Development of a new carbon - carbon bond forming reaction. New organic chemistry of sulfur dioxide. Asymmetric four-component synthesis of polyfunctional sulfones

Article abstract of DOI:10.1021/jo0101712

At low temperature 1-alkoxy-1,3-dienes add to sulfur dioxide activated by a Lewis or Bronstedt acid and generate zwitterionic intermediates that can be quenched by enoxysilanes. The resulting β,γ-unsaturated silyl sulfinates can be desilylated and reacted with methyl iodide to provide polyfunctional sulfones. Exploratory studies of this four-component synthesis of sulfones are reported. Enantiomerically pure derivatives containing up to three new stereogenic centers can be obtained using enantiomerically pure (E,E)-1 -alkoxy-2-methylpenta-1,3-dienes derived from α-methyl benzyl alcohols, including the Greene's chiral auxiliary. The stereochemistry of the reactions is consistent with a mechanism involving the suprafacial hetero-Diels - Alder addition of sulfur dioxide to the 1-alkoxy-1,3-dienes that are rapidly ionized into zwitterionic intermediates.

Full text of DOI:10.1021/jo0101712

5080
J . Org. Chem. 2001, 66, 5080-5093
Develop m en t of a New Ca r bon -Ca r bon Bon d F or m in g Rea ction .
New Or ga n ic Ch em istr y of Su lfu r Dioxid e. Asym m etr ic
F ou r -Com p on en t Syn th esis of P olyfu n ction a l Su lfon es
Vera Narkevitch, Sophie Megevand, Kurt Schenk, and Pierre Vogel*
Section de Chimie, Universite´ de Lausanne, BCH, CH-1015 Lausanne-Dorigny, Switzerland, and
Institut de Cristallographie, BSP, Universite´ de Lausanne, CH-1015 Lausanne-Dorigny, Switzerland
pierre.vogel@ico-unil-ch
Received February 13, 2001
At low temperature 1-alkoxy-1,3-dienes add to sulfur dioxide activated by a Lewis or Brønstedt
acid and generate zwitterionic intermediates that can be quenched by enoxysilanes. The resulting
â,γ-unsaturated silyl sulfinates can be desilylated and reacted with methyl iodide to provide
polyfunctional sulfones. Exploratory studies of this four-component synthesis of sulfones are
reported. Enantiomerically pure derivatives containing up to three new stereogenic centers can be
obtained using enantiomerically pure (E,E)-1-alkoxy-2-methylpenta-1,3-dienes derived from R-meth-
yl benzyl alcohols, including the Greene’s chiral auxiliary. The stereochemistry of the reactions is
consistent with a mechanism involving the suprafacial hetero-Diels-Alder addition of sulfur dioxide
to the 1-alkoxy-1,3-dienes that are rapidly ionized into zwitterionic intermediates.
In tr od u ction
folene), a reaction known since 1914.11,12 Our group has
shown that simple alkyl-substituted 1,3-dienes can un-
dergo hetero-Diels-Alder additions with SO2 giving the
corresponding 3,6-dihydro-1,2-oxathiin-2-oxides (sul-
tines).13 These cycloadducts are unstable above -50 °C
and undergo fast cycloreversions liberating the starting
dienes and SO2.14,15 Both the hetero-Diels-Alder and
cycloreversion are catalyzed by protic or Lewis acids and
by SO2 itself.16,17 Electron-rich 1,3-dienes such as (E)-1-
methoxybutadiene (1) adds SO2 below -60 °C without
catalyst, giving sulfolene 2 exclusively (Scheme 1).18 No
trace of the corresponding sultine 3 could be detected for
Lewis acid catalyzed reactions, even at -110 °C. When
diene 1 and enoxysilane 4 are mixed in SO2 precomplexed
with a Lewis acid such as Yb(OTf)3 or (t-Bu)Me2SiOTf, a
carbon-carbon bond is formed between the electron-rich
alkene and the electron-rich diene to give the silyl
sulfinate 5. At -78 °C the reaction is terminated in 4-5
h. The sulfinate 5 can be converted either into alkene 6
by hydrolysis and retro-ene elimination of SO2 or into
sulfone 7 by desilylation with Bu4NF and reaction with
methyl iodide.19 Mixtures of sulfolene 2, enoxysilane 4,
SO2, and Lewis acids do not lead to the formation of the
corresponding sulfinate 5 but are polymerized above -20
The organic chemistry of sulfur dioxide has been
limited to the formation of arenesulfinic acids (Friedel-
Crafts sulfinylation1), the copolymerization of SO2 with
alkenes or alkynes (polysulfone synthesis2), the synthesis
of sulfinates by reaction with organometallic com-
pounds,3,4 the ring opening of oxiranes and oxetanes4,5
leading to polysulfites,4,6 the synthesis of sulfones,4,7 the
isomerization of alkenes via ene reaction/sigmatropic
shift/retro-ene elimination sequence,8 and the cheletropic
additions of conjugated polyenes9,10 forming cyclic sul-
fones, as the [ω2s+π4s] addition of SO2 to isoprene
producing 2,5-dihydro-3-methylthiophene-1,1-dioxide (sul-
(1) See, for example: Friedel, C.; Crafts, J . Ann. 1888, 14, 442.
Knoevenagel, E.; Kenner, H. Ber. Dtsch. Chem. Ges. 1908, 41, 3318.
(2) See, for example: Marvel, C. S.; Glavis, F. J . J . Am. Chem. Soc.
1938, 60, 2622. Marvel, C. S.; Audrieth, L. F.; Sharkey, W. H. J . Am.
Chem. Soc. 1942, 64, 1229. Florjanæzyk, Z. Prog. Polym. Sci. 1991,
16, 509.
(3) See, for example: Kitching, W.; Fung, C. W. Organomet. Chem.
Rev. 1970, A5, 281. Wo´jcicki, A. Adv. Organomet. Chem. 1974, 12, 31.
(4) Florjanczyk, Z.; Raducha, D. Pol. J . Chem. 1995, 69, 481.
(5) Florjanczyk, Z.; Raducha, D. Makromol. Chem. 1993, 194, 2605.
(6) Soga, A.; Hattori, I.; Kinoshita, J .; Ikeda, S. J . Polym. Sci., Polym.
Chem. Ed. 1972, 15, 745. Soga, A.; Kiyochari, K.; Hattori, I.; Ikeda, S.
Makromol. Chem. 1980, 101, 2151. Tillett, J . G. Chem. Rev. 1976, 76,
747.
(7) See, for example: Simpkin, N. S. Sulfones in Organic Chemistry;
Tetrahedron Organic Chemistry Series; Pergamon Press: Elmsford,
NY, 1993; Vol. 10, Chapter 8. Takeuchi, H.; Nagai, T.; Tokura, N. Bull.
Chem. Soc. J pn. 1973, 46, 695. Barton, D. H. R.; Lacher, B.; Misterk-
iewicz, B.; Zard, S. Z. Tetrahedron 1988, 44, 1153.
(8) Rogic, M.; Masilamani, D. J . Am. Chem. Soc. 1977, 99, 5219.
Capozzi, G.; Lucchini, V.; Marcuzzi, F.; Melloni, G. Tetrahedron Lett.
1980, 21, 3289.
(9) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Academic Press: New York, 1970. Turk, S. D.; Cobb, R. L.
In 1,4-Cycloaddition Reactions; Hamer, J ., Ed.; Academic Press: New
York, 1967; p. 13. Dewar, M. J . S. J . Am. Chem. Soc. 1984, 106, 209.
(10) Homoconjugated dienes that cannot be rearranged into conju-
gated 1,3-dienes via ene reactions add to SO2, giving sulfones via
homocheletropic additions. De Lucchi, O.; Lucchini, V. J . Chem. Soc.,
Chem. Commun. 1982, 1105. Roulet, J .-M.; Deguin, B.; Vogel, P. J .
Am. Chem. Soc. 1994, 116, 3639. Roulet, J .-M.; Vogel, P. Bull. Soc.
Chim. Fr. 1994, 131, 822. Roulet, J .-M.; Vogel, P.; Wieseman, F.;
Pinkerton, A. A. Tetrahedron 1995, 51, 1685.
(11) De Bruin, G. Proc. K. Ned. Akad. Wet. 1914, 17, 585. See also:
Backer, H. J .; Strating, J . Recl. Trav. Chim. Pays-Bas 1934, 53, 525.
(12) Ketene undergoes a [ω2s + π2s]-cycloaddition with SO2. Bohem,
J . M.; J oullie´, M. M. J . Org. Chem. 1973, 38, 2652.
(13) Earlier examples involve extremely reactive dienes (1,4,5,6-
tetramethyl-2,3-dimethylidenetricyclo[2.1.1.05,6]hexane and o-quin-
odimethane): Heldeweg, R. F.; Hogeveen, H. J . Am. Chem. Soc. 1976,
98, 2341. Durst, T.; Te´treault-Ryan, L. Tetrahedron Lett. 1978, 26,
2353.
(14) Deguin, B.; Vogel, P. J . Am. Chem. Soc. 1992, 114, 9210.
(15) Deguin, B.; Vogel, P. Tetrahedron Lett. 1993, 34, 6269.
(16) Fernandez, T.; Sordo, J . A.; Monnat, F.; Deguin, B.; Vogel, P.
J . Am. Chem. Soc. 1998, 120, 13276.
(17) For rare examples of photoinduced [2 + 2]-cycloadditions of SO2,
see: Dunkin, I. R.; MacDonald, J . G. J . Chem. Soc., Perkin Trans. 2
1984, 2079. Sianesi, D.; Bernardi, G. C.; Moggi, G. Tetrahedron Lett.
1970, 16, 1313.
(18) Roversi, E.; Monnat, F.; Schenk, K.; Vogel, P.; Bran˜a, P.; Sordo,
J . A. Chem. Eur. J . 2000, 6, 1858.
10.1021/jo0101712 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/04/2001

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5081
Sch em e 1
Sch em e 3
Pure (1E,3E)-1-methoxy-2-methylpenta-1,3-diene (12)
was prepared following Mikami’s procedure.22 Attempts
to prepare diene 12 through O-methylation of the lithium
or sodium enolate of 2-methylpent-2-enal, the product of
crotonalization of propanal, all failed. Similarly, attempts
to prepare diene 13 by O-benzylation of enolates of
2-methylpent-2-enal were not met with success. We thus
turn to the method developed by Danishefsky and co-
workers23 for the synthesis of electron-rich 1,3-dienes.24
Pentan-3-one was condensed with ethyl formate to give
23, which reacted with benzyl alcohol in the presence of
p-toluenesulfonic acid to furnish 24. Reduction of 24 with
LiAlH4 in THF generated allylic alcohol 25. It was
esterified with p-nitrobenzoyl chloride, giving ester 26,
which eliminated p-nitrobenzoic acid at room tempera-
ture to provide diene 13 (60%). The same procedure
(Scheme 3) applied to 23 and 2-(trimethylsilyl)ethanol
furnished diene 14 (40%).
Sch em e 2
When a 1:1 mixture of diene 12 and enoxysilane 9, 10,
or 11 was added to a 1:4 solution of SO2/CH2Cl2 contain-
ing 0.2-0.8 equiv of Yb(OTf)3, a deep yellow solution was
immediately formed at -78 °C (probably charge-transfer
complexes of alkenes, dienes with SO2). After 12 h at -78
°C, the yellow color faded. Evaporation of SO2, followed
by the addition of Bu4NF and an excess of methyl iodide,
led to a complicated mixture from which a single, pure
compound could be isolated in 6% yield by column
chromatography on silica gel. This compound was identi-
fied as 16 by its spectral data and by single-crystal X-ray
radiocrystallography. This product resulted from the
diastereoselective R-methylation (by MeI, Bu4NF) of the
expected ketone 15. Attempts, including changing con-
centrations, mode of addition and the nature of the Lewis
acid, to improve the yield of the reaction cascade 9 + 12
+ SO2 + MeI f 15 all failed. With (t-Bu)Me2SiOTf,
Sn(OTf)2, MgBr2, TiCl4, ZnCl2, ZnBr2, Ti(OEt)4, Bu3BOTf,
BCl3, and BF3‚OEt2 only polymeric materials were formed.
No better results were obtained using enoxysilanes 10
or 11.
°C, thus demonstrating that sulfolene 2 is not able to
generate any electrophilic species responsible for the
oxyallylation of enoxysilane 4 at low temperature. We
have assumed that sultine 3 is formed faster than
sulfolene 2 and is quickly heterolyzed into a zwitterionic
intermediate of type 8 able to add to the enoxysilane.
Preliminary experiments with enantiomerically pure
1-alkoxy-2-methyl-1,3-dienes has opened an asymmetric
version of our new four-component synthesis of allyl
methyl sulfones.20 We report further exploratory studies
on this reaction and shall show that enantiomerically
pure polyfunctional sulfones containing up to three
stereogenic centers and a (Z)-allylic moiety can be pre-
pared readily. The results shed light on the mechanism
of the reaction cascade involved in the new carbon-
carbon bond forming reaction we have discovered.21
Resu lts a n d Discu ssion
We then explored the reactivity of the 1-benzyloxydiene
13 and enoxysilane 9. Under conditions similar to those
described above for the preparation of 16 and using Yb-
(OTf)3 as Lewis acid promoter, we obtained the expected
methyl sulfone 17 in 6% yield, together with products of
benzyl alcohol elimination from 17. Testing a number of
alternative acid promoters, we finally discovered that
(CF3SO2)NH25 led to the formation of 17 with a better
The first series of experiments were designed to
evaluate the best possible 1-alkoxy-2-methylpenta-1,3-
diene for optimal yields in the four-component synthesis
of polyfunctional alkyl methyl sulfones (Scheme 2). We
explored a number of conditions with enoxysilanes 9-11
and (E,E)-1-alkoxy-2-methylpenta-1,3-dienes 12-14.
(19) Deguin, B.; Roulet, J .-M.; Vogel, P. Tetrahedron Lett. 1997, 38,
6197. Roulet, J .-M.; Puhr, G.; Vogel, P. Tetrahedron Lett. 1997, 38,
6201.
(20) Narkevitch, V.; Schenk, K.; Vogel, P. Angew. Chem., Int. Ed.
2000, 39, 1806.
(21) For a preliminary study on the intermediacy of sultines, see:
Megevand, S.; Moore, J .; Schenk, K.; Vogel, P. Tetrahedron Lett. 2001,
42, 673.
(22) Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994,
116, 2812.
(23) Danishefsky, S.; Yan, C.-F.; Singh, R. K.; Gammill, R. B.;
McMurry, P. M., J r.; Fritsch, N.; Clardy, J . J . Am. Chem. Soc. 1979,
101, 7001.
(24) Myles, D. C.; Bigham, M. H. Org. Synth. 1992, 70, 231.
(25) Mathieu, B.; Ghosez, L. Tetrahedron Lett. 1997, 38, 5497.

5082 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
Sch em e 4
Sch em e 5
number of Diels-Alder additions, competitive Michael
additions can occur, especially if the difference in stability
between the s-cis-diene (necessary for the Diels-Alder
addition) and the s-trans conformer (most stable con-
former) is high.26 We propose that the formation of 29
arises from a concurrent Michael addition of the more
stable s-trans conformer of diene 13 with SO2, leading to
the (E)-zwitterionic intermediate 32 (Scheme 4), which
reacts with the enoxysilane 11. This implies that the
competition between the hetero-Diels-Alder addition and
the Michael addition of dienes with SO2 depends on the
nature of the acid promoter. This statement implies that
the (Z)-alkenes (e.g., 19, Scheme 4) formed in our four-
component synthesis of sulfones arise exclusively from
the corresponding (Z)-zwitterionic intermediates (e.g., 35)
and that the latter are formed by ionization of the
corresponding sultines (e.g., 34) arising from the suprafa-
cial hetero-Diels-Alder addition of SO2 to the starting
1-oxy-1,3-dienes. These hypotheses are confirmed by the
â,ꢀ-unlike relative configuration found for all of our
ketones with (Z)-alkene moieties21 (X-ray of 16, 19, 20).
The â,ꢀ-like relative configuration observed for 29 can be
interpreted in terms of the formation of zwitterionic
intermediate 32, which adds to the enoxysilane 11 on the
face anti with respect to that occupied by the sulfinate
moiety, as in the case of 35.
yield (45%). Under similar conditions the reaction cas-
cades involving enoxysilanes 10 and 11 gave sulfones 18
and 19, respectively, in 69% and 62% yield, respectively.
By using Yb(OTf)3 instead of (Tf)2NH, 18 and 19 were
isolated in 71% and 32% yield, respectively. For the
combination 11 + 13 + SO2 + MeI the best promoter
appeared to be (t-Bu)Me2SiOTf, giving methyl sulfone 19
in 77% yield. These exploratory studies show that the
choice of the acid promoter must take into account the
nature of the starting diene and that of the enoxysilane.
All experiments using TiCl4 or TiBr4 as Lewis acid led
to polymerization. With MgBr2‚OEt2, the condensation
was slower than with other acid promoters and gave
mostly polymeric material. Nevertheless, in the case of
enoxysilane 11 reacting with 13, a low yield of a mixture
of the expected methyl sulfone 19 and its (E)-isomer 29
was obtained, from which pure 29 could be isolated in
8% yield (Scheme 4). The structures of 17-19 and 29
The condensation of diene 14 with enoxysilanes 9, 10,
and 11 (SO2/Yb(OTf)3), followed by methylation (MeI) of
the intermediate silyl sulfinates, generated the methyl
sulfones 20, 21, and 22, respectively, which were isolated
in 47%, 20%, and 50% yield, respectively. Lower yields
were obtained using acid promoters ((Tf)2NH, (t-Bu)-
Me2SiOTf) different from Yb(OTf)3. The structures of
20-22 were deduced from their spectral data. That of
20 was confirmed by single-crystal X-ray diffraction
studies.
As already demonstrated in the case of the reaction
cascade involving 1-methoxybutadiene 1 (Scheme 1),18
dienes 13 and 14 reacted with pure SO2 in CFCl3/
CD2Cl2 at -74 °C, giving the corresponding sulfolenes
37 and 38, respectively (Scheme 5). These unstable
compounds were polymerized when mixed with enoxysi-
lane 9, 10, or 11 and an acid promoter (Yb(OTf)3, (t-Bu)-
Me2SiOTf or (Tf)2NH). The structures of sulfolenes 37
1
were established by their spectral data (2D NOESY H
NMR). That of 19 was confirmed by single-crystal X-ray
diffraction studies.21 Reduction of 29 with NaBH4 in
MeOH led to a 4:1 mixture of diastereomeric alcohols 30
and 31. Single-crystal X-ray diffraction studies on 30
confirmed the structure of 29. The (Z)-alkene 19 was not
isomerized into 29 in the presence of SO2 and MgBr2‚
OEt2 at -78 °C (2 weeks). When diene 13 and enoxysi-
lane 11 were allowed to react first with SO2/(t-Bu)-
Me2SiOTf and then with SO2/MgBr2‚OEt2, subsequent
SO2 evaporation and treatment with Bu4NF and MeI
gave 19 exclusively. These results demonstrated that the
formation of the (E)-alkene 29 follows a different route
than the formation of its (Z)-isomer 19. As for a large
1
and 38 were given by their H and 13C NMR data. That
of 37 was confirmed by its ozonolysis in CH2Cl2/SO2
followed by workup with anhydrous MeOH and CeCl3,
which gave a mixture from which 39 was isolated and
1
characterized by its H and 13C NMR spectra.
We have also explored the possibility to prepare methyl
sulfones containing an oxy-substituted alkene moiety
(26) See, for example: Bargagna, A.; Schenone, P.; Badavalli, F.;
Lugobradi, M. J . Heterocycl. Chem. 1980, 17, 1201. Clever, H. A.; Wang,
G.; Mollberg, W. C.; Padias, A. B.; Hall, H. K., J r. J . Org. Chem. 1992,
57, 6837. Kataoka, F.; Shimizu, N.; Nishida, S. J . Am. Chem. Soc. 1980,
102, 711. Gompper, R.; Heinemann, U. Angew. Chem., Int. Ed. Engl.
1980, 19, 216.

