Sulfur dioxide mediated one-pot, four-component synthesis of polyfunctional sulfones and sulfonamides, including medium-ring cyclic derivatives

Article abstract of DOI:10.1016/j.tet.2005.08.067

In previous papers (Synthesis 2002, 232 and J. Org. Chem. 2004, 69, 6413), we have shown that the hetero-Diels-Alder addition of sulfur dioxide to 1-oxy or 1,3-dioxy-1,3-dienes generates zwitterions that add to enoxysilanes or allylsilanes giving silyl su

Full text of DOI:10.1016/j.tet.2005.08.067

Tetrahedron 61 (2005) 11473–11487
Sulfur dioxide mediated one-pot, four-component synthesis of
polyfunctional sulfones and sulfonamides, including medium-ring
cyclic derivatives
Laure C. Bouchez, Ma¯ris Turks, Srinivas Reddy Dubbaka, Freddy Fonquerne, Cotinica Craita,
*
Sylvain Laclef and Pierre Vogel
` ´ ´ ´
Laboratoire de glycochimie et de synthese asymetrique, Ecole Polytechnique Federale de Lausanne (EPFL),
BCH CH-1015 Lausanne, Switzerland
Received 1 July 2005; revised 11 August 2005; accepted 17 August 2005
Available online 19 September 2005
Abstract—In previous papers (Synthesis 2002, 232 and J. Org. Chem. 2004, 69, 6413), we have shown that the hetero-Diels–Alder addition
of sulfur dioxide to 1-oxy or 1,3-dioxy-1,3-dienes generates zwitterions that add to enoxysilanes or allylsilanes giving silyl sulfinates that can
be converted in the same pot into polyfunctional sulfones, sulfonamides or sulfonic esters. We are presenting further applications of this
method, including the synthesis of new medium-size heterocyclic systems of the type tetrahydro-2H-thiocines and hexahydro-1,2-thiazonine.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
hypoglycemic anti-thyroid, anti-hypertensive, anti-inflam-
matory, and antiviral properties.11,12 Recently, structurally
novel sulfonamide derivatives have shown substantial
antitumor activities,13,14 or are caspase-115 inhibitors.16
The majority of sulfonamides are prepared from the reaction
of sulfonyl chlorides with ammonia, primary or secondary
amines.17 Arenesulfonyl chlorides are prepared from arenes
by electrophilic substitution with ClSO3H or from arene-
sulfonic acids by reaction with PCl5,18 POCl319 or COCl2.20
Other methods imply the reactions of arenediazonium salts
with SO2/CuCl2,21 the oxidation of thioesters22 or sulfenyl
chlorides,23 or the reaction of organolithium24 or organo-
magnesium25 reagents with SO2Cl2 or SO2CCl2. Alkane-
sulfonyl chlorides can be obtained by reaction of the
corresponding alkane with SO2 and Cl2 under radical
conditions.26 All these methods27 are relatively harsh
(acidic, basic) and cannot be applied to polyfunctional
substrates. Recently, the direct synthesis of sulfonamides
and sulfonic esters from sulfonic acids28 and a one-pot
Organosulfones are important compounds1 because of their
chemical properties2 and biological properties.3 They are
important synthetic targets and are widely used synthons.4
The sulfone functional group is found in various drugs,
including the recently selective COX-2 inhibitor Vioxx.5
Sulfones have been shown also to inhibit HIV-1 reverse
transcriptase.6 Their preparation involves oxidation of the
corresponding sulfides and sulfoxides7a–d or displacement
reaction of sodium arenesulfinate with an appropriate alkyl
halides.7e,f Diaryl sulfones are prepared also through the
classical Friedel–Crafts sulfonylation using of arenesulfonyl
chlorides and arenes, and Lewis acids catalysts.7g,h
Recently, biaryl sulfones were derived from sulfinic acid
salts and aryl iodides using copper8 and palladium catalyst.9
In 2004, we10a and Bandgar1n have reported that diaryl
sulfones can be prepared through palladium-catalyzed
cross-coupling reactions between areneboronic acids and
arenesulfonyl chlorides.
synthesis of sulfonamides from Grignard reagents and
28,29
SO2 has been reported. Both procedures are amenable
to aromatic and heteroaromatic sulfonamides.
The sulfonamides constitute an important class of drugs (the
sulfa drugs), with several types of pharmacological agents
possessing antibacterial, anticarbonic anhydrase, diuretic
Enoxysilanes 1,30 allylsilanes 2,30 and allylstannanes 331
undergo ene-reactions with sulfur dioxide giving the
corresponding silyl or stannyl sulfinate intermediates 4
that react with Bu4NF and carbon electrophiles R3Y to
produce the corresponding sulfones 5 in one-pot operations
(Scheme 1).30 Chlorination (Cl2 or NCS) or bromination
Keywords: Ene reaction; Oxyallytion; Silyl sulfinates; Polyfunctional
sulfones; Polyfunctional sulfonamides; Thiocines; 1,2-Thiazonines.
Corresponding author. Tel.: C41 21 693 9371; fax: C41 21 693 9375;
e-mail: pierre.vogel@epfl.ch
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.067

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L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
addition of electrophile R3Y generates the corresponding
sulfones 13, thus, realizing a one-pot, four-component
method for the synthesis of polyfunctional sulfones.34,39
Chlorination or bromination of silyl sulfinates 12 provides
the corresponding sulfonyl chlorides or bromides that react
with primary or secondary amines in pyridine to produce the
corresponding polyfunctional sulfonamides 15.32,40 Using
enantiomerically enriched dienes 9 (R*Z1-arylethyl),
enantiomerically enriched sulfones 13 and sulfonamides
15 are obtained.
We present here new applications of our one-pot, four-
component synthesis of sulfones and sulfonamides.41 New
b,g-unsaturated sulfones have been obtained, including
cyclic derivatives resulting from intramolecular sulfinates
allylation. Furthermore, we have found that not only (Z)-
b,g-unsatured sulfones can be formed. Depending on the
nature of the enoxysilanes and 1-oxydienes and upon the
nature of the acid catalyst, the (E)-isomeric sulfones can
also be obtained. For the first time, intramolecular allylation
of sulfonamides have allowed to prepare hexahydro-1,2-
thiazonine derivatives, a new kind of medium-size
heterocyclic compounds.42
Scheme 1. One-pot, three-component synthesis of polyfunctional sulfones
5, sulfonamides 7 and sulfonic esters 8.
(Br2 or NBS) of silyl sulfinates 4 generate the corresponding
sulfonyl halides 6 that react in situ with primary or
secondary amines to produce the corresponding sulfona-
mides 7, or with alcohols to generate the corresponding
sulfonic esters 8 (Scheme 1).32
2. Results and discussion
2.1. Diastereoselectivity of the oxyallylations of
enoxysilanes
In our previous work34,38 we found that the d,3-syn versus
anti diastereoselectivity of the oxyallylations of (Z)-
enoxysilane 16a using (E,E)-1-oxy-2-methylpenta-1,3-
dienes never surpass 3:1 (product ratio 18/19, Scheme 3).
As we shall see, the diasteroselectivity varies with the nature
of the enoxysilane 16 and of the diene 17 and that it can be
increased to 9:1.
We have found a new C–C bond forming reaction
(Scheme 2),33–38 involving a cascade of reactions starting
with the hetero-Diels–Alder addition of sulfur dioxide to
1,3-dienyl ethers 9. This generates unstable sultines 10 that
are ionized in the presence of an acid promoter giving
zwitterionic species 11. In the presence of enoxysilanes 1 or
allylsilanes 2, the latter are quenched forming the
corresponding silyl sulfinates 12 with high diastereo-
selectivity. Desilylation of 12 with Bu4NF followed by
For instance, when a 2:1 mixture of enoxysilane 16b (RZp-
MeOC6H4) and diene 17b (RZBn) was reacted with an
excess of SO2 premixed with 0.2 equiv of Tf2NH (TfZ
trifluoromethanesulfonyl) or TfOSiR3 (RZMe, t-Bu) at
K78 8C for 12 h, a mixture of silyl sulfinates was obtained
that was quenched with 1 equiv of Bu4NF and 2.5 equiv of
methallyl bromide to give a 5:1 mixture of sulfonylketones
(G)-18b and (G)-19b from which the major isomer (G)-
18b was isolated pure in 76% yield (Table 1). Its structure
was not established unambigiously but it is proposed to be
similar (d,3-syn, a,d-unlike) to those of similar compounds
obtained under similar conditions.34,38
Under the same conditions, enoxysilane 16cC diene 17b
gave a 6:1 mixture of sulfonylketones (G)-18c and (G)-19c
from which (G)-18c could be isolated pure in 70% yield.
With enoxysilane 16d [(Z)-1,2-bis(trimethyl-silyloxy)but-1-
ene]43 and racemic diene (G)-17c a 3:1 mixture of (G)-18d
and (G)-19d (electrophile, EXZMeI) was obtained. Pure
(G)-19d could be isolated by flash column chromatography
on silica gel. The combination of more sterically bulky
diene 17d (R0ZSiMe2t-Bu) with enoxysilane 16c (RZ
2,4,6-(MeO)3–C6H2) resulted in enhanced 9:1 d,3-syn
versus anti diastereoselectivity (Table 1, entry 6).
Scheme 2. One-pot, four-component synthesis of polyfunctional sulfones
13 and sulfonamides 15.

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11475
Table 1. Synthesis of (Z)-b,g-unsaturated sulfones
Entry
Reactants
Products
Total yield
(%)
16
17
EX
A
Ratio
17a: R0ZSiMe3
17b: R0ZBn
1
2
16a: RZMe
16b: RZp-MeOC6H4
MeI
Tf2NTMS, 45% 18a:19aZ1:1a
72 [Ref. 38]
91
Tf2NH, 20%
18b:19bZ5:1
17b: R0ZBn
3
16c: RZ2,4,6-(MeO)3C6H2
Tf2NH, 20%
18c:19cZ6:1
90
17c: R0Z(RS)-2,4,6-(i-Pr)3C6H2(Me)CH
17a: R0ZSiMe3
4
5
16d: RZCH2OSiMe3
16c: RZ2,4,6-(MeO)3C6H2
MeI
Tf2NH, 20%
Tf2NH, 20%
18d:19dZ3:1
18e:19eZ6:1a
29
82
17d: R0ZSiMe2t-Bu
6
16c: RZ2,4,6-(MeO)3C6H2
Tf2NH, 20%
18f:19fZ9:1b
60
a Products 18a/19a and 18e/19e are obtained in their desilylated form where R0ZH.
b This represents the yield and ratio of 18f/19f after additional silylation of the crude reaction mixture. For more details see Section 4.
On increasing the amount of the protic acid promoter the
oxyallylation reaction produced mixtures of (Z)- and (E)-b,
g-unsatured sulfinates.38 For instance, when using 0.5 equiv
(instead of 0.1–0.2 equiv) of Tf2NH, the reaction of
enoxysilane 16a with diene 17a led to a mixture of (E)-
b,g-unsatured silyl sulfinates that reacted with Bu4NF and
Me2CHCH2I giving a 1:1 mixture of (E)-b,g-unsatured
sulfones (G)-20a and (G)-21a. When treated with TfOH in
THF, this mixture generated a single (E,E)-dienone (G)-22
demonstrating that the relating configuration for (G)-20a
and (G)-21a are d,3-syn, a,d-unlike and d,3-anti, a,d-
unlike, respectively, (Table 2).
However, the (E)- or (Z)-configurations of the alkene units
were confirmed by NOESY H NMR experiments.
1
2.2. Oxyallylation of allylsilanes
We had shown35 that the oxyallylation of allylsilanes 23
fails when reacting them with 1-oxy-1,3-dienes such as 17
and SO2 activated by a Lewis or protic acid. Nevertheless,
successful oxyallylation of allylsilanes could be realized
using 1,3-dioxy-1,3-dienes of type 24. As a new illustration
of the reaction, we report here that 2:1 mixture of allylsilane
23a with the enantiomerically enriched diene (K)-24a
(97% ee, derived from the inexpensive (1S)-1-phenyl-
ethanol)35 produces a single silyl sulfinate 25a, when treated
in anhyd CH2Cl2/SO2 premixed with 0.3 equiv of Tf2-
NSiMe3 (Scheme 3). After evaporation of SO2 and CH2Cl2
at K50–20 8C, the residue was treated with N-chloro-
succinimide (NCS) in acetonitrile at K30 8C. This produced
the corresponding sulfonyl chloride that was not isolated but
mixed with benzylamine (10 equiv) in pyridine at K40 8C.
Similarly, when enoxysilane 16c and diene 17d were treated
as above with 0.5 equiv of Tf2NH in an excess of SO2 at
K78 8C, a mixture of (E)-b,g-unsaturated sulfones (G)-
20b and (G)-21b was obtained. Flash chromatography of
this mixture allowed the obtainment of a 9:1 mixture of
(G)-20b and (G)-21b in 60% yield. The relative
configuration of these compounds was not established
unambiguously, it is proposed to be the same as that of
related compounds prepared under similar conditions.38
After 4 h at K20 8C, the formation of sulfonamides was
Table 2. Synthesis of (E)-b,g-unsaturated sulfones
Entry
Reactants
Products
16
17
EX
Ratio
Total yield (%)
82
17a: R0ZSiMe3
1
2
16a: RZMe
20a:21aZ1:1a
17d: R0ZSiMe2t-Bu
16c: RZ2,4,6-(MeO)3C6H2
20b:21bZ9:1b
60
a Products 20a/21a are obtained in their desilylated form where R0ZH.
b This represents the yield and ratio of 20b/21b after additional silylation of the crude reaction mixture. For more details see Section 4.

