Sulfoxide-modified Julia-Lythgoe olefination: Highly stereoselective di-, tri-, and tetrasubstituted double bond formation

Article abstract of DOI:10.1135/cccc20051953

A novel modification of the classical Julia-Lythgoe olefination, using sulfoxides instead of sulfones, affords, after in situ benzoylation and SmI ₂/HMPA or SmI₂/DMPU-mediated reductive elimination, 1,2-di-, tri- and tetrasubstituted olefins in moderate to good yields and E/Z selectivity. The conditions are mild and the procedure is widely applicable. The reaction mechanism was studied and a general model, describing the reaction selectivity, is proposed.

Full text of DOI:10.1135/cccc20051953

Sulfoxide-Modified Julia–Lythgoe Olefination
1953
SULFOXIDE-MODIFIED JULIA–LYTHGOE OLEFINATION:
HIGHLY STEREOSELECTIVE DI-, TRI-, AND TETRASUBSTITUTED
DOUBLE BOND FORMATION
1
2
3,
Jiří POSPÍŠIL , Tomáš POSPÍŠIL and István E. MARKÓ *
Département de Chimie, Université catholique de Louvain,
Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium;
e-mail: pospisil@chim.ucl.ac.be, t.pospisil@chim.ucl.ac.be, marko@chim.ucl.ac.be
1
2
3
Received July 21, 2005
Accepted August 24, 2005
A n ovel m odification of th e classical Julia–Lyth goe olefin ation , usin g sulfoxides in stead of
sulfon es, affords, after in situ ben zoylation an d Sm I2/HMPA or Sm I2/DMPU-m ediated reduc-
tive elim in ation , 1,2-di-, tri- an d tetrasubstituted olefin s in m oderate to good yields an d E/Z
selectivity. Th e con dition s are m ild an d th e procedure is widely applicable. Th e reaction
m ech an ism was studied an d a gen eral m odel, describin g th e reaction selectivity, is proposed.
Keyw ord s: Olefin ation s; Sam arium ; Reaction m ech an ism s; Addition s; Syn th etic m eth ods;
Julia–Lyth goe olefin ation ; Sulfoxides; Alken es; Reductive elim in ation .
Th e Julia olefin ation ran ks am on g m ost powerful m eth ods for th e form a-
tion of C–C double bon ds in m odern organ ic ch em istry. Origin ally, th is
procedure was based on th e reaction of sulfon es with carbon yl com poun ds.
In th e first step, an an ion in α-position to sulfon e group was added to a
carbon yl com poun d, furn ish in g th e correspon din g β-h ydroxysulfon e1
(Sch em e 1). In th e secon d step, th is β-h ydroxysulfon e was treated with
Na–Hg an d un derwen t reductive elim in ation to give th e desired olefin .
Later on , it was observed th at th e tran sform ation of th e alcoh ol fun ction of
th e β-h ydroxysulfon e in to a better leavin g group led to in creased yields in
th e reductive-elim in ation step. Th erefore, β-m esyloxy- or (acyloxy)sulfon es
are preferen tially used n owadays as th e in term ediates subjected to th e
reductive elim in ation . As an addition al advan tage, acylatin g or m esylatin g
reagen ts can be em ployed as trappin g agen ts durin g th e addition of th e sul-
fon yl an ion to th e carbon yl fun ction . Th e in situ capture of th e β-alkoxy-
sulfon e an ion in term ediate furth er in creases th e yields of th e addition step.
Gradually, th e origin al reductive-elim in ation m eth od usin g Na–Hg am al-
gam h as been superseded by m ild, m ore selective an d less toxic reducin g
agen ts such as Sm I2 (ref.2) or Mg (ref.3).
Collect. Czech. Chem. Commun. (Vol. 70) (2005)
doi:10.1135/cccc20051953

1954
Pospíšil J., Pospíšil T., Markó:
SCHEME 1
Disappoin tin gly, th is widely used m eth od still suffers from several
drawbacks. On e of th em is th e relatively h igh stability of th e sulfon yl
an ion wh ich lim its its reactivity. For exam ple, if an addition al electron -
with drawin g substituen t is presen t on th e an ion -bearin g carbon , th is n ega-
tively ch arged organ om etallic species becom es so stable th at it does n ot add
even to activated aldeh ydes2c. Moreover, in th e case of th e reaction of
un stabilized sulfon es with h in dered aldeh ydes an d with keton es, th e posi-
tion of th e equilibrium between th e startin g carbon yl com poun ds an d th e
sulfon e an ion is sh ifted towards th e reactan ts. Th e desired adduct (tertiary
alkoxide) is th erefore presen t in th e reaction m ixture as a m in or com po-
n en t. Trappin g th is in term ediate in situ with som e electroph iles, such as
ben zoyl ch loride, m esyl ch loride or acyl ch loride, is a com m on trick em -
ployed to sh ift th e equilibrium towards th e products. However, in th e case
of h igh ly crowded sulfon es an d/or keton es, even if th e electroph ile-
trappin g protocol is em ployed, th e addition reaction does n ot proceed at all
or on ly in a very low yield.
Moreover, th is in situ capture m eth od is n ot useful if th e an ion α to th e
sulfon e is so stable th at it does n ot add even to h igh ly activated aldeh ydes.
