Efficient preparation of trisubstituted alkenes using the SmI2 modification of the Julia-Lythgoe olefination of ketones and aldehydes

Article abstract of DOI:10.1016/S0040-4020(01)00079-5

High yields of di- and tri-substituted alkenes are obtained by a modification of the Julia-Lythgoe olefination reaction involving the in situ capture of intermediate β-alkoxy-sulfones by benzoyl or trimethylsilyl chloride, followed by SmI₂-mediated reductive elimination. This novel protocol also provides a connective preparation of dienyl ethers, which are important partners in Diels-Alder cycloadditions.

Full text of DOI:10.1016/S0040-4020(01)00079-5

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2609±2619
Ef®cient preparation of trisubstituted alkenes using the SmI2
modi®cation of the Julia±Lythgoe ole®nation of ketones
and aldehydes
a,p
a
a
a
a
Â
Â
Istvan E. Marko, Fiona Murphy, Lucien Kumps, Ali Ates, Roland Touillaux,
Donald Craig,b,p Santiago Carballaresb and Simon Dolanc
a
  Ã
Laboratory de Chimie Organique, Departement de Chimie, Universite catholique de Louvain, Batiment Lavoisier, Place Louis Pasteur 1,
B-1348 Louvain-la-Neuve, Belgium
bImperial College of Science, Technology and Medicine, Department of Chemistry, London SW7 2AY, UK
cGlaxo-Wellcome Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
Dedicated with deep respect to Professor Henri B. Kagan
Received 17 August 2000; accepted 12 October 2000
AbstractÐHigh yields of di- and tri-substituted alkenes are obtained by a modi®cation of the Julia±Lythgoe ole®nation reaction involving
the in situ capture of intermediate b-alkoxy-sulfones by benzoyl or trimethylsilyl chloride, followed by SmI2-mediated reductive elimination.
This novel protocol also provides a connective preparation of dienyl ethers, which are important partners in Diels±Alder cycloadditions.
q 2001 Elsevier Science Ltd. All rights reserved.
The formation of carbon±carbon double bonds is of para-
mount importance in organic chemistry.1 Amongst the
plethora of methods known for the connective synthesis of
alkenes, the Julia±Lythgoe ole®nation, the combination of a
sulfone 2 with a carbonyl derivative 1 followed by reductive
elimination, occupies a cardinal position (Fig. 1).2
to dienyl ethers, which are important partners in Diels±
Alder cycloadditions.6
Examination of the literature revealed that trisubstituted
alkenes 8 are usually prepared by the coupling of disubsti-
tuted sulfone anions such as 4 with aldehydes 5, followed by
the reductive elimination of the corresponding b-hydroxy
sulfones 7 with Na amalgam. The high yields obtained using
this protocol stem from the equilibrium between reactants 4
and 5 and alkoxide 6 largely favouring the addition product
6. In stark contrast, the same equilibrium is strongly shifted
to the left in the case of the addition of a primary sulfone
anion 9 to a ketone 10 and only poor conversions to the
desired b-hydroxy sulfone 12 can be achieved.7 Moreover,
the reductive elimination employing Na(Hg) not only
affords the corresponding alkene 8, but also produces,
even under buffered conditions, some alkoxide 11 which
undergoes competitive retro-aldol type reaction, regener-
ating the starting material and decreasing even further the
overall yields of this ole®nation process (Fig. 2).
The versatility of this procedure has been demonstrated by
its numerous applications in the synthesis of complex
natural products.3 Despite its prominence, the Julia±
Lythgoe method suffers from a number of drawbacks,
including the production of mixtures of E/Z ole®nic isomers
and the poor yields of trisubstituted alkenes obtained during
attempted coupling between ketones and primary sulfone
anions. An elegant solution to the ®rst problem has been
recently provided by Kocienski et al., who showed that
sulfones bearing a modi®ed phenyltetrazolyl substituent
afforded disubstituted alkenes with virtually complete
control of the double bond geometry in favour of the
E-isomer.4
In this article, we wish to describe in full detail our contri-
bution to the establishment of a novel and ef®cient pro-
cedure for the preparation of trisubstituted ole®ns by the
direct coupling between primary sulfone anions and
ketones.5 In addition, this methodology offers an easy access
In order to improve this approach and transform it into a
Keywords: alkenes; ole®nation; sulfones; Julia reaction; samarium.
Corresponding authors. Tel.: 132-10-478773; fax: 132-10-472788
p
Figure 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00079-5

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2610
Figure 2.
viable synthetic methodology, two key problems have to be
solved: (1) shifting the unfavorable equilibrium towards the
product b-hydroxy sulfone 12, and (2) de®ning neutral
conditions for the reductive elimination of 12 in order to
minimise any competing retrograde process.
capturing the intermediate b-alkoxy-sulfone 11 by an
oxophilic reactant such as trimethylsilyl chloride or a
suitable acyl halide. Gratifyingly, addition of either
TMSCl or PhCOCl to the in situ generated tertiary alkoxide
11 resulted in excellent yields of b-hydroxy sulfones 12 and
the corresponding b-benzoyloxy sulfones, respectively
(Table 1).
Inspired by some elegant solutions used in reluctant aldol
condensations between enolates and ketones,8 we decided to
enhance the yields of the sulfone anion addition reaction by
As can be seen from Table 1, both acyclic and cyclic
Table 1. Synthesis of b-alkoxy- and b-benzoyloxy-sulfones by in situ electrophilic trapping
a
All yields are for pure, isolated products. A 70:30 mixture of diastereoisomers was obtained in entries 1±5.
The reaction mixture was quenched by addition of TMSCl at 2788C.
The reaction mixture was quenched by addition of PhCOCl at 2788C.
b
c

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2611
Table 2. Sml2-mediated reductive elimination
a
All yields are for pure, isolated products.
b The reaction was performed at 08C.
The reaction mixture was effected at 2788C.
c
d The reaction was performed at 2848C. The E/Z ratios are typically in the range of 2:1.
ketones reacted ef®ciently with a variety of primary sulfone
anions. Apart from entry 6, the addition products were
typically obtained as a 70:30 mixture of diastereoisomers.
single electron acceptor, as a surrogate for the inert phenyl
sulfonyl group. Whilst this substitution provides an elegant
solution to this problem, we decided to test the in¯uence of
various adjuvants, known to modify the reactivity of SmI2,11
on the outcome of the reductive elimination of the more
commonly employed phenylsulfonyl derivatives.
With an expedient and high-yielding method to access the
desired adducts in hand, attention was focused on the
reductive elimination step. The use of Na(Hg), whether
buffered or not rapidly proved to be unsuitable for our
purposes, resulting either in poor yields of the alkene,
large amounts of retro-aldol product or complete decompo-
sition of the starting material. Several other standard
reducing agents were shown to be equally ineffective. The
powerful, though selective, reducing abilities of the lantha-
nides and of some of their complexes triggered our interest
and we decided to investigate the use of SmI2 in this trans-
formation.9
Much to our delight, the addition of 1±5 mol% of HMPA or
DMPU to SmI2 in THF resulted in the smooth transfor-
mation of the b-benzoyloxy sulfones into the desired
alkenes, in good to excellent yields, at temperatures as
low as 2848C. Table 2 summarises some of our results.