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L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
pure diene 24b (derived from (1R)-1(2,4,6-tri(isopropyl))-
phenylethanol: the Greene’s chiral auxiliary)46 in the
presence of SO2 and an acid promoter. For 2:1–1:3 mixtures
of 23c and 24b as major product only sulfone 28 (10:1
epimers at C(3)) was isolated in 65% yield, when the
reaction mixture was methylated with MeI/Bu4NF. Under
the conditions used, only one oxyallylation occurred and the
second allylsilane moiety in intermediate underwent
desilylation with Bu4NF. The relative configuration in 28
was not established unambiguously, but it is proposed to be
similar to that observed in related product proposed under
similar conditions.35 When the reaction mixture 23cC24b
was submitted to desilylation and desulfitation by retro-ene
reaction (triethylamonium trifluoromethanesulfonate buffer,
see Scheme 3), a 10:1 mixture of diastereomeric dienes 29a
and 29b was obtained. As the analogous retro-ene
eliminations have all shown high stereoselectivity in the
chirality transfer between centers C(10) and C(2) in the
corresponding diene, the 10:1 mixture of diastereomers
29aC29b is proposed to correspond to the like (100R, 3R) for
the major isomer 29a, and unlike (100R, 3S) for the minor
product 29b.
The reaction of a 2:1 mixture of allylsilane 23b and
enantiomerically enriched (ee 97%) diene (K)-24a in SO2/
toluene premixed with 0.3 equiv of Tf2NSiMe3 (K78 8C,
1
36 h) gave a single silyl sulfinate 25b (by H NMR of the
crude) that was oxidized with NCS to the corresponding
sulfonyl chloride that was not isolated but treated with an
excess of benzylamine in pyridine. Flash column chroma-
tography provided pure sulfonamides (K)-26b and (K)-
27b each in 35% yield (Scheme 3). Both compounds were
treated with 1 equiv of Cs2CO3 in anhyd DMF in the
presence of 0.1 equiv of (Ph3P)4Pd. After heating to 100 8C
for 40 min., the 1,2-thiazonin-8-yl benzoates (K)-30 (81%)
and (K)-31 (79%) were obtained. They resulted from
intramolecular N-allylation47 of the N-benzylsulfonamides
(Scheme 4). Except for the relative configuration between
the (1S)-phenylethyl group and the stereogenic centers C(6),
which was assumed to be the same as that observed for other
related systems obtained under similar conditions,35 the
Scheme 3. Oxyallylation of allysilanes and synthesis of sulfonamides and
sulfones.
over and, after flash column chromatography on silica gel,
isomeric N-benzylsulfonamides (K)-26a and (K)-27a were
isolated in 19 and 20% yield, respectively. Although the
sulfonamide formation reaction was carried out low
temperature, these results demonstrated that basicity of the
medium is sufficient to promote a complete epimerization
(K)-26a4(K)-27a. The structure of sulfonamide (K)-27a
was established by X-ray diffraction studies (Fig. 1). That of
(K)-26a was deduced from its spectral data and by
comparison with those collected for (K)-27a.
With the hope to carry out two successive oxyallylations on
disilyl system 23c45 we reacted it with the enantiomerically
Figure 1. Representation of the X-ray molecular structure of (K)-27a.44
Scheme 4. Synthesis of 1,2-thiazonin-8-yl derivatives.

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11477
3. Conclusion
Our one-pot, four-component syntheses of polyfunc-
tional sulfones and sulfonamides have been extended to
a large variety of 1,3-dienes, enoxysilanes and allyl-
silanes. In the case of sulfonamide formation, epimeri-
zation of the stereogenic a-center of the b,g-unsaturated
sulfonamides cannot be avoided in several instances.
For the first time new heterocyclic synthesis such as 2,
3,4,5,6,9-hexahydro-1,2-thiazonine derivatives have been
obtained. This was possible by intramolecular Pd-
catalyzed N-allylation reactions. In a similar way,
intramolecular S-allylation of intermediate silyl sulfinate
has allowed the preparation of a new tetrahydro-2H-
thiocine derivatives. Using enantiomerically enriched
1-oxy- or 1,3-dioxy-1,3-dienes enantiomerically enriched
polyfunctional sulfones and sulfonamides are prepared
readily.
Scheme 5. Synthesis of a 5,6,7,8-tetrahydro-2H-thiocines.
relative configuration 6,9-cis in (K)-30 and 6,9-trans in
(K)-31 was established by the 2D-1H NMR spectra and
especially by the NOESY spectra. Compounds (K)-30 and
(K)-31 are the first members of the 2,3,4,5,6,9-hexahydro-
1,2-thiazonine class of heterocycles.42
4. Experimental
We have also explored the possibility to generate 5,6,7,8-
tetrahydro-2H-thiocine derivatives by intramolecular
electrophilic quenching of our intermediate silyl sulfinates.
An example is given (Scheme 5) by the reaction of the
racemic silyl sulfinate 25c obtained by oxyallylation of
allylsilane 23b with diene (G)-24c. Its treatment with
2 equiv of Et3N and 0.1 equiv of (Ph3P)4Pd in THF provided
the cyclic sulfone (G)-32b, which was purified by column
chromatography on silica gel and isolated in 44% yield. Its
structure has been established by single crystal X-ray
diffraction studies (Fig. 2). The same reaction sequence has
been applied to the enantiomerically enriched (97% ee)
diene (C)-24a35,37 (Scheme 5), which produced (C)-32a
through 25b in 41% overall yield. As for other related
systems obtained under similar conditions35 the relative
configuration between C(100) of the 1-phenylethyl group
(chiral auxiliary) and the adjacent stereogenic center C(3) in
the open chain system 25b is assumed to be like. Moreover,
NMR data proved the unlike relative configuration between
C(5) and C(2) in the thiocine structure (C)-32a.
4.1. General remarks
Reagents were purchased from Acros, Fluka, Senn, Aldrich
or Merk and used without further purification. All solvents
for extraction and chromatography were distilled prior to
use. Anhyd THF, Et2O and toluene were distilled from
sodium benzophenone, CH2Cl2 from CaH2, and methanol
from magnesium. Reactions were monitored by TLC (Merk
Kiesegel 60F254) silica gel plates; detection with UV
(254 nm) light or molybdic reagent (21 g of (NH4)6-
Mo7O24$4H2O, 1 g of Ce(SO4)2, 31 mL H2SO4 and
470 mL of H2O). Flash chromatography (FC) used 230–
400 mesh silica gel (Merk no.9385). Melting points were
measured with a Mettler FP52 and were uncorrected.
Optical rotations were measured with a JASCO DIP-370
digital polarimeter. UV spectra were recorded on a Kontron
Uvikon 810 CW spectrophotometer. IR spectra were
recorded on Perkin Elmer Paragon 1000 FT-IR
spectrometer. Mass spectra were recorded on a Nermag R
10-10C in chemical ionisation mode. Electron spray mass
analyses were recorded on a Finnigan MAT SSQ 710C
spectrometer in positive ionisation mode.1H NMR spectra
were recorded on Bruker DPX-400 FT, Bruker ARX-400
FT spectrometers. 13C NMR spectra were recorded on
Bruker DPX-400 FT (100.61 MHz), Bruker ARX-400 FT
(100.61 MHz) machines; all 13C signal assignments were
confirmed by HMQC spectra. Chemical shifts in ppm,
relative to internal standard such as residual signals of
solvents, coupling constants in hertz. All structures and
signal assignments were confirmed by 2D-NOESY 1H NMR
and 2D-COSY 1H NMR spectra. Microanalyses were
performed by the Ilse Beetz Laboratory, Kronach
(Germany).
Starting materials 16a49 (risk of explosion in the preparation
of this compound!), 16b,50 16c,51 16d,43 17a,33b,51 17b,32,52
17c,34,39b 17d,53 24a,35–37 and 24c,35–37 were prepared
according to the literature procedures.
Figure 2. Molecular structure of (G)-32b by single crystal X-ray
diffraction.48