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5083
Sch em e 6
Sch em e 7
(Scheme 6). With this goal in mind we prepared the (E,E)-
1-alkoxy-3-oxy-2-methylpenta-1,3-dienes 40-43. Diene
40 (97%) was derived from 24 following Danishefsky’s
method.23 Diene 40 was reacted with benzoyl fluoride in
the presence of Bu4NF27 to give 41 in 72% yield. Simi-
larly, 27 was converted into 42 (93%) and 43 (31%).
Attempts to carry out oxyallylations with the 3-silyloxy-
dienes 40 and 42 were not met with success. With the
more stable 3-benzoyloxydienes 41 and 43, their conden-
sation with enoxysilane 10, SO2, and MeI following
procedures similar to those described above provided
sulfones 44 and 45 in 67% and 42% yield, respectively.
Their structures were deduced from their spectral data,
and that of 45 was confirmed by single-crystal X-ray
radiocrystallography.
Sch em e 8
Iter a tive Oxya llyla tion s. The condensation of enox-
ysilane 10 with 1-benzyloxydiene 13 and SO2 in the
presence of Yb(OTf)3 (-78 °C, 5 h) generated a silyl
sulfinate that was converted into the corresponding â,γ-
unsaturated sulfinic acid 46 on treatment with NH4Cl
in 1:1 MeOH/H2O. At 0 °C 46 underwent a retro-ene
28
elimination of SO2 in about 15 h, giving oct-6-en-2-one
47 in 71% yield.19 The kinetic lithium enolate of 47 was
quenched with Me3SiCl to give enoxysilane 48 in quan-
titative yield. When 48 was reacted with 1-benzyloxydi-
ene 13 and SO2 in the presence of (t-Bu)Me2SiOTf (-78
°C, 15 h), a mixture of silyl sulfinates was formed. After
SO2 evaporation, treatment with Bu4NF and MeI (0 °C,
4 h) a 1:1 mixture of sulfones 49 and 50 was obtained
and isolated in 47% yield. Although the yield of this
reaction remains modest, this experiment demonstrates
the possibility to run two successive oxyallylations of
acetone (Scheme 7).
coholysis of 3-ethoxy-2-methylacrolein29 led to racemiza-
tion. We thus used basic conditions for that transalco-
holysis, reacting 3-ethoxy-2-methylacrolein with the
sodium alcoholate derived from (-)-(S)-1-(2,4,6-triisopro-
pylphenyl)ethanol. This gave enal (-)-57e in 79% yield.
It was then reacted with methyltriphenylphosphonium
bromide and lithium diisopropylamide giving (+)-55 in
87% yield.
Dienes (-)-51, (+)-52, (-)-53, (+)-54, and (+)-55 mixed
with 1-phenyl-1-(trimethylsilyloxy)ethene (9) were al-
lowed to react with a large excess of SO2 precomplexed
with Yb(OTf)3 in CH2Cl2. After disappearance of the
starting diene (yellow complex with SO2) (-90 to -78 °C,
5-24 h) the solvents were evaporated at -78 °C (0.1
Torr), and then at 0 °C a solution of Bu4NF in THF and
an excess of MeI were added. After 16-24 h at 0-20 °C
the products were isolated by flash chromatography on
silica gel. The fraction containing the methyl sulfones
were analyzed by 1H and 13C NMR; the results are shown
in Table 1. The best diastereoselectivity was observed for
the reaction of diene (+)-55, which provided a 25:1
mixture of sulfones (-)-66 and 67 (79% yield, recovery
of 20% of (+)-55). The structure of (-)-66 was established
by X-ray radiocrystallography.20 The trifluoroacetolysis31
(Scheme 9) of sulfone mixtures 58 + 59, 60 + 61, and 62
Asym m etr ic Ver sion of th e Fou r -Com p on en t Syn -
th esis of Su lfon es. In a first series of experiments we
explored the behavior of enantiomerically pure (>99% ee)
1-benzyloxy-2-methylbutadienes 51-55, which were pre-
pared (Scheme 8) following Breitmaier’s diene synthesis29
and using readily available enantiomerically pure sec-
ondary alcohols 56a -e.29,30
In the case of the synthesis of (+)-55 bearing the
Greene’s chiral auxiliary,30 we found that acidic transal-
(27) Limat, D.; Schlosser, M. Tetrahedron Lett. 1995, 51, 5799.
(28) King, M. D.; Sue, R. E.; White, R. H.; Young, D. J . J . Chem.
Soc., Chem. Commun. 1993, 1797. Hiscock, S. D.; Isaacs, N. S.; King,
M. D.; Sue, R. E.; White, R. H.; Young, D. J . J . Org. Chem. 1995, 60,
7166. Baudin, J .-B.; J ulia, S. A. Tetrahedron Lett. 1988, 29, 3255.
Peterson, P. E.; Brockington, R.; Dunham, M. J . Am. Chem. Soc. 1975,
97, 3517.
(29) (a) Rieger, R.; Breitmaier, E. Synthesis 1990, 697. (b) Flock,
M.; Nieger, M.; Breitmaier, E. Liebigs Ann. Chem. 1993, 451. (c) Zadel,
G.; Rieger, R.; Breitmaier, E. Liebigs Ann. Chem. 1991, 1343.
(30) De Arevedo, M. B. M.; Greene, A. E. J . Org. Chem. 1995, 60,
4940. Nebois, P.; Greene, A. E. J . Org. Chem. 1996, 61, 5210.
Kanazawa, A.; Delair, P.; Pourashraf, M.; Greene, A. E. J . Chem. Soc.,
Perkin Trans. 1 1997, 1911.
(31) Posner, G. H.; Wettlaufer, D. G. J . Am. Chem. Soc. 1986, 108,
7373.

5084 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
Ta ble 1. Asym m etr ic F ou r -Com p on en t Syn th esis of Su lfon es w ith (E)-1-Ben zyloxy-2-m eth ylbu ta d ien esa
a
Standard conditions: 10- to 20-fold excess of SO2, 0.5-1 equiv of Yb(OTf)3, -78 °C; then evaporation, Bu4NF, MeI, 20 °C. Ee (>99%)
of sulfones determined by Mosher’s esters on derivatives; see text and ref 20. By 1H NMR of the mixture of sulfones, after flash
b
chromatography. Similar product ratios were found from the 1H NMR spectra of crude reaction mixture, when analyzable. c Considering
the recovery of the starting diene. Using (Tf)2NH at -100 °C, instead of Yb(OTf)3 at -78 °C. e Minor compound is the (E)-alkene 84.
d
f Structure by chemical correlation with aldols obtained by trifluoroacetolyis (Scheme 9). g Racemic diene use in this experiment. Structure
h
i
by single-crystal X-ray radiocrystallography. The change over of diastereoselectivity is due to the fact that chiral auxiliaries (-)-51,
(+)-52, and (-)-53 have the (1R) configuration, whereas (+)-54 and (+)-55 have the (1S) configuration.
Sch em e 9
slow in their quenching of the zwitterionic sulfinate
intermediates. The structures of 76 and 77 were not
established unambiguously. We turned then to the
electron-rich 1-cyclopropyl-1-(trimethylsilyloxy)ethene (78).
Its reaction with (+)-55, SO2, and then MeI provided a
10.5:1 mixture of sulfones (-)-79 and (-)-80 in good yield.
The major product (-)-79 was isolated pure, and its
structure was established by X-ray radiocrystallography.
Trifluoroacetoylsis of pure (-)-79 provided aldol (-)-81
(85%).
We have also tested the reactivity of the less electron-
rich vinyloxytrimethylsilane (82) and were surprised that
it was able to quench the zwitterionic intermediate
assumed to be formed in the reactions of diene (+)-55
with SO2 in the presence of acid promoters. Using Yb-
(OTf)3 (-78 °C, 16 h) a 6.1:1 mixture of sulfones (-)-83
and 84 was obtained in 31% yield (56% yield considering
the recovery of unreacted (+)-55). Pure (()-83 derived
from (()-55 gave crystals suitable for X-ray radiocrys-
tallography. The structure of the minor sulfone 84 was
deduced from its 1H NMR spectrum (2D NOESY): it
contains an (E)-alkene moiety. Unfortunately we could
not establish whether it has the (1′S,3S) or (1′S,3R)
configuration. A similar experiment using (Tf)2NH as acid
promoter (-78 °C, 2 h) led to a 4:1 mixture of sulfones
84 and 85 isolated in 23% yield. The major sulfone
crystallized, but the crystals were not suitable for X-ray
radiocrystallography. In the latter experiment, the iso-
meric (Z)-sulfone (-)-83 was not observed!
+ 63 (homogeneous mixtures after flash chromatography
on silica gel) (Table 1) gave aldol (+)-68 (with [R]D25
)
+30 ( 2, 35 ( 3 and 23 ( 3, respectively. Pure (-)-66
gave (-)-68 with [R]2D5 ) -52 ( 2.
By using the silyl enol ether of acetone 10 for the
oxyallytion with dienes (-)-51, (+)-52, and (+)-55, mix-
tures of sulfones 69 + 70, 71 + 72, and 73 + 74,
respectively, were obtained (Table 1). In this case too,
the best diastereoselectivity was observed with diene (+)-
55 bearing the Greene’s chiral auxiliary. When the
oxyallylation is promoted with Yb(OTf)3 at -78 °C, the
product ratio (73/74) reaches 5.2:1. Using (Tf)2NH as acid
promoter and running the reaction at -100 °C, the
product ratio increases to 7.0:1. The structure of the
major sulfone (-)-73 was established by X-ray radiocrys-
tallography. The structures of sulfones 69-72 were
deduced from their spectral data and by their trifluoro-
acetolysis (Scheme 9).31 The mixture of 69 + 70 gave (+)-
75 ([R]2D5 ) +4.6 ( 1). That of 71 + 72 furnished (+)-75
([R]2D5 ) +8.8 ( 1). Pure (-)-73 gave aldol (-)-75 ([R]2D5
-11.0 ( 1).
)
These interesting results led us to apply our asym-
metric four-component synthesis of sulfones to other
enoxysilanes. With 1-(tertiobutyl)-1-(trimethylsilyloxy)-
ethene and diene (+)-55 a 3.3:1 mixture of sulfones 76 +
77 was obtained in mediocre yield. This observation
suggested that sterically hindered enoxysilanes are too

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5085
Ta ble 2. Asym m etr ic F ou r -Com p on en t Syn th esis of Su lfon es w ith Dien e (-)-89a
a
Standard conditions: (Tf2)NH, -78 °C (3-5 h); then evaporation at -78 °C, Bu4NF/THF + MeI, -78 to 20 °C (15 h); purification by
column chromatography on silica gel. By 1H NMR of the crude reaction mixture. c Structure by single-crystal X-ray radiocrystallography.
b
Experiments described for the reactions with (()-89 derived from (+)-56e. e Using (t-Bu)Me2SiOTf as acid promotor. f Structure not
d
g
established unambiguously. Assumed structure; diastereomeric structure with the (4S,5R,6Z,8S) configuration cannot be ruled out.
The enantiomeric purity of the pure sulfones isolated
above was established by converting aldols (-)-68 and
(-)-75 into cis- or trans-1,3-diols and by 19F NMR of the
corresponding Mosher’s diesters.20 The method is il-
lustrated for aldol (-)-81. Its reduction under Nasaraka’s
conditions32 (Et2BMe/NaBH4) afforded diol (+)-86 (83%).
The syn relationship of the diol was confirmed by the 13C
NMR spectrum of its acetonide 87 (δC ) 30.2, 19.5 ppm,
for Me2C(2)).33 The 19F NMR spectrum of Mosher’s
diester34 88 (δ(19F) ) -71.406, -71.652 ppm) showed (13C
satellites) that (+)-86 has an ee >99%.
ously by X-ray radiocrystallography of the major isomers
obtained pure by column chromatography on silica gel.
Except for reaction 11 + (-)-89 + SO2 + MeI f (-)-94
the diastereoselectivities observed with the other enoxy-
silanes are lower with diene (-)-89 (Table 2) than with
diene (+)-55. These observations are not explained
readily. Nevertheless they demonstrate that steric hin-
drance between the zwitterionic intermediate (arising
from the reaction of the 1-oxydiene with SO2 and the acid
promoter) and the enoxysilane is not the unique factor
affecting yield and diastereoselectivity of the oxyallyla-
tion.
The reaction of diene (-)-89 with the (Z)-enoxysilane
98 derived from pentan-3-one35 led to a 2.6:1 mixture of
isomeric sulfones (-)-99 and (-)-100, which were sepa-
rated in 63% and 22% yield, respectively. The structure
of (-)-99 was established by X-ray radiocrystallography.
Since other diastereomers represented less than 5% of
the reaction mixture, we can state that the diastereose-
lectivity (1′S,5S) is better than 15:1 in the case of (-)-99
and better than 4.4:1 for the formation of (-)-100. As for
the other sulfones of Table 2, trifluoroacetolysis of
pure (()-90, (-)-94, (-)-99, and (-)-100 (Table 2) fur-
nished the unprotected aldols (()-101 (90%), (-)-102
(95%), (-)-103 (99%), and (-)-104 (86%), respectively, in
good yields. Unfortunately, the chiral auxiliary (Greene’s
alcohol 56e) was completely racemized during these
reactions.
Asym m etr ic F ou r -Com p on en t Syn th esis of Su l-
fon es Usin g a En an tiom er ically P u r e (E,E)-1-Alkoxy-
2-m eth ylp en t-1,3-d ien e. The Wittig olefination of enal
(-)-57e (Scheme 8) with ethyltriphenylphosphonium
bromide and lithium diisopropylamide was highly ste-
reoselective and afforded diene (-)-89 in 93% yield. Its
condensation with various enoxysilanes, SO2, and MeI
were explored, and the results are presented in Table 2.
The best yield of methyl sulfones were observed when
using (Tf)2NH as acid promoter. The best diastereose-
lectivity was found for the reaction involving the most
sterically hindered enoxysilane 11, which led to a 13.4:1
mixture (91% yield) of sulfones (-)-94/95 using (Tf)2NH
as acid promoter. With (t-Bu)Me2SiOTf, the diastereose-
lectivity was increased to 17.1:1. Except for the sulfones
96 and 97 derived from enoxysilane 78, all other sulfones
of Table 2 have their structure established unambigu-
Tow a r d a Mech a n ism for th e Oxya llyla tion . Al-
though more work is required to approach a global view
of the overall processes intervening in our four-compo-
nent synthesis of sulfones, we think that all of the results
(32) Nasaraka, K.; Pai, F. G. Tetrahedron 1984, 40, 2233. Chen, K.
M.; Hardtmann, G. E.; Prasad, K.; Repic, O.; Shapiro, M. J . Tetrahe-
dron Lett. 1987, 28, 155.
(33) Rychnovsky, S. D.; Rogers, B. N.; Richardson, T. I. Acc. Chem.
Res. 1998, 31, 9 and references therein.
(34) Dale, T. A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512.
Dale, T. A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34, 2543.
(35) Nakamura, E.; Hashimoto, K.; Kuwajima, I. Tetrahedron Lett.
1978, 24, 2079.