As can be seen from Table 2, a range of trisubstituted
alkenes may ef®ciently be prepared by the SmI2-mediated
reductive elimination (entries 3±6). Unfortunately, no reac-
tion took place with the corresponding b-hydroxy sulfones
under the same reaction conditions and the starting material
was recovered unchanged. Gratifyingly, increasing the
temperature to 08C resulted in the rapid formation of the
desired ole®ns in good to excellent yields (Table 2, entries
1±2).
Disappointingly, SmI2 in THF proved to be completely
unreactive in the reductive elimination of b-hydroxy
sulfones, even after prolonged reaction times at room
temperature. This lack of reactivity has been observed by
Kende10, who used the N-phenyl imidazolyl sulfone, a better

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2612
Figure 3.
Figure 4.
From these results, it transpires that the use of a suitable in
situ oxophilic trapping reagent, combined with a neutral
SmI2-mediated reductive elimination, provides for the ®rst
time an ef®cient access to trisubstituted alkenes by the
previously inaccessible condensation of ketones with
primary sulfone anions. This methodology can also be
applied to the preparation of disubstituted ole®ns as illus-
trated in Fig. 3.
using SmI2 in THF/HMPA, at 2788C for 1 h, smoothly led
to the desired disubstituted alkene 15 (64% yield). In
contrast to the trisubstituted alkenes, which are typically
obtained as mixtures of isomers, ole®n 15 was shown to
possess solely the E-double bond geometry. The stereo-
chemistry of the trisubstituted ole®nic linkage was assigned
in each case using the 13C chemical shift method, as illus-
trated in Fig. 4.12
Thus, deprotonation of sulfone 13, followed by sequential
addition of dihydrocinnamaldehyde and benzoyl chloride,
afforded benzoate ester 14 in 89% yield, as a 60:40 mixture
of diastereoisomers. Subsequent reductive elimination of 14
It is interesting to note that the ratio of trisubstituted ole®nic
isomers is independent of the relative stereochemistry of the
starting hydroxide or benzoate derivatives. For example,
the same 1.7:1 ratio of alkenes 18 and 19 was obtained by
Figure 5.
Figure 6.

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2613
Figure 7.
the SmI2-mediated reductive elimination of a 4:96 or 90:10
ratio of the diastereoisomeric b-benzoyloxy sulfones 16 and
17 (Fig. 5).
We believe that in the case of the b-hydroxy sulfones, a
single electron transfer from SmI2 to the aromatic sulfone
nucleus takes place, generating the radical anion 26. This
step, which appears to be rather unfavourable, is followed
by the ejection of phenylsul®nate ion, producing the new
radical species 27. A second electron transfer from SmI2 to
radical 27 then affords the intermediate organosamarium
derivative 28, which undergoes b-elimination, leading to
the observed alkene product 8.
During the course of this work, Fukumoto13 and Keck,14
independently reported a similar use of the SmI2/HMPA
system in the preparation of disubstituted ole®ns. Further-
more, SinayÈ and co-workers have also successfully
employed the Inanaga's conditions for the reductive
elimination of a variety of b-acetoxy sulfone derivatives.15
In contrast to this mechanism, the transfer of a single elec-
tron to the benzoate moiety appears to be an easier process,
taking place rapidly even at 2848C and leading to radical
anion 30. Subsequent collapse of this intermediate liberates
the benzoate ion and produces radical 31.16 Further trans-
formation of 31 into the organosamarium intermediate 32
and elimination of the phenylsul®nyl group eventually
affords the ole®n 8. It is noteworthy that, in accord with
the results of Keck, no deuterium incorporation could be
detected in the alkene product upon attempted quenching
of a putative vinyl anion intermediate using MeOD as an
additive in the SmI2 reductive elimination. This observation,
which contrasts with the passage via a vinyl anion in the
Na(Hg) mediated reductive elimination, offers further
evidence for our proposed reaction mechanism.14,17 This
powerful methodology was then applied to the preparation
of dienyl ethers, which are useful substrates for Diels±Alder
cycloadditions (Fig. 8).
The large difference in reactivity between the b-hydroxy
sulfones and the corresponding b-benzoyloxy sulfones can
be further illustrated using competition experiments (Fig.
6).
For example, treatment of an equimolar mixture of sulfones
20 and 21 with SmI2, in THF/HMPA, at 2788C for 1 h,
resulted in the chemoselective transformation of benzoate
20 into alkene 22. After work-up, ole®n 22 could be isolated
in 68% yield and the starting b-hydroxy sulfone 21 was
recovered unchanged in 86% yield. Similarly, bis-sulfone
23, bearing a free hydroxyl function and a benzoate sub-
stituent reacted smoothly with SmI2, at 2788C, affording
exclusively and in good yields the unsaturated hydroxy-
sulfone 24, resulting from the chemo- and regio-selective
elimination of the benzoate moiety.
The enormous difference in reactivity between the
b-hydroxy sulfones and the b-benzoyloxy sulfones strongly
suggests that the reductive elimination of these substrates
proceeds via a different mechanism (Fig. 7).
The requisite b-sulfonyl benzoates were readily prepared
by sequential deprotonation of a-benzyloxy sulfone 33
with BuLi, addition of cinnamaldehyde (or its 2-methyl
Figure 8.

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2614
Figure 9.
derivative) and capture of the in situ generated b-alkoxy
sulfones with benzoyl chloride. In both cases, the products
34 and 37 consisted of a mixture of syn- and anti-dia-
stereoisomers. However, the geometric integrity of the
C±C double bond of the substrate aldehydes was retained
in the products. Reductive elimination of benzoates 34 and
37, using SmI2 in THF, in the presence of DMPU, proceeded
smoothly, affording the desired dienyl ethers 35/36 and 38/
39 in excellent yields. Interestingly, the transformation of
sulfones 34 and 37 into the corresponding enol ethers
displayed noteworthy differences.
41, 42 and 43,18 but also lends further credit to our proposed
mechanism for the reductive elimination of b-benzoyloxy
sulfones.
In summary, we have developed a novel variant of the Julia±
Lythgoe ole®nation reaction, involving the addition of a
suitable oxophilic electrophile and the utilisation of SmI2 to
promote, under neutral conditions, the subsequent reductive
elimination. This novel methodology allows for the ®rst time,
the ef®cient preparation of trisubstituted alkenes directly
from ketones and primary sulfone anions, a transformation
that only proceeded previously with extremely poor yields.
The synthetic utility of this protocol was further extended to
the preparation of disubstituted ole®ns anddienyl ethers.
Indeed, dienes 36 and 35 are obtained as a 1.7:1 mixture of
E/Z-isomers at the newly formed enol±ether double bond.
No isomerisation of the styrenyl double bond occured under
these conditions. In sharp contrast, products 38 and 39 were
isolated as a 1:1 mixture of (E,E)/(E,Z) geometric isomers,
resulting from the loss of the stereochemical integrity of the
trisubstituted ole®n.
1. Experimental
1.1. General methods
All the reactions were carried out under anhydrous con-
ditions and in an atmosphere of argon unless otherwise
stated. NMR spectra were recorded on Varian XL-200,
Gemini 200 and 300 and Brucker 270 MHz instruments.
