O), 71.7ϩ (C–O), 71.4ϩ
(C–O), 55.5Ϫ (CSPh), 32.3Ϫ (CH2), 25.8ϩ (CMe3), 25.8ϩ (Me),
22.2ϩ (Me), 18.0Ϫ (CMe3), 17.7ϩ (Me), Ϫ4.30ϩ (SiMeAMeB) and
Ϫ4.80ϩ (SiMeAMeB); m/z (ϩFAB) 385 (4%, MHϩ), 367 (53),
309 (28), 235 (88), 151 (92, Me2CSPhϩ), 143 (83) and 131 (100,
tBuMe2SiOϩ); (Found: MHϩ, 385.2224. C20H37O3SSi requires
M, 385.2233).
(3S,5S,6S )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldimethyl-
siloxy)heptane-3,5-diol 23
Using the method described for compound 10, ketone 19
(140 mg, 366 µmol) and tetramethylammonium triacetoxyboro-
hydride (1.16 g, 4.39 mmol) in 1:1 MeCN:AcOH (5.0 cm3)
gave the diol (3S,5S,6S)-23 as an oil (109 mg, 77%), spectro-
scopically identical to the racemic sample, [α]D Ϫ16.5 (c. 1.60 in
CH2Cl2; 97% ee).
(3R,5R,6S )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldimethyl-
siloxy)heptane-3,5-diol 21
(1RS,2SR,4SR)-1-[5,5-Dimethyl-4-(phenylsulfanyl)tetrahydro-
furan-2-yl]ethanol 24
Using the method described for compound 10, ketone 18
(104 mg, 272 µmol) and tetramethylammonium triacetoxyboro-
hydride (859 mg, 3.26 mmol) in 1:1 MeCN:AcOH (5.0 cm3)
gave the diol (3R,5R,6S)-21 as an oil (81 mg, 77%), spectro-
scopically identical to the racemic sample, [α]D ϩ18.4 (c. 0.70 in
CH2Cl2; 97% ee).
Toluene-p-sulfonic acid (1.3 mg, 6.9 µmol) was added to a
stirred solution of syn,anti-triol 12 (37 mg, 0.137 mmol) in
dichloromethane (2 cm3). The reaction temperature was raised
to 50 ЊC to initiate reflux and heating continued for 48 hours.
The reaction mixture was cooled to room temperature and
filtered through a short plug of silica, eluting with dichloro-
methane, to give the 2,4syn-tetrahydrofuran 24 (31 mg, 89%) as
an oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 1:1]
0.23;νmax(CH2Cl2)/cmϪ1 3561 (O–H), 3063, 2988, 2935, 2855,
1481, 1447, 1439, 1195, 1141, 1085 and 909; δH(400 MHz;
CDCl3) 7.47–7.42 (2 H, m, PhS), 7.34–7.22 (3 H, m, PhS), 3.97–
3.89 (1 H, m, CH–O), 3.86 (1 H, qd, J 5.7 and 3.4 Hz, CHMe),
3.48 (1 H, dd, J 10.7 and 6.8 Hz, CHSPh), 2.23 (1 H, dt, J 12.6
and 6.1 Hz, CHAHB), 2.12–2.06 (2 H, m, CHAHB and OH), 1.31
(3 H, s, MeA), 1.30 (3 H, s, MeB) and 1.10 (3 H, d, J 6.5 Hz,
CHMe); δC(100.6 MHz; CDCl3) 135.5Ϫ (i-PhS), 131.7ϩ, 129.0ϩ,
127.1ϩ, 82.6Ϫ (C–O), 80.4ϩ (CH–O), 67.1ϩ (CH–O), 56.1ϩ,
33.0Ϫ (CH2), 28.0ϩ (Me), 25.2ϩ (Me) and 17.9ϩ (Me); m/z (EI)
(3SR,5RS,6RS )-2-Methyl-2-phenylsulfanyl-6-(tert-butyldi-
methylsiloxy)heptane-3,5-diol 22
Using the method described for compound 11, ketone 19 (500
mg, 1.31 mmol), diethylmethoxyborane (1.6 cm3, 1.6 mmol)
and sodium borohydride (59 mg, 1.56 mmol) in 4:1 tetrahydro-
furan:methanol (12.5 cm3) gave a crude product as an oil.