Th is problem occurs wh en th e an ion is presen t on th e sulfon yl carbon bear-
in g also ph en yl or an electron -with drawin g group. To overcom e th is disad-
van tage, Satoh et al. rein troduced4 recen tly sulfoxides as sulfon e equiva-
len ts in th e Julia–Lyth goe olefin ation 5. To advan tage, th e carban ion gen er-
ated ( to th e sulfoxide group is far less stabilized6 th an in th e case of th e
correspon din g sulfon e an d th e addition reaction , leadin g to th e form ation
of th e C–C bon d, is favored even in th e case of keton es. Th e β-h ydroxy-
sulfoxides were th en m esylated an d subjected to BuLi (4 equivalen ts) m edi-
ated reductive elim in ation to give th e desired olefin s (Sch em e 2). Usin g th is
m odification , styren e an d stilben e derivatives were prepared by th e Julia
olefin ation m eth od for th e first tim e. Disappoin tin gly, th e E/Z stereo-
selectivity was rath er low. For exam ple, 1,2-disubstituted olefin s were gen -
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Sulfoxide-Modified Julia–Lythgoe Olefination
1955
erally prepared in 60–90% yields, with E/Z ratios varyin g, in th e best cases,
between 75:25 an d 25:75. Trisubstituted alken es were obtain ed from vari-
ous α-bran ch ed sulfoxides an d cycloh exan on e in 60–90% yields. Un sym -
m etrical keton es were n ot studied. It was reported, th ough , th at tetrasubsti-
tuted olefin s could n ot be gen erated usin g th is m eth od.
SCHEME 2
Mech an istic studies of th is reaction by Satoh sh owed th at th is elim in a-
tion was h igh ly stereospecific an d th at th e geom etry of th e n ewly form ed
olefin depen ded on th e relative con figuration of th e β-h ydroxysulfoxide.
Th us, if th e anti-diastereoisom er was subjected to BuLi-m ediated reductive
elim in ation , th e E isom er was preferen tially form ed. In con trast, if th e syn-
diastereoisom er was used, th e Z isom er was gen erated as th e m ajor product.
Th e in fluen ce of addition al stereogen ic cen tres presen t on sulfur atom s, on
th e stereoselectivity of th e reaction was n ot studied (Sch em e 3).
SCHEME 3
For som e tim e n ow, we h ave been in terested in th e m odification an d
developm en t of various Julia–Lyth goe olefin ation m eth ods2c,7. Recen tly,
we h ave in troduced th e Sm I2/HMPA-m ediated reductive elim in ation of
β-(ben zoyloxy)sulfon es, form ed by th e addition of α-sulfon e an ion s to ke-
ton es, as an efficien t an d stereoselective route to trisubstituted olefin s.
Based upon our previous results, we en visaged th at th e Sm I2-m ediated
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1956
Pospíšil J., Pospíšil T., Markó:
reductive elim in ation of β-(ben zoyloxy)sulfoxides m igh t produce th e de-
sired olefin s in h igh yields an d with good E/Z selectivity. Moreover, we en -
vision ed th at th e trappin g of th e β-oxysulfoxide an ion in term ediate by th e
ben zoyl group would in crease th e yield of th e addition product. Th e result-
in g β-(ben zoyloxy)sulfoxides, if properly substituted, m igh t lead, for th e
first tim e, to tetrasubstituted olefin s.
In th is article, we wish to report in detail th e results of our in vestigation
in th e developm en t of a sulfoxide version of th e Julia–Lyth goe olefin ation
based on th e con cepts described above8.
RESULTS AND DISCUSSION
At th e on set of our work, it was crucial to assess th e feasibility of th e
9
Sm I2-m ediated reductive elim in ation . Th erefore, sulfoxide 1a was reacted
with aldeh yde 2 an d th e in situ gen erated β-h ydroxysulfoxide 3 was
trapped with ben zoyl ch loride to give th e β-(ben zoyloxy)sulfoxide 4. Dur-
in g th e addition of th e sulfoxide an ion to aldeh yde 2, two n ew stereogen ic
cen tres are form ed an d in term ediate 4 is th us obtain ed as a m ixture of all
four possible diastereoisom ers. To avoid th eir tedious separation , it was de-
cided to use th e m ixture of adducts 4 in th e subsequen t reductive-
elim in ation step10. Som e pertin en t results are collected in Table I 11
.
As can be seen from Table I, Sm I2 itself does n ot prom ote th e reductive
elim in ation , n ot even at room tem perature (Table I, en tries 1 an d 2). Th ere-
fore, HMPA an d DMPU were added as additives12 to in crease th e reduction
poten tial of Sm I2 (–1.33 V)13. It was foun d th at th e presen ce of on ly sm all
quan tities of HMPA (0.25 equivalen t) prom oted th e reductive elim in ation
an d furn ish ed th e desired olefin 5a in 25% yield (Table I, en try 3). Furth er
optim ization of th e reaction con dition s sh owed th at addition of on e equiv-
alen t of HMPA was optim al (Table I, en try 6). Furth er in crease in th e HMPA
loadin g did n ot give better results (Table I, en try 7). Th is observation sug-
gests th at a reduction poten tial of –1.43 V (HMPA/Sm I2 = 1:1) is th e opti-
m um poten tial required for th e reductive-elim in ation . If th e poten tial is in -
creased (Table I, en try 7) to –1.46 V (HMPA/Sm I2 = 2:1), th e reaction does
n ot proceed faster or with better yields.
DMPU was n ext em ployed as an altern ative, n on -toxic HMPA equivalen t.