Chemical shifts are expressed as parts per million (d) down-
®eld from tetramethylsilane or calibrated from CDCl3. The
chemical shifts of the minor diastereoisomers are high-
lighted whenever discernable from the major isomers and
are underlined. Mass spectra were obtained using Varian
MAT-44 and Finnigan MAT-TSQ 70 spectrometers with
electron impact (70 eV) and chemical ionisation (100 eV,
ionisation gas, isobutane). IR spectra were taken with a
Perkin±Elmer 681 spectrometer. Thin layer chroma-
tography was performed on Merck 0.2 mm aluminium-
backed TLC plates and visualised using UV light followed
by development with iodine, alkaline KMnO4 and/or cerium
(IV) nitrate solution. Column chromatography was
performed using Merck silica gel 60 (230±400 mesh)
under pressure. Microanalyses were provided by the ana-
lytical department, University College, London. We are
grateful to Professors John S. Svendsen and Ari M. P.
Koskinen for performing the HRMS analysis.
These observations can be rationalised by invoking the
intermediacy of either an allylic radicalor the corresponding
allylic organosamarium species 40 (Fig. 9).
Based upon our previous explanation (Fig. 7), treatment of
benzoate 37 with SmI2 should result in the formation of the
allylsamarium species 40. The fate of this key intermediate
is decisive for the ultimate ratio of (E,E)/(E,Z) isomeric
dienyl ethers 38 and 39. Direct b-elimination of phenyl-
sul®nyl anion should lead to the (E,E)-geometric isomer
38, via a transition state that should minimise A1,3 repulsive
interactions between the benzyloxy moiety and the adjacent
methyl substituent. However, a competitive [1,3]-shift of
SmI2 might also take place, affording samarium derivative
41. Rapid rotation around the newly formed C±C bond,
followed by another [1,3]-shift then leads to allylic
samarium species 43, in which the trisubstituted double
bond has undergone E/Z isomerisation. Examination of
molecular models clearly reveals negligeable differences in
steric interactions between intermediates 41 and 42, further
supporting our hypothesis of a rapid equilibrium between
these two conformers. Finally, b-elimination of phenylsul®-
nate ion from 43, via a transition state with minimum A1,3-
strain, ultimately forms the (E,Z)-isomer 39 (Fig. 9).
1.2. General procedure for the addition of a primary
sulfone to a ketone. Method A: capture by TMSCl
We believe that the 1:1 ratio of (E,E)/(E,Z) isomers obtained
in this reaction not only supports our assumption of a rapid
equilibrium between the various allylsamarium species 40,
1.2.1. 3-Methyl-2-phenylsulfonyl heptan-3-ol (Table 1,
entry 1). A solution of ethyl phenyl sulfone (0.5 g,

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2615
2.9 mmol) in anhydrous THF (9.0 mL) at 2788C was
treated with a solution of n-BuLi in hexane (1.6 M,
2.2 mL, 3.5 mmol). After stirring for 30 min, a solution of
2-hexanone (0.44 mL, 3.5 mmol) in THF (5.0 mL) was
added dropwise and the yellow solution was stirred for
another 45 min at 2788C. Trimethylsilyl chloride
(0.49 mL, 3.8 mmol) was then added. The cooling bath
was removed and, after stirring for 60 min, the mixture
was diluted with CH2Cl2 (50 mL) and washed with water
(30 mL). The aqueous phase was extracted with CH2Cl2
(2£20 mL) and the combined organic extracts were washed
sequentially with 10% H2SO4 (2£20 mL), 5% NaHCO3
(20 mL) and brine (20 mL). After removal of the solvents
in vacuo, puri®cation of the residue on silica gel using
8:2 Et2O/hexane as the eluent, gave 0.685 g (86%) of
the title compound as a clear oil. IR (neat) nm1axˆ3518,
3067, 2954, 1584, 1298, 1161, 1139, 720 cm21. H NMR
(CDCl3, 200 MHz) dHˆ0.89 (3H, t, Jˆ7.2 Hz), 0.93 (3H, t,
Jˆ7.3 Hz), 1.18±1.36 (6H, m), 1.32 (3H, d, Jˆ7.2 Hz), 1.53
(3H, s), 3.12 (1H, q, Jˆ7.3 Hz), 3.31 (1H, q, Jˆ7.2 Hz),
7.54±7.7 (3H, m), 7.87±7.96 (2H, m). 13C NMR (CDCl3,
50 MHz) dCˆ11.36, 11.41, 13.55, 13.65, 22.49, 22.68,
23.80, 24.26, 25.10, 25.18, 37.68, 40.70, 66.86, 68.24,
74.24, 74.73, 127.86, 127.90, 128.80, 128.84, 133.32,
133.41, 139.06, 139.16. HRMS: Calcd mass for
C14H22O3S: [M1], 270.3920. Found: 270.3922.
none (0.441 mL, 3.53 mmol) in THF (5.0 mL) was added
dropwise and the yellow solution was stirred at 2788C for
2 h. Benzoyl chloride (0.64 mL, 5.50 mmol) was then
added. The cooling bath was removed and the reaction
mixture was stirred for 50 min before adding 3-dimethyl-
aminopropylamine (0.70 mL, 5.50 mmol). The mixture was
diluted with ether (50 mL) and washed with water (30 mL).
The aqueous phase was washed with ether (2£20 mL) and
the combined organic layers washed sequentially with 10%
HCl (20 mL), 5% NaHCO3 (20 mL) and brine (20 mL).
Puri®cation of the residue on silica gel using 3:1 hexane±
ether as the eluent gave the title compound (1.03 g, 93%,
d.r.ˆ7:3) as a clear oil. IR (neat) nmaxˆ3065, 1713, 1601,
1584, 1315, 1147, 1070, 714 cm21. MS (CI) m/zˆ375 (3),
234 (10), 205 (100), 179 (65), 171 (24), 123 (94), 111 (54),
105 (34). 1H NMR (CDCl3, 300 MHz) dHˆ0.91 (3H, t, Jˆ
7.2 Hz), 0.92 (3H, t, Jˆ7.2 Hz), 1.30 (3H, d, Jˆ7.2 Hz),
1.33 (3H, d, Jˆ7.1 Hz), 1.17±1.54 (6H, m), 1.74 (3H, s),
1.90 (3H, s), 4.50 (1H, q, Jˆ7.2 Hz), 4.55 (1H, q, Jˆ
7.1 Hz), 7.45±7.58 (6H, m), 7.84±7.96 (4H, m). 13C NMR
(CDCl3, 50 MHz) dCˆ11.20, 11.40, 13.93, 21.90, 22.02,
22.77, 24.98, 25.69, 35.68, 36.71, 64.18, 64.45, 85.07,
85.39, 128.13, 128.22, 128.40, 128.93, 128.99, 129.51,
129.54, 130.63, 130.76, 132.82, 132.89, 133.18, 133.30,
140.10, 165.78. Anal. Calcd for C21H26O4S: C, 67.35; H,
7.00; S, 8.56. Found: C, 67.42; H, 7.18; S, 8.15.
