Reaction of arylsulfonylhydrazones of aldehydes with α-magnesio sulfones. A novel olefin synthesis

Article abstract of DOI:10.1021/jo015699l

Reactions of representative tosylhydrazones of aldehydes and ketones with α-metalated sulfones were examined in order to develop a practical olefination method. Treatment of aldehyde tosylhydrazone 2 with an excess of α-lithiated methyl phenyl or dimethyl sulfones yielded 3a. The reaction of 2 with sterically unhindered lithiated alkyl sulfones gave mixtures of the respective olefination products 3b-d along with the Shapiro fragmentation product 4. Sterically hindered lithiated sulfones afforded Shapiro products exclusively. In contrast, aldehyde tosylhydrazones 2 or 6 in reactions with a variety of α-magnesio primary or secondary alkyl sulfones gave olefination products 3a-j and 7a-c in high yields (Tables 1 and 2). β-Branched alkyl sulfones afforded predominantly (E)-alkenes, whereas unhindered primary sulfones gave mixtures of (E)- and (Z)- alkenes with low selectivity. Reaction of the 2,4,6-triisopropylbenzenesulfonylhydrazone (trisylhydrazone) of cyclodecanone 11c with α-magnesio methyl phenyl sulfone afforded the methylidene derivative 12a contaminated with the Shapiro product 13. Tosylhydrazone 2 resisted reaction with i-PrMgCl and gave only a small amount of the addition product in reaction with Bu₂Mg. Some mechanistic aspects of the reaction of tosylhydrazones with organomagnesium compounds are discussed.

Full text of DOI:10.1021/jo015699l

6994
J . Org. Chem. 2001, 66, 6994-7001
Rea ction of Ar ylsu lfon ylh yd r a zon es of Ald eh yd es w ith r-Ma gn esio
Su lfon es. A Novel Olefin Syn th esis
Alicja Kurek-Tyrlik, Stanislaw Marczak, Karol Michalak, J erzy Wicha,* and Andrzej Zarecki
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warsaw, Poland
jwicha@icho.edu.pl
Received April 20, 2001
Reactions of representative tosylhydrazones of aldehydes and ketones with R-metalated sulfones
were examined in order to develop a practical olefination method. Treatment of aldehyde
tosylhydrazone 2 with an excess of R-lithiated methyl phenyl or dimethyl sulfones yielded 3a . The
reaction of 2 with sterically unhindered lithiated alkyl sulfones gave mixtures of the respective
olefination products 3b-d along with the Shapiro fragmentation product 4. Sterically hindered
lithiated sulfones afforded Shapiro products exclusively. In contrast, aldehyde tosylhydrazones 2
or 6 in reactions with a variety of R-magnesio primary or secondary alkyl sulfones gave olefination
products 3a -j and 7a -c in high yields (Tables 1 and 2). â-Branched alkyl sulfones afforded
predominantly (E)-alkenes, whereas unhindered primary sulfones gave mixtures of (E)- and (Z)-
alkenes with low selectivity. Reaction of the 2,4,6-triisopropylbenzenesulfonylhydrazone (trisylhy-
drazone) of cyclodecanone 11c with R-magnesio methyl phenyl sulfone afforded the methylidene
derivative 12a contaminated with the Shapiro product 13. Tosylhydrazone 2 resisted reaction with
i-PrMgCl and gave only a small amount of the addition product in reaction with Bu2Mg. Some
mechanistic aspects of the reaction of tosylhydrazones with organomagnesium compounds are
discussed.
In tr od u ction
organolithium reagents, Vedejs and co-workers13 have
discovered that arylsulfonylhydrazones of aldehydes react
with sterically unhindered R-lithio sulfones to afford the
corresponding olefins (Scheme 2, route a). However, this
olefination reaction was inefficient when branched sul-
fones were used, owing to competing Shapiro fragmenta-
tion.
In contrast to plentiful literature on transformations
of arylsulfonylhydrazones by organolithium reagents
(reactions of lithium cuprates have also been examined14),
the corresponding organomagnesium reagents have re-
ceived little attention. Only recently, it was reported that
some tosylhydrazones, bearing a leaving group such as
an alkoxy or an amino group in the R-position, react with
Grignard reagents to yield the corresponding alkenes,15-18
in a reaction pathway analogous to that with organo-
lithiums.16,18,19 On the other hand, it was noted that
organomagnesium reagents do not reactsor react very
slowlyswith N-silylated tosylhydrazones.11
A number of useful synthetic methods have emerged
from reactions of arylsulfonylhydrazones of aldehydes or
ketones with organometallic reagents. Most notably,
alkyllithium acts as a base, inducing fragmentation of
arylsulfonylhydrazones of ketones bearing a proton in the
â position i (Scheme 1, route a, the Shapiro reaction) to
afford the corresponding vinyllithium derivatives iv,
which can be protonated or used as synthetic intermedi-
ates.1-4 The reaction involves exchange of the sulfamidic
proton with Li+ to give ii, followed by 1,4-elimination of
lithium arylsulfinate and then nitrogen expulsion from
the intermediate iii. Some previous reports have indi-
cated that Shapiro fragmentation of ketone tosylhydra-
zones may be accompanied by reductive alkylation reac-
5-9
tion in certain cases
(Scheme 1, route b). It has been
shown10 that reductive alkylation products (viii, R2 ) H)
are typically generated in reactions of aldehyde tosylhy-
drazones (i, R2 ) H) with alkyllithiums. Improved
synthetic procedures for reductive alkylation, involving
initial N-silylation of arylsulfonylhydrazones of alde-
hydes, have been developed.11,12 With regard to stabilized
The purpose of this work was to explore the reaction
of arylsulfonylhydrazones of aldehydes and, possibly, of
(11) Myers, A. G.; Movassaghi, M. J . Am. Chem. Soc. 1998, 120,
8891-8892.
(1) Chamberlin, A. R.; Bloom, S. H. Org. React. (N.Y.) 1990, 39, 1.
(2) Addlington, R. M.; Barrett, A. G. M. Acc. Chem. Res. 1983, 16,
55.
(3) Shapiro, R. H. Org. React. (N.Y.) 1976, 23, 405.
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5735.
(12) Myers, A. G.; Kukkola, P. J . J . Am. Chem. Soc. 1990, 112,
8208-8210.
(13) Vedejs, E.; Dolphin, J . M.; Stolle, W. T. J . Am. Chem. Soc. 1979,
101, 249-251.
(14) Bertz, S. H. Tetraheron Lett. 1980, 21, 3151-3154.
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41, 10131-10134.
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1994, 50, 8837-8852.
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1997, 38, 8765-8768.
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(7) Herz, J . E.; Ortiz, C. V. J . Chem. Soc. C 1971, 2294-2295.
(8) Bessiere-Chretien, Y.; Bras, J .-P. C. R. Acad. Sc. Paris, Ser. C
1969, 221-2224.
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1995, 36, 307-310.
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(19) Schneider, C.; Kazmaier, U. Synthesis 1998, 1314-1320.
10.1021/jo015699l CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/19/2001