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L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
4.2. General procedure for the preparation of oxo-(Z)-b,
g-unsaturated sulfones 18, 19 using enoxysilanes
4.2.2. (G)-(2RS,3RS,4Z,6SR)-3-benzyloxy-6-[(2-methyl-
prop-2-en-yl)sulfonyl]-2,4-dimethyl-1-(2,4,6-trimethoxy-
phenyl)hept-4-en-1-one ((G)-18c). This preparation
followed the above general procedure using tri-
methyl{[(1E)-1-(2,4,6,-trimethoxyphenyl)prop-1-enyl]-
oxy}silane51 (16c, 3.5 g, 11.8 mmol, 2.8 equiv), (E,E)-1-
benzyloxy-penta-1,3-diene32 (17b, 800 mg, 4.2 mmol,
1 equiv) and 3-bromo-2-methylpropene (1.72 g, 1.3 mL,
12.8 mmol, 3 equiv). A 6:1 mixture of (G)-18c and (G)-
19c was obtained. FC (light petroleum ether/EtOAc 4:1,
RfZ0.27), gave 1.63 g (77%) of pure (G)-18c and 0.27 g
(13%) of (G)-19c, both yellowish oils. Data of 18c: UV
(CH3CN): lmaxZ214 nm (3Z19600). IR (film): n 2973,
2842, 1693, 1645, 1587, 1455, 1414, 1305, 1229, 1207,
Tf2NH (0.5 M in CH2Cl2, 1.35 mL, 0.68 mmol, 0.2 equiv)
in anhyd CH2Cl2 (2 mL) was degassed by freeze-thaw
cycles on the vacuum line. SO2 (5 mL, 114.0 mmol,
34 equiv), dried through a column packed with basic
alumina and phosphorus pentoxide, was transferred on the
vacuum line to the CH2Cl2 solution frozen at K196 8C. The
mixture was allowed to melt and to warm to K78 8C. After
1 h at this temperature a solution of 1,3-diene 17 (1 equiv)
and the enoxysilane 16 (2–5 equiv) in CH2Cl2 (3 mL) was
added slowly. The mixture was stirred at K78 8C for 12 h.
Excess of SO2 and solvent were evaporated under reduced
pressure (10K1 Torr) to dryness, while temperature was
rising to 25 8C in ca. 1 h. A 1 M solution of Bu4NF in THF
(1 equiv) and electrophile EX (2.5–7 equiv) were added
under Ar atmosphere. The mixture was stirred at K40 8C for
1 h, then allowed to reach 20 8C in about 10 h. After the
addition of H2O (40 mL) and neutralization with satd aq
soln of NaHCO3 (10 mL), the mixture was extracted with
CH2Cl2 (30 mL, three times). The combined organic
extracts were washed with brine (30 mL, two times), dried
(Na2SO4) and the solvent evaporated under reduced
pressure. The residue was purified by flash column
chromatography on silica gel (FC).
1
1158, 1130, 1068, 1029, 968, 914, 856 cmK1. H NMR
3
(400 MHz, CDCl3): d 7.39 (d, 2H, JZ7.7 Hz, H–C(ar)),
3
3
7.34 (t, 2H, JZ7.7 Hz, H–C(ar)), 7.28 (t, 1H, JZ7.7 Hz,
3
H–C(ar)), 6.10 (s, 2H, H–C(ar)), 5.42 (d, 1H, J(H5–H6)Z
9.6 Hz, H–C(5)), 5.27 (br s, 1H, H–C(30)), 5.15 (br s, 1H,
2
H–C(30)), 4.58 (d, 1H, JZ11.8 Hz, H–CH2–Bn), 4.55 (d,
1H, 3J(H3,H2)Z8.6 Hz, H–C(3)), 4.47 (dq, 1H, 3J(H6,H5)Z
9.6 Hz, 3J(H6,H7)Z6.7 Hz, H–C(6)), 4.42 (d, 1H, 2JZ
11.8 Hz, CH2–Bn), 3.84 (s, 3H, H–OMe), 3.76 (s, 6H,
H–OMe), 3.73 (d, 1H, 2JZ13.4 Hz, Ha–C(10)), 3.64 (d, 1H,
2JZ13.4 Hz, Hb–C(10)), 3.43 (dq, 1H, 3J(H2–H3)Z8.6 Hz,
3J(H2–Me2)Z7.1 Hz, H–C(2)), 2.02 (s, 3H, Me-C(4)), 1.85
(s, 3H, Me-C(20)), 1.49 (d, 3H, 3J(H7,H6)Z6.7 Hz, H–C(7)),
1.29 (d, 3H, 3J(Me, 2H)Z7.1 Hz, Me-C(2)). 13C NMR
(100.6 MHz, CDCl3): d 206.2 (s, CO), 163.1–158.9 and
139.3 (s, 5C(ar)), 143.1 (s, C(20)), 133.6 (s, C(4)), 128.1–
128.06 (d, 7C, 1J(C,H)Z149 Hz, C(ar)), 122.1 (t, 1J(C,H)Z
4.2.1. (G)-(2RS,3RS,4Z,6SR)-3-benzyloxy-1-(4-methoxy-
phenyl)-2,4-dimethyl-6-((2-methylprop-2-enyl)sulfonyl-
(-1-phenylhept-4-en-1-one ((G)-18b). This preparation
followed the above procedure and used (Z)-1-(4-methoxy-
phenyl)-1-trimethylsilyloxypropylene (16b)50 (2.09 g,
8.8 mmol) and (E,E)-1-benzyloxy-2-methyl-penta-1,3-
diene 17b32 (870 mg, 4.41 mmol) and 3-bromo-2-methyl-
propene (1.11 mL, 11.01 mmol). A 5:1 mixture of (G)-18b
and (G)-19b was obtained. FC (light petroleum ether/
EtOAc 8:2, RfZ0.30), gave 1.04 g (76%) of pure (G)-18b
as a colorless oil. IR (film): n 2975, 2935, 1670, 1405, 1375,
1
159 Hz, C(30)), 120.7 (d, J(C,H)Z152 Hz, C(5)), 79.9 (t,
1J(C,H)Z156 Hz, CH2–Bn), 71.1 (t,1J(C,H)Z148 Hz,
C(10)), 58.5 (d, 1J(C,H)Z132 Hz, C(3)), 57.4 (d,
1J(C,H)Z140 Hz, C(6)), 55.5 (q, 1J(C,H)Z138 Hz,
C(OMe)), 51.4 (d, 1J(C,H)Z128 Hz, C(2)), 23.5 (q,
1J(C,H)Z125 Hz, Me-C(20)), 19.4 (q, 1J(C,H)Z129 Hz,
Me-C(4)), 15.8 (q, 1J(C,H)Z134 Hz, C(7)), 14.6 (q,
1J(C,H)Z130 Hz, Me-C(2)). CI-MS (NH3): C29H38SO7,
m/z 548 (12, [MC18]C), 531 (100, [MC1]C), 225 (69).
MALDI-HRMS: calcd for C29H38SO7CNaC: 553.2236;
found: 553.2229.
1305, 1210, 1120, 1070, 970, 735 cmK1 1H NMR
.
3
(400 MHz, CDCl3): d 7.92 (d, 2H, JZ8.9 Hz, H–C(ar)),
7.51 (t, 2H, 3JZ8.8 Hz, H–C(ar)), 7.41 (d, 2H, 3JZ8.0 Hz,
3
H–C(ar)), 7.38 (t, 2H, JZ7.1 Hz, H–C(ar)), 7.30 (d, 1H,
3JZ7.5 Hz, H–C(ar)), 5.32 (br s, 1H, H–C(30)), 5.29 (d, 1H,
3J(H5,H6)Z10.7 Hz, H–C(5)), 5.18 (br s, 1H, H–C(30)),
4.63 (d, 1H, 2JZ11.8 Hz, H–CH2Bn), 4.54 (d, 1H,
3J(H3,H2)Z9.8 Hz, H–C(3)), 4.49 (d, 1H, 2JZ11.8 Hz,
4.2.3. (G)-(3RS,4RS,5Z,8SR)-1-hydroxy-3,5-dimethyl-7-
(methylsulfonyl)-4-{1-(RS)-[2,4,6-tris(isopropyl)phenyl]-
ethoxy}octa-5-en-2-one ((G)-18d). This compound was
prepared applying the above general procedure using (Z)-
1,2-bis(trimethylsilyloxy)but-1-ene (16d)43 (0.3 g,
1.28 mmol, 1.2 equiv), (G)-1,3,5-triisopropyl-2-{(R,S)-1-
[(E,E)-2-methylpenta-1,3-dien-1-yloxy]ethyl}benzene
(17c)34,39c (0.2 g, 0.64 mmol) and MeI (0.3 mL, 4.8 mmol).
A 3:1 mixture of (G)-18d and (G)-19d was obtained. FC
(light petroleum ether/AcOEt 2:1) gave 66 mg (23%) of
3
3
CH2Bn), 4.34 (dq, 2H, J(H6,H5)Z10.7 Hz, J(H6,H7)Z
6.6 Hz, H–C(2)) 3.89 (m, 1H, H–C(6)), 3.89 (s, 3H, OMe),
2
2
3.79 (d, 1H, JZ13.2 Hz, Hb–C(10)), 03.59 (d, 1H, JZ
13.2 Hz, Ha–C(10)), 2.03 (s, 3H, Me-C(2 )), 1.79 (s, 3H, Me-
C(4)), 1.39 (d, 6H, 3JZ6.6 Hz, Me-C(2) and Me-C(6)). 13
NMR (100.6 MHz, CDCl3): d 164.0 (s, CO), 133.2 (s,
C
C(20)), 129.8 (m, C(ar)), 126.3 (s, C(4)), 122.3 (t, 1J(C,H)Z
1
1
152 Hz, C(30)), 114.1 (d, J(C,H)Z160 Hz, C(5)), 78.7 (d,
pure (G)-18d, colorless oil. Data for (G)-18d: H NMR
1J(C,H)Z167 Hz, C(6)), 70.9 (t, J(C,H)Z158 Hz, CH2–
(CDCl3, 400 MHz): d 7.0–6.9 (m, 2H arom); 5.45 (d, 1H,
1
1
1
3
Bn), 58.1 (t, J(C,H)Z157 Hz, C(10)), 56.6 (q, J(C,H)Z
3J(H6,H7)Z11 Hz, H–C(6)); 4.98 (q, 1H, J(H1 –H2 )Z
6.7 Hz, H–C(10)); 4.43 (d, 1H, 3J(H4,H3)Z9.9 Hz, H–C(4));
4.35 (s, 1H, H1); 4.21 (dq, 1H, 3J(H7,H6)Z11 Hz,
3J(H7,H8)Z6.7 Hz, H–C(7)); 3.7, 3.09 (2 sept. 2H,
3J((CH3)2CH-Ar, (CH3)2CH-Ar)Z6.7 Hz, 2 (CH3)2CH-
Ar); 2.9 (s, 3H, –SO2CH3); 2.87 (m, 1H, (CH3)2CH-Ar);
0
0
1
125 Hz, OMe), 55.5 (d, J(C,H)Z168 Hz, C(3)), 43.5 (d,
1J(C,H)Z138 Hz, C(2)), 23.1 (q, 1J(C,H)Z126 Hz, Me-
C(4)), 18.6 (q, 1J(C,H)Z132 Hz, Me-C(6)), 16.3 (q,
1J(C,H)Z126 Hz, Me-C(20)), 15.5 (q, 1J(C,H)Z132 Hz,
Me-C(2)). CI-MS (NH3): m/z 392 (100, [MC18]C), 375
(57, [MC1]C). MALDI-HRMS: calcd for C27H34SO4C
NaC: 493.2025; found: 493.2019.
4
2.87 (m, 1H, H–C(3)); 1.91 (d, 3H, J(Me5–H6)Z1.3 Hz,
3
0
0
0
Me-C(5)); 1.52 (d, 3H, J(Me2 –H1 )Z6.7 Hz, Me(2 )); 1.43