However, un der all th e reaction con dition s tested, th e yields rem ain ed
lower th an with HMPA (Table I, en tries 8–15). Moreover, a large excess of
DMPU an d h igh er tem peratures (0 °C to room tem perature) h ad to be em -
ployed (Table I, en tries 11–15). Usin g th is additive, as for HMPA, th e best
results were obtain ed wh en a reduction poten tial of –1.42 V was reach ed14
.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Sulfoxide-Modified Julia–Lythgoe Olefination
1957
TABLE I
Optim ization of th e reductive elim in ation step
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1958
Pospíšil J., Pospíšil T., Markó:
Havin g design ed suitable reaction con dition s to successfully effect th is
sulfoxide varian t of th e Julia–Lyth goe olefin ation , th e scope an d lim itation s
of th is protocol were n ext in vestigated.
In itially, our atten tion focused on th e form ation of 1,2-disubstituted
olefin s. Th us, sulfoxide 1a was reacted with aliph atic an d arom atic alde-
h ydes, affordin g th e correspon din g 1,2-disubstituted olefin s 5a–5e in good
yields an d with excellen t stereoselectivities (Table II, en tries 1–5). It is n ote-
worth y th at som e of th e m ost com m on ly used OH-protectin g groups are
perfectly tolerated in th is tran sform ation (Table II, en tries 3–5).
TABLE II
Preparation of 1,2-disubstituted olefin s
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Sulfoxide-Modified Julia–Lythgoe Olefination
1959
TABLE III
Preparation of trisubstituted olefin s
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1960
Pospíšil J., Pospíšil T., Markó:
Next, th e couplin g of th e m ore h in dered sulfoxide 1b was exam in ed un -
der th ese reaction con dition s. It was foun d th at if 1b was reacted with
aliph atic aldeh ydes (Table II, en try 7), th e desired olefin 5g was form ed in
good yield an d with very h igh selectivity (E/Z = 94:6). Surprisin gly, wh en
1b was reacted with ben zaldeh yde, th e desired alken e 5f was form ed with
on ly m oderate selectivity E/Z = 76:24, th ough in a sim ilar yield (Table II,
en try 6).
Th e form ation of trisubstituted olefin s also proceeded sm ooth ly (Table III).
Sulfoxides 1a an d 1b were reacted with various keton es furn ish in g th e de-
sired adducts 6a–6i in un optim ized yields ran gin g from 51 to 71%. Th e
stereoselectivity of th e C–C bon d lin kage was lower with trisubstituted
olefin s th an in th e case of 1,2-disubstituted on es. Gen erally, aryl-substituted
alken es form ed by th e reaction of 1a with keton es, gave sligh tly h igh er E/Z
ratios th an th ose bearin g an isopropyl side ch ain . Addition ally, it was ob-
served th at th e E/Z selectivity depen ded upon th e steric discrim in ation be-
tween th e groups presen t in th e keton e m olecule. Wh en th e carbon yl fun c-
tion was bon ded to a m eth yl group on on e side an d a lin ear alkyl on th e
oth er side, th e n ewly form ed double bon d was gen erated with low selectiv-
ity (Table III, en tries 4 an d 7). In th e case of bulkier alkyl, th e E isom er was
form ed preferen tially (Table III, en tries 2, 6 an d 9). Rem arkably, th is m odi-
fied Julia–Lyth goe olefin ation proceeds sm ooth ly wh en en on es are em -
ployed as substrates th ough th e h igh ly con jugated, th erm odyn am ically
m ore favored olefin was form ed on ly in a m oderate E/Z ratio (Table III, en -
tries 3 an d 8).
Based on th ese results, it can be con cluded th at, durin g th e reductive
elim in ation step, th e steric requirem en ts of th e substrate are overrulin g th e
con jugative effect presen t in th e fin al adduct.
Fin ally, th e form ation of tetrasubstituted olefin s was exam in ed un der our
15
stan dard con dition s. Accordin gly, sulfoxide 7
was reacted with various
keton es to give tetrasubstituted olefin s 8 in low yield but excellen t E/Z se-
lectivity (Table IV). To th e best of our kn owledge, th is is th e first report de-
scribin g th e successful preparation of tetrasubstituted alken es, usin g th is
sulfoxide varian t of th e Julia–Lyth goe olefin ation , with such h igh selectiv-
ity levels.
At th is stage, it was deem ed im portan t to fin d out wh eth er th e reductive
elim in ation , m ediated by th e Sm I2/HMPA system , was a stereoselective or a
stereospecific process. Th erefore, th e syn- an d anti-β-(ben zoyloxy)sulfoxides
12 were prepared16 (Sch em e 4) an d in depen den tly subjected to th e re-
ductive elim in ation con dition s.
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Sulfoxide-Modified Julia–Lythgoe Olefination
1961
SCHEME 4
In both cases, olefin 5b was obtain ed in an excellen t E/Z ratio of >95:1,
in dicatin g th at th e reductive-elim in ation step proceeded via a stereo-
selective process (Sch em e 5).
SCHEME 5
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1962
Pospíšil J., Pospíšil T., Markó:
To gen eralize our observation , th e syn- an d anti-sulfoxides 13 were pre-
pared an d th eir reductive elim in ation was exam in ed (Sch em e 6). Sin ce di-
rect access to each in dividual diastereoisom ers of 13 would h ave been pro-
h ibitive, 13 was syn th esized accordin g to our stan dard Julia olefin ation pro-
cedure, as a m ixture of isom ers. Th e desired four diastereoisom ers (a pair of
syn-13 an d a pair of anti-13) were th en separated via tedious colum n ch ro-
m atograph y (7 colum n s required). Th e relative stereoch em istry of m ore an d
less polar (R,R)-13 an d m ore an d less polar (S,R)-13 was establish ed by th eir
con version to th e correspon din g sulfon e derivatives, (R,R)-14 an d (S,R)-14,
respectively, an d by com parison with th eir reported literature data.