5086 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
Sch em e 10
with the 1′,â-like and â,ꢀ-unlike configurations found for
all the ketones obtained in this work.
Con clu sion
Our four-component sulfone synthesis can be applied
to generate a variety of polyfunctional methyl sulfones
with one (Z)-alkene unit and containing up to three new
stereogenic centers. Enantiomerically pure derivatives
can be obtained using enantiomerically pure (E)-1-alkoxy-
2-methylbutadienes or (E,E)-1-alkoxy-2-methylpenta-1,3-
dienes derived from readily available enantiomerically
pure R-methyl benzyl alcohols. The best diastereoselec-
tivities have been found with dienes bearing the Greene’s
chiral auxiliary [(-)-(S)-(2,4,6-triisopropylphenyl)etha-
nol].30 The methyl sulfones derived from (E,E)-1-alkoxy-
2-methylpenta-1,3-dienes are γ,δ-unsaturated ketones
with an allylic sulfone moiety and unlike â,ꢀ-disubstitu-
tion. Using the trimethylsilyl ether of the (Z)-enol of
diethyl ketone, enantiomerically pure (4S,5S,6Z,8R)- and
(4R,5S,6Z,8R)-5-hydroxy-4,6-dimethyl-8-(methylsulfonyl-
)non-6-en-3-one have been prepared. In this case the R,â-
diastereoselectivity of the oxyallylation (face selectivity
of the enoxysilane addition) does not surpass 2.6:1 (4R,5S
vs 4S,5S). Further exploratory studies will have to be
undertaken in order to find suitable dienes and enoxysi-
lanes for better control of the R,â-diastereoselectivity in
the ketone formation.
presented so far can be interpreted in terms of the
mechanisms proposed in Schemes 1 and 4. In particular,
the diastereoselectivity (like configuration for the center
of the chiral benzyl ethers and the â-center of the final
ketones) can be explained by assuming that SO2 is
activated by the acid promoter and that it reacts with a
s-cis-conformer of the 1,3-diene, placing the C-H bond
of the chiral auxiliary in the plane of the diene moiety
as shown with 105 in Scheme 10. This conformer reduces
A1,2-allylic strain and gauche interactions.36 For steric
reasons, the face of the diene syn to the large aromatic
moiety of the chiral auxiliary is less prone to the attack
by the SO2-LA complex. This hypothesis is corroborated
by the observation that the oxyallylation of enoxysilane
9 is more diastereoselective with diene (+)-55 with the
largest aromatic substituent than with the other dienes
(Table 1). Thus dienes 105 undergo face-selective, su-
prafacial hetero-Diels-Alder additions with SO2, giving
the corresponding sultines of type 106, which are ionized
by the acid promoter into zwitterions of type 107.
Alternatively, direct reaction of acid-SO2 complex with
105 giving 107 in one step cannot be ruled out. If
quenching of zwitterions of type 107 by an enoxysilane
should be rapid, i.e., if it does not allow for 107 to
equilibrate with diastereomeric zwitterionic species or
sultines, a good diastereoselectivity is obtained for the
oxyallylation reaction. It implies the addition of the
enoxysilane on the face of the zwitterion anti with respect
to that occupied by the sulfinate moiety (Scheme 10). This
is confirmed firmly by the fact that all oxyallylations give
major products with â,ꢀ-unlike configuration of the
final ketones. At this moment, we cannot exclude an
alternative hypothesis that implies concerted reactions
of enoxysilanes with sultine intermediates of type 106.
The latter hypothesis is consistent with our observation
that the least electron-rich enoxysilane 82 (vinyloxytri-
methylsilane) did not react much more slowly than the
electron-richer derivatives such as 9 (Ph(TMSO)CdCH2)
and 78 (cyclopropyl(TMSO)CdCH2). As already discussed
for the reaction of achiral 1-alkoxy-2-methylpenta-1,3-
dienes (Scheme 4), the path 105 ) 106 ) 107 f 108 or
105 ) 107 f 108 or 105 ) 106 f 108 are all consistent
Exp er im en ta l Section
Gen er a l Rem a r k s. See ref 37. None of the procedures were
optimized. Flash column chromatography (FC) was performed
on Merck silica gel (230-400 mesh).38 Thin-layer chromatog-
raphy (TLC) was carried out on silica gel (Merck aluminum
1
foils). H NMR signal assignments were confirmed by double
irradiation experiments and, when required, by 2D NOESY
and COSY spectra; J values are given in hertz. Dry SO2 was
prepared by passing through a column of alkaline alumina
(Merck, act. I) and redistilled twice under vacuum (vacuum
line, degassing by freeze/thaw cycles).
(E,E)-1-Meth oxy-2-m eth ylp en ta -1,3-d ien e (12). A 1:1
mixture of (E,E)- and (Z,E)-1-methoxy-2-methylpentadiene was
obtained according to the procedure of Mikami.22 FC separated
the two dienes. Data for 12: 1H NMR (400 MHz, CDCl3) δ
6.04 (dqd, 1H, J ) 15.4, 1.4, 1.3), 5.47 (dd, 1H, J ) 15.4, 6.6),
3.62 (s, 3H), 1.76 (ddd, 1H, J ) 6.6, 1.4, 0.5), 1.69 (d, 3H, J )
1.3).
(E)-1-(Ben zyloxy)-2-m eth ylp en t-1-en -3-on e (24). A mix-
ture of 1-hydroxy-2-methylpent-1-en-3-one (23) (9.91 g, 86.9
mmol),23 benzyl alcohol (10.5 mL, 100 mmol), toluene (150 mL),
and p-toluenesulfonic acid (2 mg) was heated under reflux in
a Dean-Stark apparatus for 3 h. After the mixture cool to 20
°C, NaHCO3 (1 g) was added, and the mixture was washed
with a saturated aqueous solution of NaHCO3 (50 mL). The
aqueous layer was extracted with CH2Cl2 (150 mL, 5 times).
The combined organic extracts were dried (MgSO4), and the
solvent was evaporated in vacuo (0.3 Torr, 80 °C) giving a
colorless oil (13.8 g, 77%): 1H NMR (400 MHz, CDCl3) δ 7.34-
7.40 (m, 6H), 5.06 (s, 2H), 2.51 (q, 2H, J ) 7.3), 1.78 (d, 2H, J
) 1.1), 1.08 (t, 3H, J ) 7.3).
(E,E)-1-(Ben zyloxy)-2-m eth ylp en ta -1,3-d ien e (13). A so-
lution of 24 (5.5 g, 29.2 mmol) in anhydrous THF (50 mL) was
added dropwise to a stirred suspension of LiAlH4 (1.2 g, 31.6
mmol) in anhydrous THF (200 mL) cooled to -78 °C. The
mixture was stirred overnight, and the temperature was
allowed to reach 25 °C. After the mixture cooled to 0 °C, an
(37) Sevin, A. F.; Vogel, P. J . Org. Chem. 1994, 59, 5920. Kraehen-
buehl, K.; Picasso, S.; Vogel, P. Helv. Chim. Acta 1998, 81, 1439.
(38) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(36) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841. See also: Giese,
B.; Damm, W.; Batra, R. Chemtracts. Org. Chem. 1994, 7, 355.

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5087
ice-cold saturated aqueous solution of NH4Cl (50 mL) and ice
(50 g) were added under vigorous stirring. The mixture was
extracted with CH2Cl2 (200 mL, 4 times). The combined
organic extracts were dried (MgSO4), and the solvent was
evaporated in vacuo. The residue was taken up in anhydrous
CH2Cl2 (150 mL) and cooled to -10 °C. After the addition of
triethylamine (16 mL, 114 mmol), p-nitrobenzoyl chloride (15.8
g, 85 mmol), and 4-(dimethylamino)pyridine (10 mg), the
mixture was stirred at 20 °C for 56 h. The mixture was washed
with saturated aqueous solution of NaHCO3 (100 mL). The
aqueous layer was extracted with CH2Cl2 (200 mL, 5 times).
The combined organic extracts were dried (MgSO4). The
solvent was evaporated in vacuo. The residue was taken up
with pentane (200 mL). The precipitate was filtered off, and
the solvent was evaporated. FC (Florisil, 1:2 CH2Cl2/light
petroleum ether) gave a yellowish oil (3.3 g, 60%). 1H NMR
(400 MHz, CDCl3) δ 7.39-7.27 (m, 5H), 6.19 (dqd, 1H, J )
1.4, 0.9, 0.5), 5.93 (dqd, 1H, J ) 15.4, 1.4, 1.4), 5.47 (dqd, 1H,
J ) 15.4, 6.5, 0.5), 4.83 (s, 2H), 1.76 (d, 3H, J ) 0.9), 1.74 (dd,
3H, J ) 6.5, 1.4).
(E)-2-Met h yl-1-[2-(t r im et h ylsilyl)et h oxy]p en t -1-en -3-
on e (27). The procedure was the same as for the preparation
of 24, using 1-hydroxy-2-methylpent-1-en-3-one (23, 1.18 g,
10.4 mmol), 2-(trimethylsilyl)ethanol (1.78 mL, 1.47 g, 12.5
mmol), toluene (15 mL), and p-TsOH (2 mg). Purification by
distillation (Kugelrohr, Bu¨chi, 10 Torr, 50-120 °C) gave a
yellowish oil (1.49 g, 67%): 1H NMR (400 MHz, CDCl3) δ 7.28
(q, 1H, J ) 1.0), 4.05 (m, 2H), 2.48 (q, 2H, J ) 7.4), 1.65 (d,
3H, J ) 1.0), 1.03 (t, 1H, J ) 7.4), 1.02 (m, 2H), 0.00 (s, 9H).
(E,E)-2-Met h yl-1-[2-(t r im et h ylsilyl)et h oxy]p en t a -1,3-
d ien e (14). The procedure was the same as for the preparation
of 13, using 27 (1.65 g, 7.73 mmol), LiAlH4 (316 mg, 8.5 mmol).
Yellowish oil (500 mg, 40%): 1H NMR (400 MHz, CDCl3) δ
6.09 (br. s, 1H), 5.95 (dq, 1H, J ) 15.4, 1.5). 5.44 (dq, 1H, J )
15.4, 6.6), 3.96 (m, 2H), 1.76 (dd, 3H, J ) 6.6, 1.5), 1.71 (d,
3H, J ) 1.1), 1.01 (m, 2H), 0.04 (s, 9H).
mg, 45%, Rf ) 0.62, 1:1 EtOAc/light petroleum ether): 1H NMR
(400 MHz, CDCl3) δ 7.96-7.25 (m, 5H), 5.40 (dd, 1H, 3J ) 10.8,
1.4), 4.97 (dd, 1H, J ) 6.8, 6.2), 4.50 (m, 2H), 4.33 (dq, 1H, J
) 10.8, 6.7), 3.53 (dd, 1H, J ) 16.6, 6.2), 3.20 (dd, 1H, J )
16.2, 6.8), 2.82 (s, 3H), 1.89 (d, 3H, J ) 1.4), 1.42 (d, 3H, J )
6.7).
(4RS,5Z,7SR)-4-(Ben zyloxy)-5-m eth yl-7-(m eth ylsu lfo-
n yl)oct-5-en -2-on e (18). The procedure was the same as for
the preparation of 16, starting with 13 (37 mg, 0.19 mmol)
and 2-(trimethylsilyloxy)propene (10, 70 µL, 0.38 mmol) and
using Yb(OTf)3 (0.19 mmol) as acid promoter. FC (1:3 EtOAc/
light petroleum ether) gave a colorless oil (13 mg, 70%, Rf )
0.07): 1H NMR (400 MHz, CDCl3) δ 7.35-7.28 (m, 5H), 5.40
(dq, 1H, J ) 10.7, 1.2), 4.75 (dd, 1H, J ) 7.1, 5.8), 4.43 (m,
2H), 4.24 (dq, 1H, J ) 10.7, 6.7), 2.97 (dd, 1H, J ) 7.1, 16.6),
2.81 (s, 3H), 2.57 (dd, 3H, J ) 16.6, 5.8), 2.17 (s, 3H), 1.84 (d,
3H, J ) 1.2), 1.43 (d, 3H, J ) 6.7).
(5RS,6Z,8SR)-5-(Ben zyloxy)-2,2,6-tr im eth yl-8-(m eth yl-
su lfon yl)n on -6-en -3-on e (19). The procedure was the same
as for the preparation of 16, starting from 13 (37 mg, 0.19
mmol) and 1-(tert-butylvinyloxy)trimethylsilane (11, 50 µL,
0.19 mmol) and using (t-Bu)Me2SiOSO2CF3 (0.04 mmol) as acid
promoter. FC (1:3 EtOAc/light petroleum ether) gave a yel-
lowish oil (32 mg, 77%, Rf ) 0.28) that crystallized from Et2O/
pentane: mp 101.5-103 °C; 1H NMR (400 MHz, CDCl3) δ
7.35-7.27 (m, 5H), 5.37 (dq, 1H, J ) 11.0, 1.4), 4.83 (dd, 1H,
J ) 6.7, 6.2), 4.47-4.39 (m, 2H), 4.33 (dq, 1H, J ) 11.0, 6.7),
3.00 (dd, 1H, J ) 11.0, 6.7), 2.81 (s, 3H), 2.72 (dd, 1H, J )
11.0, 6.2), 1.84 (d, 3H, J ) 1.4), 1.42 (d, 3H, J ) 6.7), 1.12 (s,
9H).
(3RS,4Z,6SR)-4-Meth yl-6-(m eth ylsu lfon yl)-1-p h en yl-3-
[2-(tr im eth ylsilyl)-eth oxy]h ep t-4-en -1-on e (20). In a two
necked-round-bottom flask dried in a flame under vacuum
(vacuum line)were placed anhydrous CH2Cl2 (10 mL) and
Yb(OSO2CF3)3 (615 mg) under an Ar atmosphere. After freez-
ing (-196 °C) and evacuation (vacuum line) SO2 (4 mL) was
transferred. The system was pressurized with Ar (1 atm) and
allowed to warm to -86 °C (EtOH/liquid N2 bath). After stirred
at -86 °C for 15 min, 1 (0.2 g, 1 mmol) and 9 (192 mg, 1 mmol)
were added (syringe) dropwise. After stirring at -86 °C for 3
h, the solvents were evaporated. A 1 M solution of Bu4NF in
THF (6 mL) and MeI (1.2 mL) were added, and the mixture
was stirred at 20 °C for 15 h. A saturated aqueous solution of
NaHCO3 (30 mL) was added, and the mixture was extracted
with CH2Cl2 (20 mL, 5 times). The combined organic extracts
were dried (MgSO4), and the solvent was evaporated. The
residue was taken in 1:1 Et2O/light petroleum ether. The
precipitate was filtered off, and the solution was concentrated
in vacuo. FC (1:3 Et2O/light petroleum ether) gave a colorless
oil (174 mg, 47%) that crystallized from EtOAc/pentane: mp
(2RS,3SR,4Z,6RS)-2,4-Dim et h yl-6-m et h ylsu lfon yl-3-
m eth oxy-1-p h en ylh ep t-4-en -1-on e (16). SO2 (1 mL) was
transferred (vacuum line) to a frozen solution of Yb(OTf)3 (15
mg) in anhydrous CH2Cl2 (2 mL). The mixture was allowed to
melt and to warm to -78 °C. After 15 min, 10 (39 mg, 0.2
mmol) and 1-phenyl-1-(trimethylsilyloxy)ethene (9, 41 µL, 0.22
mmol) were added (syringe) slowly (Ar atmosphere, -78 °C,
stirring). After stirring at -78 °C for 12 h, the solvent was
evaporated at -78 °C (0.1 Torr). Acetone (1 mL) and then 1
M Bu4NF in THF (1.5 mL) and MeI (0.5 mL) were added. The
mixture was stirred at 20 °C for 22 h and washed with a
saturated aqueous solution of NaHCO3 (30 mL). The aqueous
layer was extracted with CH2Cl2 (30 mL, 3 times). The
combined organic extracts were concentrated under reduced
pressure. FC (1:3 EtOAc/light petroleum ether) gave a colorless
oil (7 mg, 6%, Rf ) 0.45) that crystallizes from ether/light
petroleum ether): mp 104-106 °C; 1H NMR (400 MHz, CDCl3)
δ 7.91-7.40 (m, 5H), 5.22 (br.d, 1H, J ) 10.7), 4.30 (d, 1H, J
) 9.7), 4.26 (dq, 1H, J ) 10.7, 6.7), 3.84 (dq, 1H, J ) 9.7, 6.8),
3.34 (s, 3H), 1.70 (d, 3H, J ) 1.4), 1.39 (d, 3H, J ) 6.7), 1.36
1
62-64 °C; H NMR (400 MHz, CDCl3) δ 7.96-7.46 (m, 5 H),
5.35 (dq, 1H, J ) 10.8, 1.3), 4.79 (dd, 1H, J ) 6.4, 6.3), 4.39
(dq, 1H, J ) 10.8, 6.7), 3.52, 3.39 (m, 3H), 3.10 (dd, 1H, J )
16.6, 6.4), 2.85 (s, 3H), 1.82 (d, 3H, J ) 1.3), 1.41 (d, 3H, J )
6.7), 0.97-0.80 (m, 3H), 0.10 (s, 9H).
(4R S ,5Z,7S R )-5-Me t h yl-7-(m e t h ylsu lfon yl)-4-[2-(t r i-
m eth ylsilyl)eth oxy]oct-5-en -2-on e (21). The procedure was
the same as for the preparation of 20, starting from 14 (0.2 g,
1 mmol) and 10 (131 mg) and using Yb(OSO2CF3)3 as acid
promoter (615 mg). FC (1:3 EtOAc/light petroleum ether) gave
a colorless oil (61 mg, 20%): 1H NMR (400 MHz, CDCl3) δ 5.34
(dq, 1H; J ) 10.7, 1.3), 4.55 (dd, 1H, J ) 7.5, 5.5), 4.30 (dq,
1H, J ) 10.7, 6.8), 3.47-3.31 (m, 2H), 2.88 (dd, 1H, J ) 16.5,
7.5), 2.83 (s, 3H), 2.48 (dd, 1H, J ) 16.5, 5.5), 2.17 (s, 3H),
1.76 (d, 3H, J ) 1.3), 1.42 (d, 3H, J ) 6.8), 0.95-0.78 (m, 3H),
-0.01 (s, 9H).
(5RS,6Z,8SR)-2,2,6-Tr im eth yl-8-(m eth ylsu lfon yl)-5-[2-
(tr im eth ylsilyl)eth oxy]n on -6-en -3-on e (22). The procedure
was the same as for the preparation of 20, starting from 14
(0.2 g, 1 mmol) and 11 (327 mg, 1.9 mmol) and using Yb(OSO2-
CF3)3 (615 mg) as acid promoter. FC (1:4 EtOAc/light petro-
leum ether) gave a colorless oil (173 mg, 50%) that crystallizes
from Et2O/pentane: mp 63-64 °C; 1H NMR (400 MHz, CDCl3)
δ 5.29 (br.d, 1H, J ) 10.8), 4.59 (dd, 1H, J ) 6.6, 6.4), 4.34
(dq, 1H, J ) 10.8, 6.8), 3.43-3.29 (m, 2H), 2.87 (dd, 1H, J )
3
(d, 3H, J ) 6.8).
(3RS,4Z,6SR)-3-(Ben zyloxy)-4-m eth yl-6-m eth ylsu lfon yl-
1-p h en ylh ep t-4-en -1-on e (17). In a two-necked round-bottom
flask, anhydrous CH2Cl2 (1 mL) and 0.5 M (CF3SO2)2NH in
CH2Cl2 (0.1 mL) were degassed on the vacuum line (-196 °C).
Then dry SO2 (1 mL) (basic alumina column, two distillations
on the vacuum line) was transferred. The system was pres-
surized with Ar (1 atm) and allowed to warm to -78 °C. After
15 min at -78 °C, a mixture of 9 (102 mg, 0.53 mmol) and
13 (50 mg, 0.26 mmol) was added dropwise (automatic
syringe) to the stirred mixture maintained at -78 °C. The
stirring was continued at -78 °C for 15 h (oxyallytion step).
The solvents were evaporated (-78 °C, 0.1 Torr). Acetone (1
mL), 1 M Bu4NF in THF (1.5 mL), and MeI (0.3 mL) were
added, and the mixture was stirred at 20 °C for 15 h. A
saturated aqueous solution of NaHCO3 (30 mL) was added,
and the mixture was extracted with CH2Cl2 (30 mL, 3 times).
The combined organic extracts were dried (MgSO4) and the
solvent was evaporated in vacuo. FC gave a colorless oil (45.8