1.2.2. 3-Methyl-1-phenyl-4-phenylsulfonyl decan-3-ol
(Table 1, entry 2). Following Method A, a solution of
phenyl heptyl sulfone (1.0 g, 5.90 mmol) in THF (20 mL)
was treated with n-BuLi in hexane (1.6 M, 4.1 mL,
6.5 mmol) and 4-phenyl-2-butanone (0.99 mL, 6.5 mmol)
in THF (9 mL). After addition of trimethylsilyl chloride
(2.58 mL, 16 mmol), the cooling bath was removed and
the solution stirred for 60 min. Usual work-up gave a
crude mixture which was bulb±bulb distilled (1508C,
0.5 mmHg), affording 3.87 g of essentially pure product
as a 7:3 mixture of diastereoisomers. This material was
recrystallised from hot Et2O±hexane, providing the title
compound as a white solid in analytically pure form
(3.58 g, 69%). Mp: 54±568C. IR (neat) nmaxˆ3507, 3062,
1601, 1288, 1143, 722 cm21. MS (EI) m/zˆ283 (3), 299
(32), 143 (100), 125 (10), 91 (18), 57 (15). 1H NMR
(CDCl3, 300 MHz) dHˆ0.76 (3H, t, Jˆ7.1 Hz), 0.89±1.46
(10H, m), 1.41 (3H, s), 1.57 (3H, s), 1.60±2.41 (2H, m),
2.61±2.97 (2H, m), 3.17 (1H, dd, Jˆ5.6, 4.9 Hz), 3.24
(1H, dd, Jˆ5.7, 3.5 Hz), 4.25 (1H, s), 4.56 (1H, s), 7.11±
7.30 (5H, m), 7.49±7.66 (3H, m), 7.85±7.96 (2H, m). 13C
NMR (CDCl3, 50 MHz) dCˆ13.74, 22.29, 24.18, 25.99,
27.01, 27.15, 28.78, 28.96, 29.05, 29.45, 29.62, 29.89,
31.13, 40.27, 43.52, 73.30, 74.45, 75.35, 76.03, 125.80,
125.85, 128.18, 128.31, 128.37, 128.42, 129.20, 133.62,
140.69, 141.10, 142.07. Anal. Calcd for C23H32O3S: C,
71.10, H, 8.30; S, 8.25. Found: C, 70.85; H, 8.12; S, 8.25.
1.3.2. 1-Methyl-3-phenyl-1-(1-phenylsulfonylethyl) propyl
benzoate (Table 1, entry 4). According to Method B, a
solution of phenylethyl sulfone (1.0 g; 5.90 mmol) in THF
(20 mL) was treated with n-BuLi in hexane (1.6 M, 4.1 mL,
6.5 mmol) and 4-phenyl-2-butanone (0.99 mL, 6.5 mmol)
in THF (9 mL) and benzoyl chloride (1.18 mL, 10 mmol).
The title compound was isolated in 93% yield (2.35 g) after
puri®cation by the following procedure. A ®rst crop of pure
material was obtained by trituration of the crude product
with hexane (40%, 1.0 g). The mother liquors were pooled
and the solvent was evaporated in vacuo. The residue was
bulb-to-bulb distilled (608C, 0.2 mmHg) to remove traces of
4-phenyl-2-butanone. The remaining solid was recrystal-
lised from hot hexane±ether, affording an additional
1.35 g (53%) of pure compound as a white solid. It is
interesting to note that the ®rst crop consisted of a 4:96
mixture of diastereoisomers while the second crop was
composed of a 90:10 mixture of isomers. Mpˆ106±
1078C. IR (neat) nmaxˆ3068, 1712, 1601, 1586, 1315,
1149, 1069, 703 cm21. MS (EI) m/zˆ423 (3), 345 (5), 159
1
(72), 158 (100), 143 (16), 105 (17). H NMR (CDCl3,
300 MHz) dHˆ1.31 (3H, d, Jˆ7.0 Hz), 1.32 (3H, d, Jˆ
7.2 Hz), 1.84 (3H, s), 2.0 (3H, s), 2.19±2.33 (1H, m),
2.52±3.09 (3H, m), 4.52 (1H, q, Jˆ7.0 Hz), 4.59 (1H, q,
Jˆ7.2 Hz), 7.14±7.28 (5H, m), 7.36±7.58 (6H, m), 7.86±
7.95 (4H, m). 13C NMR (CDCl3, 50 MHz) dCˆ11.28, 11.51,
22.00, 22.24, 29.46, 30.09, 38.86, 38.94, 64.09, 64.42,
84.78, 85.14, 125.97, 126.04, 128.24, 128.34, 128.36,
128.40, 128.46, 128.49, 129.00, 129.08, 129.62, 129.64,
130.56, 130.65, 132.97, 133.09, 133.29, 133.43, 139.93,
139.99, 140.07, 141.38, 165.72, 165.85. Anal. Calcd for
C25H26O4S: C, 71.01; H, 6.20; S, 7.59. Found: C, 71.01;
H, 6.16; S, 7.62.
1.3. General procedure for the addition of a primary
sulfone to a ketone. Method B: capture by PhCOCl
1.3.1. 1-Methyl-1-(1-phenylsulfonylethyl) pentyl benzo-
ate (Table 1, entry 3). A solution of ethyl phenyl sulfone
(0.5 g, 2.94 mmol) in anhydrous THF (9.0 mL) at 2788C
was treated with n-BuLi in hexane (1.6 M, 2.20 mL,
3.53 mmol). After stirring for 30 min, a solution of 2-hexa-
1.3.3. 1-Methyl-1-(2-phenylethyl)-2-phenylsulfonyloctyl
benzoate (Table 1, entry 5). According to Method B, a

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2616
solution of heptyl phenyl sulfone (0.842 g; 3.50 mmol) in
THF (10 mL) was treated with n-BuLi in hexane (1.6 M,
2.38 mL, 3.8 mmol) and 4-phenyl-2-butanone (0.575 g,
3.8 mmol) in THF (5 mL) and benzoyl chloride (0.77 mL,
6.60 mmol). The title compound was isolated in 85% yield
(1.46 g), after puri®cation by silica gel column chroma-
tography using 3:1 hexane±ether as the eluent, as a clear,
colourless oil. IR (neat) nmaxˆ3062, 1714, 1602, 1314,
1146, 1070, 700 cm21. MS (EI) m/zˆ289 (2), 148 (65),
1.5. Method B. General procedure for the reductive
elimination of b-benzoyloxy sulfones
1.5.1. 3-Methyl-1-phenyl dec-3-ene19 (Table 2, entry 5).
Freshly distilled HMPA (1.3 mL, 7.4 mmol) was added to
a solution of 1-methyl-1-(2-phenylethyl)-2-phenylsulfonyl-
octyl benzoate (0.642 g, 1.3 mmol, d.r.ˆ7:3) dissolved in
0.1 M SmI2 in THF (65 mL, 6.5 mmol) at 2788C and the
solution was stirred for 1 h. Saturated NH4Cl (10 mL) was
then added and, upon warming to room temperature, the
solution was diluted with ether (200 mL) and washed with
10% aq. sodium thiosulfate (150 mL). The aqueous layer
was extracted with ether (2£50 mL) and the combined
organic layers were washed with water (50 mL), dried and
the solvents were removed in vacuo. The crude product was
puri®ed by column chromatography on silica gel using
100% petroleum ether as the eluent. The title compound
was obtained as a colourless liquid (0.22 g, 72%, 2.5:1
mixture of E/Z isomers). IR (neat) nmaxˆ3070, 3030,
1675, 1600, 1495, 1454, 742, 697 cm21. MS (EI) m/zˆ
231 (13), 230 (100), 146 (14), 104 (73), 91 (98), 83 (51).