Purification by column chromatography [silica, light petroleum
(bp 40–60 ЊC)–diethyl ether, 4:1] gave the 3,5syn,5,6syn-diol 22 as
an oil (427 mg, 85%); Rf[light petroleum (bp 40–60 ЊC)–diethyl
ether, 4:1] 0.14; νmax(CH2Cl2)/cmϪ1 3491 (O–H), 2957, 2931,
2885, 2858, 1472, 1463 and 1438; δH(400 MHz; CDCl3) 7.52–
7.48 (2 H, m, PhS), 7.39–7.28 (3 H, m, PhS), 3.81* (1 H, s, OH),
3.73 (1 H, dt, J 11.4 and 6.1 Hz, CHMe), 3.66–3.55 (2 H, m,
CHOH and CHOH), 3.17* (1 H, d, J 3.4 Hz, OH), 1.91 (1 H, br
d, J 14.2 Hz, CHAHB), 1.48 (1 H, dt, J 14.1 and 10.1 Hz,
CHAHB), 1.26 (3 H, s, Me), 1.20 (3 H, s, Me), 1.17 (3 H, d, J 6.2
Hz, CHMe), 0.86 (9 H, s, SitBu) 0.07 (3 H, s, SiMeAMeB) and
0.03 (3 H, s, SiMeAMeB); δC(100.6 MHz; CDCl3) 137.6ϩ, 130.8Ϫ
(i-Ph), 129.0ϩ, 128.7ϩ, 76.6ϩ (C–O), 76.4ϩ (C–O), 71.1ϩ (C–O),
54.1Ϫ (CSPh), 32.7Ϫ (CH2), 25.8ϩ (CMe3), 24.6ϩ (Me), 23.7ϩ
(Me), 19.2ϩ (Me), 18.0Ϫ (CMe3), Ϫ4.27ϩ (SiMeAMeB) and
252 (57%, Mϩ), 207 (81, Mϩ Ϫ MeCHOH), 194 (411, Mϩ
Ϫ
Me2CO), 179 (11), 163 (45), 150 (61) and 110 (100, PhSHϩ);
(Found: Mϩ, 252.1191. C14H20O2S requires M, 252.1184).
(1RS,2SR,4RS )-1-[5,5-Dimethyl-4-(phenylsulfanyl)tetrahydro-
furan-2-yl]ethanol 25
By the method described for compound 24, toluene-p-sulfonic
acid (1.8 mg, 9.5 µmol) and a solution of anti,anti-triol 13
(50 mg, 185 µmol) in dichloromethane (2.5 cm3) gave the 2,4anti-
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662
2659

View Article Online
tetrahydrofuran 25 (35 mg, 75%) after 72 hours as an oil; Rf[light
petroleum (bp 40–60 ЊC)–diethyl ether, 1:1] 0.25;νmax(CH2Cl2)/
cmϪ1 3589 (O–H), 2995, 2963, 2928, 2855, 1604, 1584, 1480,
1460, 1381, 1369, 1091, 1046 and 1014; δH(400 MHz; CDCl3)
7.45–7.38 (2 H, m, PhS), 7.33–7.19 (3 H, m, PhS), 3.97 (1 H,
ddd, J 8.4, 5.3 and 3.0 Hz, CH–O), 3.90 (1 H, qd, 6.5 and
3.2 Hz, CHOH), 3.32 (1 H, t, J 8.9 Hz, CHSPh), 2.48 (1 H, ddd,
J 13.1, 8.8 and 5.3 Hz, CHAHB), 2.01* (1 H, br s, OH), 1.96
(1 H, dt, J 13.0 and 8.8 Hz, CHAHB), 1.29 (3 H, s, MeA), 1.28
(3 H, s, MeB) and 1.11 (3 H, d, J 6.5 Hz, CHMe); δC(100.6 MHz;