5088 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
17.0, 6.4), 2.80 (s, 3H), 2.59 (dd, 1H, J ) 17.0, 6.6), 1.73 (d,
3H, J ) 1.3), 1.77 (d, 3H, J ) 6.8), 1.08 (s, 9H), 0.92-0.75 (m,
2H), -0.04 (s, 9H).
gave a colorless oil (37 mg, 18%): 1H NMR (400 MHz, CDCl3)
δ 7.40-7.27 (m, 5H), 4.65 (d, 1H, J ) 11.6), 4.37 (d, 1H, J )
11.6), 4.25 (d, 1H, J ) 8.1), 4.00 (d, 1H, J ) 3.9), 3.31 (s, 3H),
3.26 (s, 3H), 2.26 (ddq, 1H, J ) 8.1, 3.9, 7.0), 2.17 (s, 3H), 0.93
(d, 3H, J ) 7.0). 13C NMR (100.6 MHz, CDCl3) δ 137.6 (s),
128.4, 127.9 (2d), 127.8 (s), 105.9 (s), 105.1 (d, 1J (C,H) ) 165),
85.0 (d, 1J (C,H) ) 142), 72.9 (t), 54.3 (q), 52.4 (q), 38.9 (d,
(5RS,6E,8RS)-5-(Ben zyloxy)-2,2,6-tr im eth yl-8-(m eth yl-
su lfon yl)n on -6-en -3-on e (29). The procedure was the same
as for the preparation of 19 starting from 11 (425 mg, 2.7
mmol) and 13 (0.5 g, 2.7 mmol) and using MgBr2 (666 mg, 2.7
mmol) as acid promoter (instead of (t-Bu)Me2SiOSO2CF3). FC
(1:3 EtOAc/light petroleum ether) gave a fraction from which
a white solid was obtained (80 mg, 8%) that was recrystallized
from Et2O/pentane, giving thin needles: mp 76-78 °C; 1H
NMR (400 MHz, CDCl3) δ 7.35-7.27 (m, 5H), 5.37 (dq, 1H, J
) 11.0, 1.4), 4.83 (dd, 1H, J ) 6.7, 6.2), 4.47-4.39 (m, 2H),
4.33 (dq, 1H, J ) 11.0, 6.7), 3.00 (dd, 1H, J ) 11.0, 6.7), 2.81
(s, 3H), 2.72 (dd, 1H, J ) 11.0, 6.2), 1.84 (d, 3H, J ) 1.4), 1.42
(d, 3H, J ) 6.7), 1.12 (s, 9H).
1
1J (C,H) ) 128), 26.7 and 9.95 (2q, J (C,H) ) 128).
(1E,3Z)-1-(Ben zyloxy)-2-m eth yl-3-(tr im eth ylsilyloxy)-
p en ta -1,3-d ien e (40). Me3SiOSO2CF3 (3.2 mL) was added
dropwise to a stirred solution of 24 (3.2 g, 15.7 mmol) in
anhydrous Et3N (5 mL) containing ZnCl2 (50 mg) cooled to 10
°C. After stirring at 10 °C for 15 h, the solid was extracted
with pentane (50 mL, 6 times). The combined organic extracts
were washed with a saturated aqueous solution of NaHCO3
(100 mL), then with H2O (200 mL), and finally with a solution
of citric acid (7.2 g) in H2O (200 mL). Drying (MgSO4) and
solvent evaporation gave a colorless oil (4.2 g, 97%): 1H NMR
(400 MHz, CDCl3) δ 7.37-7.30 (m, 5H), 6.46 (s, 1H), 4.86 (s,
2H), 4.75 (q, 1H, J ) 6.9), 1.75 (d, 3H, J ) 1.1), 1.62 (d, 3H, J
) 6.9), 0.12 (s, 9H).
(1E,3Z)-3-Ben zoyloxy-1-(ben zyloxy)-2-m eth ylp en ta -1,3-
d ien e (41, (1E,3Z)-1-(ben zyloxy)-2-m eth ylp en ta -1,3-d ien -
3-yl ben zoa te). A mixture of 40 (4 g, 14.5 mmol), anhydrous
THF (15 mL), benzoyl fluoride (1.58 mL, 14.5 mmol), and 1 M
tetrabutylammonium trihydrate in THF (0.3 mL, 0.29 mmol)
was stirred at 20 °C for 15 h. The solvent was evaporated in
vacuo. FC (CH2Cl2) gave a colorless oil (3.22 g, 72%): 1H NMR
(400 MHz, CDCl3) δ 8.17-7.26 (m, 10 H), 6.40 (s, 1H), 5.34 (q,
1H, J ) 7.0), 4.79 (s, 1.86 (s, 3H), 1.61 (d, 3H, J ) 7.0).
(1E,3Z)-3-[(ter t-Bu tyl)d im eth ylsilyloxy]-2-m eth yl-1-[2-
(t r im et h ylsilyl)et h oxy]p en t a -1,3-d ien e (42). (t-Bu)Me2-
SiOSO2CF3 (0.57 mL) was added dropwise to a stirred so-
lution of 27 (530 mg, 2.5 mmol) in anhydrous Et3N (2 mL)
and Et2O (2 mL) cooled to 0 °C. After stirring at 20 °C for 5 h
the solvent was evaporated in vacuo. A saturated aqueous
solution of NaHCO3 (50 mL) was added, and the mixture was
extracted with pentane (50 mL, 4 times). The combined organic
extracts were washed with H2O (50 mL) and then with a 2 M
solution of citric acid in H2O (100 mL). Drying (MgSO4) and
solvent evaporation gave a colorless oil (763 mg, 93%): 1H
NMR (400 MHz, CDCl3) δ 6.39 (s, 1H), 4.69 (q, 1H, J ) 6.9),
3.87 (t, 2H, J ) 8.4), 1.69 (s, 1H), 1.61 (d, 3H, J ) 6.9), 1.00
(m, 11H).
(1E,3Z)-2-Meth yl-1-[2-(tr im eth ylsilyl)eth oxy]p en ta -1,3-
d ien -3-yl Ben zoa te (43). Me3SiOSO2CF3 (3.86 mL) was added
dropwise to a stirred solution of 42 (4 g, 18.7 mmol) in
anhydrous Et3N (5 mL). After stirring at 20 °C for 15 h the
solid was extracted with pentane (100 mL, 5 times). The
combined organic extracts were washed with a saturated
aqueous solution of NaHCO3 (100 mL), then with H2O (100
mL), and finally with a solution of citric acid (3.6 g) in H2O
(100 mL). After drying (MgSO4) and solvent evaporation in
vacuo, the residue was dissolved in anhydrous THF (18.5 mL)
and cooled to 0 °C. Benzoyl fluoride (2 mL, 18.7 mmol) and
then 1 M Et4NF in THF (0.4 mL, 0.37 mmol) were added. After
stirring at 20 °C for 15 h the solvent was evaporated in vacuo.
FC (CH2Cl2) gave a colorless oil (1.82 g, 31%): 1H NMR (400
MHz, CDCl3) δ 8.21-7.50 (m, 5H), 6.27 (s, 1H), 5.29 (q, 1H, J
) 6.9), 3.81 (m, 2H), 1.80 (s, 3H), 1.60 (d, 3H, J ) 6.9), 0.96
(m, 2H), 0.00 (s, 9H).
(3RS,5SR,6E,8SR)- (30) a n d (3RS,5RS,6E,8RS)-5-(Ben -
zyloxy)-2,2,6-t r im et h yl-8-(m et h ylsu lfon yl)n on -6-en -3-ol
(31). A mixture of 29 (50 mg, 0.14 mmol), anhydrous MeOH
(2 mL), and NaBH4 (10 mg, 0.56 mmol) was stirred at 20 °C
for 2 h. EtOAc (1 mL) was added, and the solvent was
evaporated to dryness. The residue was washed with water
(50 mL) and then extracted with CH2Cl2 (50 mL, 4 times).
Drying (MgSO4), solvent evaporation, and FC (1:3 EtOAc/light
petroleum ether) gave a first fraction (38.4 mg) of 30 and a
second (10.1 mg) of 31. Overall yield: 97%. Diol 30 crystallized
from Et2O/pentane. Data for 30: colorless crystals; mp 116-
118 °C; 1H NMR (400 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.48
(d, 1H, J ) 10.0), 4.50 (d, 1H, J ) 11.3), 4.34 (d, 1H, J ) 11.3),
4.05 (d, 1H, J ) 9.1), 3.93 (dq, 1H, J ) 10.0, 6.9), 3.43 (br. s,
1H), 3.36 (d, 1H, J ) 9.4), 2.84 (s, 3H), 1.80-1.62 (m, 2H),
1.80 (s, 3H), 1.50 (d, 3H, J ) 6.9), 0.89 (s, 9H). Data for 31:
1
colorless oil. H NMR (400 MHz, CDCl3) δ 7.38-7.29 (m, 5H),
5.50 (d, 1H, J ) 10.2), 4.54 (d, 1H, J ) 11.9), 4.33 (d, 1H, J )
11.9), 4.06 (dd, 1H, J ) 8.7, 3.0), 3.93 (dq, 1H, J ) 10.2, 6.8),
3.43 (d, 1H, J ) 10.3), 2.82 (s, 3H), 1.80 (m, 1H), 1.78 (d, 3H,
J ) 1.1), 1.50 (d, 3H, J ) 6.9), 1.43 (ddd, 1H, J ) 14.0, 3.0,
10.3), 0.89 (s, 9H).
2-(Ben zyloxy)-3,5-d im et h yld ih yd r ot h iop h en e-1,1-d i-
oxid e (37). On the vacuum line, SO2 (0.4 mL) was condensed
onto a degassed mixture of CD2Cl2 (0.5 g), 13 (24.4 mg, 0.13
mmol), and CFCl3 (0.1 g). The mixture was allowed to stand
1
at -74 °C for 6 h. H NMR demonstrated the disappearance
of diene 13 and the exclusive formation of sulfolene 37,
unstable above -20 °C: 1H NMR (400 MHz, CDCl3, -65 °C)
δ 7.47-7.32 (m, 5H), 5.88 (s, 1H), 5.04 and 4.69 (2d, 2H, J )
11.5), 4.72 (s, 1H), 3.66 (m, 1H), 1.83 (s, 3H), 1.35 (d, 3H, J )
7.1). 13C NMR (100.6 MHz, CDCl3, -65 °C) δ 136.6, 134.6 (2s),
129.6, 129.5, 128.6 (3d), 93.5 (d, 1J (C,H) ) 165), 78.6 (t, 1J (C,H)
1
) 144), 59.9 (d, J (C,H) ) 145), 17.0, 15.8 (2q).
3,5-Dim e t h yl-2-[2-(t r im e t h ylsilyl)e t h oxy]d ih yd r o-
th iop h en e-1,1-d ioxid e (38). The procedure was the same as
for the preparation of 37: 1H NMR (400 MHz, CD2Cl2, -75
°C) δ 5.81 (m, 1H), 4.64 (s, 1H), 4.07 (m, 1H), 3.65 (m, 2H),
1.84 (s, 3H), 1.30 (d, 3H, J ) 7.1), 1.03 (m, 2H); 13C NMR (100.6
MHz, CD2Cl2, -75 °C) δ 135.4 (s), 128.4 (d, 1J (C,H) ) 169),
95.5 (d, 1J (C,H) ) 159), 71.7 (t, 1J (C,H) ) 143), 60.2 (d, 1J (C,H)
) 143), 18.8 (t, 1J (C,H) ) 121), 17.8, 15.6 (2q), -0.8 (q, 1J (C,H)
) 119).
(2R S ,3S R ,5S R ,6S R )-3-(Be n zyloxy)-2,5-d im e t h yl-2,6-
d im eth oxy-1,4-oxa th ia n e-4,4-d ioxid e (39). SO2 (2 mL) was
condensed onto frozen (-196 °C) CH2Cl2 (4 mL) and Yb(OSO2-
CF3)3 (100 mg). The mixture was allowed to stand at -78 °C
for 15 min. Diene 13 (120 mg, 0.63 mmol) was added slowly
(syringe) to the stirred solution at -78 °C. After stirring at
-78 °C for 5 h, O3 (2% in O2) was bubbled through the solution
until persistence of the blue color. SO2 (1 mL) was transferred
to the mixture. After stirring at -78 °C for 30 min, the solvents
were half-evaporated at -60 °C (0.5 Torr), ethyl orthoformiate
(940 mg, 6.3 mmol), CeCl3 (160 mg, 0.63 mmol), and anhydrous
MeOH (1 mL) were added, and the mixture was stirred at -78
°C for 15 min and then at 20 °C for 15 h. A saturated aqueous
solution of NaHCO3 (30 mL) was added, and the mixture was
extracted with CH2Cl2 (30 mL, 3 times). Drying (MgSO4),
solvent evaporation, and FC (1:3 EtOAc/light petroleum ether)
(4RS,5Z,7SR)-6-Ben zoyloxy-4-b en zyloxy-5-m et h yl-7-
(m eth ylsu lfon yl)oct-5-en -2-on e (44, (2RS,3Z,5SR)-5-ben -
zyloxy-4-m eth yl-2-(m eth ylsu lfon yl)-7-oxooct-3-en -3-yl ben -
zoa te). The procedure was the same as for the preparation of
16 using anhydrous CH2Cl2 (2 mL), SO2 (0.6 mL), 41 (163 mg,
0.53 mmol), 2-(trimethylsilyloxy)propene (10, 104 mg, 0.8
mmol), and (t-Bu)Me2SiOSO2CF3 as acid promoter (0.1 mL).
FC (1:2 EtOAc/light petroleum ether) gave a colorless oil
(157 mg, 67%): 1H NMR (400 MHz, CDCl3) δ 8.13-7.28 (m,
10H), 4.86 (dd, 1H, J ) 6.6, 6.5), 4.66 (q, 1H, J ) 6.9), 4.56
(AB, 2H), 3.00 (dd, 1H, J ) 16.8, 6.6), 2.95 (s, 3H), 2.80 (dd,
1H, J ) 16.8, 6.5), 2.23 (s, 3H), 1.69 (s, 3H), 1.54 (d, 3H, J )
6.9).