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11479
(d, 3H, 3J(Me8,H7)Z6.7 Hz, Me-C(8)); 1.27–1.19 (m, 3H, 3
(CH3)2CH-Ar); 1.15 (d, 3H, 3J(Me3,H3)Z6.7 Hz, Me-
C(3)). 13C NMR (CDCl3, 100.61 MHz): d 211.9 148.0,
147.5, 145.8, 141.6, 135.0, 123.1, 120.4, 121.8, 84.6, 73.7,
68.0, 58.2, 46.7, 36.8, 34.0, 29.6, 29.2, 24.99, 24.56, 24.05,
23.9, 21.4, 14.5, 14.2, 10.46. CI-MS (NH3): 512 (36, [MC
18]C), 479 (6), 231 (100), 189 (3), 167 (8.29), 141 (17), 84
(26).
trimethyl{[(1E)-1-(2,4,6,-trimethoxyphenyl)prop-1-enyl]-
oxy}silane (1.7 g, 5.8 mmol, 1.7 equiv) in CH2Cl2 (3 mL).
The reaction mixture was quenched with a 1 M solution of
Bu4NF in THF (3.41 mL, 3.41 mmol, 1 equiv) and
3-bromo-2-methylpropene (1.15 g, 0.86 mL, 8.52 mmol,
2.5 equiv) in CH2Cl2 (5 mL). Then 2,6-lutidine (1.82 g,
1.97 mL, 17.05 mmol, 5 equiv) followed by TBSOTf
(2.69 g, 2.35 mL, 10.23 mmol, 3 equiv) were added to the
resulting residue stirred at K78 8C (1.49 g, 3.41 mmol,
1 equiv) in anhyd CH2Cl2 (10 mL). After 2 h at K78 8C, the
crude reaction mixture was allowed to warm to room
temperature within 1 h. The mixture was then treated with
2 M aqueous solution of NaOH (2 mL) and extracted with
CH2Cl2 (40 mL, three times). The combined organic
extracts were washed with 1 M HCl (20 mL) and with
brine (40 mL, twice), dried (Na2SO4) and the solvent
eliminated under reduced pressure. Crude reaction mixture
contains (G)-18f and (G)-19f with the ratio 9:1. FC (light
petroleum ether/EtOAc 4:2, RfZ0.30) gives 1.14 g (60%)
of a 9:1 mixture of (G)-18f and (G)-19f as a yellow oil.
Both diastereoisomers can be analyzed from the specta of
the mixture. UV (CH3CN): lmaxZ209 nm (3Z7924). IR
(film): n 2987, 1694, 1606, 1456, 1421, 1305, 1266, 1157,
1132, 898, 740 cmK1. 1H NMR (400 MHz, CDCl3) of (G)-
4.2.4. 6:1 Mixture of (G)-(2RS,3RS,4Z,6SR)-3-hydroxy-
6-[(3-hydroxy-2-methylpropen-2-yl)sulfonyl]-2,4-
dimethyl-1-(2,4,6-trimethoxyphenyl)hept-4-en-1-one
(G)-18e and (G)-(2RS,3SR,4Z,6RS)-3-hydroxy-6-[(3-
hydroxy-2-methylpropen-2-yl)sulfonyl]-2,4-dimethyl-1-
(2,4,6-trimethoxyphenyl)hept-4-en-1-one (G)-19e. This
preparation followed the above general procedure using
(E,E)-2-methyl-1-trimethylsilyloxy-1,3-pentadiene
(580 mg, 3.41 mmol, 1 equiv) and trimethyl{[(1E)-1-
(2,4,6,-trimethoxyphenyl)prop-1-enyl]oxy}silane (1.7 g,
5.8 mmol, 1.7 equiv). The reaction mixture was quenched
with a 1 M solution of Bu4NF in THF (3.41 mL, 3.41 mmol,
1 equiv) and 3-bromo-2-methylpropene (1.15 g, 0.86 mL,
8.52 mmol, 2.5 equiv) in CH2Cl2 (5 mL). Crude reaction
mixture contains (G)-18e and (G)-19e with the ratio 6:1.
FC (light petroleum ether/EtOAc 1:1, RfZ0.33) gives
0.95 g (82%) of 6:1 mixture of (G)-18e and (G)-19e as a
yellowish oil. Only (G)-18e can be analyzed from the
spectra of the mixture. UV (CH3CN): lmaxZ224 nm (3Z
13737), 200.6 (9177). IR (film): n 3410, 2980, 2940, 2840,
1670, 1605, 1455, 1415, 1300, 1205, 1160, 1000, 900,
735 cmK1. 1H NMR (400 MHz, CDCl3) of (G)-18e: d 6.12
(s, 2H, H–C(ar)), 5.26 (br s, 1H, H–C(30)), 5.18 (d, 1H,
3J(H5–H6)Z9.6 Hz, H–C(5)), 5.11 (br s, 1H, H–C(30)), 4.80
3
18f: d 6.09 (s, 2H, Har), 5.54 (d, 1H, J(H5–H6)Z10.5 Hz,
H–C(5)), 5.26 (br s, 1H, H–C(30)), 5.05 (br s, 1H, H–C(30)),
3
4.58 (d, 1H, J(H3–H2)Z6.2 Hz, H–C(3)), 3.92 (dq, 1H,
3J(H6–H5)Z10.5 Hz, 3J(H6–H7)Z7.1 Hz, H–C(6)), 3.82 (s,
3H, H–OMe), 3.77 (s, 6H, H–OMe), 3.59 (d, 1H, 2JZ
2
12.1 Hz, Ha–C(10)), 3.57 (d, 1H, JZ12.1 Hz, Hb–C(10)),
3.2 (qd, 1H, 3J(H2–Me2)Z7.4 Hz, 3J(H2–H3)Z6.2 Hz,
H–C(2)), 1.97 (s, 3H, Me-C(4)), 1.73 (s, 3H, Me-C(20)),
1.42 (d, 3H, 3J(H7–H6)Z7.1 Hz, H–C(7)), 1.11 (d, 3H,
3J(Me2–H2)Z7.4 Hz, Me-C(2)). 13C NMR (100.6 MHz,
CDCl3) of (G)-18f: d 209.2 (s, CO), 162.3–158.4 (s, 4C,
C(ar)), 144.4 (s, C(20)), 133.1 (s, C(4)), 120.4 (t, 1J(C,H)Z
149 Hz, C(30)), 117.9 (d, 1J(C,H)Z161 Hz, C(5)), 90.6 and
90.5 (d, 2C, 1J(C,H)Z161 Hz, C(ar)), 70.4 (t,1J(C,H)Z
3
3
(d, 1H, J(H3–H2)Z7.0 Hz, H–C(3)), 4.43 (dq, 1H, J(H6–
H5)Z9.6 Hz, 3J(H6–H7)Z7.0 Hz, H–C(6)), 3.83 (s, 3H,
2
H–OMe), 3.79 (s, 6H, H–OMe), 3.71 (d, 1H, JZ13.4 Hz,
2
Ha–C(10)), 3.64 (d, 1H, JZ13.4 Hz, Hb–C(10)), 3.28 (qd,
3
1H, J(H2–Me2)Z(H2–H3)Z7.0 Hz, H–C(2)), 2.73 (br s,
1
1H, H–OH)), 1.98 (s, 3H, Me-C(4)), 1.84 (s, 3H, Me-C(20)),
1.49 (d, 3H, 3J(H7–H6)Z7.0 Hz, H–C(7)), 1.23 (d, 3H,
3J(Me2–H2)Z7.1 Hz, Me-C(2)). 13C NMR (100.6 MHz,
CDCl3) of (G)-18e: d 206.0 (s, CO), 162.6–158.4 (s, 4Car),
145.4 (s, C(20)), 133.2 (s, C(4)), 122.8 (t, 1J(C,H)Z162 Hz,
C(30)), 119.4 (d, 1J(C,H)Z159 Hz, C(5)), 90.8 and 90.6 (d,
2C, 0 1J(C,H)Z159 Hz, C(ar)), 70.8 (t, 1J(C,H)Z144 Hz,
C(1 )), 58.1 (d, 1J(C,H)Z134 Hz, C(3)), 55.9 (d, 1J(C,H)Z
140, Hz C(6)), 55.6 (q, 1J(C,H)Z145 Hz, C(OMe)), 51.1 (d,
1J(C,H)Z131 Hz, C(2)), 23.1 (q, 1J(C,H)Z129 Hz, Me-
C(20)), 19.2 (q, 1J(C,H)Z130 Hz, Me-C(4)), 14.7 (q,
1J(C,H)Z131 Hz, C(7)), 12.4 (q, 1J(C,H)Z130 Hz, Me-
C(2)). CI-MS (NH3): C22H32O7S: m/z 441 (62, [MC1]C),
225 (100). Anal. Calcd for C28H50O3Si2 (440.19): C, 59.98;
H, 7.32. Found: C, 59.83; H, 7.29.
154 Hz, C(10)), 58.1 (d, J(C,H)Z148 Hz, C(3)), 56.9 (d,
1J(C,H)Z133 Hz, C(6)), 55.6 (q, 1J(C,H)Z151 Hz,
C(OMe)), 51.6 (d, 1J(C,H)Z146 Hz, C(2)), 25.8 (q,
1J(C,H)Z142 Hz, t-Bu), 23.1 (q, 1J(C,H)Z133 Hz, Me-
C(20)), 18.3 (q, 1J(C,H)Z132 Hz, Me-C(4)), 15.1 (s, Cquat-
tBu)), 14.6 (q, 1J(C,H)Z131 Hz, Me-C(6)), 12.6 (q,
1J(C,H)Z139 Hz, Me-C(2)), K4.2 (q, 1J(C,H)Z127 Hz,
Me2Si–C(3)), K5.0 (q, 1J(C,H)Z129 Hz, Me2Si–C(3)). 1H
NMR (400 MHz, CDCl3) of (G)-19f: d 6.09 (s, 2H,
H–C(ar)), 5.54 (d, 1H, 3J(H5–H6)Z10.5 Hz, H–C(5)),
5.21 (br s, 1H, H–C(30)), 5.14 (br s, 1H, H–C(30)), 4.80
3
3
(d, 1H, J(H3–H2)Z7.6 Hz, H–C(3)), 4.4 (qd, 1H, J(H6–
3
H5)Z10.5 Hz, J(H6–H7)Z6.5 Hz, H–C(6)), 3.82 (s, 3H,
2
H–OMe), 3.77 (s, 6H, H–OMe), 3.56 (d, 1H, JZ12.7 Hz,
H–C(10)), 3.54 (d, 1H, 2JZ12.7 Hz, H–C(10)), 3.2 (dq, 1H,
3J(H2–Me2)Z7.4 Hz, 3J(H2–H3)Z6.5 Hz, H–C(2)), 2.01 (s,
3
3H, Me-C(4)), 1.82 (s, 3H, Me-C(20)), 1.37 (d, 3H, J(H7–
4.2.5. 9:1 Mixture of (G)-(2RS,3RS,4E,6RS)-3-{[(tert-
butyl)dimethylsilyl]oxy}-6-[(2-methylprop-2-enyl) sul-
fonyl]-2,4-dimethyl-1-(2,4,6-trimethoxyphenyl)hept-4-
en-1-one ((G)-18f) and (G)-(2RS,3RS,4E,6SR)-3-{[(tert-
butyl)dimethylsilyl]oxy}-6-[(2-methylprop-2-enyl) sul-
fonyl]-2,4-dimethyl-1-(2,4,6-trimethoxyphenyl)hept-4-
en-1-one ((G)-19f). This preparation followed the above
general procedure using from (E,E)-2-methyl-1-trimethyl-
silyloxy-1,3-pentadiene (580 mg, 3.41 mmol, 1 equiv) and
3
H6)Z6.5 Hz, H–C(7)), 1.11 (d, 3H, J(Me2–H2)Z7.4 Hz,
Me-C(2)). 13C NMR (100.6 MHz, CDCl3) of (G)-19f: d
209.1 (s, CO), 162.3–158.4 (s, 4C, C(ar)), 145.6 (s, C(20)),
133.3 (s, C(4)) 120.6 (t, 1J(C,H)Z146 Hz, C(30)), 117.9 (d,
1J(C,H)Z161 Hz, C(5)), 90.6 and 90.5 (d, 2C, J(C,H)Z
1
161 Hz, C(ar)), 70.4 (t,1J(C,H)Z154 Hz, C(20)), 57.6
(d, 1J(C,H)Z143 Hz, C(3)), 56.7 (d, 1J(C,H)Z131 Hz,
C(6)), 55.6 (q, 1J(C,H)Z151 Hz, C(OMe)), 53.4 (d,

11480
L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
1
1J(C,H)Z139 Hz, C(2)), 25.8 (q, J(C,H)Z142 Hz, t-Bu),
C(4)), 56.7 (t, 1J(C,H)Z132 Hz, C(10)), 49.1 (d, 1J(C,H)Z
1
1
1
23.2 (q, J(C,H)Z130 Hz, Me-C(20)), 18.2 (q, J(C,H)Z
140 Hz, C(20)), 29.3 (q, J(C,H)Z133 Hz, C(1)), 23.4 (q,
129 Hz, Me-C(4)), 15.4 (q, 1J(C,H)Z128 Hz, Me-C(6)),
1J(C,H)Z133 Hz, Me-C(5)), 23.2 (q, 1J(C,H)Z136 Hz,
C(8)), 14.9 (q, 1J(C,H)Z132 Hz, Me-C(3)), 10.7 (q,
1
15.0 (s, Cquat-tBu), 13.8 (q, J(C,H)Z132 Hz, Me-C(2)),
K4.7 (q, 1J(C,H)Z126 Hz, MeSi–C(3)), K5.3 (q,
1J(C,H)Z129 Hz, C(30)), 9.8 (q, J(C,H)Z130 Hz, C(30)).
1
1J(C,H)Z129 Hz,
MeSi–C(3)).
CI-MS
(NH3):
MALDI-HRMS: calcd for C14H26O4SCKC: 329.1189 and
C14H26O4SCNaC: 313.1449, found: 313.2285. Anal. Calcd
for C14H26O4S (290.16): C, 57.90; H, 9.02. Found: C, 57.86;
H, 9.02.
C28H46SSiO7, m/z 555 (25, [MC1]C), 108 (100). Anal.
Calcd for C28H46O7SSi (554.27): C, 60.62; H, 8.36. Found:
C, 60.80; H, 8.49.
4.3. General procedure for the preparation of oxo-(E)-b,
g-unsaturated sulfones (20,21) using enoxysilanes
4.3.2. 9:1 Mixture of (G)-(2RS,3RS,4E,6RS)-3-{[(tert-
butyl)dimethylsilyl]oxy}-6-[(2-methylprop-2-enyl) sul-
fonyl]-2,4-dimethyl-1-(2,4,6-trimethoxyphenyl)hept-4-
en-1-one ((G)-20b) and (G)-(2RS,3RS,4E,6SR)-3-{[(tert-
butyl)dimethylsilyl]oxy}-6-[(2-methylprop-2-enyl) sul-
fonyl]-2,4-dimethyl-1-(2,4,6-trimethoxyphenyl)hept-4-
en-1-one ((G)-21b). This preparation followed the above
general procedure and used 16c49 (1.7 g, 5.8 mmol,
1.7 equiv), (E,E)-2-methyl-1-[(tert-butyl)dimethylsilyl]-
oxy-penta-1,3-diene 17d33b,51 (580 mg, 3.41 mmol,
1 equiv) and 3-bromo-2-methylpropene (1.15 g, 0.86 mL,
8.52 mmol, 2.5 equiv) in CH2Cl2 (5 mL). This provided a
mixture of alcohols that was treated with 2,6-lutidine
(1.82 g, 1.97 mL, 17.05 mmol, 5 equiv) and by TBSOTf
(2.7 g, 2.35 mL, 10.23 mmol, 3 equiv) at K78 8C (1.49 g,
3.41 mmol, 1 equiv) in anhyd CH2Cl2 (10 mL). for 1 h. The
mixture was then treated with 2 M aq soln of NaOH (2 mL)
and extracted with CH2Cl2 (40 mL, three times). The
combined organic extracts were washed with 1 M HCl
(20 mL) and with brine (40 mL, twice), dried (Na2SO4) and
the solvent was eliminated under reduced pressure. The
residue contained a,b-syn and a,b-anti diastereoisomers
(G)-20c and (G)-21c with the ratio 9:1. FC (light
petroleum ether/EtOAc 4:2, RfZ0.30) gave 1.14 g (60%)
of a 9:1 mixture of (G)-20c and (G)-21c, yellow oil. UV
(CH3CN): lmaxZ209 nm (3Z7924). IR (film): n 2987,
1694, 1606, 1456, 1421, 1305, 1265, 1155, 1130, 900,
740 cmK1. 1H NMR (400 MHz, CDCl3) of (G)-20c: d 6.09
Same procedure for the preparation of 18, 19, but using
0.5 equiv of Tf2NH introduced to the SO2CCH2Cl2
solution as a 0.5 M solution in anhyd CH2Cl2.
4.3.1. 1:1 Mixture of (G)-(3RS,4RS,5E,7RS)-4-hydroxy-
7-(2-methyl-propyl-1-sulfonyl)-3,5-dimethyloct-5-en-2-
one and ((G)-20a) (G)-(3RS,4SR,5E,7SR)-4-hydroxy-7-
(2-methyl-propyl-1-sulfonyl)-3,5-dimethyloct-5-en-2-
one ((G)-21a). This preparation applies the above
procedure using a 1:1 mixture of (E) and (Z)- 2-triethyl-
silyloxybut-2-ene (7.92 g, 43 mmol, 2 equiv), (E,E)-2-
methyl-1-trimethylsilyloxypenta-1,3-diene (4 g, 21.25
mmol, 1 equiv) and 1-iodo-2-methylpropane (4.84 g,
26.3 mmol, 5 equiv) in CH3CN (15 mL) DMF (55 mL).
FC (light petroleum ether/EtOAc 7:3, RfZ0.31) gave 6.7 g
(82%), colorless oil. UV (CH3CN): lZ219 nm (3Z5800).
IR (film, cmK1): n 3470, 2970, 2930, 2855, 1710, 1650,
1460, 1340, 1285, 1195, 1135, 1040, 740. 1H NMR
(400 MHz, CDCl3, 283 K) of (G)-20a: d 5.58 (d, 1H,
3J(H6,H7)Z10.3 Hz, H–C(6)), 4.46 (m, 2H, H–C(4)), 3.87
(dq, 1H, 3J(H7,H6)Z10.3 Hz, 3J(H7,H8)Z7.1 Hz, H–C(7)),
3
3.15 (d, 1H, J(H4,OH)Z2.6 Hz, H–OH), 2.77 (m, 3H, H–
3
3
0
0
0
0
C(1 ), H–C(3)), 2.41 (tqq, 1H, J(H2 ,H1 )Z6.4 Hz, J(H2 ,-
3
H3 a)Z6.4 Hz, J(H2 ,H3 b)Z6.4 Hz, H–C(20)), 2.26 (s, 3H,
0
0
0
3
H–C(1)), 1.87 (s, 3H, Me-C(5)), 1.50 (d, 3H, J(H8,H7)Z
7.1 Hz, H–C(8)), 1.16 (d, 3H, 3J(Me3,H3)Z6.4 Hz, Me-
(s, 2H, Har), 5.54 (d, 1H, J(H5,H6)Z10.5 Hz, H–C(5)),
3
3
0
C(3)), 1.15 (d, 3H, J(H3 ,H2 )Z6.4 Hz, H–C(3 )), 1.13 (d,
5.26 (br s, 1H, H–C(30)), 5.05 (br s, 1H, H–C(30)), 4.58 (d,
1H, 3J(H3,H2)Z6.2 Hz, H–C(3)), 3.92 (dq, 1H, 3J(H6,H5)Z
10.5 Hz, 3J(H6,H7)Z7.1 Hz, H–C(6)), 3.82 (s, 3H,
0
0
3H, J(H3 ,H2 )Z6.4 Hz, H–C(3 )). 13C NMR (100 MHz,
CDCl3, 283K) of (G)-20a: d 211.2 (s, C(2)), 142.7 (s, C(5)),
121.1 (d, 1J(C,H)Z155 Hz, C(6)), 75.2 (d, 1J(C,H)Z
3
0
0
0
2
H–OMe), 3.77 (s, 6H, H–OMe), 3.59 (d, 1H, JZ12.1 Hz,
1
2
140 Hz, C(7)), 64.1 (d, J(C,H)Z130 Hz, C(3)), 58.9 (d,
Ha–C(10)), 3.57 (d, 1H, JZ12.1 Hz, Hb–C(10)), 3.2 (qd,
1J(C,H)Z142 Hz, C(4)), 56.9 (t, J(C,H)Z136 Hz, C(10)),
1H, 3J(H2,Me2)Z7.4 Hz, 3J(H2,H3)Z6.2 Hz, H–C(2)), 1.97
(s, 3H, Me-C(4)), 1.73 (s, 3H, Me-C(20)), 1.42 (d, 3H,
3J(H7,H6)Z7.1 Hz, H–C(7)), 1.11 (d, 3H, 3J(Me2,H2)Z
7.4 Hz, Me-C(2)). 13C NMR (100.6 MHz, CDCl3) of (G)-
20c: d 209.2 (s, CO), 162.3–158.4 (s, 4C, C(ar)), 144.4 (s,
1
49.5 (d, J(C,H)Z135 Hz, C(20)), 29.4 (q, 1J(C,H)Z
1
1
129 Hz, C(1)), 23.5 (q, J(C,H)Z140 Hz, Me-C(5)), 23.3
(q, 1J(C,H)Z134 Hz, C(8)), 15.3 (q, 1J(C,H)Z131 Hz, Me-
C(3)), 14.2 (q, 1J(C,H)Z132 Hz, C(30)), 14.1 (q, 1J(C,H)Z
133 Hz, C(30)). 1H NMR (400 MHz, CDCl3, 283 K) of (G)-
21a: d 5.57 (d, 1H, 3J(H6,H7)Z10.3 Hz, H–C(6)), 4.46 (m,
2H, H–C(4)), 3.86 (dq, 1H, 3J(H7,H6)Z10.3 Hz,
3J(H7,H8)Z7.1 Hz, H–C(7)), 3.08 (d, 1H, 3J(H4,OH)Z
2.6 Hz, H–OH), 2.77 (m, 3H, H–C(10), H–C(3)), 2.41 (tqq,
1
C(20)), 133.1 (s, C(4)), 120.4 (t, J(C,H)Z149 Hz, C(30)),
1
117.9 (d, J(C,H)Z161 Hz, C(5)), 90.6 and 90.5 (d, 2C,
1J(C,H)Z161 Hz, C(ar)), 70.4 (t, 1J(C,H)Z154 Hz, C(10)),
58.1 (d, 1J(C,H)Z148 Hz, C(3)), 56.9 (d, 1J(C,H)Z133 Hz,
C(6)), 55.6 (q, 1J(C,H)Z151 Hz, C(OMe)), 51.6 (d,
3
3
3
1
1H, J(H2 ,H1 )Z6.4 Hz, J(H2 ,H3 a)Z6.4 Hz, J(H2 ,-
1J(C,H)Z146 Hz, C(2)), 25.8 (q, J(C,H)Z142 Hz, t-Bu),
0
0
0
0
0
1
1
H3 b)Z6.4 Hz, H–C(20)), 2.24 (s, 3H, H–C(1)), 1.86 (s,
23.1 (q, J(C,H)Z133 Hz, Me-C(20)), 18.3 (q, J(C,H)Z
132 Hz, Me-C(4)), 15.1 (s, Cquat-tBu)), 14.6 (q, 1J(C,H)Z
131 Hz, Me-C(6)), 12.6 (q, 1J(C,H)Z139 Hz, Me-C(2)),
K4.2 (q, 1J(C,H)Z127 Hz, Me2Si–C(3)), K5.0 (q,
1J(C,H)Z129 Hz, Me2Si–C(3)). 1H NMR (400 MHz,
CDCl3) of (G)-21c: d 6.09 (s, 2H, H–C(ar)), 5.54 (d, 1H,
3J(H5,H6)Z10.5 Hz, H–C(5)), 5.21 (br s, 1H, H–C(30)),
0
3
3H, Me-C(5)), 1.48 (d, 3H, J(H8,H7)Z7.1 Hz, H–C(8)),
3
1.16 (d, 3H, J(Me,H3)Z6.4 Hz, Me-C(3)), 1.15 (d, 3H,
3
3
0
0
0
0
0
J(H3 ,H2 )Z6.4 Hz, H–C(3 )), 1.13 (d, 3H, J(H3 ,H2 )Z
6.4 Hz, H–C(30)). 13C NMR (100 MHz, CDCl3, 283K) of
(G)-21a: d 211.1 (s, C(2)), 142.2 (s, C(5)), 119.5 (d,
1J(C,H)Z150 Hz, C(6)), 74.3 (d, J(C,H)Z148 Hz, C(7)),
1
63.9 (d, 1J(C,H)Z130 Hz, C(3)), 58.5 (d, 1J(C,H)Z141 Hz,
5.14 (br s, 1H, H–C(30)), 4.80 (d, 1H, J(H3,H2)Z7.6 Hz,
3