CDCl3) 135.7Ϫ (i-PhS), 131.0ϩ, 129.0ϩ, 126.8ϩ, 83.1Ϫ (C–O),
79.3ϩ (CH–O), 67.9ϩ (CH–O), 55.1ϩ (CSPh), 33.0Ϫ (CH2),
27.4ϩ (Me), 22.0ϩ (Me) and 17.8ϩ (Me); m/z (EI) 252 (50%,
Mϩ), 207 (47, Mϩ – MeCHOH), 194 (46, Mϩ – Me2CO), 163
(29), 150 (78), 136 (76) and 110 (100, PhSHϩ); (Found: Mϩ,
252.1188. C14H20O2S requires M, 252.1184).
νmax(CH2Cl2)/cmϪ1 3560 (O–H), 2928, 2855, 1584, 1480, 1455,
1377, 1196 and 909; δH(250 MHz; CDCl3) 7.36–7.14 (10 H, m,
Ph and PhS), 4.45 (1 H, d, J 7.0 Hz, PhCHOH), 4.21 (1 H, dt, J
7.4 and 5.8 Hz, CH–O), 3.32 (1 H, t, 7.7 Hz, PhSCH), 2.26 (1
H, ddd, 13.4, 7.7 and 5.7 Hz, CHAHB), 1.94 (1 H, dt, 13.3 and
7.7 Hz, CHAHB) and 1.83–1.15 (10 H, m); δC(100.6 MHz;
CDCl3) 140.4Ϫ, 135.8Ϫ, 130.7ϩ, 129.0ϩ, 128.4ϩ, 128.0ϩ, 127.2ϩ,
126.6ϩ, 84.9Ϫ (C–O), 79.5ϩ (CH–O), 77.6ϩ (CH–O), 54.8ϩ (C–
SPh), 37.2Ϫ, 35.7Ϫ, 31.5Ϫ, 29.7Ϫ, 25.6Ϫ, 23.3Ϫ and 22.3Ϫ; m/z
(EI) 354 (7%, Mϩ), 247 (100, Mϩ Ϫ PhCHOH), 203 (24), 137
(94), 119 (43) and 84 (65); (Found: Mϩ, 354.1654. C22H26O2S
requires M, 354.1653).
(1RS,2RS,4RS )-1-Phenyl-(4-phenylsulfanyl-1-oxaspiro[4.5]dec-
2-yl)methanol 30
By the method described for compound 24, but without heating
at reflux, toluene-p-sulfonic acid (0.6 mg, 3.2 µmol) and a
solution of syn,syn-triol 11 (25 mg, 67.1 µmol) in dichloro-
methane (2.5 cm3) gave the 2,4syn-tetrahydrofuran 30 (19 mg,
81%) after 3 days as an oil; Rf[light petroleum (bp 40–60 ЊC)–
diethyl ether, 4:1] 0.14; νmax(CH2Cl2)/cmϪ1 3567 (O–H), 3063,
2986, 2936, 2859, 1584, 1480, 1449, 1439, 1388, 1194, 1145,
1085 and 909; δH(400 MHz; CDCl3) 7.46–7.17 (10 H, m, Ph and
PhS), 4.53 (1 H, dd, J 7.8 and 1.7 Hz, PhCHOH), 4.00 (1 H, br
q, J 8.0 Hz, CH–O), 3.37 (1 H, dd, J 9.7 and 7.1 Hz, PhSCH),
3.12* (1 H, d, J 1.9 Hz, OH), 2.16 (1 H, dt, J 13.2 and 6.9 Hz,
CHAHB), 1.90 (1 H, dt, J 12.9 and 9.5 Hz, CHAHB), 1.79–1.48
(9 H, m) and 1.30–1.17 (1 H, m); δC(100.6 MHz; CDCl3) 140.1Ϫ,
135.6Ϫ, 131.2ϩ, 129.1ϩ, 128.4ϩ, 127.9ϩ, 127.0ϩ, 126.9ϩ, 125.9ϩ,
84.4Ϫ (C–O), 80.8ϩ, 78.7ϩ, 56.2ϩ (CHSPh), 36.4Ϫ, 36.3Ϫ, 25.6Ϫ,
(1RS,2RS,4RS )-1-[5,5-Dimethyl-4-(phenylsulfanyl)tetrahydro-
furan-2-yl]ethanol 26
By the method described for compound 24, toluene-p-sulfonic
acid (1.3 mg, 6.9 µmol) and a solution of syn,syn-triol 14
(37 mg, 137 µmol) in dichloromethane (2.5 cm3) gave the 2,4syn-
tetrahydrofuran 26 (32 mg, 93%) after 72 hours as an oil;
Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 1:1] 0.21;
νmax(CH2Cl2)/cmϪ1 3577 (O–H), 3056, 2974, 2927, 2855, 1583,
1480, 1461, 1380, 1368, 1096, 1049 and 896; δH(400 MHz;
CDCl3) 7.47–7.40 (2 H, m, PhS), 7.34–7.21 (3 H, m, PhS), 3.71
(1 H, dt, J 9.5 and 6.7 Hz, CH–O), 3.61 (1 H, qnd, J 6.5 and 3.1
Hz, CHOH), 3.47 (1 H, dd, J 11.0 and 7.0 Hz, CHSPh), 2.46*
(1 H, d, J 3.1 Hz, OH), 2.38 (1 H, dt, 12.9 and 6.7 Hz, CHAHB),
1.82 (1 H, ddd, J 12.6, 11.0 and 9.5 Hz, CHAHB), 1.30 (3 H, s,
MeA), 1.26 (3 H, s, MeB) and 1.10 (3 H, d, J 6.3 Hz, CHMe);
δC(100.6 MHz; CDCl3) 135.4Ϫ (i-PhS), 131.5ϩ, 129.1ϩ, 127.1ϩ,
82.9Ϫ (C–O), 81.2ϩ (C–O), 71.6ϩ (C–O), 56.2ϩ (CSPh), 36.7Ϫ,
29.7Ϫ, 27.9ϩ (Me), 25.2ϩ (Me), and 18.7ϩ (Me); m/z (EI) 252
(58%, Mϩ), 220 (100), 207 (29, Mϩ Ϫ MeCHOH), 194 (35, Mϩ
Ϫ Me2CO), 163 (24), 150 (56) and 110 (62, PhSHϩ); (Found:
Mϩ, 252.1183. C14H20O2S requires M, 252.1184).