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5089
(4RS,5Z,7SR-6-Ben zoyloxy-5-m eth yl-7-(m eth ylsu lfon yl)-
4-[2-tr im eth ylsilyl)eth oxy]oct-5-en -2-on e (45,(2RS,3Z,5SR)-
4-m eth yl-2-(m eth ylsu lfon yl)-5-[2-(tr im eth ylsilyl)eth oxy]-
7-oxooct-3-en -3-yl ben zoa te). SO2 (0.6 mL) was condensed
in vacuo (vacuum line) onto frozen (-196 °C) anhydrous
CH2Cl2 (2 mL) containing (CF3SO2)2NH (0.2 mL). The mixture
was melted at -78 °C. After 15 min at -78 °C, 43 (163 mg,
0.53 mmol) and 10 (104 mg, 0.8 mmol) were added slowly
(syringe) under stirring. After stirring at -78 °C for 15 h, the
solvent was evaporated (-78 °C, 0.1 Torr). Then, 1 M Bu4NF
in THF (2 mL) and MeI (0.5 mL) were added, and the mixture
was stirred at 0 °C for 3.5 h. A saturated aqueous solution of
NaHCO3 (50 mL) was added, and the mixture was extracted
with CH2Cl2 (30 mL, 4 times). The combined extracts were
dried (MgSO4), and the solvent was evaporated in vacuo. The
residue was taken up in 1:3 EtOAc/light petroleum ether. The
precipitate was filtered off. The solvent was evaporated. FC
(1:2 EtOAc/light petroleum ether) gave a colorless oil (102 mg,
(400 MHz, CDCl3) δ 7.33-7.25 (m, 5H), 5.44 (m, 1H), 5.36 (m,
2H), 4.77 and 4.75 (2dd, 1H, J ) 6.3, 6.4), 4.58-4.37 (m, 2H),
4.24 (m, 1H), 3.90 (m, 1H), 2.98 (dd, 0.5H, J ) 17.0, 7.3), 2.94
(dd, 0.5H, J ) 17.0, 7.2), 2.79 and 2.78 (2s, 3H), 2.67 (dd, 0.5H,
J ) 16.0, 8.5), 2.63 (dd, 0.5H, J ) 16.2, 8.9), 2.58 (dd, 0.5H, J
) 17.0, 1.4), 2.56 (dd, 0.5H, J ) 17.0, 1.4), 2.48 (m, 1H), 2.44
(dd, 0.5H, J ) 16.2, 3.5), 2.41 (dd, 0.5H, J ) 16.2, 3.8), 1.80
(d, 1.5H, J ) 1.4), 1.78 (d, 1.5H, J ) 1.1), 1.66 (m, 3H), 1.42
(d, 1.5H, J ) 6.7), 1.39 (d, 1.5H, J ) 6.8), 1.1 (d, 3H, J ) 6.8).
(+)-(1′S,1E)-2-Meth yl-1-[1-(p en ta flu or op h en yl)eth oxy]-
bu ta d ien e ((+)-54). A mixture of 3-ethoxy-2-methylacrolein
(0.6 mL, 5 mmol), (-)-(S)-1-(pentafluorophenyl)ethanol (56d ),
and p-toluenesulfonic acid (16 mg) was stirred at 20 °C for 14
h
under vacuum (1 Torr). This gave 2-methyl-3-{1-(S)-
[pentafluorophenyl)ethoxy}prop-2-enal (57d ). In another flask,
1.6 M BuLi in hexane (4.7 mL) was added dropwise to a stirred
solution of (i-Pr)2NH in anhydrous THF (20 mL) cooled to -78
°C. After stirring at 0 °C for 1.5 h, methyltriphenylphospho-
nium bromide (2.65 g, 7.5 mmol) was added. After stirring at
20 °C for 2 h, the mixture was cooled to 0 °C, and 57d obtained
above was added. After stirring at 0 °C for 1.5 h, ice-cold H2O
(30 mL) was added, and the mixture was extracted with light
petroleum ether (20 mL, 3 times). The combined organic
extracts were dried (anhydrous Na2SO4), and the solvent was
evaporated. The residue was distilled (Kugelrohr, Bu¨chi) under
reduced pressure, giving a yellowish oil (bp 80 °C, 1 Torr), 2:1
mixtures of (E)- and (Z)-diene (0.408 g, 20%). [R]2D5 ) +66 (c )
1.0, CHCl3). Data for the major diene (+)-54: 1H NMR (400
MHz, CDCl3) δ 6.20 (dd, 1H, J ) 17.0, 10.5), 6.18 (q, 1H, J )
1.2), 5.23 (q, 1H, J ) 6.8), 5.02 (dd, 1H, J ) 17.0, 1.2), 4.84
(dd, 1H, J ) 10.5, 1.2), 1.733 (d, 3H, J ) 1.2), 1.70 (d, 3H, J )
6.8). Data for the minor diene (1Z): 1H NMR (400 MHz, CDCl3)
δ 6.19 (dd, 1H, J ) 17.0, 10.5), 6.16 (q, 1H, J ) 1.2), 5.27 (q,
1H, J ) 6.8), 4.98 (dd, 1H, J ) 17.0, 1.2), 4.87 (dd, 1H, J )
10.5, 1.2), 1.730 (d, 3H, J ) 1.2), 1.70 (d, 3H, J ) 6.8).
(-)-2-Meth yl-3-[1-(S)-(2,4,6-tr iisop r op ylp h en yl)eth oxy]-
p r op -2-en a l ((-)-57e). A solution of (-)-(S)-1-(2,4,6-triiso-
propylphenyl)ethanol30 (1.89 g, 7.6 mmol) in anhydrous THF
(10 mL, dried with 4 Å molecular sieves) was added slowly to
a stirred solution of activated NaH (0.36 g, 8.36 mmol) in
anhydrous THF (5 mL). After stirring at 20 °C for 3 h, the
solution was cooled to 0 °C, and 3-ethoxy-2-methylacrolein
(1.03 mL, 8.36 mmol) in anhydrous THF (5 mL, dried over 4
Å molecular sieves, 20 °C, 2 h) was added. After stirring at 20
°C for 20 h a saturated aqueous solution of NH4Cl (20 mL)
was added. The mixture was extracted with CH2Cl2 (40 mL, 3
times). The combined organic extracts were washed with H2O
(50 mL, twice) and dried (MgSO4). Solvent evaporation and
FC (CH2Cl2) gave a white solid (1.9 g, 79%, Rf ) 0.13): mp
87.5-89 °C; [R]2D5 ) -27 (c ) 0.98, CHCl3); 1H NMR (400
MHz, CDCl3) δ 9.14 (s, 1H), 7.05-7.00 (m, 2H), 6.96 (q, 1H, J
) 0.9), 5.69 (q, 1H, J ) 6.9), 3.40 (m, 1H), 2.88 (sept. 3H, J )
6.9), 1.76 (d, 3H, J ) 6.9), 1.72 (d, 3H, J ) 0.9), 1.31-1.09 (m,
6H), 1.26 (d, 3H, J ) 6.9).
(+)-1,3,5-Tr iisop r op yl-2-{1-(S)-{(1E)-2-m eth ylbu ta -1,3-
d ien yloxy]eth yl}ben zen e ((+)-55). A 1.6 M solution of BuLi
in hexane (3.6 mL, 5.74 mmol) was added dropwise to a stirred
solution of (i-Pr)2NH (0.85 mL, 5.74 mmol) in anhydrous THF
(20 mL) cooled to -78 °C under an Ar atmosphere. After
stirring at 0 °C for 1 h, methyltriphenylphosphonium bromide
(1.865 g, 5.2 mmol) was added portionwise. After stirring at
20 °C for 45 min the mixture was cooled to 0 °C. A solution of
(-)-57e (1.5 g, 4.74 mmol) in anhydrous THF (15 mL) was
added, and the mixture stirred at 0 °C for 1 h. Ice-cold H2O
(50 mL) was added, and the mixture was extracted with light
petroleum ether (30 mL, 3 times). The combined organic
extracts were dried (MgSO4), and the solvent was evaporated.
The residue was taken up with pentane, and the precipitate
(Ph3PO) was filtered off. Solvent evaporation gave a white solid
(1.3 g, 87%): mp 39.5-41 °C; [R]2D5 ) +17 (c ) 1.02, CHCl3);
1H NMR (400 MHz, CDCl3) δ 7.03-7.01 (m, 2H), 6.22 (q, 1H,
J ) 1.2), 6.20 (dd, 1H, J ) 17.2, 10.8), 5.41 (q, 1H, J ) 6.9),
4.92 (dd, 1H, J ) 17.2, 1.1), 4.76 (dd, 1H, J ) 10.8, 1.1), 3.48
1
42%) that crystallized from Et2O/pentane: mp 93-95 °C; H
NMR (400 MHz, CDCl3) δ 8.11-7.48 (m, 5H), 4.68 (q, 1H, J )
6.9), 4.66 (t, 1H, J ) 6.6), 3.60, 3.47 (2m, 2H), 2.98 (s, 3H),
2.92 (dd, 1H, J ) 16.7, 6.6), 2.70 (dd, 1H, J ) 16.7, 6.6), 2.22
(s, 3H), 1.61 (s, 3H), 1.54 (d, 3H, J ) 6.9), 0.95, 0.87 (2m, 2H),
0.03 (s, 9H).
(4RS,5SR,6E)-4-(Ben zyloxy)-5-m eth yloct-6-en -2-on e (47).
In a two-necked round-bottom flask dried under vacuum
in
a flame were placed anhydrous CH2Cl2 (40 mL) and
Yb(OSO2CF3)3 (3.2 g) under an Ar atmosphere. After complete
dissolution, the mixture was frozen (liquid N2), and the flask
was evacuated (vacuum line). Dry SO2 (16 mL) was condensed,
and the mixture was allowed to warm slowly to -78 °C. After
15 min at -78 °C and pressurizing (1 atm) with Ar, 13 (1 g,
5.3 mmol) and 10 (2.4 g, 18.4 mmol) were added slowly
(syringe) under stirring. After stirring at -78 °C for 5 h the
solvents were evaporated (-78 °C, 0.1 Torr). A 1:1 mixture of
MeOH and saturated aqueous solution of NH4Cl (40 mL) was
added, and the mixture was stirred at 0 °C for 1 h and then
at 20 °C for 15 h. A saturated aqueous solution of NaHCO3
(300 mL) was added, and the mixture was extracted with
CH2Cl2 (300 mL, 3 times). Drying (MgSO4), solvent evapora-
tion, and FC (1:2 light petroleum ether/CH2Cl2) gave a colorless
oil (1.09 g, 71%, Rf ) 0.27): 1H NMR (400 MHz, CDCl3) δ
7.35-7.24 (m, 5H), 5.47 (dqd, 1H, J ) 15.3, 6.0, 0.8), 5.38 (dd,
1H, J ) 15.3, 7.1, 1.3), 4.53 (m, 2H), 3.91 (ddd, 1H, J ) 8.5,
4.0, 3.9), 2.67 (dd, 1H, J ) 16.2, 8.5), 2.47-2.50 (m, 1H), 2.44
(dd, 1H, J ) 16.2, 4.0), 2.14 (s, 3H), 1.68 (ddd, 3H, J ) 6.0,
1.3, 0.9), 1.03 (d, 3H, J ) 6.9).
(4RS,5RS,6E)-4-(Ben zyloxy)-5-m et h yl-2-(t r im et h ylsi-
lyloxy)octa -1,6-d ien e (48). A 1.6 M solution of BuLi in
hexane (0.95 mL, 1.52 mmol) was added dropwise to a stirred
solution of (Me3Si)NH (0.32 mL, 1.52 mmol) in anhydrous THF
(2 mL) cooled to -20 °C. After cooling to -78 °C, (CH3)3SiCl
(0.93 mL) in anhydrous THF (2 mL) was added (cannulated)
and then a solution of 46 (183 mg, 0.74 mmol) in anhydrous
THF (2 mL). Both solutions were cooled to -78 °C before the
addition. After stirring at -78 °C for 5 min, anhydrous Et3N
(2 mL) was added. The mixture was poured into a saturated
aqueous solution of NaHCO3 (50 mL) under vigorous stirring.
The mixture was extracted with pentane (100 mL, 4 times).
The combined organic extracts were washed with H2O and
then with a solution of citric acid (0.48 g) in H2O (50 mL).
Drying (MgSO4) and solvent evaporation gave a colorless oil
(239 mg, 100%): 1H NMR (400 MHz, CDCl3) δ 7.35-7.25 (m,
5H), 5.49-5.39 (m, 2H), 4.61 and 4.50 (2d, 2H, J ) 11.6), 4.13
and 4.10 (2d, 2H, J ) 0.5), 3.55 (ddd, 1H, J ) 7.0, 5.5, 3.7),
2.41 (m, 1H), 2.26 (dd, 1H, J ) 14.1, 7.0), 2.17 (dd, 1H, J )
14.1, 5.5), 1.68 (dd, 1H, J ) 4.6, 0.4), 1.01 (d, 3H, J ) 6.9),
0.21 (s, 9H).
1:1 Mixtu r e of (2E,4RS,5SR,9RS,10Z,12SR)- (49) a n d
(2E,4RS,5SR,9SR,10Z,12RS)-5,9-Di(b en zyloxy)-4,10-d i-
m eth yl-12-(m eth ylsu lfon yl)tr id eca -2,10-d ien -7-on e (50).
The procedure was the same as for the preparation of 45, using
13 (0.1 g, 0.54 mmol) and 48 (110 mg, 0.35 mmoL) and (t-Bu)-
Me2SiOSO2CF3 (0.1 mL) as acid promoter. FC (1:3 EtOAc/light
petroleum ether) gave a colorless oil (84 mg, 47%): 1H NMR