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11481
H–C(3)), 4.4 (qd, 1H, 3J(H6,H5)Z10.5 Hz, 3J(H6,H7)Z
6.5 Hz, H–C(6)), 3.82 (s, 3H, H–OMe), 3.77 (s, 6H,
ethoxy]pent-1-en-3-one (C). In a 25 mL round bottom
flask were added successively (E)-1-methoxypent-1-en-3-
one (A) (1.02 g, 8.93 mmol, 1.03 equiv), (R)-(C)-Greene’s
alcohol (B) (2.15 g, 8.65 mmol), pyridinium p-toluene-
sulfonic acid (0.024 g, 0.095 mmol, 1.1%) and toluene
(0.5 mL). The flask was placed under vacuum (20 mbar,
30 8C) for 15 h. The mixture was purified by column
chromatography (light petroleum ether/ether 4:1) to give
2
H–OMe), 3.56 (d, 1H, JZ12.7 Hz, H–C(10)), 3.54 (d, 1H,
3
2JZ12.7 Hz, H–C(10)), 3.2 (dq, 1H, J(H2,Me2)Z7.4 Hz,
3J(H2,H3)Z6.5 Hz, H–C(2)), 2.01 (s, 3H, Me-C(4)), 1.82 (s,
3
3H, Me-C(20)), 1.37 (d, 3H, J(H7,H6)Z6.5 Hz, H–C(7)),
1.11 (d, 3H, 3J(Me2,H2)Z7.4 Hz, Me-C(2)). 13C NMR
(100.6 MHz, CDCl3) of (G)-21c: d 209.1 (s, CO), 162.3–
158.4 (4s, C(ar)), 145.6 (s, C(20)), 133.3 (s, C(4)) 120.6 (t,
1J(C,H)Z146 Hz, C(30)), 117.9 (d, 1J(C,H)Z161 Hz,
C(5)), 90.6 and 90.5 (d, 2C, 1J(C,H)Z161 Hz, C(ar)),
70.4 (t, 1J(C,H)Z154 Hz, C(20)), 57.6 (d, 1J(C,H)Z143 Hz,
C(3)), 56.7 (d, 1J(C,H)Z131 Hz, C(6)), 55.6 (q, 1J(C,H)Z
151 Hz, C(OMe)), 53.4 (d, 1J(C,H)Z139 Hz, C(2)), 25.8 (q,
1J(C,H)Z142 Hz, t-Bu), 23.2 (q, 1J(C,H)Z130 Hz, Me-
C(20)), 18.2 (q, 1J(C,H)Z129 Hz, Me-C(4)), 15.4 (q,
1J(C,H)Z128 Hz, Me-C(6)), 15.0 (s, Cquat-tBu), 13.8 (q,
1J(C,H)Z132 Hz, Me-C(2)), K4.7 (q, 1J(C,H)Z126 Hz,
MeSi–C(3)), K5.3 (q, 1J(C,H)Z129 Hz, MeSi–C(3)).
CI-MS (NH3): C28H46SSiO7, m/z 555 (25, [MC1]C), 108
(100). Anal. Calcd for C28H46O7SSi (554.27): C, 60.62; H,
8.36. Found: C, 60.80; H, 8.49.
25
25
2.664 g (90%) of C, colorless solid. [a] C32; [a] C37;
589
577
25
546
25
435
25
405
[a] C40; [a] C98; [a] C130 (c 1.0, CHCl3). RfZ
0.24 (light petroleum ether/ether 4:1). UV (CH3CN): lmax
Z
261 (3Z7605), 249 (8300), 225 (7060), 218 (6770), 203
(5400), 188 (1170). IR (KBr): n 2960, 2930, 2870, 1680,
1660, 1635, 1610, 1590, 1460, 1380, 1360, 1225, 1190,
1110, 1060, 1030, 1000, 945, 880, 650. 1H NMR (400 MHz,
3
CDCl3): d 7.50 (d, 1H, JZ12.1 Hz, H–C(1)), 7.02 (s, 2
arom CH), 5.67 (d, 1H, 3JZ12.1 Hz, H–C(2)), 5.64 (q, 1H,
3JZ7.0 Hz, H–C(10)), 2.88 (sept, 1H, 3JZ6.8 Hz, Me2CH),
2.39 (q, 2H, 3JZ7.7 Hz, H–C(4)), 1.71 (d, 3H, 3JZ7.0 Hz,
H–C(20)), 1.31–1.22 (m, 20H, Me2CH, Me2CH), 1.06 (t, 3H,
3JZ7.7 Hz, H–C(5)). 13C NMR (100.6 MHz, CDCl3): d
200.3 (C(3)), 161.0 (C(1)), 148.5 (arom C), 131.3 (arom C),
122.2 (arom C), 106.7 (C(2)), 77.6 (C(10)), 34.0 (Me2CH),
29.3 (Me2CH), 24.6, 24.4, 23.9, 23.8, 22.4, 8.5 (C(5)). MS-
CI (NH3): 331 (4, [MC1]), 231 (100), 215 (20), 189 (12),
147 (28), 131 (15), 91 (9). Anal. Calcd for C22H34O2
(330.51): C, 79.95; H, 10.37; O, 9.68. Found: C, 79.80; H,
10.34.
4.3.3. Tributyl{2-[(tributylsilyl)methyl]prop-2-enyl}-
silane (23c). A mixture of 3-chloro-2-(chloromethyl)prop-
1-ene (0.84 mL, 7.93 mmol) and tributylsilyl chloride
(4.30 mL, 16.00 mmol, 2 equiv) in anhyd THF (16 mL)
was added dropwise (cannulated) to a stirred mixture of
anhyd THF (16 mL), naphthalene (104 mg, 0.81 mmol,
0.1 equiv) and lithium shots (0.420 g, 60.51 mmol,
7.6 equiv) at K78 8C. The mixture was stirred overnight
after removal of the cooling bath. The mixture was then
treated with water (10 mL), extracted with ether (15 mL,
three times), the organic phase dried (MgSO4). The crude
yellow liquid was distilled over CaH2 under reduced
pressure (0.2 mbar, TZ170 8C) to yield 2.0 g (4.43 mmol,
56%) of a colorless oil. UV (CH3CN): lmaxZ274 (3Z225),
217 (5160), 200 (3990), 186 (330). IR (neat): 2955, 2920,
2870, 2860, 1620, 1465, 1410, 1375, 1340, 1295, 1275,
1195, 1160, 1080, 1030, 1000, 965, 885, 850, 790, 760, 730.
1H NMR (400 MHz, CDCl3): d 4.37 (s, 2H, H–C(1)), 1.48
(s, 4H, H–C(3)), 1.35–1.24 (m, 24H, H–C(20), H–C(30)),
4.3.5. 3:1 Mixture of (C)-(1E,3E and 1E,3Z,1R0)-1-[10-(2,
4,6-triisopropylphenylethoxy)]penta-1,3-dien-3-yl acetate
(24b). To a solution of (C)-(1E)-1-[1-(1R)-(2,4,6-triiso-
propylphenyl)ethoxy]pent-1-en-3-one (C) (1.995 g,
6.04 mmol), in 22 mL of anhyd ether were added at
K20 8C triethylamine (1.90 mL, 13.63 mmol, 2.25 equiv)
and trimethylsilyl triflate (1.22 mL, 6.75 mmol, 1.11 equiv).
The mixture was stirred at K20 8C for 2 h and 50 mL of
precooled (K78 8C) pentane were added. The organic phase
was extracted with a satd soln of aq NaHCO3 (50 mL, three
times), CuSO4 (50 mL), brine (50 mL) and dried over
Na2SO4 and concentrated under vacuum. To the crude
mixture were added 4.6 mL of anhyd THF and acetyl
fluoride (0.8 mL, 12.89 mmol) was transferred on the
vacuum line to the THF frozen solution at K196 8C. The
solution was warmed up to K20 8C and TBAF (1 M
solution in THF, 0.1 mL) was added dropwise. The
temperature was then rised to K15 8C and the reaction
mixture was stirred overnight. THF was evaporated under
vacuum. FC (light petroleum ether/ether 4:1): 1.35 g
(3.62 mmol, 60%), unseparable 3:1 mixture of 1E,3E and
1E,3ZE geometric isomers of 24b. RfZ0.44 (light
petroleum ether/ether 9:1). UV (CH3CN): lmaxZ250 (3Z
8345), 198 (4510), 189 (1100). IR (KBr): n 2960, 2930,
2870, 1760, 1675, 1635, 1610, 1575, 1460, 1375, 1210,
3
0.89 (t, 18H, JZ7.0 Hz, H–C(40)), 0.57–0.53 (m, 12H,
H–C(10)). 13C NMR (100.6 MHz, CDCl3): d 145.4 (C(2)),
105.3 (C(10 )), 26.8 (C(20) or C(30)), 26.1 (C(20) or C(30)),
17.8 (C(4 )), 12.2 (C(10)). MS-CI (NH3): 453 (1, [MC1]),
425 (1), 397 (2), 374 (4), 340 (4), 199 (49), 143 (100), 87
(29). Anal. Calcd for C28H60Si2 (452.42): C, 74.25; H,
13.65; Si, 12.40. Found: C, 74.36; H, 13.26.
Diene 24b was prepared according to the synthetic sequence
shown below (Scheme 6).
4.3.4.
(C)-(1E)-1-[1(R)-(2,4,6-triisopropylphenyl)
Scheme 6.