23.1Ϫ and 22.4Ϫ; m/z (EI) 354 (11%, Mϩ), 247 (100 Mϩ
Ϫ
PhCHOH), 203 (26), 137 (85) and 110 (21, PhSHϩ); (Found:
Mϩ, 354.1652. C22H26O2S requires M, 354.1653).
(2RS,3SR,5RS )-2-Methyl-5-(1-Methyl-1-phenylsulfanylethyl)-
tetrahydrofuran-3-yl ethanoate 36 and (2RS,3SR,5SR)-2,6,6-
Trimethyl-5-phenylsulfanyltetrahydropyran-3-yl ethanoate 37
Syn,anti-triol 12 (41 mg, 152 µmol) was dissolved in dry
dichloromethane (2.0 cm3) and pyridinium toluene-p-sulfonate
(10 mg, 38.0 µmol) was added. The reaction vessel was sealed
with a septum and trimethyl orthoacetate (20 µl, 19.2 mg,
160 µmol) was injected in one portion. The reaction was stirred
at room temperature until TLC indicated that the starting
material had been completely consumed (approximately 24
hours). The reaction mixture was then filtered through a short
plug of silica, eluting with dichloromethane, and the solvent
was evaporated under reduced pressure to give a crude product.
This product was redissolved in dichloromethane (2.5 cm3) and
toluene-p-sulfonic acid (2.0 mg, 10 µmol) was added. The reac-
tion temperature was raised to 35 ЊC and allowed to stand at
this temperature for 4 days. The reaction mixture was cooled to
room temperature and filtered through a short plug of silica,
again eluting with dichloromethane. The solvent was evapor-
ated under reduced pressure to give a crude product (37 mg,
83%) which consisted of a 26:74 mixture of THF 36 and THP
37. These compounds were not successfully separated and
therefore not fully characterised. 1H NMR spectroscopy on the
crude mixture showed three characteristic peaks: δH 5.00 (1 H,
td, J 9.6 and 5.0 Hz, CHaxOAc, THP), 4.83 (1 H, dt, J 5.1 and
2.4 Hz, CHOAc, THF) and 3.27 (1 H, t, J 4.0 Hz, CHeqSPh).
(1RS,2RS,4SR)-1-[5,5-Dimethyl-4-(phenylsulfanyl)tetrahydro-
furan-2-yl]ethanol 27
By the method described for compound 24, toluene-p-sulfonic
acid (1.8 mg, 9.5 µmol) and a solution of anti,syn-triol 15
(50 mg, 185 µmol) in dichloromethane (2.5 cm3) gave the
2,4anti-tetrahydrofuran 27 (45 mg, 96%) after 72 hours as an oil;
Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 1:1] 0.25;
νmax(CH2Cl2)/cmϪ1 3574 (O–H), 2962, 2928, 1583, 1480, 1459,
1382, 1370, 1090, 1042 and 1025; δH(400 MHz; CDCl3) 7.43–
7.38 (2 H, m, PhS), 7.33–7.21 (3 H, m, PhS), 3.84 (1 H, ddd,
J 8.4, 6.1 and 5.1 Hz, CH–O), 3.56 (1 H, qnd, J 6.3 and 4.7 Hz,
CHOH), 3.36 (1 H, t, J 8.8 Hz, CHSPh), 2.28* (1 H, d, J 4.6 Hz,
OH), 2.22 (1 H, ddd, J 13.2, 8.4 and 4.9 Hz, CHAHB), 2.13 (1 H,
dt, J 13.1 and 8.7 Hz, CHAHB), 1.28 (3 H, s, MeA), 1.27 (3 H, s,
MeB) and 1.14 (3 H, d, J 6.3 Hz, CHMe); δC(100.6 MHz;