5090 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
(m, 2H), 2.87 (sept, 1H, J ) 6.9), 1.73 (d, 3H, J ) 1.2), 1.64 (d,
3H, J ) 6.9), 1.35-1.21 (m, 6H), 1.25 (d, 3H, J ) 6.9).
(dd, 1H, J ) 5.8, 4.4), 3.94 (m, 1H), 3.83 (m, 1H), 3.53 (dd,
1H, J ) 17.0, 5.8), 3.34 (dd, 1H, J ) 17.0, 4.4), 2.77 (s, 3H),
1.68 (d, 3H, J ) 1.1), 1.60 (d, 3H, J ) 6.7).
1:5.4 Mixtu r e of (3S,4Z)- a n d (3R,4Z)-4-Meth yl-6-
(m eth ylsu lfon yl)-1-p h en yl-3-[(R)-1-p h en yleth oxy]h ex-4-
en -1-on e ((1′R,3S)-58 a n d (1′R,3R)-59). The procedure was
the same as for the preparation of 16, starting from (-)-{1-
(R)-[(1E)-2-methylbuta-1,3-dienyloxy]ethyl}benzene29 ((-)-51,
56 mg, 0.3 mmol) and 1-phenyl-1-trimethylsilyloxyethene (9,
130 mg, 0.75 mmmol) and using Yb(OSO2CF3)3 (0.132 g, 0.2
mmol) as acid promoter in anhydrous CH2Cl2 (2 mL). FC (24:1
CH2Cl2/Et2O) gave a colorless oil, 1:5.4 mixture of (1′R,3S)-58
and (1′R,3R)-59 (103 mg, 89%): 1H NMR (400 MHz, CDCl3)
of (1′R,3R′)-59 (major) δ 7.99-7.40 (m, 5H), 7.40-7.10 (m, 5H),
5.61 (tq, 1H, J ) 8.0, 1.2), 4.59 (t, 1H, J ) 6.5), 4.35 (q, 1H, J
) 6.5), 3.61 (dd, 1H, J ) 13.3, 8.0), 3.50 (dd, 1H, J ) 13.3,
8.0), 3.37 (dd, 1H, J ) 16.5, 6.5), 3.22 (dd, 1H, J ) 16.5, 6.5),
(-)-(3S,4Z)-4-Meth yl-6-(m eth ylsu lfon yl)-1-ph en yl-3-[(S)-
1-(2,4,6-tr iisop r op ylp h en yl)eth oxy]h ex-4-en -1-on e ((-)-
(1′S,3S)-66). In a 25 mL round-bottom flask were dissolved
in anhydrous CH2Cl2 (6 mL) (+)-55 (192 mg, 0.6 mmol), 9 (0.3
mL, 3 mmol), and Yb(OSO2CF3)3 (292 mg, 0.48 mmol). After
degassing and freezing (-196 °C, vacuum line), SO2 (1.28 mg,
20 mmol, dried by basic alumina and two distillations on the
vacuum line) was transferred. The mixture was stirred at -90
°C for 24 h. The solvents were evaporated at -90 °C (0.1 Torr).
After pressuring with Ar (1 atm), 1 M Bu4NF in THF (6 mL,
6 mmol) and MeI (1.2 mL, 20 mmol) were added. The mixture
was stirred at 20 °C for 16 h. H2O (30 mL) was added, and
the mixture was extracted with CH2Cl2 (20 mL, 5 times).
Drying (MgSO4), solvent evaporation, and FC (24:1 CH2Cl2/
Et2O) gave (-)-66 as colorless crystals (244 mg, 79%) and (+)-
55 (36 mg, 20%). Data for (-)-66: mp 116-118 °C (MeOH);
1
2.79 (s, 3H), 1.89 (d, 3H, J ) 1.2), 1.377 (d, 3H, J ) 6.5); H
NMR (400 MHz, CDCl3) (1′R,3S)-58 (minor) δ 7.99-7.10 (m,
10H), 5.29 (tq, 1H, J ) 6.9, 1.0), 4.87 (dd, 1H, J ) 7.4, 5.4),
4.52 (q, 1H, J ) 6.4), 3.50-2.80 (m, 4H), 2.72 (s, 3H), 1.79 (d,
3H, J ) 1.0), 1.374 (d, 3H, J ) 6.4).
[R]2D5 ) -0.7 (c ) 1.02, CHCl3); H NMR (400 MHz, CDCl3) δ
1
7.86-7.41 (m, 5H), 7.06-6.98 (m, 2H), 5.55 (ddq, 1H, J ) 9.4,
4.7, 1.3), 5.01 (q, 1H, J ) 6.7), 4.70 (dd, 1H, J ) 8.8, 4.0), 4.03
(dd, 1H, J ) 15.2, 9.4), 3.93 (m, 1H), 3.47 (dd, 1H, J ) 17.3,
8.8), 3.25 (dd, 1H, J ) 15.2, 4.7), 3.19 (dd, 1H, J ) 17.3, 4.0),
3.12 (m, 1H), 2.85 (sept, 1H, J ) 6.9), 2.78 (s, 3H), 1.88 (d,
3H, J ) 1.3), 1.54 (d, 3H, J ) 6.7), 1.40-1.13 (m, 6H), 1.26 (d,
3H, J ) 6.9).
1:6.7 Mixtu r e of (3S,4Z)- a n d (3R,4Z)-4-Meth yl-6-
(m eth ylsu lfon yl)-1-p h en yl-3-[(R-1-p h en ylp r op oxy]h ex-4-
en -1-on e ((1′R,3S)-60 a n d (1′R,3R)-61). The procedure was
the same as for the preparation of 16, starting from (+)-{1-
(R)-[(1E)-2-methylbuta-1,3-dienyloxy]propyl}benzene29 ((+)-52,
59 mg, 0.3 mmol), 9 (95 mg, 0.55 mmol), and Yb(OSO2CF3)3
(132 mg, 0.2 mmol). FC (39:1 CH2Cl2/Et2O) gave a colorless
oil containing a 1:6.7 mixture of (1′R,3S)-60 and (1′R,3R)-61
(65 mg, 54%): 1H NMR (400 MHz, CDCl3) of (1′R,3R)-61
(major) δ 7.99-7.40 (m, 5H), 7.40-7.10 (m, 5H), 5.60 (tq, 1H,
J ) 8.3, 1.0), 4.58 (t, 1H, J ) 6.6), 4.05 (t, 1H, J ) 6.7), 3.55
(dd, 1H, J ) 14.8, 8.3), 3.44 (dd, 1H, J ) 14.8, 8.3), 3.36 (dd,
1H, J ) 16.3, 6.6), 3.20 (dd, 1H, J ) 16.3, 6.6), 2.78 (s, 3H),
1.89 (d, 3H, J ) 1.0), 1.78 (dqd, 1H, J ) 13.9, 7.4, 6.7), 1.61
(dqd, 1H, J ) 13.9, 7.4, 6.7), 0.85 (t, 3H, J ) 7.4). 1H NMR
(400 MHz, CDCl3) of (1′R,3S)-60 (minor) δ 8.0-7.0 (m, 10H),
5.48 (tq, 1H, J ) 7.7, 1.1), 4.82 (dd, 1H, J ) 6.9, 5.4), 4.28 (t,
1H, J ) 6.6), 3.66-3.25 (m, 2H), 3.24-3.06 (m, 2H), 2.68 (s,
3H), 1.76 (d, 3H, J ) 1.1), 1.82-1.54 (m, 2H), 0.76 (t, 3H, J )
7.4).
1:2.9 Mixtu r e of (4S,5Z)- a n d (4R,5Z)-5-Meth yl-7-
(m e t h ylsu lfon yl)-4-[(R )-1-p h e n yle t h oxy]h e p t -5-e n -2-
on e ((1′R,4S)-69 a n d (1′R,4R)-70). A mixture of (-)-51 (56
mg, 0.3 mmol), (isopropenyloxy)trimethylsilane (10, 0.1 mL,
0.55 mmol) and Yb(OSO2CF3)3 (132 mg, 0.2 mmol) in anhy-
drous CH2Cl2 (2 mL) was degassed and cooled to -196 °C. SO2
(0.64 g, 10 mmol, dried on basic Al2O3, Merck, act. I, degassed
3 times on the vacuum line) was transferred (vacuum line).
The mixture was stirred at -78 °C for 5 h. Solvent evaporation
(-78 °C, 0.1 Torr) was followed by addition of 1 M Bu4NF in
THF (1.5 mL, 1.5 mmol) and MeI (0.3 mL, 5 mmol), stirring
at 0 °C for 16 h, addition of H2O (100 mL), and extraction with
CH2Cl2 (60 mL, 3 times). The combined organic extracts were
washed with H2O (100 mL, twice) and dried (Na2SO4), and the
solvent was evaporated. FC (9:1 CH2Cl2/EtOAc) gave a color-
less oil (96 mg, 99%), a 1:2.9 mixture of (1′R,4S)-69 and
(1′R,4R)-70: 1H NMR (400 MHz, CDCl3) of (1′R,4R)-70 (major)
δ 7.40-7.10 (m, 5H), 5.55 (tq, 1H, J ) 7.8, 1.3), 4.41 (dd, 1H,
J ) 7.7, 5.2), 4.25 (q, 1H, J ) 6.5), 3.50 (d, 2H, J ) 7.8), 2.83
(dd, 1H, J ) 16.2, 7.7), 2.75 (s, 3H), 2.58 (dd, 1H, J ) 16.2,
5.2), 2.10 (s, 3 H), 1.83 (d, 3H, J ) 1.3), 1.38 (d, 3H, J ) 6.5).
1H NMR (400 MHz, CDCl3) of (1′R,4S)-69 (minor) δ 7.40-7.10
(m, 5H), 5.25 (tq, 1H, J ) 7.4, 1.3), 4.68 (dd, 1H, J ) 8.1, 4.5),
4.45 (q, 1H, J ) 6.4), 3.62 (dd, 1H, J ) 15.9, 7.4), 3.54 (dd,
1H, J ) 15.9, 7.4), 2.95 (dd, 1H, J ) 16.7, 8.1), 2.70 (s, 3H),
2.57 (dd, 1H, J ) 16.7, 4.5), 2.20 (s, 3H), 1.72 (d, 3H, J ) 1.3),
1.38 (d, 3H, J ) 6.4).
1:4.1 Mixtu r e of (3S,4Z)- a n d (3R,4Z)-4-Meth yl-6-
(m eth ylsu lfon yl)-3-[(R)-(2-n aph th yl)eth oxy]-1-ph en ylh ex-
4-en -1-on e ((1′R,3S)-62 a n d (1′R,3R)-63). The procedure was
the same as for the preparation of 16 starting from (-)-2-
{1-(R)-[(1E )-2-m et h ylbu t a -1,3-dien yloxy]et h yl}n a ph t h a -
lene29 ((-)-53, 71 mg, 0.3 mmol), 9 (95 mg, 0.55 mmol), and
Yb(OSO2CF3)3 (132 mg, 0.2 mmol). FC (24:1 CH2Cl2/Et2O) gave
a colorless oil (107 mg, 82%), a 1:4.1 mixture of (1′R,3S)-62
and (1′R,3R)-63: 1H NMR (400 MHz, CDCl3) of (1′R,3R)-63
(major) δ 8.00-7.40 (m, 12H), 5.66 (tq, 1H, J ) 7.5, 1.2), 4.62
(t, 1H, J ) 6.6), 4.52 (q, 1H, J ) 6.7), 3.59 (dd, 1H, J ) 18.1,
7.5), 3.58 (dd, 1H, J ) 18.1, 7.5), 3.40 (dd, 1H, J ) 16.0, 6.6),
3.22 (dd, 1H, J ) 16.0, 6.6), 2.71 (s, 3H), 1.95 (d, 3H, J ) 1.2),
1
1.46 (d, 3H, J ) 6.7). H NMR (400 MHz, CDCl3) of (1′R,3S)-
1:5.0 Mixtu r e of (4S,5Z)- a n d (4R,5Z)-5-Meth yl-7-
(m et h ylsu lfon yl)-4-[(R)-1-p h en ylp r op oxy]h ep t -5-en -2-
on e ((1′R,4S)-71 a n d (1′R,4R)-72). The procedure was the
same as for the preparation of 69 + 70, starting from (+)-52
(59 mg, 0.3 mmol) and 10 (100 mg, 0.55 mmol) and using Yb-
(OSO2CF3)3 (40 mg, 0.06 mmol) as acid promoter. FC (14:1
CH2Cl2/EtOAc) gave a colorless oil (52 mg, 51%), a 1:5.0
mixture of (1′R,4S)-71 and (1′R,4R)-72: 1H NMR (400 MHz,
CDCl3) of (1′R,4R)-72 (major) δ 7.38-7.18 (m, 5H), 5.55 (tq,
1H, J ) 7.2, 1.1), 4.39 (dd, 1H, J ) 7.7, 5.3), 3.98 (t, 1H, J )
6.8), 3.45 (dd, 1H, J ) 14.7, 7.2), 3.41 (dd, 1H, J ) 14.7, 7.2),
2.84 (dd, 1H, J ) 16.1, 7.7), 2.75 (s, 3H), 2.56 (dd, 1H, J )
16.1, 5.3), 2.10 (s, 3H), 1.84 (d, 3H, J ) 1.1), 1.75 (dqd, 1H, J
) 13.9, 7.6, 6.8), 1.60 (dqd, 1H, J ) 13.9, 7.6, 6.8), 0.84 (t, 3H,
62 (minor) δ 8.0-7.4 (m, 12 H), 5.26 (tq, 1H, J ) 7.6, 1.2),
4.95 (dd, 1H, J ) 7.6, 5.2), 4.73 (q, 1H, J ) 6.4), 3.65 (dd, 1H,
J ) 15.1, 7.6), 3.55-3.48 (m, 1H), 3.15 (dd, 1H, J ) 17.2, 7.6),
3.12 (dd, 1H, J ) 17.2, 5.2), 2.58 (s, 3H), 1.81 (d, 3H, J ) 1.2),
1.45 (d, 3H, J ) 6.4).
3.8:1 Mixtu r e of (3S,4Z)- a n d (3R,4Z)-4-Meth yl-6-
(m eth ylsu lfon yl)-3-[(S)-1-(p en ta flu or op h en yl)eth oxy]-1-
p h en ylh ex-4-en -1-on e (1′S,3S)-64 a n d (1′S,3R)-65). The
procedure was the same as for the preparation of 16, starting
from (+)-54 (83 mg, 0.3 mmol) and 9 (95 mg, 0.55 mmol) and
using Yb(OSO2CF3)3 (40 mg, 0.06 mmol) as acidic promoter.
FC (34:1 CH2Cl2/Et2O) gave a colorless oil (32 mg, 22%), 3.8:1
mixture of (1′S,3S)-64 and (1′S,3R)-65: 1H NMR (400 MHz,
CDCl3) of (1′S,3S)-64 (major) δ 7.99-7.40 (m, 5H), 5.68 (ddq,
1H, J ) 7.1, 6.3, 1.4), 4.75 (q, 1H, J ) 6.7), 4.62 (dd, 1H, J )
7.0, 5.6), 3.97 (dd, 1H, J ) 14.3, 7.1), 3.80 (dd, 1H, J ) 14.3,
6.3), 3.40 (dd, 1H, J ) 16.8, 7.0), 3.15 (dd, 1H, J ) 16.8, 5.6),
2.88 (s, 3H), 1.90 (d, 3H, J ) 1.4), 1.53 (d, 3H, J ) 6.7). 1H
NMR (400 MHz, CDCl3) of (1′S,3R)-65 (minor) δ 7.99-7.40
(m, 5H), 5.35 (tq, 1H, J ) 6.1, 1.1), 4.97 (q, 1H, J ) 6.7), 4.95
1
J ) 7.6). H NMR (400 MHz, CDCl3) of (1′R,4S)-71 (minor) δ
7.40-7.18 (m, 5H), 5.16 (tq, 1H, J ) 7.9, 1.4), 4.62 (dd, 1H, J
) 7.9, 4.5), 4.22 (t, 1H, J ) 6.5), 3.55 (dd, 1H, J ) 13.8, 7.9),
3.48-3.38 (m, 1H), 2.94 (dd, 1H, J ) 16.7, 7.9), 2.67 (s, 3H),
2.55 (dd, 1H, J ) 16.7, 4.5), 2.20 (s, 3H), 1.81-1.54 (m, 2H),
1.68 (d. 3H, J ) 1.4), 0.79 (t, 3H, J ) 7.4).