11482
L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
1165, 1125, 1100, 1065, 1020, 910, 880, 840, 780, 650. 1H
NMR (400 MHz, CDCl3): d 7.00 (s, 2 arom CH), 6.35 (d,
[a] K94; [a] K192; [a] K247 (c 0.25, CHCl3). IR
(film): n 3295, 3060, 2970, 2930, 2355, 1735, 1640, 1600,
1490, 1450, 1375, 1315, 1275, 1230, 1155, 1080, 1070. H
25
577
25
435
25
405
3
3
1
1H, JZ12.3 Hz, H–C(1) E,Z), 6.30 (d, 1H, JZ12.3 Hz,
3
3
H–C(2) E,E), 5.67 (d, 1H, JZ12.3 Hz, H–C(1) E,E), 5.47
NMR (CDCl3, 400 MHz): d 8.17 (d, 2H, JZ7.7 Hz), 7.64
(t, 1H, JZ7.7 Hz), 7.50 ((t, 2H, JZ7.7 Hz), 7.39–7.35,
7.33–7.31, 7.28–7.24, 7.23–7.19, 7.05–7.03 (5m, 10H,
(d, 1H, 3JZ12.3 Hz, H–C(2) E,Z), 5.42 (q, 3H, 3JZ6.8 Hz,
H–C(10) E,ECE,Z), 5.04 (q, 1H, 3JZ7.4 Hz, H–C(4) E,Z),
4.94 (q, 1H, 3JZ7.4 Hz, H–C(4) E,E), 2.85 (sept, 2H, 3JZ
6.8 Hz, Me2CH E,ZCE,E), 2.08 (s, 3H, MeCO E,Z), 2.08 (s,
3H, MeCO E,E), 1.64 (d, 3H, 3JZ6.8 Hz, H–C(5) E,E), 1.62
3
3
3
H–C(Ar)), 5.68 (ddt, 1H, JZ17.3 Hz, 9.6, 7.4, H–C(5)),
5.05 (d, 1H, 3JZ17.3 Hz, Ha–C(6)), 5.03 (d, 1H, 3JZ
9.6 Hz, Hb–C(6)), 4.71 (q, 1H, 3JZ6.4 Hz, H–C(100)), 4.55
3
3
2
(d, 3H, JZ6.8 Hz, H–C(5) E,Z), 1.53 (d, 3H, JZ6.8 Hz,
H–C(20) E,E), 1.49 (d, 3H, 3JZ6.8 Hz, H–C(20) E,Z), 1.26–
1.20 (m, 20H, Me2CH, Me2CH). 13C NMR (100.6 MHz,
CDCl3): d 169.1 (CO), 148.1–147.8 (C(3), E,ZCE,E), 146.3
(C(1)), 144.8 (arom C), 144.0 (arom C), 132.2 (arom C),
122.2 (arom C), 110.4 (C(4)), 103.0 (C(2)), 75.6 (C(10)),
34.0 (Me2CH), 29.0 (Me2CH), 24.5 (Me2CH), 23.9, 23.8,
22.4 (C(20)), 20.2 (MeCO)), 11.0 (C(5)). MS (EI): 372 (11,
M), 305 (15), 245 (3), 231 (100), 215 (7), 147 (10), 91 (3).
MS (EI): calcd for C24H36O3: 372.2664; found: 372.2679.
(m, 1H, H–N), 4.20 (dd, 1H, AB syst, JZ14.71, 5.8 Hz,
2
Ha-PhCH2), 4.10 (dd, 1H, AB syst, JZ14.7, 6.4 Hz, Hb-
3
PhCH2), 3.98 (q, 1H, JZ7.0 Hz, H–C(10)), 3.98 (t, 1H,
3JZ7.0 Hz, H–C(3)), 2.47 (dt, 1H, 2JZ14.1 Hz, 3JZ
2
3
7.0 Hz, Ha–C(4)), 2.35 (dt, 1H, JZ14.08 Hz, JZ7.0 Hz,
Hb–C(4)), 1.69 (s, 3H, CH3–C(2)), 1.41 (d, 3H, 3JZ6.4 Hz,
3
H–C(20)), 1.35 (d, 3H, JZ7.0 Hz, H–C(200)). 13C NMR
(C6D6, 100.6 MHz): d 164.9, 144.7, 138.8, 137.9, 137.3,
134.1, 132.3, 130.7, 129.3, 128.9, 128.7, 127.9, 118.3, 75.8,
75.2, 59.2, 47.7, 39.5, 30.11, 25.6, 13.7. MALDI-HRMS:
calcd for C31H35NO5SKC 572.1873; found: 572.1870.
Anal. Calcd for C31H35NO5S (533.22): C, 69.77; H, 6.61;
N, 2.62; O, 14.99; S, 6.01. Found: C, 69.69; H, 6.69; N,
2.75; O, 14.90; S, 5.97. Data of (K)-27a: white crystals, mp
4.4. General procedure for the preparation of methyl-
idene (Z)-b,g-unsaturated sulfonamides 26, 27 using
allysilanes
25
589
25
25
435
25
97–99 8C. [a] K56; [a] K57; [a] K106; [a] K
405
577
125 (c 0.5, CHCl3). IR (KBr): n 3295, 3060, 2970, 2930,
2355, 1735, 1640, 1600, 1490, 1450, 1375, 1315, 1275,
A mixture of allyltrimethylsilane (0.12 mL, 0.61 mmol,
0.3 equiv) and 0.5 M bistrifluoromethanesulfonimide
Tf2NH in CH2Cl2 (1.21 mL, 0.61 mmol, 0.3 equiv) were
mixed and stirred at 20 8C for 30 min. The mixture frozen at
K196 8C (vacuum line, freeze/thaw cycles for degassing)
and SO2 (through a column of P2O5 and alumina) was
transferred (9 mL). The mixture was allowed to melt at
K78 8C. After 30 min at this temperature a mixture of
allylsilane (23a or 23b) (4 mmol, 2 equiv) and diene 24a
(2 mmol, 1.0 equiv) in anhyd CH2Cl2 (5 mL) was added.
After stirring at K78 8C 16 h, the solvents were evaporated
under vacuum to dryness (K78–20 8C, 1.5 h). The residue
was taken in CH3CN (10 mL) and a solution of
N-chlorosuccinimide (1.35 g, 10.1 mmol, 5 equiv) in
CH3CN (10 mL) was added slowly under stirring at
K40 8C. The mixture was stirred at K40 8C for 15 min,
then for more 15 min at K30 8C. It was cannulated into a
solution of BnNH2 (2.16 g, 20.2 mmol) in pyridine (10 mL)
under stirring at K30 8C. The mixture was stirred for 4 h at
K20 8C, then 1 h at 0 8C, and 1.5 h at 20 8C. EtOAc
(600 mL) was added and the solution washed with a satd aq
soln of CuSO4. The aq phase was separated and extracted
with EtOAc (100 mL). The combined organic extracts were
washed with satd aq soln of NaHCO3 (100 mL), then with
brine (100 mL), dried (Na2SO4). After solvent evaporation
under vacuum, the residue was purifed by FC.
1
1230, 1155, 1080, 1070. H NMR (CDCl3, 400 MHz): d
8.14 (d, 2H, 3JZ7.7 Hz), 7.66 (t, 1H, 3JZ7.7 Hz), 7.52 ((t,
3
2H, JZ7.7 Hz), 7.42–7.34, 7.35–7.33, 7.31–7.28, 7.23–
3
7.24, 7.22–7.21 (5m, 10H, H–C(Ar)), 5.91 (ddt, 1H, JZ
3
17.3, 10.2, 7.0 Hz, H–C(5)), 5.13 (dd, 1H, JZ17.3 Hz,
2JZ3.5 Hz, Ha–C(6)), 5.10 (dd, 1H, 3JZ10.3 Hz, 2JZ
3.5 Hz, Hb–C(6)), 4.51 (m, 1H, H–C(100)), 4.51 (d, 1H, 3JZ
2
5.8 Hz, H–N), 4.16 (dd, 1H, AB syst, JZ14.1, 5.8 Hz,
2
Ha-PhCH2), 4.05 (dd, 1H, AB syst, JZ14.1, 5.8 Hz, Hb-
3
PhCH2), 4.06 (dd, 1H, JZ7.0, 2.9 Hz, H–C(3)), 3.69 (q,
1H, 3JZ6.4 Hz, H–C(10)), 2.54 (ddd, 1H, 2JZ14.4 Hz, 3JZ
9.9, 7.0 Hz, Ha–C(4)), 2.41 (ddd, 1H, 2JZ14.4 Hz, 3JZ7.0,
2.9 Hz, Hb–C(4)), 1.69 (s, 3H, CH3–C(2)), 1.45 (d, 3H, 3JZ
3
6.4 Hz, H–C(20)), 1.44 (d, 3H, JZ5.1 Hz, H–C(200)). 13C
NMR (C6D6, 100.6 MHz): d 164.9, 144.6, 139.2, 137.9,
136.3, 133.9, 132.7, 130.8, 129.1, 129.0, 128.9, 127.1,
117.3, 74.6, 74.5, 58.7, 47.8, 38.6, 25.5, 13.0, 11.5. MALDI-
HRMS: calcd for C31H35NO5SKC 572.1873; found:
572.1879. Anal. Calcd for C31H35NO5S (533.22): C,
69.77; H, 6.61; N, 2.62; O, 14.99; S, 6.01. Found: C,
69.75; H, 6.61; N, 2.59; O, 14.99; S, 6.06.
4.4.2. (K)-(1E,3S)-5-((acetyloxy)methyl)-1-((1S)-1-
((benzylamino)sulfonyl)ethyl)-2-methyl-3-((1S)-1-
phenylethoxy)hexa-1,5-dien-1-yl benzoate ((K)-26b) and
(K)-(1E,3S)-5-((acetyloxy)methyl)-1-((1R)-1-((benzyl-
amino)sulfonyl)ethyl)-2-methyl-3-((1S)-1-phenyl-
ethoxy)hexa-1,5-dien-1-yl benzoate ((K)-27b). A 1:1
mixture of a (K)-26b and (K)-27b was obtained applying
the above procedure and using (2-acetoxy)allyltrimethyl-
silane54 (23b, 5 g, 26.8 mmol, 2 equiv) and diene (K)-24a
(4.3 g, 13.4 mmol). FC (toluene/EtOAc 95:5) gave (K)-
26b, RfZ0.29 (2.85 g, 35%) and (K)-27b, RfZ0.38
(toluene/EtOAc 9:1) (2.85 g, 35%). Their structures
were established by their transformation into the cyclic
derivatives (K)-30 and (K)-31 (see below). Data of (K)-
4.4.1. (K)-(1E,3S)-1-((1S)-1-((benzylamino)sulfonyl)
ethyl)-2-methyl-3-((1S)-1-phenylethoxy)hexa-1,5-dien-1-
yl benzoate ((K)-26a) and (K)-(1E,3S)-1-((1R)-1-
((benzylamino)sulfonyl)ethyl)-2methyl-3-((1S)-1-phenyl-
ethoxy)hexa-1,5-dien-1-yl benzoate ((K)-27a). A 1:1
mixture of (K)-26a and (K)-27a was prepared following
the above procedure. FC (toluene/EtOAc 97:3) gave 0.202 g
(19% of (K)-26a, RfZ0.37, toluene/EtOAc 9:1) and
0.208 g (20%) of (K)-27a (RfZ0.45, toluene/EtOAc 9:1).
Compound (K)-27a was recrystallized from light pet-
roleum ether and submitted to X-ray diffraction studies
(Fig. 1). Data of (K)-26a: yellowish oil; [a] K111;
25
589
25
25
25
26b: colorless oil. [a] K32; [a] K34; [a] K64;
589 577 435