CDCl3) 135.6Ϫ (i-PhS), 131.2ϩ, 129.1ϩ, 126.9ϩ, 83.5Ϫ (C–O),
79.7ϩ (CH–O), 70.7ϩ (CH–O), 55.0ϩ (CSPh), 36.4Ϫ (CH2),
27.8ϩ (Me), 22.4ϩ (Me), 19.2ϩ (Me); m/z (EI) 252 (70%, Mϩ),
207 (72, Mϩ Ϫ MeCHOH), 194 (63, Mϩ Ϫ Me2CO), 179 (20),
163 (45), 150 (100), 135 (64) and 110 (93, PhSHϩ); (Found: Mϩ,
252.1181. C14H20O2S requires M, 252.1184).
(1RS,2RS,4SR)-1-Phenyl(4-phenylsulfanyl-1-oxaspiro[4.5]dec-
2-yl)methanol 29
(2RS,3SR,5RS )-2,6,6-Trimethyl-5-phenylsulfanyltetrahydro-
pyran-3-yl ethanoate 38
By the method described for compound 24, toluene-p-sulfonic
acid (1.2 mg, 6.3 µmol) and a solution of the anti,syn-triol 10
(50 mg, 134 µmol) in dichloromethane (2.5 cm3) gave the 2,4anti-
tetrahydrofuran 29 (44 mg, 93%) after 24 hours as an oil;
Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.14;
By the method described for compounds 36 and 37, anti,anti-
triol 13 (55 mg, 203 µmol), pyridinium toluene-p-sulfonate
(12.8 mg, 50.8 µmol) and trimethyl orthoacetate (27 µl, 25.6 mg,
214 µmol) in dry dichloromethane (2.5 cm3) gave a crude
product after 24 h which was treated with toluene-p-sulfonic
2660
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662

View Article Online
acid (3.8 mg, 20.3 µmol, 10 mol%) in dichloromethane (2.5 cm3)
at 35 ЊC for 24 hours to give a second product. Purification by
chromatography [silica, light petroleum (bp 40–60 ЊC)–diethyl
ether, 4:1] gave the 2,3anti,3,5syn-tetrahydropyran 38 (53 mg, 88%)
as an oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1]
294 (20%, Mϩ), 220 (47), 143 (100, Mϩ Ϫ Me2CSPh), 125 (34)
and 109 (18, PhSϩ); (Found: Mϩ, 294.1290. C16H22O3S requires
M, 294.1290).
(1RS,3SR,5SR,6SR)-1-Methyl-3-(1-cyclohexyl-1-phenylsulf-
anyl)-6-phenyl-2,7,8-trioxabicyclo[3.2.1]octane 42
0.32; νmax(CH2Cl2)/cmϪ1 2999, 2922, 2855, 1732 (C᎐O), 1583,
᎐
1464, 1369, 1230, 1145, 1106, 1053 and 910; δH(400 MHz;
CDCl3) 7.42–7.37 (2 H, m, PhS), 7.31–7.19 (3 H, m, PhS), 4.40
(1 H, ddd, J 11.2, 9.8 and 4.9 Hz, CHaxOAc), 3.64 (1 H, dq,
J 9.9 and 6.1 Hz, CHMe), 3.10 (1 H, dd, J 13.1 and 4.3
Hz, CHaxSPh), 2.31 (1 H, dt, J 12.8 and 4.6 Hz, CHaxHeq), 2.01
(3 H, s, Ac), 1.76 (1 H, td, J 12.9 and 11.4 Hz, CHaxHeq), 1.40
(3 H, s, MeA), 1.31 (3 H, s, MeB) and 1.10 (3 H, d, J 6.1 Hz,
By the method described for compound 41, anti,syn-triol 10
(45 mg, 121 µmol), pyridinium toluene-p-sulfonate (7.6 mg,
30.3 µmol) and trimethyl orthoacetate (16 µl, 15.3 mg, 127
µmol) in dry dichloromethane (2.5 cm3) gave the orthoester 42
(44 mg, 92%) as an oil after 5 minutes; Rf[light petroleum (bp
40–60 ЊC)–diethyl ether, 4:1] 0.43; νmax(CH2Cl2)/cmϪ1 3046,
2986, 2935, 2857, 1474, 1448, 1400, 1292, 1152, 1121, 1093, 991,
909 and 870; δH(400 MHz; CDCl3) 7.67–7.19 (10 H, m, Ph and
PhS), 4.98 (1 H, s, PhCH ), 4.56 (1 H, br s, CHeqO), 4.04 (1 H,
dd, J 11.5 and 3.9 Hz, CHaxO), 2.43 (1 H, td, J 11.7 and 3.4 Hz,
CHaxHeqCHaxO), 2.17–1.13 (11 H, m) and 1.67 (3 H, s, Me);
δC(100.6 MHz; CDCl3) 141.1Ϫ, 137.4ϩ, 137.3ϩ, 131.8Ϫ, 128.6ϩ,
128.5ϩ, 127.9ϩ, 125.8ϩ, 120.0Ϫ (CO3), 81.3ϩ (CH–O), 79.7ϩ
(CH–O), 73.8ϩ (CH–O), 56.0Ϫ (CSPh), 31.2Ϫ, 30.6Ϫ, 29.0Ϫ,
26.0Ϫ, 22.1ϩ (Me) and 21.7Ϫ; m/z (EI) 396 (6%, Mϩ), 227 (62),
205 (76, Mϩ – C6H10SPh) and 145 (100); (Found: Mϩ, 396.1757.