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5091
crystals, mp 97-98 °C (CH2Cl2/light petroleum ether); [R25
)
(-)-(4S,5Z)- a n d (-)-(4R,5Z)-5-Meth yl-7-(m eth ylsu lfo-
n yl)-3-[(S)-1-(2,4,6-tr iisop r op ylp h en yl)eth oxy]h ep t-5-en -
2-on e ((-)-(1′S,4S)-73 a n d (-)-1′S,4R)-74). Dry SO2 (1.28 g,
20 mmol) was transferred (vacuum line) to a frozen (liquid N2)
solution of Yb(OSO2CF3)3 (315 mg, 0.51 mmol) in anhydrous
CH2Cl2 (2 mL). The mixture was stirred at -78 °C for 30 min
and cooled to -90 °C. A solution of (+)-55 (200 mg, 0.64 mmol)
and 10 (0.48 mL, 3 mmol) in anhydrous CH2Cl2 (4 mL) was
added slowly to the mixture and stirred at -90 °C for 21 h.
The solvents were evaporated at -78 °C (0.1 Torr). After
pressurizing (1 atm) with Ar, 1 M Bu4NF in THF (6 mL, 6
mmol) and MeI (1.2 mL, 20 mmol) were added. The mixture
was stirred at 20 °C for 15 h. H2O (30 mL) was added, and
the mixture was extracted with CH2Cl2 (20 mL, 5 times). The
combined organic extracts were dried (MgSO4), and the solvent
was evaporated. FC (24:1 CH2Cl2/Et2O) gave a first fraction
of (-)-(1′S,4S)-73 (196 mg, 68%, Rf ) 0.13) and a second of
(-)-(1′S,4R)-74 (52 mg, 18%). The same procedure using 0.5
M (CF3SO2)2NH in CH2Cl2 (0.24 mL, 0.12 mmol) (instead of
Yb(OTf)3), (+)-55 (197 mg, 0.626 mmol), and 10 (0.48 mL, 3
mmol) in anhydrous CH2Cl2 (1 mL) at -100 °C provided
(-)-73 (198 mg, 70%) and (-)-74 (28 mg, 10%), overall yield
of 80%. Data for (-)-(1′S,4S)-73: colorless crystals, mp
121.5-123 °C (MeOH); [R2D5 ) -12 (c ) 1.05, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 7.05-6.95 (m, 2H), 5.54 (ddq, 1H, J )
9.3, 4.8, 1.4), 4.93 (q, 1H, J ) 6.8), 4.48 (dd, 1H, J ) 7.8, 4.9),
3.93 (m, 1H), 3.84 (dd, 1H, J ) 14.9, 9.3), 3.30 (dd, 1H, J )
14.9, 4.8), 3.08 (m, 1H), 2.88 (sept, 1H, J ) 7.2), 2.87 (dd, 1H,
J ) 17.1, 7.8), 2.84 (s, 3H), 2.75 (dd, 1H, J ) 17.1, 4.9), 2.05
(s, 3H), 1.85 (d, 3H, J ) 1.4), 1.50 (d, 3H, J ) 6.8), 1.35-1.04
(m, 12 H), 1.25 (d, 6H, J ) 7.2). Data for (-)-(1′S,4R)-74:
colorless solid, mp 84-86 °C; [R2D5 ) -62.4 (c ) 1.1, CHCl3);
1H NMR (400 MHz, CDCl3) δ 7.00-6.92 (m, 2H), 5.41 (tq, 1H,
J ) 7.9, 1.1), 4.95 (q, 1H, J ) 6.7), 4.77 (dd, 1H, J ) 7.9, 4.6),
3.71 (dd, 1H, J ) 14.4, 7.9), 3.70 (m, 1H), 3.58 (dd, 1H, J )
14.4, 7.9), 3.13 (m, 1H), 2.89 (dd, 1H, J ) 16.5, 7.9), 2.83 (sept,
1H, J ) 6.9), 2.69 (s, 3H), 2.58 (dd, 1H, J ) 16.5, 4.6), 2.21 (s,
3H), 1.69 (d, 3H, J ) 1.1), 1.49 (d, 3H, J ) 6.7), 1.26-1.16 (m,
12H), 1.23 (d, 6H, J ) 6.9).
(5RS,6Z)- a n d (5SR,6Z)-2,2,6-Tr im eth yl-8-(m eth ylsu l-
fon yl)-5-[(RS)-1-(2,4,6-t r iisop r op ylp h en yl)et h oxy)oct -6-
en -3-on e ((1′RS,5RS)-76) a n d (1′RS,5SR)-77). The proce-
dure was the same as for the preparation of (-)-73 and (-)-
74 starting from (()-55 (50 mg, 0.16 mmol), 11 (0.15 mL, 0.67
mmol), and 0.5 M (CF3SO2)2NH in CH2Cl2 (60 µL, 0.03 mmol).
FC (1:4 EtOAc/light petroleum ether) gave a first fraction of a
colorless oil (15 mg of 1′RS,5RS-76, 19%). Then with 1:3 EtOH/
light petroleum ether a second fraction delivered another oil
(6 mg of 1′RS,5SR)-77, 8%). Data for (1′RS,5RS)-76 (major):
1H NMR (400 MHz, CDCl3) δ 7.28-6.96 (m, 2H), 5.54 (ddq,
1H, J ) 9.5, 4.4, 1.2), 4.93 (q, 1H, J ) 6.8), 4.50 (dd, 1H, J )
9.4, 3.7), 3.98 (dd, 1H, J ) 15.2, 9.5), 3.92 (m, 1H), 3.21 (dd,
1H, J ) 15.2, 4.4), 3.07 (m, 1H), 3.04 (dd, 1H, J ) 17.9, 9.4),
2.86 (sept, 3H, J ) 6.9), 2.77 (s, 3H), 2.70 (dd, 1H, J ) 17.9,
3.7), 1.83 (d, 3H, J ) 1.2), 1.51 (d, 3H, J ) 6.8), 1.31-1.17 (m,
12H), 1.21 (d, 6H, J ) 6.9), 1.04 (s, 9H). Data for (1′RS,5SR)-
77: 1H NMR (400 MHz, CDCl3) δ 7.00-6.92 (m, 2H), 5.54 (tq,
1H, J ) 7.8, 1.4), 4.94 (q, 1H, J ) 6.6), 4.80 (dd, 1H, J ) 7.2,
5.2), 3.72 (m, 1H), 3.72 (dd, 1H, J ) 14.8, 7.8), 3.63 (dd, 1H, J
) 14.8, 7.8), 3.17 (sept, 1H, J ) 6.6), 3.04 (dd, 1H, J ) 17.2,
7.2), 2.86 (sept, 1H, J ) 6.9), 2.63 (s, 3H), 2.60 (dd, 1H, J )
17.2, 5.2), 1.70 (d, 3H, J ) 1.4), 1.50 (d, 1H, J ) 6.6), 1.27-
1.15 (m, 6H), 1.24 (d, 6H, J ) 6.6), 1.17 (d, 6H, J ) 6.9), 1.15
(s, 9H).
D
-23 (c ) 1.02, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.05-
6.96 (m, 2H), 5.53 (ddq, 1H, J ) 9.2, 5.0, 1.3), 4.94 (q, 1H, J )
6.7), 4.50 (dd, 1H, J ) 8.3, 4.4), 3.91 (dd, 1H, J ) 15.1, 9.2),
3.90 (m, 1H), 3.30 (dd, 1H, J ) 15.1, 5.0), 3.10 (m, 1H), 2.96
(dd, 1H, J ) 17.2, 8.3), 2.86 (dd, 1H, J ) 17.2, 4.4), 2.85 (sept,
1H, J ) 6.9), 2.76 (s, 3H), 1.85 (d, 3H, J ) 1.3), 1.82 (m, 1H),
1.50 (d, 3H, J ) 6.7), 1.35-1.12 (m, 12H), 1.25 (d, 6H, J )
6.9), 0.90-0.80 (m, 4H). Data for (1′S,3R)-80: colorless oil; [R
25
D
) -24 (c ) 0.65, CHCl3); 1H NMR (400 MHz, CDCl3) δ
7.07-6.92 (m, 2H), 5.42 (tq, 1H, J ) 7.6, 1.3), 4.94 (q, 1H, J )
6.7), 4.76 (dd, 1H, J ) 7.8, 4.9), 3.76 (m, 1H), 3.72 (dd, 1H, J
) 14.3, 7.6), 3.58 (dd, 1H, J ) 14.3, 7.6), 3.11 (m, 1H), 3.03
(dd, 1H, J ) 16.0, 7.8), 2.84 (sept, 1H, J ) 6.9), 2.69 (dd, 1H,
J ) 16.0, 4.9), 2.65 (s, 3H), 2.00 (m, 1H), 1.72 (d, 3H, J ) 1.3),
1.48 (d, 3H, J ) 6.7), 1.35-1.15 (m, 12 H), 1.24 (d, 6H, J )
6.9), 0.96-0.83 (m, 4H).
(-)-(3S,4Z)-4-Meth yl-6-(m eth ylsu lfon yl)-3-[(S)-1-(2,4,6-
t r iisop r op ylp h en yl)et h oxy]h ex-4-en a l ((-)-(1′S,3S)-83).
The procedure was the same as for the preparation of (-)-73
and (-)-74, starting from (+)-55 (48 mg, 0.15 mmol) and
vinyloxytrimethylsilane (82, 0.11 mL, 0.75 mmol) and using
Yb(OSO2CF3)3 (73 mg, 0.12 mmol) as promoter. Reaction time
was 16 h at -78 °C. FC (24:1 CH2Cl2/Et2O) gave a first fraction
(20 mg) containing a 6.1:1 mixture of (-)-83/84 + 85. A second
fraction gave (+)-55 (18 mg). Crystallization of the first fraction
from Et2O/pentane gave pure (-)-83 (48% yield, considering
the recovery of (+)-55): colorless solid, mp 111.5-112 °C; [RD25
) -30 (c ) 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 9.69 (t,
1H, J ) 1.9), 7.08-6.92 (m, 2H), 5.52 (tq, 1H, J ) 7.9, 1.2),
4.95 (q, 1H, J ) 6.8), 4.56 (t, 1H, J ) 6.5), 3.86 (m, 1H), 3.45
(dd, 1H, J ) 14.6, 7.9), 3.32 (dd, 1H, J ) 14.6, 7.9), 3.10 (m,
1H), 2.86 (sept, 1H, J ) 6.9), 2.76 (s, 3H), 2.75 (dd, 1H, J )
6.5, 1.9), 2.73 (dd, 1H, J ) 6.5, 1.9), 1.87 (d, 3H, J ) 1.2), 1.52
(d, 3H, J ) 6.8), 1.35-1.04 (m, 12H), 1.25 (d, 6H, J ) 6.9).
(3S,4E)- a n d (3R,4E)-4-Met h yl-6-(m et h ylsu lfon yl)-3-
[(S)-1-[2,4,6-tr iisopr opylph en yl)eth oxy]h ex-4-en al (84 an d
85). The procedure was the same as for the preparation of
(-)-73 + (-)-74 starting from (+)-75 (100 mg, 0.318 mmol)
and 82 (0.7 mL, 4.8 mmol) and using (CF3SO2)2NH (0.5 M in
CH2Cl2, 0.12 mL, 0.06 mmol) as promoter (-78 °C, 2 h). FC
(29:1 CH2Cl2/Et2O) gave a colorless oil containing a 4:1 mixture
(32 mg, 32%) of 84 and 85. Crystallization from Et2O/pentane
gave pure 84 (or 85). Major diastereomer: mp 105-107 °C;
1H NMR (400 MHz, CDCl3) δ 9.83 (t, 1H, J ) 2.0), 7.05-6.90
(m, 2H), 5.72 (tq, 1H, J ) 8.4, 1.2), 4.97 (q, 1H, J ) 6.7), 4.54
(dd, 1H, J ) 8.4, 4.4), 3.72 (m, 1H), 3.72 (d, 1H, J ) 8.4), 3.71
(d, 1H, J ) 8.4), 3.07 (m, 1H), 2.83 (sept, 1H, J ) 6.9), 2.76
(ddd, 1H, J ) 16.1, 8.4, 2.0), 2.75 (s, 3H), 2.55 (ddd, 1H, J )
16.1, 4.4, 2.0), 1.63 (d, 3H, J ) 1.2), 1.51 (d, 3H, J ) 6.7), 1.29-
1.16 (m, 12 H), 1.27 (d, 6H, J ) 6.9). Minor diastereomer: 1H
NMR (400 MHz, CDCl3) δ 9.62 (t, 1H, J ) 2.4), 7.05-6.90 (m,
2H), 5.66 (tq, 1H, J ) 8.6, 1.2), 5.00 (q, 1H, J ) 6.7), 4.18 (t,
1H, J ) 6.5), 3.86 (m, 1H), 3.77 (d, 1H, J ) 8.6), 3.75 (d, 1H,
J ) 8.6), 3.15 (m, 1H), 2.82 (sept, 1H, J ) 6.9), 2.83 (s, 3H),
2.85-2.74 (m, 2H), 1.81 (d, 3H, J ) 1.2), 1.52 (d, 3H, J ) 6.7),
1.29-1.16 (m, 18H).
(-)-(3S ,4Z)-1-C y c lo p r o p y l-3-h y d r o x y -4-m e t h y l-6-
(m eth ylsu lfon yl)h ex-4-en -1-on e ((-)-81). A mixture of (-)-
79 (46 mg, 0.096 mmol), CD2Cl2 (1.5 mL), and CF3COOH (0.1
1
mL) was stirred at 20 °C for 25 min (control by H NMR). A
saturated aqueous solution of NaHCO3 (30 mL) was added,
and the mixture was extracted with CH2Cl2 (20 mL, 3 times).
The combined organic extracts were dried (MgSO4), and the
solvent was evaporated. FC (1:10 EtOAc/CH2Cl2) gave a white
(-)-(3S,4Z)- a n d (3R,4Z)-1-Cyclop r op yl-4-m eth yl-6-
(m e t h ylsu lfon yl)-3-[(1S )-1-(2,4,6-t r iisop r op ylp h e n yl)-
eth oxy]h ex-4-en -1-on e ((-)-(1′S,3S)-79 a n d (1′S,3R)-80).
The procedure was the same as for the preparation of (-)-73
and (-)-74 starting from (+)-55 (102 mg, 0.32 mmol), 1-cyclo-
propyl-1-(trimethylsilyloxy)ethene (78, 0.3 mL, 1.5 mmol), and
Yb(OSO2CF3)3 (121 mg, 0.19 mmol). FC (24:1 CH2Cl2/Et2O)
gave (-)-(1′S,3S)-79 (Rf ) 0.24, 106 mg, 69%) and a 1:2 mixture
of (-)-79 and (1′S,3R)-80. A second FC gave pure (1′S,3R)-80
as a colorless oil (Rf ) 0.14). Data for (-)-(1′S,3S)-79: colorless
solid (20 mg, 85%, Rf ) 0.19): mp 78-80 °C; [R25 ) -18 (c )
D
1
1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 5.39 (tq, 1H, J )
8.2, 1.5), 4.89 (dd, 1H, J ) 8.4, 4.0), 3.90 (d, 2H, J ) 8.2), 3.23
(s, 1H), 2.87 (dd, 1H, J ) 17.5, 8.4), 2.82 (s, 3H), 2.81 (dd, 1H,
J ) 17.5, 4.0), 1.96 (m, 1H), 1.84 (d, 3H, J ) 1.5), 1.04-0.90
(m, 4H).
(+)-(1R,3S,4Z)-1-Cyclop r op yl-4-m eth yl-6-(m eth ylsu lfo-
n yl)h ex-4-en -1,3-d iol ((+)-86). A 1 M solution of Et2BOMe
in THF (0.1 mL, 0.1 mmol) was added slowly (syringe) to a

5092 J . Org. Chem., Vol. 66, No. 15, 2001
Narkevitch et al.
stirred solution of (-)-81 (17 mg, 0.035 mmol) in anhydrous
4:1 THF/MeOH (0.5 mL) cooled to -78 °C under an Ar
atmosphere. After stirring at -78 °C for 15 min, NaBH4 (3
mg, 0.1 mmol) was added. After stirring at -78 °C for 5 h,
AcOH (0.3 mL) was added, and the mixture was allowed to
warm to 0 °C. A saturated aqueous solution of NH4Cl (5 mL)
was added, and the mixture was extracted with CH2Cl2 (5 mL,
twice). The combined organic extracts were dried (MgSO4), and
the solvent was evaporated to dryness. The residue was taken
up in MeOH (10 mL) and heated under reflux for 45 min.
Solvent evaporation and FC (EtOAc) gave a colorless oil (8 mg,
stirring at 20 °C for 2 h the mixture was cooled to 0 °C, and
(-)-57e (2.45 g, 7.74 mmol) was added. After stirring at 0 °C
for 2 h, ice-cold H2O (100 mL) was added, and the mixture
was extracted with light petroleum ether (50 mL, 3 times).
The combined organic extracts were dried (MgSO4), and the
solvent was evaporated to dryness. The residue was taken up
in light petroleum ether (50 mL). The precipitate (Ph3PO) was
filtered off. Solvent evaporation gave a white solid (2.365 g,
93%): mp 68-69.5 °C; [R2D5 ) -17 (c ) 1.08, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 7.03-7.01 (m, 2H), 6.11 (q, 1H, J ) 1.2),
5.88 (dq, 1H, J ) 15.2, 1.4), 5.41 (dq, 1H, J ) 15.2, 6.6), 5.35
(q, 1H, J ) 6.7), 3.54 (2m, 2H), 2.86 (sept, 1H, J ) 6.9), 1.73
(d, 3H, J ) 1.2), 1.70 (dd, 3H, J ) 6.6, 1.4), 1.62 (d, 3H, J )
6.7), 1.28-1.20 (m, 12H), 1.25 (d, 6H, J ) 6.9).
(3RS,4Z,6SR)- a n d (3SR,4Z,6RS)-4-Meth yl-6-(m eth yl-
su lfon yl)-1-p h en yl-3-[(RS)-1-(2,4,6-t r iisop r op ylp h en yl)-
eth oxy]h ep t-4-en -1-on e ((()-90) a n d (()-91). The procedure
was the same as for the preparation of 17 starting from (()-9
(0.2 mL, 1 mmol) and (()-89 (50 mg, 0.15 mmol, made from
(()-56e) and using (CF3SO2)2NH (0.5 M in CH2Cl2, 60 µL, 0.03
mmol) and 0.5 g of SO2 (-78 °C, 90 min for the oxyallylation
step). FC (1:3 EtOAc/light petroleum ether) gave (()-90 (39
mg, 55%, Rf ) 0.22) and (()-91 (22 mg, 31%, Rf ) 0.16). Data
for (()-90 (major): white crystals, mp 132-133.5 °C (Et2O/
pentane); 1H NMR (400 MHz, CDCl3) δ 7.76-7.37 (m, 5H),
7.05-6.94 (m, 2H), 5.25 (dq, 1H, J ) 10.7, 1.3), 5.17 (q, 1H, J
) 6.8), 4.91 (t, 1H, J ) 6.5), 4.40 (dq, 1H, J ) 10.7, 6.8), 3.88,
3.21 (2m, 2H), 3.20 (d, 2H, J ) 6.5), 2.90 (s, 3H), 2.86 (sept,
1H, J ) 7.0), 1.88 (d, 3H, J ) 1.3), 1.54 (d, 3H, J ) 6.8), 1.43
(d, 3H, J ) 6.8), 1.29-1.19 (m, 12 H), 1.24 (d, 6H, J ) 7.0).
Data for (()-91 (minor): white crystals, mp 138-140 °C (Et2O/
pentane); 1H NMR (400 MHz, CDCl3) δ 8.00-7.42 (m, 5H),
6.98-6.91 (m, 2H), 5.20 (dq, 1H, J ) 10.8, 1.3), 5.01 (q, 1H, J
) 6.7), 4.93 (t, 1H, J ) 7.4), 4.17 (dq, 1H, J ) 10.8, 6.7), 3.65
(sept, 1H, J ) 6.8), 3.54 (dd, 1H, J ) 15.9, 7.4), 3.12 (sept, 1H,
J ) 6.8), 3.06 (dd, 1H, J ) 15.9, 7.4), 2.83 (sept, 1H, J ) 6.9),
2.42 (s, 3H), 1.78 (d, 3H, J ) 1.3), 1.47 (d, 3H, J ) 6.7), 1.27
(d, 3H, J ) 6.7), 1.25-1.06 (m, 18H).
(4RS,5Z,7SR)- a n d (4SR,5Z,7RS)-5-Meth yl-7-(m eth yl-
su lfon yl)-4[(RS)-1-(2,4,6-tr iisop r op ylp h en yl)eth oxy]oct-
5-en -2-on e ((()-92) a n d (()-93). The procedure was the same
as for the preparation of 17 starting from 10 (0.3 mL, 1.9
mmol) and (()-89 (56 mg, 0.17 mmol), SO2 (0.5 g) and using
(CF3SO)2NH (0.03 mmol), oxyallylation step at -78 °C for 2
h. FC (1:2 EtOAc/light petroleum ether) gave (()-92 (48 mg,
60%, Rf ) 0.24) and (()-93 (29 mg, 37%, Rf ) 0.12). Data for
(()-92 (major): white crystals, mp 134-136 °C (Et2O/pentane);
1H NMR (400 MHz, CDCl3) δ 7.21-6.94 (m, 2H), 5.27 (dq, 1H,
J ) 10.8, 1.4), 5.08 (q, 1H, J ) 6.8), 4.66 (dd, 1H, J ) 7.4, 5.6),
4.40 (dq, 1H, J ) 10.8, 6.8), 3.83, 3.18 (2m, 2H), 2.89 (s, 3H),
2.84 (sept, 1H, J ) 6.6), 2.73 (dd, 1H, J ) 16.7, 5.6), 2.65 (dd,
1H, J ) 16.7, 7.4), 2.01 (s, 3H), 1.84 (d, 3H, J ) 1.4), 1.50 (d,
3H, J ) 6.8), 1.48 (d, 3H, J ) 6.8), 1.28-1.22 (m, 12H), 1.25
(d, 6H, J ) 6.6). Data for (()-93 (minor): white crystals, mp
129-131 °C; 1H NMR (400 MHz, CDCl3) δ 7.00-6.91 (m, 2H),
5.23 (dq, 1H, J ) 10.5, 1.3), 4.98 (q, 1H, J ) 6.8), 4.79 (dd,
1H, J ) 7.1, 5.9), 4.12 (dq, 1H, J ) 10.5, 6.8), 3.73, 3.14 (2
sept, 2H, J ) 6.8), 2.93 (dd, 1H, J ) 16.3, 7.1), 2.84 (sept, 1H,
J ) 6.8), 2.54 (dd, 1H, J ) 16.3, 5.9), 2.51 (s, 3H), 2.22 (s, 3H),
1.69 (d, 3H, J ) 1.3), 1.49 (d, 3H, J ) 6.8), 1.24 (d, 3H, J )
6.8), 1.26-1.17 (m, 12 H), 1.22 (d, 6H, J ) 6.8).
83%, Rf ) 0.20): [R25 ) +2.0 (c ) 0.75, CHCl3); 1H NMR (400
D
MHz, CDCl3) δ 5.39 (q, 1H, J ) 8.2, 1.3), 4.66 (dd, 1H, J )
9.2, 3.8), 3.99 (dd, 1H, J ) 14.2, 8.2), 3.90 (dd, 1H, J ) 14.2,
8.2), 3.55 (br. s, 1H), 3.06 (ddd, 1H, J ) 10.8, 8.6, 2.5), 2.90 (s,
3H), 2.90 (br. s, 1H), 1.90 (ddd, 1H, J ) 14.3, 10.8, 9.2), 1.82
(d, 3H, J ) 1.3), 1.80 (ddd, 1H, J ) 14.3, 3.8, 2.5), 0.95 (m,
1H), 0.54 (m, 2H), 0.33-0.22 (m, 2H).
10:1 Mixtu r e of (2′Z,4S,6S)- a n d (2′Z,4S,6R)-6-Cyclo-
p r op yl-2,2-d im eth yl-4-[(4-m eth ylsu lfon yl)bu t-2-en -2-yl]-
1,3-d ioxa n e ((2′Z,4S,6S)-87 a n d (2′Z,4S,6R)-87). A mixture
of Me4NBH(OAc)3 (265 mg, 1 mmol), MeCN (0.4 mL), and
AcOH (0.15 mL) was stirred at 20 °C for 15 min. After cooling
to -40 °C a solution of (-)-81 (25 mg, 0.1 mmol) in MeCN
(1.5 mL) was added slowly. After stirring at -40 °C for 48 h,
H2O (10 mL) and CH2Cl2 (10 mL) were added. The organic
layer was washed with
a saturated aqueous solution of
NaHCO3 (10 mL, twice). The aqueous layers were extracted
with CH2Cl2 (10 mL, 5 times). The combined organic extracts
were dried (MgSO4). Solvent evaporation and FC (EtOAc) gave
a colorless oil (16 mg, 64%, Rf ) 0.10), a 10:1 mixture of anti-
and syn-1,3-diol. A total of 7 mg (0.028 mmol) of this mixture
was dissolved in 2,2-dimethoxypropane (0.8 mL) and acetone
(0.2 mL). After the addition of pyridinium p-toluenesulfonate
(2 mg) the mixture was stirred at 20 °C for 2 h. The mixture
was poured into a saturated aqueous solution of NaHCO3 (10
mL) and extracted with CH2Cl2 (10 mL, 3 times). The combined
organic extracts were dried (MgSO4). Solvent evaporation and
FC (12:1 CH2Cl2/EtOAc) gave a colorless oil (7 mg, 86%, Rf )
0.30), a 10:1 mixture of anti- and syn-1,3-diol acetonide, which
are hydrolyzed in a few hours in CDCl3 solution. Data for
(2′Z,4S,6S)-87: 1H NMR (400 MHz, CDCl3) δ 5.40 (tq, 1H, J
) 8.5, 1.1), 4.62 (dd, 1H, J ) 8.8, 7.3), 4.02 (dd, 1H, J ) 14.3,
8.5), 3.88 (dd, 1H, J ) 14.3, 8.5), 3.11 (dt, 1H, J ) 8.7, 7.0),
2.86 (s, 3H), 1.90 (m, 2H), 1.88 (d, 3H, J ) 1.1), 1.41, 1.36 (2s,
6H), 0.95 (m, 1H), 0.57 (m, 2H), 0.31-0.20 (m, 2H); 13C NMR
(100.6 MHz, CDCl3) δ 145.2, 112.4, 100.5, 72.0, 66.8, 54.1, 39.3,
36.4, 24.9 (Me-C(2)), 24.8 (Me-C(2)) 20.3, 15.5, 3.4, 2.0. Data
for (2′Z,4S,6R)-87: 1H NMR (400 MHz, CDCl3) δ 5.43 (tq, 1H,
J ) 8.5, 1.1), 4.56 (dd, 1H, J ) 11.3, 2.6), 4.11 (dd, 1H, J )
14.4, 8.5), 3.97 (dd, 1H, J ) 14.4, 8.5), 3.20 (td, 1H, J ) 8.5,
3.1), 2.87 (s, 3H), 2.03 (dd, 1H, J ) 14.4, 11.3, 3.1), 1.86 (d,
3H, J ) 1.1), 1.72 (ddd, 1H, J ) 14.4, 8.5, 2.6), 1.47, 1.43 (2s,
6H), 0.95 (m, 1H), 0.57 (m, 2H), 0.34 (m, 2H); 13C NMR (100.6
MHz, CDCl3) δ 145.0, 113.5, 99.9, 74.0, 68.1, 53.4, 39.4, 34.7,
30.2 (Me-C(2)), 20.8, 19.5 (Me-C(2)), 16.1, 3.3, 2.3.
10:1 Mixtu r e of (1S,3S,4R)- a n d (1R,3S,4Z)-1-Cyclop r o-
pyl-4-m eth yl-6-(m eth ylsu lfon yl)h ex-4-en -1,3-diyl bis{[(R)-
R-m eth oxy-R-tr iflu or om eth ylp h en yl]a ceta te} ((1S,3S,4Z)-
88 a n d (1R,3S,4Z)-88). The 10:1 mixture of 1,3-diols obtained
above (5 mg, 0.02 mmol) was mixed with pyridine (0.5 mL),
4-(dimethylamino)pyridine (2 mg), and (S)-(R-methoxy-R-tri-
fluoromethylphenyl)acetyl chloride (25 mg, 0.11 mmol). After
stirring at 20 °C for 40 min, the solvent was evaporated in
vacuo to dryness. FC (CH2Cl2) gave a colorless oil (13 mg, 96%,
Rf ) 0.20): 19F NMR (376.7 MHz, CDCl3, CCl3F) δ -71.375
(s), -71.580 (s).
(-)-1,3,5-Tr iisop r op yl-2-{1-(S)-[(1E)-2-m eth ylp en ta -1,3-
d ien yloxy]eth yl}ben zen e ((-)-89). A 1.6 M solution of BuLi
in hexane (6.44 mL, 9.35 mmol) was added dropwise to a
stirred solution of (i-Pr)2NH (1.54 mL, 0.35 mmol) in anhy-
drous THF (30 mL) cooled to -78 °C under an Ar atmosphere.
After stirring at 0 °C for 1 h, ethyltriphenylphosphonium
bromide (3.21 g, 8.5 mmol) was added portionwise. After
(-)-(5S,6Z,8R)-
a n d
(5R,6Z,8S)-2,2,6-Tr im eth yl-8-
(m eth ylsu lfon yl)-5-[(S)-1-(2,4,6-tr iisopr opylph en yl)eth oxy]-
n on -6-en -3-on e ((-)-94) a n d 95). The procedure was the
same as for the preparation of 17, starting from (-)-89 (48
mg, 0.15 mmol) and 11 (0.15 mL, 0.67 mmol) and using 0.5 M
(CF3SO2)NH (6 µL, 0.03 mmol) in CH2Cl2 and 0.5 g of SO2.
Oxyallylation was at -100 to -92 °C for 2 h. FC (EtOAc/light
petroleum ether 1:4) gave (-)-94 (55 mg, 74%, Rf ) 0.14) and
a 1:1 mixture of (-)-94 + 95 (9 mg). Pure 95 was obtained by
FC (1:4 EtOAc/light petroleum ether): 4 mg (5%). Data for
(-)-94: colorless crystals, mp 101-103 °C (Et2O/pentane); 1H
NMR (400 MHz, CDCl3) δ 7.03-6.93 (m, 2H), 5.23 (dq, 1H, J
) 10.8, 1.4), 5.08 (q, 1H, J ) 6.8), 4.75 (dd, 1H, J ) 8.6, 4.3),