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11483
25
[a] K77 (c 1.0, CHCl3). IR (film): n 3060, 3030, 2970,
room temperature and CH2Cl2 (10 mL) was added. The
organic phase was washed with a satd aq solution of
NaHCO3, dried (Na2SO4) and concentrated under vacuum.
FC (light petroleum ether/EtOAc 3:2) 220 mg (65%) of a
10:1 mixture of diastereoisomers 28 and 3-epi-28. Only the
isomer 28 can be analyzed from the spectra of the mixture
UV (CH3CN): lmaxZ265 (3Z488), 225 (5565), 189 (660).
IR (neat): n 3075, 2960, 2930, 2870, 1760, 1700, 1645,
405
2925, 1735, 1730, 1600, 1490, 1450, 1375, 1325, 1275,
1235, 1150, 1085, 1065. H NMR (DMSOd-6, 400 MHz,
1
3
C80 8C): d 8.12 (dm, 2H, JZ8.0 Hz, H–C(Bz)), 7.72 (t,
1H, 3JZ7.5 Hz, H–C(Bz)), 7.58 (t, 2H, 3JZ7.5 Hz,
H–C(Bz)), 7.39–7.22 (5m, 10H, H–C(Ar)), 5.08, 5.03 (2
br s, 2H, H–C(6)), 4.60, 4.53 (2d, 2H, AB syst, 2JZ13.7 Hz,
AcOCH2–C(5)), 4.50 (q, 1H, 3JZ6.5 Hz, H–C(100)), 4.15 (t,
1H, 3JZ6.1 Hz, H–C(3)), 4.04, 3.95 (2dd, 2H, AB syst, 2JZ
1
1460, 1370, 1220, 1180, 1075, 1020, 890, 880, 780. H
NMR (400 MHz, CDCl3): d 7.03–6.94 (2s, 2 arom CH),
5.55 (d, 1H, 3JZ6.9 Hz, H–C(2)), 5.18 (q, 1H, 3JZ6.6 Hz,
3
3
15.1 Hz, JZ6.2 Hz, PhCH2–N), 3.66 (q, 1H, JZ6.9 Hz,
H–C(10)), 3.61–3.39 (br s, 1H, NH), 2.41 (d, 2H, 3JZ
6.5 Hz, H–C(4)), 2.02 (s, 3H, CH3COOCH2–C(5)), 1.64 (s,
3
H–C(100)), 4.78–4.68 (2s, 2H, H–C(6)), 4.38 (q, 1H, JZ
3H, CH3–C(2)), 1.38 (d, 3H, 3JZ6.5 Hz, H–C(200)), 1.31 (d,
7.0 Hz, H–C(10)), 4.19 (m, 1H, H–C(3)), 3.85–3.25 (2 br s,
2H, Me2–CH)), 3.06 (s, 3H, SO2Me), 2.85 (sept, 3JZ
6.5 Hz, Me2–CH), 2.40 (br d, 1H, H–C(4)), 2.23 (sCm, 4H,
MeCOCH–C(4)), 1.63 (s, 3H, Me-C(5)), 1.57 (2d, 6H, 3JZ
7.0 Hz, H–C(20), 3JZ6.6 Hz, H–C(200)), 1.26–1.22 (m, 18H,
Me2–CH). 13C NMR (100.6 MHz, CDCl3): d 168.8 (CO),
147.5–147.1–140.9–140.7–133.9–129.0 (4 arom CC
C(5)CC(1)), 128.2 (C(2)), 123.2–120.5 (2 arom C.),
114.2 (C(6)), 74.4 (C(3)), 73.0 (C(100)), 59.9 (C(10)), 44.3
(C(4)), 38.6 (SO2Me), 34.0 (Me2C), 29.1–28.6 (Me2–C),
24.8–24.3–23.9–23.3 (2Me2–CCMe-C(7)CC(200)), 20.9
(MeCO), 14.2 (Me2–C)), 11.2 (C(1)). HRMS (MALDI):
calcd for C29H46O5SNaC 529.2963 [MCNaC]; found:
529.2912.
3
3H, JZ6.9 Hz, CH3–C(20)). 13C NMR (DMSOd-6
,
100.6 MHz, C80 8C): d 169.1, 163.1, 142.6, 141.0, 138.2,
137.8, 133.2, 130.3, 129.2, 128.2, 127.7, 127.6, 127.0,
126.8, 126.5, 125.8, 113.0, 110.7, 73.3, 73.1, 65.8, 57.3,
46.0, 36.2, 23.6, 19.8, 11.6, 10.3. MALDI-HRMS: calcd for
C34H39NO7SNaC 628.2345; found: 628.2349. Anal. Calcd
for C34H39NO7S (605.74): C, 67.42; H, 6.49; N, 2.31; S,
5.29. Found: C, 67.35; H, 6.63; N, 2.33; S, 5.33. Data of
25
589
25
577
25
(K)-27b: colorless oil. [a] K114; [a] K123; [a] K
435
25
246; [a] K301 (c 0.5, CHCl3). IR (film): n 3060, 3030,
2970, 2925, 1735, 1600, 1490, 1450, 1375, 1325, 1275,
405
1235, 1150, 1085, 1065. 1H NMR (C6D6, 400 MHz,
3
C70 8C): d 8.23 (dm, 2H, JZ7.7 Hz, H–C(Bz)), 7.52 (d,
3
2H, JZ6.8 Hz, H–C(Ar)), 7.21–7.02 (m, 11H, H–C(Ar)),
3
5.06, 5.03 (2 br s, 2H, H–C(6)), 4.86 (q, 1H, JZ6.5 Hz,
4.4.4. (1Z)-1-ethylidene-5-methyl-3-[1-(2,4,6-triiso-
propyl-phenyl)ethoxy]hex-5-enyl acetate (29a). Allyl-
trimethylsilane (0.03 mL, 0.19 mmol, 0.20 equiv) and
Tf2NH (0.5 M in CH2Cl2) (0.33 mL, 0.17 mmol,
0.20 equiv) were mixed and stirred for 20 min at room
temperature. Anhyd CH2Cl2 (1.8 mL) was added. SO2
(0.5 mL, 11.18 mmol, 13.8 equiv) dried over a column of
P2O5 and alumina was transferred on the vacuum line to the
CH2Cl2 solution frozen at K196 8C. The mixture was
allowed to melt and to warm at K78 8C. After 30 min at this
temperature a mixture of diene 24b (304.0 mg, 0.81 mmol)
and 23c (477 mg, 1.67 mmol, 2.06 equiv) in anhyd CH2Cl2
(1.8 mL) was added dropwise at K80 8C. The resulting
reaction mixture was stirred at K78 8C for 16 h. SO2 was
then evaporated at K78 8C for 1 h. A solution of
triethylamine (0.14 mL, 1.00 mmol, 1.22 equiv), trimethyl-
silyl trifluoromethanesulfonate (0.18 mL, 0.99 mmol,
1.22 equiv) in anhyd MeOH (0.20 mL) was added. The
temperature was kept at K78 8C for 3 h and a satd aq
solution of NaHCO3 (10 mL) was added. The reaction
mixture was warmed to room temperature and diluted with
CH2Cl2 (10 mL). The organic phase was washed with
saturated NaHCO3, dried (Na2SO4) and concentrated. The
crude was purified on chromatographic column (petroleum
ether 95/Ethyl acetate 5) to yield 237 mg (70%) as a 10:1
mixture of diastereoisomers 29a/29b. RfZ0.51 (petrol
ether/ether 85:15). Only 29a can be analyzed from the
spectra of the mixture. UV (CH3CN): 265 (490), 225 (5560),
189 (660). IR (neat): 30745 2960, 2930, 2870, 1760, 1700,
1645, 1460, 1370, 1220, 1180, 1080, 1020, 890, 880,
H–C(10)), 4.54, 4.45 (2d, 2H, AB syst, 2JZ010 3.6 Hz,
3
AcOCH2–C(5)), 4.45 (q, 1H, JZ6.5 Hz, H–C(1 )), 4.36
3
3
(t, 1H, JZ6.5 Hz, H–C(3)), 4.14 (br t, 1H, JZ5.9 Hz,
2
NH), 4.05 (m, 2H, PhCH2–N), 2.56 (dd, 1H, AB syst, JZ
13.6 Hz, 2JZ7.4 Hz, Ha–C(4)), 2.40 (dd, 1H, AB syst, 2JZ
13.6 Hz, 2JZ6.2 Hz, Ha–C(4)), 1.74 (s, 3H, CH3COOCH2–
3
C(5)), 1.68 (s, 3H, CH3–C(2)), 1.45 (d, 3H, JZ6.8 Hz,
H–C(200)), 1.40 (d, 3H, JZ6.5 Hz, CH3–C(20)). 13C NMR
3
(C6D6, 100.6 MHz, C70 8C): d 169.7, 164.4, 144.7, 140.8,
139.9, 138.8, 133.4, 132.3, 130.7, 130.2, 128.9, 128.8,
128.6, 127.9, 127.2, 116.5, 115.3, 75.8, 75.6, 67.1, 59.7,
47.7, 39.5, 24.8, 20.3, 13.7, 12.5. MALDI-HRMS: calcd for
C34H39NO7SNaC 628.2345; found: 628.2346. Anal. Calcd
for C34H39NO7S (605.74): C, 67.42; H, 6.49; N, 2.31; S,
5.29. Found: C, 67.37; H, 6.40; N, 2.24; S, 5.30.
4.4.3. (2S,3E,5R)-5-[(1R)-(2,4,6-triisopropylphenyl)-
ethyloxy]-7-methylsulfonylocta-3,7-dien-3-yl acetate
(28). Allyltrimethylsilane (0.03 mL, 0.188 mmol,
0.28 equiv) and Tf2NH (0.5 M in CH2Cl2) (0.27 mL,
0.35 mmol, 0.20 equiv) were stirred at 20 8C for 20 min.
Anhyd CH2Cl2 (1.4 mL) was added. SO2 (0.5 mL,
11.18 mmol) dried by passing through a column of P2O5
and alumina was transfered on the vaccum line to the
CH2Cl2 solution frozen at K196 8C. The mixture was
allowed to melt and to warm to K78 8C. After 30 min at this
temperature a mixture of 24b (247.0 mg, 0.663 mmol) and
23c (607 mg, 13.4 mmol) in anhyd CH2Cl2 (0.8 mL) was
added dropwise at K80 8C After stirring at K78 8C
overnight, SO2 was evaporated at K78 8C for 1 h. Then
MeI (0.41 mL, 6.58 mmol, 10 equiv) followed by TBAF
(1 M in THF, 3.40 mmol, 5.13 equiv) were added. The
reaction mixture was allowed to reach slowly 0 8C. After 2 h
at this temperature an aqueous solution of NaHCO3 (5%)
was added (10 mL). The reaction mixture was warmed to
1
780 cmK1. H NMR (400 MHz, CDCl3): 7.03–6.94 (2s, 2
3
arom CH), 5.20 (q, 1H, JZ6.9 Hz, H–C(10)), 5.10 (q, 1H,
3JZ6.6 Hz, H–C(100)), 4.71–4.60 (2s, 2H, H–C(6)), 3.91 (br
s, 1H, Me2–CH)), 3.67 (m, 1H, H–C(3)), 3.91 (br s, 1H,
3
Me2–CH)), 2.85 (sept, JZ6.5 Hz, Me2–CH), 2.49 (br d,
1H, H–C(4)), 2.45 (s, 3H, H–C(20)), 2.44–2.42 (m, 2H,