C24H28O3S requires M, 396.1759).
CHMe); δC(100.6 MHz; CDCl3) 170.1Ϫ (C᎐O), 134.9Ϫ (i-PhS),
᎐
132.0ϩ, 129.1ϩ, 127.3ϩ, 75.5Ϫ (C–O), 73.5ϩ, 68.0ϩ, 53.5ϩ
(CHSPh), 33.9Ϫ, 29.7Ϫ, 29.1ϩ (Ac), 21.1ϩ (Me), 18.5ϩ (Me) and
18.4ϩ (Me); m/z (EI) 294 (23%, Mϩ), 152 (13) and 136 (100);
(Found: Mϩ, 294.1291. C16H22O3S requires M, 294.1290).
(2RS,3RS,5RS )-2,6,6-Trimethyl-5-phenylsulfanyltetrahydro-
pyran-3-yl ethanoate 39
By the method described for compounds 36 and 37, syn,syn-
triol 14 (50 mg, 185 µmol), pyridinium toluene-p-sulfonate
(11.6 mg, 46.2 µmol) and trimethyl orthoacetate (25 µl, 23.3 mg,
194 µmol) in dry dichloromethane (2.5 cm3) gave a crude prod-
uct after 24 h which was treated with toluene-p-sulfonic acid
(3.5 mg, 18.5 µmol) in dichloromethane (2.0 cm3) at 35 ЊC for
72 hours to give a second product. Purification by chrom-
atography [silica, light petroleum (bp 40–60 ЊC)–diethyl ether,
4:1] gave the 2,3syn,3,5anti-tetrahydropyran 39 (46 mg, 85%) as an
oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.22;
(2RS,3RS,5RS )-2-Phenyl-5-phenylsulfanyl-1-oxaspiro[5.5]-
undecan-3-yl ethanoate 43
By the method described for compounds 36 and 37, syn,syn-
triol 11 (38 mg, 102 µmol), pyridinium toluene-p-sulfonate
(6.4 mg, 25.5 µmol) and trimethyl orthoacetate (14 µl, 12.9 mg,
107 µmol) in dry dichloromethane (2.5 cm3) gave a crude
product after 24 h which was treated with toluene-p-sulfonic
acid (1.9 mg, 10 µmol) in dichloromethane (2.5 cm3) at 35 ЊC for
72 hours to give a second product. Purification by chroma-
tography [silica, light petroleum (bp 40–60 ЊC)–diethyl ether,
4:1] gave the 2,3syn,3,5anti-tetrahydropyran 43 (36 mg, 89%) as an
oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.31;
νmax(CH2Cl2)/cmϪ1 2999, 2852, 1732 (C᎐O), 1583, 1463, 1379,
᎐
1242, 1182, 1099, 1067, 1024 and 971; δH(400 MHz; CDCl3)
7.39–7.34 (2 H, m, PhS), 7.32–7.18 (3 H, m, PhS), 4.84–4.81
(1 H, s, CHeqOAc), 3.85 (1 H, qd, J 6.4 and 1.4 Hz, CHaxMe),
3.33 (1 H, dd, J 13.0 and 4.3 Hz, CHaxSPh), 2.14 (1 H, ddd,
J 14.8, 4.2 and 3.2 Hz, CHaxHeq), 2.08 (3 H, s, Ac), 1.97 (1
H, ddd, J 14.8, 13.1 and 3.0 Hz, CHaxHeq), 1.43 (3 H, s, MeA),
1.30 (3 H, s, MeB) and 1.09 (3 H, d, J 6.4 Hz, CHMe); δC(100.6
νmax(CH2Cl2)/cmϪ1 3031, 2936, 2858, 1735 (C᎐O), 1583, 1478,
᎐
1449, 1374, 1240, 1064, 1036 and 992; δH(400 MHz; CDCl3)
7.42–7.35 (2 H, m, PhS), 7.34–7.18 (3 H, m, PhS), 5.31–5.24 (1
H, m, CHeqOAc), 4.77 (1 H, s, CHaxPh), 3.36 (1 H, dd, J 11.6
and 5.9 Hz, CHaxSPh), 2.32–2.12 (3 H, m, includes CHaxHeq
and CHaxHeq), 1.96–1.16 (9 H, m) and 1.79 (3 H, s, Ac);
MHz; CDCl3) 169.6Ϫ (C᎐O), 134.1Ϫ (i-PhS), 130.3ϩ, 128.0ϩ,
᎐
125.9ϩ, 74.8Ϫ (C–O), 69.6ϩ (CHOAc), 65.7ϩ (CHMe), 48.4ϩ
(CHSPh), 32.6Ϫ (CH2), 20.3ϩ (Ac), 17.2ϩ (Me) and 16.7ϩ (Me);
m/z (EI) 294 (31%, Mϩ), 234 (8, Mϩ Ϫ AcOH), 152 (12) and
136 (100); (Found: Mϩ, 294.1300. C16H22O3S requires M,
294.1290).