1H NMR (CDCl3, 300 MHz) dHˆ0.877 (3H, t, Jˆ7.2 Hz),
0.883 (3H, t, Jˆ6.9 Hz), 1.18±1.32 (8H, m), 1.64 (3H, s,
(E)), 1.72 (3H, s, (Z)), 1.84±1.98 (2H, m), 2.24±2.34 (2H,
m), 2.64±2.72 (2H, m), 5.10±5.17 (1H, m), 7.14±7.31 (5H,
m). 13C NMR (CDCl3, 50 MHz) dCˆ14.10, 16.08 (E),
22.68, 23.43 (Z), 27.83, 27.95, 29.00, 29.11, 29.79, 29.97,
31.85, 34.02 (Z), 34.52, 34.80, 41.67 (E), 125.41, 125.59,
125.70, 126.29, 128.18, 128.22, 128.36, 134.13, 134.17,
142.46, 149.50.
1
123 (20), 105 (71), 91 (25), 85 (91), 84 (100). H NMR
(CDCl3, 200 MHz) dHˆ0.72 (3H, t, Jˆ6.7 Hz), 0.74 (3H,
t, Jˆ6.5 Hz), 0.82±1.40 (10H, m), 1.60±2.42 (2H, m), 1.83
(3H, s), 1.98 (3H, s), 2.60±2.96 (2H, m), 4.43 (1H, dd,
Jˆ6.0, 3.0), 4.46 (1H, dd, Jˆ5.8, 3.0 Hz), 7.10±7.28 (5H,
m), 7.36±7.58 (6H, m), 7.86±7.95 (4H, m). 13C NMR
(CDCl3, 50 MHz) dCˆ13.63, 22.02, 22.26, 22.51, 26.24,
26.39, 28.73, 29.26, 29.42, 29.84, 30.82, 38.71, 69.05,
69.15, 85.07, 85.47, 125.75, 125.86, 128.03, 128.25,
128.30, 128.78, 129.34, 129.40, 130.56, 130.63, 132.77,
133.03, 133.08, 140.52, 140.64, 141.12, 141.24, 165.54,
165.64. HRMS: Calcd mass for C30H36O4S: [M1],
492.6780. Found: 492.6784.
1.3.4. 4-tert-Butyl-1-benzoyloxy-1-(1-phenylsulfonyl pentyl)
cyclohexane (Table 1, entry 6). According to Method B,
a solution of pentyl phenyl sulfone (6.36 g; 29 mmol) in
THF (90 mL) was treated with n-BuLi in hexane (1.6 M,
22 mL, 35.2 mmol) and 4-tert-butylcyclohexane (5.1 g,
29 mmol) in THF (30 mL), benzoyl chloride (5.8 mL,
56.3 mmol) and dimethylaminopropyl amine (7 mL). The
title compound was isolated in 85% yield (10.4 g) as a
white solid, after puri®cation by recrystallisation from
heptane. Mpˆ1378C. IR (neat) nmaxˆ2951, 2869, 1711,
1.5.2. 3-Methyl-1-phenyl pent-3-ene20 (Table 2, entry 4).
Prepared according to Method B. Freshly distilled HMPA
(0.8 mL, 4.6 mmol) was added to a solution of 1-methyl-3-
phenyl-1-(1-phenylsulfonylethyl) propyl benzoate (0.33 g,
0.8 mmol, d.r.ˆ7:3) dissolved in 0.1 M SmI2 in THF
(40 mL, 4.0 mmol) at 2848C and the solution was stirred
for 1 h. Saturated NH4Cl (10 mL) was then added and, upon
warming to room temperature, the milky white suspension
was diluted with ether (200 mL) and washed with 10% aq.
sodium thiosulfate (100 mL). The aqueous layer was
extracted with ether (2£50 mL) and the combined organic
layers were washed with water (50 mL), dried and the
solvents were removed in vacuo. The crude product was
puri®ed by column chromatography on silica gel using
100% pentane as the eluent. The title compound was
obtained as a colourless liquid (0.108 g, 84%, 1.7:1 mixture
of E/Z isomers). IR (neat) nmaxˆ3063, 1670, 1604, 1495,
1454, 742, 698 cm21. MS (EI) m/zˆ161 (5), 160 (52), 145
1
1336, 1142 cm21. H NMR (CDCl3, 300 MHz) dHˆ0.67
(3H, t, Jˆ6.9 Hz), 0.78 (9H, s), 1.1±1.4 (7H, m), 1.6±1.85
(4H, m), 2.0 (2H, m), 2.56 (1H, dq, Jˆ14.1, 3.3 Hz), 2.86
(1H, dq, Jˆ14.4, 3.0 Hz), 4.48 (1H, dd, Jˆ4.8, 3.6 Hz), 7.35
(5H, m), 7.5 (1H, tt, Jˆ7.2, 1.5 Hz), 7.84 (4H, m). 13C NMR
(CDCl3, 50 MHz) dCˆ14.21, 22.68, 23.01, 23.17, 26.58,
28.07, 32.43, 32.62, 32.79, 33.03, 47.36, 68.97, 86.07,
128.90, 129.23, 129.59, 130.23, 131.63, 133.61, 133.75,
141.59, 166.47. Anal. Calcd for C28H38O4S: C, 71.49; H,
8.09; S, 6.81. Found: C, 71.59; H, 8.16; S, 6.92.
1.4. Method A. General procedure for the reductive
elimination of b-hydroxy sulfones
1.4.1. 3-Methyl-1-phenyl dec-3-ene19 (Table 2, entry 2).
Freshly distilled HMPA (2.0 mL, 11.4 mmol) was added to
a solution of 3-Methyl-1-phenyl-4-phenylsulfonyl decan-3-ol
(0.4 g, 1.03 mmol, d.r.ˆ7:3) dissolved in 0.1 M SmI2 in
THF (52 mL, 5.2 mmol) at 08C and the solution was stirred
for 1 h. Saturated NH4Cl (15 mL) was then added and, upon
warming to room temperature, the solution was diluted with
ether (300 mL) and washed with 10% aq. sodium thiosulfate
(200 mL). The aqueous layers were extracted with ether
(2£65 mL) and the combined organic layers were washed
with water (65 mL), dried and the solvents were removed in
vacuo. The crude product was puri®ed by column chroma-
tography on silica gel using 100% petroleum ether as the
eluent. The title compound was obtained as a colourless
liquid (0.156 g, 66%, 1.2:1 mixture of E/Z isomers).
1
(14), 91 (100), 69 (28). H NMR (CDCl3, 200 MHz) dHˆ
1.47 (3H, bd, Jˆ6.6 Hz), 1.56 (3H, bd, Jˆ6.7 Hz), 1.65 (3H,
bs), 1.72 (3H, bs), 2.23±2.36 (2H, m), 2.62±2.74 (2H, m),
5.226 (1H, m), 5.232 (1H, m), 7.09±733 (5H, m). 13C NMR
(CDCl3, 50 MHz) dCˆ13.00, 13.27, 15.76, 23.38, 33.60,
34.15, 34.79, 41.63, 118.78, 119.66, 125.62, 125.70,
128.21, 128.34, 135.23, 135.30, 142.46, 142.58.
1.5.3. 4-tert-Butyl cyclohexylidenyl butane21 (Table 2,
entry 6). Prepared according to Method B. Freshly distilled
HMPA (4 mL, 23 mmol) was added to a solution of
1-methyl-3-phenyl-1-(1-phenylsulfonylethyl) propyl benzo-
ate (0.94 g, 2.0 mmol) dissolved in 0.1 M SmI2 in THF
(250 mL, 24 mmol) at 2788C and the solution was stirred

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2617
for 15 h at room temperature. Saturated NH4Cl (30 mL) was
then added and the solution was diluted with ether (400 mL)
and washed with 10% aq. sodium thiosulfate (400 mL). The
aqueous layer was extracted with ether (2£100 mL) and the
combined organic layers were washed with water (2£
100 mL), dried and the solvents were removed in vacuo.