In terestin gly, th e reductive elim in ation of pure m ore an d less polar (R,R)-
an d (S,R)-sulfoxides 13 gave essen tially th e sam e E/Z ratio, ran gin g from
86:14 to 91:9. Wh en th e reaction was perform ed with a m ixture of all four
diastereoisom ers, th e 88:12 E/Z ratio was obtain ed, wh ich is a good average
of th e in dividually m easured stereoselectivities. Th is observation clearly
TABLE IV
Preparation of tetrasubstituted olefin s
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Sulfoxide-Modified Julia–Lythgoe Olefination
1963
SCHEME 6
suggests th at th e double bon d geom etry of th e fin al alken e 6f is in depen d-
en t of th e relative stereoch em istry of th e sulfoxide adduct 13.
Based on th ese results, a plausible m ech an ism for th e reductive elim in a-
tion , an d a m n em on ic m odel gen eralizin g th e observed E/Z selectivities, can
be proposed. We believe th at th e reductive elim in ation of β-(benzoyloxy)-
sulfoxides proceeds in the sam e way as in the case of the β-(ben zoyloxy)-
sulfon es17 (Sch em e 7). Th us, tran sfer of a sin gle electron to th e ben zoate
m oiety, wh ich appears to be th e lowest en ergy path way, leads to th e radical
an ion 16. Subsequen t collapse of th is in term ediate liberates th e ben zoate
an ion an d produces radical 17 18. Furth er tran sform ation of 17 to th e
organ osam arium in term ediate 18, followed by elim in ation of th e ph en yl-
sulfin yl group, even tually affords th e olefin 19.
It is plausible th at th e form ation of th e organ osam arium species 18 is a
slower process th an epim erization of th e radical-bearin g cen tre. Moreover,
th e sam arium derivative 18 m igh t n ot be con figuration ally stable an d in -
version m igh t occur faster th an elim in ation to 19. Th e elim in ation of th e
ph en ylsulfin yl group is believed to proceed th rough an E2 type process,
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1964
Pospíšil J., Pospíšil T., Markó:
SCHEME 7
leadin g to th e gen eral m odel for th e stereoselectivity of th e double bon d
form ation depicted in Fig. 1. Based on th is m odel, steric h in dran ce of th e
substituen ts presen t on th e sulfoxide an d on th e carbon yl substrate play a
crucial role in fin al E/Z stereoselectivity.
FIG. 1
Gen eral m odel for th e stereoselectivity of th e double bon d form ation
CONCLUSIONS
In sum m ary, we h ave developed a n ovel, h igh ly stereoselective version of
th e Julia–Lyth goe olefin ation . Th is m eth od em braces a wider scope th an
th e classical Julia olefin ation protocol. For th e first tim e, tetrasubstituted
olefin s were prepared in a h igh ly stereoselective m an n er. We h ave also sh ed
som e ligh t on th e reaction m ech an ism an d proposed a m n em on ic m odel
th at predicts th e stereoch em ical outcom e of th e olefin ation process. Th e
use of th is m eth od in n atural product syn th esis an d in th e assem bly of
products previously im possible to prepare via th e classical Julia procedure,
is curren tly in progress in our laboratory.
EXPERIMENTAL
Gen eral
IR spectra (ν, cm –1) were recorded on a FTIR ATI Mattson spectroph otom eter in NaCl cell
or KBr tablets. 1H an d 13C NMR spectra were recorded on a Varian Gem in i-2000 (300 an d
75 MHz, respectively) or on a Bruker AC-250 (250 an d 62.5 MHz, respectively) at am bien t
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Sulfoxide-Modified Julia–Lythgoe Olefination
1965
tem perature in CDCl3 (Aldrich or Rocc). Ch em ical sh ifts are given in ppm (δ-scale), couplin g
con stan ts (J) in Hz. Mass spectra were recorded on a Fin igan TSQ 7000. All com poun ds
(Acros, Aldrich an d Fluka) were used as received. THF was distilled un der argon from sodium
ben zoph en on e ketyl. Flash ch rom atograph y was perform ed on silica gel 60 (40–63 µm )
(Rocc).
Th e iden tity of every product was con firm ed by com parison with literature data. Th e
structure determ in ation of n ew com poun ds was m ade usin g 2D-COSY, HSQC, HMBC,
2D-NOESY an d NOEdiff experim en ts. Th e followin g com poun ds h ave been previously de-
8
8
scribed: 5a 19, 5b 20, 5c 21, 5d 22, 5e 23, 5f 24, 5g 25, 6a 26, 6b 27, 6e 28, 6d , 6e an d 8a–8c
.
16
Th e correspon din g sulfoxides 7 29, (R,R)-12 an d (S,R)-12
were prepared accordin g to th e
literature.