δC(100.6 MHz; CDCl3) 170.6Ϫ (C᎐O), 139.2Ϫ, 135.9Ϫ, 131.5ϩ,
᎐
129.4ϩ, 128.4ϩ, 127.6ϩ, 127.3ϩ, 126.3ϩ, 77.2Ϫ (C–O), 71.3ϩ
(CHPh), 70.5ϩ (CHOAc), 50.4ϩ (CHSPh), 37.3Ϫ, 33.3Ϫ, 26.3Ϫ,
24.7Ϫ, 21.7Ϫ, 21.2ϩ (Ac) and 21.2Ϫ; m/z (EI) 396 (14%, Mϩ), 238
(23), 162 (21), 136 (100) and 120 (45); (Found: Mϩ, 396.1763.
C24H28O3S requires M, 396.1759).
(1RS,3SR,5SR,6SR)-1,6-Dimethyl-3-[1-methyl-1-(phenyl-
sulfanyl)ethyl]-2,7,8-trioxabicyclo[3.2.1]octane 41
Anti,syn-triol 15 (70 mg, 259 µmol) was dissolved in dry
dichloromethane (3.0 cm3) and pyridinium toluene-p-sulfonate
(16.3 mg, 64.7 µmol) was added. The reaction vessel was
sealed with a septum and trimethyl orthoacetate (35 µl, 32.6 mg,
272 µmol) was injected in one portion. The reaction was stirred
at room temperature for 5 minutes and the reaction mixture
was then filtered through a short plug of silica, eluting with
dichloromethane. The solvent was evaporated under reduced
pressure to give the orthoester 41 as an oil (73 mg, 96%); Rf[light
petroleum (bp 40–60 ЊC)–diethyl ether, 4:1] 0.33; νmax(CH2Cl2)/
cmϪ1 3047, 2964, 2928, 2870, 1473, 1400, 1282, 1249, 1143,
1121, 1092, 1070, 949 and 909; δH(400 MHz; CDCl3) 7.59–7.51
(2 H, m, PhS), 7.36–7.26 (3 H, m, PhS), 4.26 (1 H, dd, J 3.4 and
2.1 Hz, CHeqO), 4.20 (1 H, q, J 6.2 Hz, CHMe), 3.89 (1 H, dd,
J 11.6 and 4.0 Hz, CHaxO), 2.11 (1 H, ddd, J 13.4, 11.6 and 3.5
Hz, CHaxHeq), 1.71 (1 H, ddd, J 13.4, 4.0 and 2.1 Hz, CHaxHeq),
1.56 (3 H, s, MeCO3), 1.22 (3 H, s, Me), 1.21 (3 H, s, Me) and
1.20 (3 H, d, J 5.4 Hz, CHMe); δC(100.6 MHz; CDCl3) 137.7ϩ,
131.5Ϫ (i-PhS), 128.8ϩ, 128.4ϩ, 119.2Ϫ (CO3), 77.7ϩ (CH–O),
76.1ϩ (CH–O), 73.6ϩ (CH–O), 50.8Ϫ (CSPh), 29.2Ϫ (CH2),
25.4ϩ (Me), 23.9ϩ (Me), 22.7ϩ (Me) and 20.3ϩ (Me); m/z (EI)
(2RS )-3-Methyl-3-phenylsulfanylbutan-2-ol 44
Methyllithium (18 cm3 of a 1.6 mol dmϪ3 solution in diethyl
ether, 28.8 mmol) was added dropwise to a stirred solution of
2-methyl-2-phenylsulfanylpropionaldehyde (5.0 g, 27.8 mmol)
in diethyl ether (100 cm3), at 0 ЊC, under an argon atmosphere.