The crude product was puri®ed by column chromatography
on silica gel using 100% hexane as the eluent. The title
compound was obtained as a colourless liquid (0.350 g,
0.65 mmol) at 2788C. The solution was stirred for
30 min. Saturated NH4Cl (0.8 mL) was then added, the
cooling bath was removed and the mixture stirred vigor-
ously for 30 min. After dilution with ether (30 mL), the
mixture was washed with 10% aq. Na2S2O3 (15 mL) and
the aqueous layers extracted with ether (2£10 mL). The
combined organic phases were washed with water
(10 mL), dried and the solvent was removed in vacuo. The
residue was puri®ed by column chromatography on silica
gel using 95:5 hexane±ether as the eluent, affording the title
compound as a clear colourless oil (45 mg, 69%, mixture of
isomers). IR (neat) nmax ˆ3504, 3064, 2934, 1603, 1448,
1312, 1145, 1045, 723 cm21. MS (EI) m/zˆ472 (23), 342
(95), 331 (100), 239 (19), 227 (80), 185 (20), 131 (55), 91
(53). 1H NMR (CDCl3, 200 MHz) dHˆ0.58±2.10 (10H, m),
1.33 (3H, s), 1.43 (3H, s), 1.50 (3H, s), 1.59 (3H, s), 2.10±
3.16 (5H, m), 4.45 (1H, s, OH), 4.47 (1H, s, OH), 4.67±4.78
(1H, m), 4.96±5.12 (1H, m), 7.08±7.28 (10H, m), 7.38±
7.61 (3H, m), 7.79±7.93 (2H, m). 13C NMR (CDCl3,
50 MHz) dCˆ16.09 (Z), 23.37 (E), 24.17, 25.98, 26.63,
26.67, 27.26, 27.32, 27.47, 27.58, 29.32, 29.43, 29.56,
29.89, 29.99, 30.37, 34.67 (E), 40.29, 41.40 (Z), 42.02,
43.55, 43.75, 73.30, 74.37, 75.33, 76.00, 123.52, 124.44,
125.70, 125.82, 128.04, 128.22, 128.30, 128.41, 129.18,
133.48, 133.66, 135.39, 135.48, 135.53, 135.61, 140.56,
140.64, 140.96, 141.01, 142.07, 142.18. Anal. Calcd for
C31H38O3S: C, 75.88; H, 7.81. Found: C, 75.96; H, 7.95.
1
85%). IR (neat) nmaxˆ2957, 2856, 1735 cm21. H NMR
(CDCl3, 200 MHz) dHˆ0.82 (9H, s), 0.87 (3H, bt, Jˆ
6.9 Hz), 0.88 (1H, m), 1.05 (1H, qt, Jˆ11.7, 2.7 Hz), 1.24
(5H, m), 1.62 (1H, tm, Jˆ13.5 Hz), 1.8 (2H, m), 1.96 (3H,
m), 2.19 (1H, dq, Jˆ14.1, 3.0 Hz), 2.61 (1H, dq, Jˆ13.5,
2.7 Hz), 5.04 (1H, t, Jˆ7.2 Hz). 13C NMR (CDCl3, 75 MHz)
dCˆ14.80, 23.12, 27.67, 28.37, 28.40, 28.46, 29.28, 30.11,
32.23, 37.84, 49.38, 121.91, 139.97.
1.5.4. 1-(2-Phenylethyl)-2-phenylsulfonyloctyl benzoate
14. Prepared according to Method B using the following
quantities: phenylheptyl sulfone (0.842 g, 3.50 mmol),
3-phenyl-1-propanal (0.537 g, 3.80 mmol). The crude
product was puri®ed by column chromatography on silica
gel using 2:1 hexane±ether as the eluent, affording the title
compound (colourless oil) as a 3:2 mixture of diastereo-
isomers in 89% yield (1.483 g). IR (neat) nmaxˆ3064,
1721, 1603, 1315, 1149, 1070, 700 cm21. MS (EI) m/zˆ
223 (23), 134 (37), 122 (51), 105 (59), 84 (77), 56 (100).
1H NMR (CDCl3, 200 MHz) dHˆ3.31 (1H, ddd, Jˆ7.9, 5.2,
2.7 Hz), 3.48 (1H, ddd, Jˆ6.0, 6.0, 2.7 Hz), 5.30 (1H, ddd,
Jˆ10.2, 2.7, 2.7 Hz), 5.55 (1H, ddd, Jˆ7.5, 5.2, 2.2 Hz),
7.10±7.62 (11H, m), 7.72±8.06 (4H, m). 13C NMR
(CDCl3, 50 MHz) dCˆ13.73, 13.83, 22.23, 22.33, 23.53,
24.52, 27.51, 28.06, 28.73, 28.97, 31.10, 31.21, 31.81,
31.90, 33.57, 65.64, 66.96, 71.09, 71.20, 126.00, 126.09,
128.11, 128.22, 128.30, 128.40, 128.50, 128.60, 128.91,
129.04, 129.49, 129.50, 132.97, 133.16, 133.28, 133.49,
138.65, 138.82, 140.25, 140.60, 165.14. Anal. Calcd for
C29H34O4S: C, 72.77; H, 7.16; S, 6.70. Found: C, 73.02;
H, 7.27; S, 6.32.
1.5.7. (E)-1-Benzyloxy-1-phenylsulfonyl-2-benzoyloxy-5-
phenyl but-3-ene 34. Prepared according to Method B
using the following quantities: sulfone 33 (0.212 g,
0.81 mmol), n-BuLi (0.4 mL, 0.97 mmol), THF (5 mL),
cinnamaldehyde (0.122 mL, 0.97 mmol) dissolved in 5 mL
of THF and PhCOCl (0.112 mL, 0.97 mmol) at 2788C.
After warming to room temperature over 45 min, the reac-
tion mixture was diluted with sat. NH4Cl (50 mL) and ether
(50 mL). The organic layer was separated and the aqueous
phase extracted with ether (3£30 mL). The combined
organic layers were washed with water (50 mL), brine
(50 mL), dried over MgSO4 and the solvents removed in
vacuo. The crude product was puri®ed by column chroma-
tography on silica gel using 70:30 petroleum ether/AcOEt as
the eluent, affording the title compound as a colourless solid
(0.358 g, 88%). Mpˆ108±1108C. IR (neat) nmaxˆ2900,
1720, 1260, 1147, 1115 cm21. MS (CI) m/zˆ516, 357,
1.5.5. (E)-1-Phenyl dec-3-ene 15. Prepared according to
Method B using the following quantities: 1-(2-phenyl-
ethyl)-2-phenylsulfonyloctyl benzoate 14 (0.488 g, 1.02
mmol), SmI2 (0.1 M, 51 mL, 5.10 mmol) and HMPA
(2.03 mL, 11.6 mmol) at 2788C. The crude product was
puri®ed by column chromatography on silica gel using
100% hexane as the eluent, affording the title compound
as a clear oil (0.164 g, 64%). IR (neat) nmaxˆ3030, 1630,
1496, 1455, 745, 698 cm21. MS (EI) m/zˆ217 (14), 216
(100), 104 (35), 91 (38), 69 (13). 1H NMR (CDCl3,
300 MHz) dHˆ0.88 (3H, t, Jˆ6.8 Hz), 1.21±1.34 (8H, m),
1.92±2.22 (2H, m), 2.39±2.45 (2H, m), 2.62±3.72 (2H, m),
5.36±5.45 (2H, m), 7.14±7.28 (5H, m). 13C NMR (CDCl3,
50 MHz) dCˆ14.06, 22.63, 28.80, 29.53, 31.76, 32.56,
34.43, 36.19, 125.68, 128.22, 128.48, 129.31, 131.22,
142.21. Anal. Calcd for C16H24: C, 88.82; H, 11.18.
Found: C, 88.65; H, 11.30.