Couplin g Step
A solution of a sulfoxide (1.0 m m ol) in dry THF (10 m l, 0.1 m ol/l) was cooled to –78 °C
an d LDA (550 µl, 1.1 m m ol) was added dropwise. Th e colour of th e m ixture ch an ged
from sligh tly yellow to oran ge-red. After stirrin g at –78 °C for 30 m in , an aldeh yde/keton e
(1.05 m m ol), dissolved in dry THF (0.5 m l), was added dropwise an d th e m ixture was stirred
at –78 °C for an addition al 2 h . Ben zoyl ch loride (1.5 m m ol) in dry THF (0.5 m l) was th en
added. Th e resultin g m ixture was stirred for 30 m in at –78 °C an d th en allowed to warm to
room tem perature over 1 h . After an addition al 30 m in at room tem perature, Me2N(CH2)3OH
(1.55 m m ol) was added an d th e resultin g suspen sion was stirred at room tem perature for
10 m in . Th e suspen sion was th en diluted with Et2O–H2O, 1:1 (10 m l) an d th e layers were
separated. Th e aqueous layer was extracted with Et2O (3 × 10 m l) an d th e com bin ed organ ic
layers were wash ed with aqueous 1.0 M HCl (10 m l), H2O (10 m l) an d brin e (10 m l), dried
over an h ydrydous MgSO4 an d evaporated un der reduced pressure to give th e crude product,
wh ich was used with out addition al purification in th e subsequen t step.
Reductive Elim in ation
To a solution of Sm I2 (35 m l, 0.1 m ol/l in THF, 3.5 equivalen ts), HMPA (613 µl, 3.5 equiva-
len ts) was added an d th e m ixture was cooled to –78 °C. Th e crude coupled product (1.0 m m ol)
in dry THF (0.5 m l) was added dropwise an d th e resultin g m ixture was stirred at –78 °C for
an addition al 30 m in . Th en , aqueous NH4Cl (20 m l) was added an d th e wh ole was allowed
to warm to room tem perature Th e layers were separated an d th e aqueous ph ase was ex-
tracted with Et2O (3 × 20 m l). Th e com bin ed organ ic layers were wash ed with 10% aqueous
Na2S2O3 (20 m l), H2O (20 m l), brin e (20 m l), dried over an h ydrous MgSO4 an d evaporated
un der reduced pressure. Th e crude product was th en purified by ch rom atograph y on silica gel.
Compound 6c (Table III, en try 3): purified by colum n ch rom atograph y (2.5 cm × 11 cm ,
SiO2, 5 m l fraction s; n-pen tan e) to give 106 m g (68%, E/Z = 65:35) of 6c as a colourless oil.
IR (NaCl, n eat): 3084 (w), 3072 (w), 3021 (w), 2954 (m ), 2923 (m ), 2868 (w), 1602 (w), 1495
(w), 1454 (w), 742 (m ), 699 (m ). 1H NMR (250 MHz, CDCl3): 1.71–1.83 (m , 2 H, H-9);
2.20–2.31 (m , 2 H, H-10); 6.19 (broad s, 1 H, H-5cis); 6.22 (m , 1 H, H-7trans); 6.49–6.52 (m ,
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1966
Pospíšil J., Pospíšil T., Markó:
1 H, H-8); 6.52 (broad s, 1 H, H-5trans); 7.25 (broad s, H-7cis); 7.02–7.68 (m , 5 H, arom . CH).
13C NMR (62.5 MHz, CDCl3): 28.3 (C-10trans); 30.4 an d 30.5 (C-9); 37.2 (C-10cis); 117.2
(C-5cis); 132.4 (C-5trans); 27.3 (C-2trans); 29.9 (C-2cis); 34.4 (C-5cis); 35.0 (C-6); 41.8 (C-5trans);
123.5–137.2 (arom . CH an d Cq ); 132.7 (C-7trans); 134.5 (C-7cis); 143.2 (C-8). MS (CI,
CH4/N2O), m/z (%): 156.11 (100) [M+], 157.25 [M+ + 1] (23), 79.2 (26), 77.5 (16). For C12H12
(156.2) calculated: 92.26% C, 7.74% H; foun d: 92.34% C, 7.66% H.
Compound 6h (Table III, en try 7): purified by colum n ch rom atograph y (2.5 cm × 11 cm ,
SiO2, 5 m l fraction s; n-pen tan e) to give 77 m g (63%, E/Z = 68:32) of 6h as a colourless oil.
IR (NaCl, n eat): 3058 (w), 2957 (m ), 2862 (w), 1604 (w), 1494 (w), 1453 (w). 1H NMR
3
3
3
(250 MHz, CDCl3): 0.92 (dd, 6 H, J1,2 = 6.7, J1,1′ = 1.4, H-1cis); 0.95 (dd, 6 H, J1,2 = 6.7,
3J1,1′ = 1.4, H-1trans); 1.52–1.74 (m , 2 H, H-7); 1.98–2.09 (m , 2 H, H-8); 2.36 (m , 1 H, H-2cis);
2.61 (m , 1 H, H-2trans); 5.17 (d, 1 H, J3,2 = 9.1, H-3trans); 5.44 (d, 1 H, J3,2 = 10.1, H-3cis);
6.28 (broad s, 1 H, H-5trans); 6.78 (m , 1 H, H-6); 7.35 (m , 1 H, H-5cis). 13C NMR (62.5 MHz,
CDCl3): 21.4 (C-1cis); 23.2 (C-1trans); 28.3 (C-2trans); 29.2 (C-8trans); 30.3 (C-2cis); 31.9 (C-7);
36.2 (C-8cis); 134.2 (C-5trans); 134.3 (C-4cis); 134.5 (C-5cis); 135.9 (C-4trans); 137.2 (C-3cis);
138.2 (C-3trans); 140.6 (C-6). MS (CI, CH4/N2O), m/z (%): 122.19 (100) [M+], 95.7 (15), 79.7
(39), 51.3 (8). For C9H14 (122.2) calculated: 88.45% C, 11.55% H; foun d: 88.51% C, 11.49% H.