11484
L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
2
H–C(2)), 2.11–2.05 (m, 2H, H–C(4)), 1.58 (s, 3H, Me-
C(5)), 1.55 (d, 3H, 3JZ6.9 Hz, H–C(200)), 1.50 (d, 3H, 3JZ
6.6 Hz, H–C(20)), 1.26–1.22 (m, 17H, Me2–CH). 13C NMR
(100.6 MHz, CDCl3): 168.7 (C(10)), 147.2 (C(1)), 147.1–
146.6–142.3–134.6, 123.1–120.3 (arom CCC(5)), 113.4
(C(100)), 112.9 (C(6)), 73.7 (C(3)), 71.6 (C(1000)), 43.3 (C(2)),
38.6 (C(4)), 34.0 (Me2–CH), 25.2–24.8–24.2–23.9–23.8
(Me2–CHCMe2–CH), 22.7 (Me-C(5)), 22.3 (C(Ac)), 20.7
(C(200)), 10.8 (C(20)). MS-CI (NH3): 446 (1, [MC18]), 429
(1, [MC1]C), 344 (1), 231 (100). El. Anal. Calcd C28H44O3
(428.66): C, 78.46; H, 10.35; O, 11.20. Found: C, 78.40; H,
10.33.
15.1 Hz, Hb–C(3)), 2.68 (dd, 1H, AB syst, JZ15.2 Hz,
3JZ8.6 Hz, Ha–C(5)), 2.54 (dd, 1H, AB syst, 2JZ15.2 Hz,
3JZ5.0 Hz, Hb–C(5)), 1.58 (s, 3H, CH3–C(7)), 1.57 (d, 3H,
3JZ6.5 Hz, CH3–C(9)), 1.43 (d, 3H, 3JZ6.5 Hz, H–C(20)).
13C NMR (CDCl3, 100.6 MHz): d 164.1, 143.4, 140.6,
137.2, 136.9, 133.9, 132.4, 130.4, 128.9, 128.8, 128.7,
128.6, 128.3, 127.8, 126.6, 122.8, 75.0, 74.8, 61.8, 54.2,
52.9, 38.7, 24.9, 20.2, 11.4. MALDI-HRMS: calcd for
C32H35NO5SKC 568.2134; found: 568.2104. Anal. Calcd
for C32H35NO5S (545.69): C, 70.43; H, 6.46; N, 2.57; S,
5.88. Found: C, 70.47; H, 6.50; N, 2.42; S, 5.77.
4.4.7. (G)-(2RS,5SR)-2,4-dimethyl-7-methylene-1,1-
dioxido-5-((1SR)-1-phenylethoxy)-5,6,7,8-tetrahydro-
2H-thiocin-3-yl isobutyrate ((G)-32b). Allyltrimethyl-
silane (0.194 mL, 1.22 mmol) was added to Tf2NH (0.5 M
in CH2Cl2) (2.44 mL, 1.22 mmol) diluted with toluene
(6 mL). The mixture was stirred at 20 8C for 20 min. SO2
(7 mL, 157 mmol, 51 equiv) dried over a column of P2O5
and alumina was transferred on the vacuum line to the
toluene solution frozen at K196 8C. The mixture was
allowed to melt and to warm at K78 8C. After 30 min at
K78 8C a mixture of (G)-24c37 (0.88 g, 3.05 mmol,
1 equiv) and 2-acetoxymethyl allyltrimethylsilane 23b
(0.68 g, 3.66 mmol, 1.2 equiv) in anhyd toluene (2 mL)
was added dropwise under stirring at K78 8C. The mixture
was stirred overnight. SO2 was then evaporated at K78 8C
for 2 h, followed by evaporation to dryness at 20 8C. The
residue (crude 25c) was taken in THF (15 mL) and added at
20 8C to a mixture of (Ph3P)4Pd (0.35 g, 0.30 mmol,
0.1 equiv) and NEt3 (0.85 mL, 6.10 mmol, 2 equiv) in
THF (15 mL) and stirred at 20 8C for 3 h. The mixture was
then poured in brine, extracted by EtOAc. The collected
organic layers were washed with brine, dried (Na2SO4) and
evaporated under vacuum. FC (light petroleum ether/EtOAc
7:3): 0.55 g (44%) of (G)-32b, that was recrystallized from
pentane/CH2Cl2 to yield a sample suitable for X-ray
crystallography (Fig. 2). White solid, mp 90 8C, RfZ0.63
(light petroleum ether/EtOAc 7:3). IR (KBr): n 2950, 2880,
1745, 1680, 1455, 1380, 1295, 1315, 1240, 1190, 1140,
1125, 1115, 1080, 1045. 1H NMR (CDCl3, 400 MHz,
C60 8C): d 7.38–7.27 (m, 5H, H–C(Ph)), 5.64, 5.45 (2s, 2H,
4.4.5. (K)-(6S,7E,9R)-2-benzyl-7,9-dimethyl-4-methyl-
ene-1,1-dioxido-6-((1S)-1 phenylethoxy)-2,3,4,5,6,9-
hexahydro-1,2-thiazonin-8-yl benzoate ((K)-30). A
mixture of (K)-26b (0.40 g, 0.66 mmol), Cs2CO3
(0.215 g, 0.66 mmol) and Pd(PPh3)4 (76 mg, 0.07 mmol)
in anhyd DMF (20 mL) was heated to 100 8C for 40 min
(control by TLC). The resulting black solution was
evaporated under vacuum to dryness. The residue was
purified by FC (toluene/EtOAc 9:1, RfZ0.62), 0.291 g
25
25
25
25
(81%), [a] K93; [a] K99; [a] K176; [a] K211 (c
0.3, CHCl3). IR (film): n 3065, 2975, 2925, 1735, 1730,
1715, 1605, 1595, 1500, 1470, 1455, 1330, 1265, 1240,
589
577
435
405
1170, 1145, 1085, 1065, 1025. 1H NMR (DMSOd-6
,
400 MHz, C80 8C): d 8.08 (dm, 2H, 3JZ7.4 Hz,
3
H–C(Bz)), 7.73 (t, 1H, JZ7.4 Hz, H–C(Bz)), 7.60 (t, 2H,
3JZ7.4 Hz, H–C(Bz)), 7.48–7.42, 7.39–7.33, 7.30–7.26,
7.17–7.13, 6.79–6.74 (5m, 10H, H–C(Ar)), 4.96, 4.82 (2s,
3
2H, CH2]C(4)), 4.50 (q, 1H, JZ6.6 Hz, H–C(10)), 4.30
3
(dd, 1H, JZ9.6, 5.5 Hz, H–C(6)), 4.07, 3.99 (2d, 2H, AB
syst, 2JZ15.8 Hz, PhCH2–N(2)), 3.81 (d, 1H, AB syst, 2JZ
15.8 Hz, Ha–C(3)), 3.62 (q, 1H, 3JZ7.0 Hz, H–C(9)), 3.50
(d, 1H, AB syst, 2JZ15.8 Hz, Hb–C(3)), 2.69–2.58 (m, 2H,
3
H–C(5)), 1.64 (s, 3H, CH3–C(7)), 1.43 (d, 3H, JZ6.6 Hz,
3
H–C(20)), 1.31 (d, 3H, JZ7.0 Hz, CH3–C(9)). 13C NMR
(DMSOd-6, 100.6 MHz, C80 8C): d 163.1, 142.9, 140.1,
138.0, 135.6, 133.3, 130.8, 129.1, 128.6, 128.4, 128.0,
127.8, 127.2, 126.9, 125.9, 118.2, 118.0, 114.9, 74.0, 71.9,
57.6, 50.8, 50.6, 38.4, 23.3, 10.5, 9.8. MALDI-HRMS: calcd
for C32H35NO5SNaC 584.1873; found: 584.1879. Anal.
Calcd for C32H35NO5S (545.69): C, 70.43; H, 6.46; N, 2.57;
S, 5.88. Found: C, 70.52; H, 6.46; N, 2.58; S, 5.86.
3
CH2]C(7)), 5.37 (br s, 1H, H–C(2)), 4.55 (q, 1H, JZ
6.2 Hz, H–C(10)), 4.03 (d, 1H, 2JZ14.2 Hz, Ha–C(8)), 3.77
2
(br s, 1H, H–C(5)), 3.67 (d, 1H, JZ14.2 Hz, Hb–C(8)),
2.77 (sept, 1H, 3JZ6.8 Hz, (CH3)2CHCOO–C(3)), 2.60 (dd,
4.4.6. (K)-(6S,7E,9R)-2-benzyl-7,9-dimethyl-4-methyl-
ene-1,1-dioxido-6-((1S)-1-phenylethoxy)-2,3,4,5,6,9-
hexahydro-1,2-thiazonin-8-yl benzoate ((K)-31). Same
procedure as that applied for the preparation of (K)-30,
2
3
1H, JZ14.2 Hz, JZ5.6 Hz, Ha–C(6)), 2.24 (br d, 1H,
2JZ14.2 Hz, Hb–C(6)), 1.48 (d, 3H, 3JZ6.8 Hz, CH3–
3
C(2)), 1.46 (s, 3H, CH3–C(4)), 1.40 (d, 3H, JZ6.8 Hz,
H–C(20)), 1.31 (2d, 6H, 3JZ7.4 Hz, (CH3)2CHCOO–
C(3))). 13C NMR (CDCl3, 100.6 MHz, C60 8C): d 174.1,
143.0, 139.5, 131.3, 130.0, 128.8, 128.0, 127.1, 126.5, 75.6,
75.4, 57.3, 54.9, 41.5, 34.2, 24.2, 19.0, 19.1, 18.4, 6.3.
MALDI-HRMS: calcd for C22H30O5SNaC 429.1712;
found: 429.1712. Anal. Calcd for C22H30O5S (406.54): C,
65.00; H, 7.44; S, 7.89. Found: C, 65.05; H, 7.46; S 7.99.
using (K)-27b (0.40 g, 0.66 mmol). Yield 0.285 g (79%).
25
RfZ0.72, toluene/EtOAc 9:1), colorless oil. [a] K108;
589
25
25
25
[a] K113; [a] K257; [a] K320 (c 0.2, CHCl3). IR
(film): n 3060, 3030, 2970, 2925, 1735, 1730, 1680, 1600,
1495, 1455, 1330, 1270, 1225, 1210, 1140, 1085, 1065,
577
435
405
1
3
1025. H NMR (CDCl3, 400 MHz): d 8.21 (d, 2H, JZ
7.4 Hz, H–C(Bz)), 7.63 (t, 1H, 3JZ7.7 Hz, H–C(Bz)), 7.70
(t, 2H, 3JZ7.4 Hz, H–C(Bz)), 7.43–7.28 (m, 10H,
H–C(Ar)), 5.23 (s, 2H, CH2]C(4)), 5.21 (q, 1H, 3JZ
7.1 Hz, H–C(9)), 4.89 (d, 1H, AB syst, 2JZ15.1 Hz,
4.4.8.
(C)-(2S,5S)-2,4-dimethyl-7-methylene-1,1-
dioxido-5-((1R)-1-phenylethoxy)-5,6,7,8-tetrahydro-2H-
thiocin-3-yl benzoate ((C)-32a). Same procedure as that
applied for the preparation of (G)-32b using (C)-24a
(0.82 g, 2.54 mmol). Yield 0.45 g (41%). RfZ0.52, light
petroleum ether/EtOAc 7:3), colorless oil. IR (film): n 2970,
3
Ha-(PhCH2–N(2))), 4.86 (q, 1H, JZ6.5 Hz, H–C(10)),
2
4.07 (d, 1H, AB syst, JZ15.1 Hz, Ha–C(3)), 4.02 (d, 1H,
2
AB syst, JZ15.1 Hz, Hb-(PhCH2–N(2))), 3.89 (dd, 1H,
3JZ8.6, 4.9 Hz, H–C(6)), 3.41 (d, 1H, AB syst, 2JZ

L. C. Bouchez et al. / Tetrahedron 61 (2005) 11473–11487
11485
Savary, K.; Williams, J. M.; Grabowski, E. J. J.; Reider, P. J.
Tetrahedron Lett. 2003, 44, 1283. (w) Skarzewski, J.;
´ ´
Siedlecka, R.; Wojaczynska, E.; Zielinska-BŁajet, M.
1735, 1450, 1315, 1270, 1220, 1140, 1120, 1080, 1020, 705,
620. H NMR (C6D6, 400 MHz, C70 8C): d 8.21 (d, 2H,
1
3JZ7.7 Hz, H–C(Bz)), 7.23 (d, 2H, 3JZ7.4 Hz, H–C(Ar)),
7.16–7.06 (m, 6H, H–C(Ar)), 5.56, 5.22 (2s, 2H,
Tetrahedron: Asymmetry 2002, 13, 2105. (x) Nose, M.;
´
Suzuki, H. Synthesis 2002, 1065. (y) Alonso, D. A.; Najera,
3
CH2]C(7)), 5.39 (br s, 1H,(( H–C(2)), 4.60 (q, 1H, JZ
2
6.2 Hz, H–C(10)), 3.76 (d, 1H, AB syst, JZ14.2 Hz, Ha–
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2
C(8)), 3.61 (br s, 1H, H–C(5)), 3.45 (d, 1H, JZ14.2 Hz,
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2
AB syst, Ha–C(6)), 1.82 (br d, 1H, JZ14.2 Hz, AB syst,
Hb–C(6)), 1.51 (d, 3H, 3JZ6.8 Hz, CH3–C(2)), 1.27 (s, 3H,
3
CH3–C(4)), 1.25 (d, 3H, JZ6.8 Hz, H–C(20). 13C NMR
(C6D6, 400 MHz, C70 8C): d 164.2, 143.4, 140.6, 133.6,
132.2, 130.6, 129.9, 129.7, 128.9, 128.8, 128.2, 126.8,
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25
463.1558. [a] C76 (c 1.0 CHCl3).
589
Acknowledgements
This project was supported by F. Hoffmann-La Roche Ltd
(Roche Research Foundation Grant), by the Swiss National
Science Foundation (grant no. 200020-100002). Secretariat
`
d’Etat a l’Education et la Recherche (SER) (TRloH FP6
project, grant no. 03.0738). We would like to thank Dr.
Rosario Scopelliti for X-ray diffraction measurements. We
´
thank also Mr. Martial Rey, Franscisco Sepulveda, and Dr.
Alain Razaname for technical help.
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