Synthesis of Polyfunctional Sulfones
J . Org. Chem., Vol. 66, No. 15, 2001 5093
4.45 (dq, 1H, J ) 10.7, 6.8), 3.87, 3.20 (2m, 2H), 2.89 (s, 3H),
2.87 (sept, 1H, J ) 6.9), 2.79 (dd, 1H, J ) 17.6, 8.6), 2.62 (dd,
1H, J ) 17.6, 4.3), 1.83 (d, 3H, J ) 1.4), 1.50 (d, 3H, J ) 6.8),
1.46 (d, 3H, J ) 6.8), 1.29-1.15 (m, 12H), 1.25 (d, 6H, J )
6.9), 0.95 (s, 9H). Data for 95: colorless oil; 1H NMR (400 MHz,
CDCl3) δ 7.00-6.92 (m, 2H), 5.16 (dq, 1H, J ) 10.6, 1.3), 4.95
(q, 1H, J ) 6.6), 4.82 (t, 1H, J ) 6.3), 4.18 (dq, 1H, J ) 10.6,
6.7), 3.76, 3.15 (2 sept, 2H, J ) 6.8), 3.05 (dd, 1H, J ) 17.1,
6.3), 2.84 (sept, 1H, J ) 6.8), 2.63 (dd, 1H, J ) 17.1, 6.3), 2.42
(s, 3H), 1.72 (d, 3H, J ) 1.3), 1.50 (d, 3H, J ) 6.6), 1.29 (d,
3H, J ) 6.7), 1.27-1.14 (m, 18H), 1.16 (s, 9H).
1.1), 1.50 (d, 3H, J ) 6.9), 1.49 (d, 3H, J ) 6.7), 1.26-1.11 (m,
12H), 1.22 (d, 6H, J ) 6.9), 0.79 (d, 3H, J ) 7.1), 0.49 (t, 3H,
J ) 7.1).
(3RS,4Z,6SR)-3-Hyd r oxy-4-m eth yl-6-(m eth ylsu lfon yl)-
1-p h en ylh ep t-4-en -1-on e ((()-101). The procedure was the
same as for the preparation of (-)-81 starting from (()-90 (29
mg, 0.057 mmol). FC (1:1 EtOAc/CH2Cl2) gave a colorless oil
(15 mg, 95%): 1H NMR (400 MHz, CDCl3) δ 5.17 (dq, 1H, J )
10.0, 1.0), 4.92 (dd, 1H, J ) 7.3, 5.6), 4.33 (dq, 1H, J ) 10.0,
6.8), 3.17 (br. s, 1H), 2.90 (dd, 1H, J ) 17.8, 7.3), 2.86 (s, 3H),
2.74 (dd, 1H, J ) 17.8, 5.6), 1.81 (d, 3H, J ) 1.0), 1.49 (d, 3H,
J ) 6.8), 1.16 (s, 9H).
(3RS,4Z,6SR)- an d (3SR,4Z,6RS)-1-Cyclopr opyl-4-m eth -
yl-6-(m eth ylsu lfon yl)-3-[(RS)-1-(2,4,6-tr iisopr opylph en yl)-
eth oxy]h ep t-4-en -1-on e ((()-96) a n d (()-97). The procedure
was the same as for the preparation of 17 starting from (()-
89 (56 mg, 0.17 mmol) and 78 (0.1 mL, 0.5 mmol) and using 5
M (CF3SO2)NH in CH2Cl2 (60 µL, 0.03 mmol) 0.5 g SO2.
Oxyallylation was at -78 °C for 1 h. FC (1:3 EtOAc/light
petroleum ether) gave (()-96 (47 mg, 56%, Rf ) 0.16) and (()-
97 (33 mg, 40%, Rf ) 0.09). Data for (()-96 (major): white
crystals, mp 120-122 °C (Et2O/pentane); 1H NMR (400 MHz,
CDCl3) δ 7.03-6.94 (m, 2H), 5.26 (dq, 1H, J ) 10.8, 1.4), 5.09
(q, 1H, J ) 6.7), 4.71 (dd, 1H, J ) 7.8, 5.3), 4.40 (dq, 1H, J )
10.8, 6.8), 3.84, 3.18 (2m, 2H), 2.89 (s, 3H), 2.88 (sept, 1H, J
) 6.9), 2.83 (dd, 1H, J ) 16.3, 5.3), 2.77 (dd, 1H, J ) 16.3,
7.8), 1.86 (d, 3H, J ) 1.4), 1.77 (m, 1H), 1.50 (d, 3H, J ) 6.7),
1.45 (d, 3H, J ) 6.8), 1.28-1.22 (m, 12H), 1.24 (d, 6H, J )
6.9), 1.12-0.74 (m, 4H). Data for (()-97 (minor): colorless oil;
1H NMR (400 MHz, CDCl3) δ 7.00-6.91 (m, 2H), 5.22 (dq, 1H,
J ) 10.7, 1.2), 4.97 (q, 1H, J ) 6.6), 4.79 (dd, 1H, J ) 7.3, 5.7),
4.13 (dq, 1H, J ) 10.7, 6.8), 3.78, 3.08 (2 sept, 2H, J ) 6.8),
3.06 (dd, 1H, J ) 15.8, 7.3), 2.84 (sept, 1H, J ) 6.8), 2.63 (dd,
1H, J ) 15.8, 5.7), 2.47 (s, 3H), 2.03 (m, 1H), 1.72 (d, 3H, J )
1.2), 1.48 (d, 3H, J ) 6.6), 1.26 (d, 3H, J ) 6.8), 1.25-1.15 (m,
12H), 1.21 (d, 6H, J ) 6.8), 1.09-0.95 (m, 4H).
(-)-(5S,6Z,8R)-5-Hyd r oxy-2,2,6-tr im eth yl-8-(m eth ylsu l-
fon yl)n on -6-en -3-on e ((-)-102). The procedure was the same
as for the preparation of (-)-81 starting from (-)-94 (29 mg,
0.057 mmol). FC (1:1 EtOAc/CH2Cl2) gave a colorless oil (15
mg, 95%, Rf ) 0.40): [R]25 ) -72 (c ) 0.85, CHCl3); 1H NMR
D
(400 MHz, CDCl3) δ 5.17 (dq, 1H, J ) 10.0, 1.0), 4.92 (dd, 1H,
J ) 7.3, 5.6), 4.33 (dq, 1H, J ) 10.0, 6.8), 3.17 (br. s, 1H), 2.90
(dd, 1H, J ) 17.8, 7.3), 2.86 (s, 3H), 2.74 (dd, 1H, J ) 17.8,
5.6), 1.81 (d, 3H, J ) 1.0), 1.49 (d, 3H, J ) 6.8), 1.16 (s, 9H).
(-)-(4S,5S,6Z,8R)-5-H yd r oxy-4,6-d im et h yl-8-(m et h yl-
su lfon yl)n on -6-en -3-on e ((-)-103). The procedure was the
same as for the preparation of (-)-81 starting from (-)-99 (9
mg, 0.018 mmol). FC (1:1 EtOAc/CH2Cl2) gave a colorless oil
(5 mg, 99%, Rf ) 0.32): [R2D5 ) -91 (c ) 0.85, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 5.08 (dq, 1H, J ) 9.7, 0.8), 4.62 (d,
1H, J ) 9.2), 4.28 (dq, 1H, J ) 9.7, 6.8), 2.92 (dq, 1H, J ) 9.2,
7.0), 2.85 (s, 3H), 2.58 (dq, 1H, J ) 21.8, 7.3), 2.36 (dq, 1H, J
) 21.8, 7.3), 1.79 (d, 3H, J ) 0.8), 1.64 (br. s, 1H), 1.49 (d, 3H,
J ) 6.8), 1.26 (d, 3H, J ) 7.0), 1.03 (t, 3H, J ) 7.3).
(-)-(4R,5S,6Z,8R)-5-H yd r oxy-4,6-d im et h yl-8-(m et h yl-
su lfon yl)n on -6-en -3-on e ((-)-104). The procedure was the
same as for the preparation of (-)-81 starting from (-)-100
(15 mg, 0.030 mmol). FC (1:1 EtOAc/CH2Cl2) gave a colorless
oil (7 mg, 89%, Rf ) 0.28): [R25 ) -40 (c ) 1.3, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 5.25 D(dq, 1H, J ) 10.0, 1.3), 4.59 (d,
1H, J ) 10.0), 4.14 (dq, 1H, J ) 10.0, 6.8), 2.86 (m, 1H), 2.61
(m, 2H), 1.84 (d, 1H, J ) 1.3), 1.63 (br. s, 1H), 1.50 (d, 3H, J
) 6.8), 1.08 (t, 3H, J ) 7.3), 0.87 (d, 3H, J ) 7.1).
(-)-(4S,5S,6Z,8R)- a n d (-)-(4R,5S,6Z,8R)-4-Dim eth yl-
8-(m et h ylsu lfon yl)-5-[(S)-1-(2,4,6-t r iisop r op ylp h en yl)-
eth oxy]n on -6-en -3-on e ((-)-99) a n d (-)-100). The proce-
dure was the same as for the preparation of 17 starting from
(-)-89 (52 mg, 0.16 mmol) and (Z)-3-trimethylsilyloxypent-3-
ene35 (98, 77 mg, 0.48 mmol) and using (CF3SO2)2NH (0.03
mmol) and SO2 (0.5 g). Oxyallylation was at -90 °C for 1h,
then -78 °C for 3 h. FC (1:3 EtOAc/light petroleum ether) gave
(-)-99 (49 mg, 63%, Rf ) 0.16) and (-)-100 (17 mg, 22%, Rf )
0.09). Data for (-)-99: colorless crystals, mp 144-146 °C
Ack n ow led gm en t . We thank the Swiss National
Science Foundation and the Fonds Herbette (Lausanne)
for support. We thank also Mr. Martial Rey and
Francisco Sepulveda for their technical help.
(MeOH); [R2D5 ) -107 (c ) 0.75, CHCl3); H NMR (400 MHz,
1
CDCl3) δ 7.03-6.92 (m, 2H), 5.18 (dq, 1H, J ) 10.7, 1.1), 5.12
(q, 1H, J ) 6.7), 4.25 (d, 1H, J ) 9.6), 4.19 (dq, 1H, J ) 10.7,
6.8), 3.81, 3.17 (2 sept, 2H, J ) 6.9), 2.88 (s, 3H), 2.87 (sept,
1H, J ) 6.9), 2.87 (m, 1H), 2.47 (dq, 1H, J ) 18.5, 7.2), 2.31
(dq, 1H, J ) 18.5, 7.2), 1.91 (d, 3H, J ) 1.1), 1.51 (d, 3H, J )
6.7), 1.43 (d, 3H, J ) 6.8), 1.27-1.20 (m, 12H), 1.25 (d, 6H, J
) 6.9), 0.98 (d, 3H, J ) 6.9), 0.95 (t, 3H, J ) 7.2). Data for
(-)-100: colorless crystals, mp 143-145 °C (Et2O/light petro-
leum ether); [R2D5 ) -19 (c ) 0.45, CHCl3); 1H NMR (400
MHz, CDCl3) δ 7.27-6.89 (m, 2H), 5.40 (dq, 1H, J ) 10.8, 1.1),
4.96 (q, 1H, J ) 6.7), 4.39 (d, 1H, J ) 9.7), 4.23 (dq, 1H, J )
10.8, 6.9), 3.72, 3.11 (2 sept, 2H, J ) 6.9), 2.91 (s, 3H), 2.89
(sept, 1H, J ) 6.9), 2.81 (dq, 1H, J ) 9.7, 7.1), 2.20 (dq, 1H, J
) 18.6, J ) 7.1), 2.09 (dq, 1H, J ) 18.9, 7.1), 1.91 (d, 3H, J )
1
Su p p or tin g In for m a tion Ava ila ble: Detailed H and 13C
NMR spectra and signal assignments, further optical rotation
data, and UV, IR, and MS spectra as well as the ORTEP
representations of all structures reported in this work. This
material is available free of charge via the Internet at http://
pubs.acs.org. Complete X-ray data has been deposited with the
Cambridge Crystallographic Data Centre for 16, CCDC-
157582; 19, CCDC-140985; 20, CCDC-157583; 22, CCDC-
157584; 30, CCDC-157585; 45, CCDC-157586; (-)-66, CCDC-
134999; (-)-73, CCDC-135000; (-)-79, CCDC-157575; (()-83,
CCDC-157576; (()-90, CCDC-157577; (()-91, CCDC-157578;
(()-92,CCDC-157579;(-)-94,CCDC-157580;(-)-99,CCDC-157581.
J O0101712