Compound 6i (Table III, en try 9): purified by colum n ch rom atograph y (2.5 cm × 11 cm ,
SiO2, 5 m l fraction s; 100% n-pen tan e) to give 117 m g (51%, E/Z = 79:21) of 6i as a colour-
3
3
less oil. 1H NMR (250 MHz, CDCl3): 0.03 (s, 6 H, SiMe2But); 0.91 (s, 9 H, SiMe2Bu t); 0.92
3
3
3
3
(dd, 6 H, J1,2 = 6.7, J1,1′ = 1.5, H-1cis); 0.96 (dd, 6 H, J1,2 = 6.7, J1,1′ = 1.4, H-1trans); 1.67
(m , 1 H, H-6trans); 1.89 (m , 1 H, H-6cis); 2.49 (m , 1 H, H-2trans); 2.75 (m , 1 H, H-2cis);
4.01–4.12 (m , 2 H, H-5); 4.76 (d, 1 H, J3,2 = 9.5, H-3trans); 5.11 (d, 1 H, J3,2 = 9.3, H-3cis).
13C NMR (62.5 MHz, CDCl3): –3.2 (SiMe2But); 14.0 (C-6trans); 18.7, 21.4 (C-6cis); 22.9 (C-1cis);
23.2 (C-1trans); 24.1 (C-2trans); 26.2 (SiMe2Bu t); 28.1 (C-2cis); 64.2 (C-5trans); 70.2 (C-5cis);
132.1 (C-4cis); 132.3 (C-4trans); 138.9 (C-3trans); 148.8 (C-3cis). MS (CI, CH4/N2O), m/z (%):
128.45 (67) [M+], 114.6 (100), 97.9 (65), 77.2 (15), 55.2 (12). For C13H28OSi (228.5) calcu-
lated: 68.35% C, 12.35% H, 12.29% Si; foun d: 68.51% C, 12.23% H, 12.24% Si.
3
3
Sulfoxides 13
Com poun ds 13 were prepared accordin g to th e stan dard couplin g procedure. Th e crude m ix-
ture was purified by repeated (7×) colum n ch rom atograph y (2.5 cm × 11 cm , SiO2, 5 m l frac-
tion s; petroleum eth er–Et2O, 20:1) to give four diastereoisom ers m ore polar (R,R)-13
(11 m g), less polar (R,R)-13 (15 m g), m ore polar (S,R)-13 (25 m g) an d less polar (S,R)-13
(28 m g).
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Sulfoxide-Modified Julia–Lythgoe Olefination
1967
3
2
More polar (R,R)-13. 1H NMR (300 MHz, CDCl3): 0.86 (dd, 3 H, J1,2 = 6.5, J1,1′ = 1.4, on e
3
3
2
of H-1); 1.06 (d, 3 H, J14,5 = 7.2, H-14); 1.21 (dd, 3 H, J1,2 = 6.8, J1,1′ = 1.3, th e oth er H-1);
3
1.17–2.27 (m , 10 H, H-2, 5–9); 3.89 (d, 1 H, J3,2 = 7.0, H-3); 7.11–8.24 (m , 10 H, arom . CH).
13C NMR (75 MHz, CDCl3): 13.5, 20.3, 21.8, 22.9, 24.3, 29.2, 31.8, 32.8, 36.2, 71.9 (C-3);
76.8 (C-4); 124.3–147.9 (arom . CH an d Cq); 166.2 (C-15). MS (CI, CH4/N2O), m/z (%):
586.46 (67) [M+], 587.67 [M+ + 1] (34), 121 (100), 181.3 (43), 96.9 (15), 77.3 (20). HR CI MS
calculated: 398.1916; foun d: 398.1924.
3
2
Less polar (R,R)-13. 1H NMR (300 MHz, CDCl3): 0.86 (dd, 3 H, J1,2 = 6.5, J1,1′ = 1.4, on e
3
3
2
of H-1); 1.07 (d, 3 H, J14,5 = 7.2, H-14); 1.20 (dd, 3 H, J1,2 = 6.8, J1,1′ = 1.2, th e oth er H-1);
3
1.17–2.28 (m , 10 H, H-2, 5–9); 4.12 (d, 1 H, J3,2 = 7.1, H-3); 7.10–8.25 (m , 10 H, arom . CH).
13C NMR (75 MHz, CDCl3): 13.6, 20.3, 21.8, 22.9, 24.4, 29.3, 31.8, 32.8, 36.2, 71.4 (C-3);
76.5 (C-4); 124.1–147.9 (arom . CH an d Cq); 166.1 (C-15). MS (CI, CH4/N2O), m/z (%): 586.4
(63) [M+], 587.6 [M+ + 1] (33), 121.4 (100), 181.3 (38), 96.9 (19), 77.3 (21). HR CI MS calcu-
lated: 398.1916; foun d: 398.1918.
3
2
More polar (S,R)-13. 1H NMR (300 MHz, CDCl3): 0.87 (dd, 3 H, J1,2 = 6.5, J1,1′ = 1.3, on e
3
3
2
of H-1); 1.07 (d, 3 H, J14,5 = 7.2, H-14); 1.21 (dd, 3 H, J1,2 = 6.8, J1,1′ = 1.3, th e oth er H-1);
3
1.17–2.25 (m , 10 H, H-2, 5–9); 4.26 (d, 1 H, J3,2 = 6.9, H-3); 7.11–8.24 (m , 10 H, arom . CH).