The mixture was allowed to warm to room temperature and
stirring continued for 1 hour. The reaction was then cooled to
0 ЊC and saturated ammonium chloride solution added
(70 cm3). The mixture was transferred to a separating funnel
and the organic layer separated. The aqueous layer was
extracted twice with diethyl ether (30 cm3) and the combined
organic extracts washed with water (30 cm3) and saturated brine
solution (30 cm3). The ether solution was dried over anhydrous
magnesium sulfate and the solvent evaporated under reduced
pressure to give the crude product as a pale yellow oil. The
product was purified by column chromatography (silica, light
petroleum (bp 40–60 ЊC)–diethyl ether, 9:1] to give alcohol 44
(5.40 g, 99%) as an oil; Rf[light petroleum (bp 40–60 ЊC)–diethyl
ether, 9:1] 0.10; νmax(CH2Cl2)/cmϪ1 3501 (br, O–H), 3075, 2971,
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662
2661

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5 (a) K. Tamao, K. Sumitani and M. Kumada, J. Am. Chem. Soc.,
1972, 94, 4374; (b) K. Tamao, K. Sumitani, Y. Kiso, M. Zembayashi,
A. Fujioka, S.-i. Kodama, I. Nakajima, A. Minato and M. Kumada,
Bull. Chem. Soc. Jpn., 1976, 49, 1958.
6 I. Fleming, J. Dunoguès and R. Smithers, Organic Reactions, 1989,
37, 57.
7 E. J. Corey and G. Schmidt, Tetrahedron Lett., 1979, 399.
8 D. A. Evans, K. T. Chapman and E. M. Carreira, J. Am. Chem. Soc.,
1988, 110, 3560.
9 K.-M. Chen, G. E. Hardtmann, K. Prasad, O. Repicˇ and
M. J. Shapiro, Tetrahedron Lett., 1987, 28, 155.
2934, 2873, 1474, 1461, 1387, 1366 and 1283; δH(400 MHz;
CDCl3) 7.53–7.50 (2 H, m, PhS), 7.38–7.30 (3 H, m, PhS), 3.53
(1 H, qd, J 6.4 and 2.2 Hz, CHOH), 2.94* (1 H, br d, J 1.4 Hz,
OH), 1.24 (3 H, s, Me), 1.18 (3 H, s, Me) and 1.12 (3 H, d, J 6.3
Hz, Me); δC(100.6 MHz; CDCl3) 137.5ϩ (m-PhS), 130.4Ϫ
(i-PhS), 129.2ϩ (p-PhS), 128.8ϩ (o-PhS), 70.7ϩ (CH–OH), 55.7Ϫ
(CSPh), 26.1ϩ (Me), 21.1ϩ (Me) and 16.1ϩ (Me); m/z (EI) 196
(22%, Mϩ), 151 (100, Me2CSPhϩ), 131 (17), 119 (11), 110 (84,
PhSHϩ) and 109 (32, PhSϩ); (Found: Mϩ, 196.0923. C11H16OS
requires M, 196.0922).
10 (a) M. Chérest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968,
2199; (b) N. T. Anh, Top. Curr. Chem., 1979, 146.
11 E. P. Lodge and C. H. Heathcock, J. Am. Chem. Soc., 1987, 109,
Acknowledgements
3353.
12 By ‘rearranged’ we mean a product that has been formed as a result
of a [1,2]-PhS migration. Conversely an ‘unrearranged’ product is
one in which the phenylsulfanyl group remains bound to the same
carbon as it was before the cyclisation.
We thank the EPSRC and AstraZeneca for a grant to DH and
Dr J. E. Davies and Dr N. Feeder for the single crystal X-ray
diffraction analysis.
13 P. Lavallée, R. Ruel, L. Grenier and M. Bissonnette, Tetrahedron
Lett., 1986, 27, 679.
14 Calculations were performed using MOPAC software with a PM3
basis set.
15 By ‘downhill’ we refer to the phenylsulfanyl group undergoing a [1,2]
shift from a more substituted to a less substituted carbon atom.
Sulfanyl groups generally only move ‘downhill’; in some cases they
may undergo ‘flat’ migration, i.e. from one secondary centre to
another. For more details see: D. J. Fox, D. House and S. Warren,
Angew. Chem., Int. Ed. Engl., 2002, 41, 2462.
Notes and References
1 (a) L. Caggiano, D. J. Fox, D. House, Z. Jones, F. Kerr and
S. Warren, J. Chem. Soc., Perkin Trans. 1, 2002 (DOI: 10.1039/
b207556a); (b) L. Caggiano, D. J. Fox, D. House, Z. Jones, F. Kerr
and S. Warren, J. Chem. Soc., Perkin Trans. 1, 2002 (DOI: 10.1039/
b207557g).
2 D. House, F. Kerr and S. Warren, Chem. Commun., 2000, 1783.
3 H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev.,
1994, 94, 2483.
16 Y. Ito, Y. Kobayashi, T. Kawabata, M. Takase and S. Terashima,
Tetrahedron, 1989, 45, 5767.
4 C. R. Hauser and C. R. Hance, J. Am. Chem. Soc., 1952, 74, 5091.
2662
J. Chem. Soc., Perkin Trans. 1, 2002, 2652–2662