1
280, 266, 149, 84, 49. H NMR (CDCl3, 270 MHz) dHˆ
4.71 (1H, d, Jˆ3.01 Hz), 4.87 (1H, d, Jˆ5.1 Hz), 4.91
(1H, d, Jˆ11.8 Hz), 5.03 (1H, d, Jˆ11.6 Hz), 5.07 (1H, d,
Jˆ11.8 Hz), 5.23 (1H, d, Jˆ11.6 Hz), 5.87 (1H, dd, Jˆ7.9,
5.08 Hz), 5.98 (1H, dd, Jˆ15.5, 7.6 Hz), 5.99 (1H, dd,
Jˆ15.7, 7.9 Hz), 6.07 (1H, dd, Jˆ7.6, 3.0 Hz), 6.62 (1H,
d, Jˆ15.7 Hz), 6.64 (1H, d, Jˆ15.5 Hz), 7.1±8.0 (20H, m).
HRMS: Calcd mass for C30H30NO5S: [M1NH41],
516.1845. Found: 516.1863.
1.5.8. (E)-1-Benzyloxy-1-phenylsulfonyl-2-benzoyloxy-3-
methyl-5-phenyl but-3-ene 37. Prepared according to
Method
B using the following quantities: n-BuLi
(0.318 mL, 0.795 mmol), sulfone 33 (0.189 g, 0.723
mmol), THF (6 mL), a-methyl cinnamaldehyde (0.116 g,
0.795 mmol) dissolved in 6 mL of THF and PhCOCl
(0.1 mL, 0.867 mmol). Usual work-up gave a crude product
which was puri®ed by column chromatography on silica gel
1.5.6. 3,9-Dimethyl-1,11-diphenyl-4-phenylsulfonyl undec-
8-en-3-ol 24. Freshly distilled HMPA (0.26 mL, 1.49
mmol), was added to a solution of bis-sulfone 23 (0.1 g,
0.13 mmol) dissolved in 0.1 M SmI2 in THF (6.5 mL,

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2618
Á
using 70:30 petroleum ether/AcOEt as the eluent, affording
the title compound as a colourless oil (0.092 g, 25%). IR
(neat) nmaxˆ2918, 1719, 1445, 1310, 1282, 1143, 1103,
1070, 743 cm21. MS (CI) m/zˆ530, 408, 372, 371, 251,
Fonds pour la Formation a la Recherche dans l'Industrie
et dans l'Agriculture (FRIA, studentship to A. A.), the
Fonds de la Recherche Fondamentale Collective (Dossier
No. 2.4601.99) and the Spanish Ministerio de Educacion y
Cienca (studentship to S. C.) is gratefully acknowledged.
1
249, 233, 159, 108, 105, 91. H NMR (CDCl3, 270 MHz)
Diastereoisomer 1, dHˆ1.7 (3H, s), 4.83 (1H, d, Jˆ
11.3 Hz), 4.89 (1H, d, Jˆ8.3 Hz), 5.05 (1H, d, Jˆ
11.1 Hz), 5.48 (1H, d, Jˆ8.3 Hz), 6.6 (1H, s), 7.2±8.1
(10H, m). Diastereoisomer 2, dHˆ1.7 (3H, s), 4.78 (1H, d,
Jˆ3.3 Hz), 5.03 (1H, d, Jˆ11.0 Hz), 5.22 (1H, d, Jˆ
11.0 Hz), 5.87 (1H, d, Jˆ3.3 Hz), 6.45 (1H, s), 7.2±8.1
(10H, m).
References
1. For some leading reviews, see: (a) Knight, D. W. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 3, pp 241. (b) Tamao, K. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 435. (c) Clough,
J. M. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 861
and references cited therein.
1.5.9. 1-Benzyloxy-4-phenyl-1,3-butadiene 35/36. A solu-
tion of sulfone 34 (0.113 g, 0.227 mmol) and DMPU
(0.433 mL, 3.585 mmol) in 2.4 mL of THF was treated
with SmI2 (12 mL of
a 0.1 M solution in THF,
1.195 mmol). The resulting blue±green solution was stirred
at room temperature for 2 h. The reaction was quenched by
the addition of a saturated solution of NH4Cl (20 mL) and
extracted with ether (3£50 mL). The combined organic
layers were washed with 10% Na2S2O3 (50 mL), water
(50 mL), brine (50 mL), dried over MgSO4 and the solvents
were removed in vacuo. The residue was puri®ed by column
chromatography on silica gel using 9:1 petroleum ether±
AcOEt as the eluent, affording the title compound as a
2. (a) Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 4833.
(b) Kocienski, P. J.; Lythgoe, B.; Waterhouse, I. J. Chem.
Soc., Perkin Trans. 1 1980, 1045. (c) Kocienski, P. J. Phos-
phorus Sulphur 1985, 24, 97. (d) Kocienski, P. J. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 6.
3. For selected examples, see: (a) Kocienski, P. J.; Lythgoe, B.
J. Chem. Soc., Perkin Trans I 1980, 1000. (b) Edwards, M.;
Ley, S. V.; Lister, S. G.; Palmer, B. D.; Williams, D. J. J. Org.
Chem. 1984, 49, 3503. (c) Kennedy, R. M.; Abiko, A.;
Takemasa, T.; Okumoto, H.; Masamune, S. Tetrahedron
Lett. 1988, 29, 451. (d) Poss, C. S.; Rychnovsky, S. D.;
Schreiber, S. L. J. Am. Chem. Soc. 1993, 115, 3360.
(e) Piers, E.; Wai, J. S. M. Can. J. Chem. 1994, 72, 146.
(f) Hoemann, M. Z.; Agrios, K. A.; Aube, J. Tetrahedron
Lett. 1996, 37, 953.
colourless oil (0.044 g, 82%, E/Zˆ1.7:1). IR (neat) nmax
ˆ
3027, 2926, 1638, 1611, 1593, 1160, 1064, 743 cm21. MS
1
(CI) m/zˆ237, 219, 145, 117, 108, 91. H NMR (CDCl3,
270 MHz) Compound 36, dHˆ4.84 (2H, s), 5.87 (1H, dd,
Jˆ12.3, 10.9 Hz), 6.38 (1H, d, Jˆ15.5 Hz), 6.69 (1H, dd,
Jˆ15.7, 10.9 Hz), 6.79 (1H, dd, Jˆ15.7, 10.9 Hz), 7.15
(10H, m). Compound 35, dHˆ4.88 (2H, s), 5.31 (1H, ddd,
Jˆ11.1, 6.2, 0.7 Hz), 6.16 (1H, dt, Jˆ6.2, 0.9 Hz), 6.45 (1H,
d, Jˆ14.6 Hz), 7.15 (10H, m11H, dd, Jˆ14.6, 11.1 Hz).
4. Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A.
Synlett 1998, 26. See also: Charrette, A. B.; Lebel, H. J. Am.
Chem. Soc. 1996, 118, 10327.
1.5.10. 1-Benzyloxy-3-methyl-4-phenyl-1,3-butadiene 38/
39. A solution of sulfone 37 (0.042 g, 0.082 mmol) and
DMPU (0.212 mL, 1.76 mmol) in 1.1 mL of THF was
treated with SmI2 (5.8 mL of a 0.1 M solution in THF,
0.58 mmol). The resulting blue±green solution was stirred
at room temperature for 2 h. The reaction was quenched by
the addition of a saturated solution of NH4Cl (20 mL) and
extracted with ether (3£50 mL). The combined organic
layers were washed with 10% Na2S2O3 (50 mL), water
(50 mL), brine (50 mL), dried over MgSO4 and the solvents
were removed in vacuo. The residue was puri®ed by column
chromatography on silica gel using 97:3 petroleum ether±
AcOEt as the eluent, affording the title compound as a
colourless oil (0.019 g, 91%, (E,E)/(E,Z)ˆ1/1). IR (neat)
nmaxˆ2957, 2831, 1550, 1449, 1131, 1021, 742 cm21. MS
Â
5. Marko, I. E.; Murphy, F.; Dolan, S. Tetrahedron Lett. 1996,
37, 2089.
6. See for example, Roush, W. R. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 5, pp 513.
7. (a) Kocienski, P. J.; Lythgoe, B. J. Chem. Soc., Perkin Trans. I
1979, 1290. (b) Guthrie, A. E.; Semple, J. E.; Joullie, M. M.
J. Org. Chem. 1982, 47, 2369. (c) Nemoto, H.; Suzuki, K.;
Tsubuki, M.; Fukumoto, K.; Kametani, T.; Furuyama, H.
Tetrahedron 1983, 39, 1123. (d) Barrett, A. G. M.; Carr,
R. A. E.; Attwood, S. V.; Richardson, G.; Walshe, N. D. A.
J. Org. Chem. 1986, 51, 4840. (e) Hanessian, S.; Ugolini, A.;
Â
Â
Dube, D.; Hodges, P. J.; Andre, C. J. Am. Chem. Soc. 1986,
108, 2776. (f) Villalobos, A.; Danishefsky, S. J. J. Org. Chem.
1989, 54, 12.
1
(CI) m/zˆ251, 233, 159, 131, 108, 91. H NMR (CDCl3,
8. For excellent reviews, see: (a) Heathcock, C. H. Aldrichim.
Acta 1990, 23, 99. (b) Hoffmann, R. W. Angew. Chem., Int.
Ed. Engl. 1987, 26, 488.
270 MHz) Compound 38, dHˆ1.7 (3H, s), 4.82 (2H, s), 6.19
(1H, s), 6.25 (1H, d, Jˆ12.7 Hz), 6.78 (1H, d, Jˆ13.2 Hz),
7.2±7.5 (10H, m). Compound 39, dHˆ1.7 (3H, s), 4.87 (2H,
s), 5.89 (1H, d, Jˆ12.7 Hz), 6.36 (1H, s), 6.73 (1H, d,
Jˆ13.2 Hz), 7.2±7.5 (10H, m).
9. For excellent reviews, see: (a) Kagan, H. B.; Sasaki, M.;
Collin, J. Pure Appl. Chem. 1988, 60, 1725. (b) Molander,
G. A. Chem. Rev. 1992, 92, 29. (c) Krief, A.; Laval, A.-M.
Chem. Rev. 1999, 99, 745.
10. Kende, A. S.; Mendoza, J. S. Tetrahedron Lett. 1990, 31,
7105.
Acknowledgements
11. (a) Inanaga, J.; Ishikawa, M.; Yamaguchi, M. Chem. Lett.
1987, 1485. (b) Ujikawa, O.; Inanaga, J.; Yamaguchi, M.
Tetrahedron Lett. 1989, 30, 2387. (c) Shabangi, M.; Flowers,
Â
Financial support of this work by the Universite catholique
de Louvain, Glaxo-Wellcome (studentship to F. M.), the

Â
I. E. Marko et al. / Tetrahedron 57 (2001) 2609±2619
2619
R. A. Tetrahedron Lett. 1997, 38, 1137. (d). Shabangi, M.;
Sealy, J. M.; Fuchs, J. R.; Flowers, R. A. Tetrahedron Lett.
1998, 39, 4429.
reduction by SmI2, affording the corresponding anion. We
have not been able so far to distinguish between these two
reaction pathways.
18. Takaki, K.; Kusudo, T.; Uebori, S.; Nishiyama, T.; Kamada,
T.; Yokoyama, M.; Takehira, K.; Makioka, Y.; Fujiwara, Y.
J. Org. Chem. 1998, 43, 9265.
12. De Haan, J. W.; van de Ven, L. J. M. Org. Magn. Reson. 1973,
5, 147.
13. Fukumoto, K.; Ihara, M.; Suzuki, S.; Taniguchi, T.; Tokunaga,
Y. Synlett 1994, 895.
19. Takeda, T.; Sasaki, R.; Fujiwara, T. J. Org. Chem. 1998, 63,
7286±7288.
14. Keck, G. E.; Savin, K. A.; Weglarz, M. A. J. Org. Chem. 1995,
60, 3194.
21. (a) Buss, A. D.; Greeves, N.; Mason, R.; Warren, S. J. J. Chem.
Soc., Perkin Trans. I 1987, 2569±2577. (b) Buss, A.; Warren,
S. Tetrahedron Lett. 1983, 24, 111±114. (c) Reich, H. J.; Shah,
S. K.; Chow, F. J. Am. Chem. Soc. 1979, 101, 6648±6656.
(d) Canonne, P.; St.-Jean, R. Bull. Soc. Chim. Fr. 1971, 3052±
3057. (e) Watanabe, S.; Suga, K.; Fujita, T. Synthesis 1971,
375±377.
15. De Pouilly, P.; Chenede, A.; Mallet, J. M.; SinayÈ, P.
Tetrahedron Lett. 1992, 33, 8065.
16. In this context, it is interesting to note that reductive cleavage
of a benzoate group could be easily effected using SmI2 or
under electrochemical conditions, attesting to the greater
acceptor ability of the benzoyl function. Kuenzer, H.; Stahnke,
M.; Sauer, G.; Wiechert, R. Tetrahedron Lett. 1991, 32, 1949.
17. Another possibility that cannot be ruled out at this stage might
involve the direct elimination of a phenylsul®nyl radical from
intermediate 31 leading directly to alkene 8. The phenyl-
sul®nyl radical might then undergo a subsequent and rapid
21. (a) Harada, T.; Katsuhira, T.; Hara, D.; Kotani, Y.; Maejima,
K.; Kaji, R.; Oku, A. J. Org. Chem. 1993, 58, 4897±4907.
(b) Harada, T.; Hara, D.; Hattori, K.; Oku, A. Tetrahedron
Lett. 1988, 29, 3821±3824. (c) Johnson, C. R.; Elliott, R. C.
J. Am. Chem. Soc. 1982, 104, 7041±7044.