13C NMR (75 MHz, CDCl3): 13.4, 20.5, 21.8, 22.8, 24.8, 29.3, 31.8, 32.8, 36.3, 72.3 (C-3);
77.1 (C-4); 124.5-147.9 (arom . CH an d Cq); 165.1 (C-15). MS (CI, CH4/N2O), m/z (%): 586.6
(78) [M+], 587.9 [M+ + 1] (40), 122.4 (100), 181.9 (43), 97.0 (17), 77.4 (21). HR CI MS calcu-
lated: 398.1916; foun d: 398.1910.
3
2
Less polar (S,R)-13. 1H NMR (300 MHz, CDCl3): 0.87 (dd, 3 H, J1,2 = 6.5, J1,1′ = 1.3, on e
3
3
2
of H-1); 1.07 (d, 3 H, J14,5 = 7.1, H-14); 1.21 (dd, 3 H, J1,2 = 6.9, J1,1′ = 1.3, th e oth er H-1);
3
1.17–2.25 (m , 10 H, H-2, H5–H9); 4.36 (d, 1 H, J3,2 = 7.1, H-3); 7.14–8.25 (m , 10 H, arom .
CH). 13C NMR (75 MHz, CDCl3): 13.4, 20.4, 21.8, 22.9, 24.8, 29.3, 31.7, 32.8, 36.8, 72.1
(C-3); 76.7 (C-4); 124.7–147.7 (arom . CH an d Cq); 164.9 (C-15). MS (CI, CH4/N2O), m/z (%):
586.4 (45) [M+], 587.6 [M+ + 1] (23), 121.7 (100), 182.1 (43), 96.7 (24), 77.0 (16). HR CI MS
calculated: 398.1916; foun d: 398.1907.
Preparation of Sulfon es (R,R) an d (S,R)-14
A solution of sulfoxide 13 (5 m g, 12.5 µm ol, 1.0 equivalen t) in CH2Cl2 (1 m l) was degassed
by th e freeze-pum p-th aw m eth od (3×) an d [MoO2(acac)2] (0.82 m g, 2.5 µm ol, 0.2 equiva-
len t) was added. Th e resultin g m ixture was cooled to 0 °C an d TBHP (15 drops, 5.5 M solu-
tion in dodecan e) was added dropwise. An exoth erm ic reaction occurred an d th e resultin g
oran ge solution was stirred at room tem perature for 4 h . A saturated solution of Na2S2O3
(1 m l) was added an d th e layers were separated. Th e aqueous layer was extracted with EtOAc
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1968
Pospíšil J., Pospíšil T., Markó:
(2 × 2 m l) an d th e pooled organ ic layers were wash ed with H2O (1 m l), brin e (1 m l), dried
over an h ydrous MgSO4 an d evaporated in vacuo to give 7–8 m g of a pale yellow oil (th e
product con tain s dodecan e). Purification by colum n ch rom atograph y (1.0 cm × 10 cm , SiO2,
2.5 m l fraction s; petroleum eth er–EtOAc, 1:1) gave 5.1–5.2 m g (99%) of colourless oil.
3
2
(R,R)-14. 1H NMR (300 MHz, CDCl3): 0.87 (dd, 3 H, J1,2 = 6.8, J1,1′ = 1.3, on e of H-1);
3
3
2
0.99 (d, 3 H, J14,5 = 7.0, H-14); 1.20 (dd, 3 H, J1,2 = 6.7, J1,1′ = 1.4, th e oth er H-1);
1.27–2.09 (m , 10 H, H-5–H9); 3.65 (m , 1 H, H-2); 3.87 (d, 1 H, J3,2 = 7.1, H-3); 7.14–8.25
3
(m , 10 H, arom . CH). 13C NMR (62.5 MHz, CDCl3): 16.4, 20.5, 23.3, 24.1, 24.9, 30.9, 34.2,
35.1, 39.2, 71.8 (C-3); 85.9 (C-4); 126.6–140.3 (arom . CH an d Cq); 167.1 (C-15). MS (CI,
CH4/N2O), m/z (%): 414.7 (100) [M+], 415.6 [M+ + 1] (22), 141.9 (34), 121.5 (56), 181.3 (28),
77.0 (15).
3
2
(S,R)-14. 1H NMR (300 MHz, CDCl3): 0.88 (dd, 3 H, J1,2 = 6.8, J1,1′ = 1.4, on e of H-1);
3
3
2
1.01 (d, 3 H, J14,5 = 7.0, H-14); 1.20 (dd, 3 H, J1,2 = 6.7, J1,1′ = 1.5, th e oth er H-1);
1.26–2.10 (m , 10 H, H-5–H9); 3.67 (m , 1 H, H-2); 3.89 (d, 1 H, J3,2 = 7.1, H-3); 7.14–8.25
3
(m , 10 H, arom . CH). 13C NMR (62.5 MHz, CDCl3): 16.3, 20.5, 23.8, 24.5, 24.9, 31.1, 34.2,
35.3, 39.2, 71.6 (C-3); 86.1 (C-4); 126.7–140.1 (arom . CH an d Cq); 167.2 (C-15). MS (CI,
CH4/N2O), m/z (%): 414.7 (100) [M+], 415.6 [M+ + 1] (21), 141.9 (34), 121.5 (48), 181.3 (23),
77.0 (16).
Financial support by the Université catholique de Louvain and Rhodia Ltd. (studentship to
J. Pospíšil) and the Socrates–Erasmus program (studentship to T. Pospíšil) is gratefully acknowledged.
I. E. Markó is grateful to the Rhodia for the 2001 Rhodia Outstanding Award.
REFERENCES AND NOTES
1. a) Dumeunier R., Markó I. E. in: Modern Carbonyl Olefination (T. Takeda, Ed.), p. 104.
Wiley-VCH, Weinheim 2004; b) Kociensky P. J. in: Comprehensive Organic Synthesis (B. M.
Trost and I. Fleming, Eds), Vol. 6. Pergamon, Oxford 1991; c) Julia M., Paris J. M.:
Tetrahedron Lett. 1973, 4833; d) Kocienski P. J., Lythgoe B., Waterhouse I.: J. Chem. Soc.,
Perkin Trans. 1 1980, 1045; e) Kocienski P. J.: Phosphorus Sulfur Relat. Elem. 1985, 24, 97.
2. a) Ihara M., Suzuki S., Taniguchi T., Tokunaga Y., Fukumoto K.: Synlett 1994, 859;
b) Keck G. E., Savin K. A., Welgarz M. A.: J. Org. Chem. 1995, 60, 3194; c) Markó I. E.,
Murphy F., Dolan S.: Tetrahedron Lett. 1996, 37, 2089; d) Kagan H. B.: Tetrahedron 2003,
59, 10351; e) Inanaga J.: Trends Org. Chem. 1990, 1, 23.
3. Lee G. H., Lee H. K., Choi E. B., Kim B. T., Pak C. S.: Tetrahedron Lett. 1995, 36, 5607.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Sulfoxide-Modified Julia–Lythgoe Olefination
1969
4. Kuwajima S.-J., Sato Y., Kurata A.: Tetrahedron Lett. 1972, 13, 737.
5. a) Satoh T., Hanaki N., Yamada N., Asano T.: Tetrahedron 2000, 56, 6223; b) Satoh T.,
Yamada N., Asano T.: Tetrahedron Lett. 1998, 39, 6935.
6. The pKa of the hydrogen on the carbon bearing the sulfoxide group is four orders of
magnitude higher than the pKa of the equivalent hydrogen on the carbon bearing the
sulfone substituent.
7. Markó I. E., Murphy F., Kumps L., Ates A., Touillaux R., Craig D., Carballaresb S., Dolan S.:
Tetrahedron 2001, 57, 2609.
8. Preliminary results of this study has been published in the form of a communication:
Pospíšil J., Pospíšil T., Markó I. E.: Org. Lett. 2005, 7, 2373.
9. Sulfoxides 1a and 7 were selected because the corresponding sulfones react very poorly
(or not at all) under the standard Julia–Lythgoe conditions for electronic (1a) or steric
(7) reasons.
10. The excess of benzoyl chloride was reacted with 3-(dimethylamino)propan-1-ol (neat)
and the amine was removed upon aqueous acid work-up.
11. All the reactions presented in Table I were carried out on the mixture of adduct 4.
12. a) Hasegawa E., Curran D. P.: J. Org. Chem. 1993, 58, 5008; b) Dahlen A., Hilmersson G.:
Eur. J. Inorg. Chem. 2004, 3393.
13. Measured vs Ag/AgNO3, reference electrode in THF. See: Shabangi M., Flowers R. A., Jr.:
Tetrahedron Lett. 1997, 38, 1137.
14. Shabangi M., Sealy J. M., Fuchs J. R., Flowers R. A., Jr.: Tetrahedron Lett. 1998, 39, 4429.
15. Screttas C. G., Micha-Screttas M.: J. Org. Chem. 1979, 44, 713.
16. a) Albanese D., Landini D., Penso M.: Synthesis 1994, 34; b) Dumeunier R., Markó I. E.:
Tetrahedron Lett. 2004, 45, 825.
17. More polar and less polar refer to more and les polar (R,R) or (S,R) diastereoisomers based
upon their migration on TLC.
18. In this context, it is interesting to note that the reductive cleavage of a benzoate group
could be easily effected using SmI2 or electrochemical conditions, suggesting to a great
acceptor ability of the benzoyl function. Kuenzer H., Stahnke M., Sauer G., Wiechert R.:
Tetrahedron Lett. 1991, 32, 1949.
19. Wylie P. L., Prowse K. S., Belill M. A.: J. Org. Chem. 1983, 48, 4022.
20. SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/ (National Institute of Advanced Industrial
Science and Technology, 23.03.2005).
21. De Ropp J. S., Troy F. A.: Biochemistry 1984, 23, 2691.
22. Aldrich Library 1, 1201 B.
23. Ikawa T., Hattori K., Sajiki H., Hirota K.: Tetrahedron 2004, 60, 6901.
24. Russell G. A., Ngoviwatchai P., Tashtoush H. I., Pla-Dalmau A., Khanna R. K.: J. Am.
Chem. Soc. 1988, 110, 3530.
25. Tamaru Y., Hioki T., Yoshida Z.: Tetrahedron Lett. 1984, 25, 5793.
26. Kikukawa K., Nagira K., Wada F., Matsuda T.: Tetrahedron 1981, 37, 31.
27. Maciagiewicz I., Dybowski P., Skowronska A.: Tetrahedron 2003, 59, 6057.
28. Martin S. F., Daniel D., Cherney R. J., Liras S.: J. Org. Chem. 1992, 57, 2523.
29. Screttas C. G., Micha-Screttas M.: J. Org. Chem. 1979, 44, 713.
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