Novel Olefin Synthesis
J . Org. Chem., Vol. 66, No. 21, 2001 6995
Sch em e 1
Sch em e 2
ketones with R-metalated sulfones.20 It was expected that
conversion of a carbonyl compound into its arylsulfonyl-
hydrazone and the reaction of the latter with R-metalated
sulfone might provide a useful alternative to the classical
J ulia olefination reaction sequence21-23 (Scheme 2, routes
a and b). The same easily accessible starting materials
are used in both cases, but the arylsulfonylhydrazone
route is shorter and avoids harsh reagents (some modi-
fications of the reduction steps are noteworthy24-26). In
particular, we were interested in examining the reaction
of arysulfonylhydrazones with organomagnesium re-
agents that are less basic than their lithium counter-
parts27 and consequently less prone to indusing the
Shapiro fragmentation. On mechanistic grounds, the
addition of a metalated sulfone (ii, Scheme 2) to an
N-metalated tosylhydrazone (i) bears some resemblance
to the carbon-carbon bond-forming sulfonyl anion-
sulfonyl anion coupling reaction28-30 and other anion-
anion reactions that have attracted considerable atten-
tion recently.31-36
Resu lts a n d Discu ssion
The olefination reaction was examined using aldehyde
tosylhydrazones 2 (Scheme 3) and 6 (Scheme 4) and a
variety of sulfones. The derivative 2 was prepared from
aldehyde 1 (several procedures for preparation of this
compound are available37-40), which is readily accessible
from stigmasterol via i-stigmasteryl methyl ether.41 It
was crystalline and could be stored for several weeks
without decomposition. Tosylhydrazone 6 was prepared
from commercially available 3â-acetoxychol-5-en-24-oic
acid via aldehyde 5.42 The derivative 6 was unstable and
was used immediately after preparation. Tosylhydrazone
2 was obtained as the pure E isomer,43 whereas com-
pound 6 was obtained as a mixture of geometric isomers
in a ratio of 3:1 as evidenced by its 1H and 13C NMR
spectra. The CdN bond in 2 is sterically rather hindered,
owing to chain branching and the proximity of the cyclic
system, whereas that in 6 is unhindered.
Rea ction of Ar ylsu lfon ylh yd r a zon es w ith R-Lith i-
a ted Su lfon es. The reaction of tosylhydrazones 2 and 6
with selected lithiated sulfones was first examined under
the conditions analogous to those described by Vedejs and
co-workers.13 Treatment of 2 with an excess of lithiated
(20) Preliminary communication: Kurek-Tyrlik, A.; Marczak, S.;
Michalak, K.; Wicha, J . Synlett 2000, 547-549.
(21) J ulia, M.; Paris, J .-M. Tetrahedron Lett. 1973, 4833-4836.
(22) Kocienski, P. J .; Lythgoe, B.; Ruston, S. J . Chem. Soc., Perkin
Trans. 1 1979, 1290-1293.
(23) For new sulfone-based olefination reactions, see: Blakemore,
P. R.; Cole, W. J .; Kocienski, P. J .; Morley, A. Synlett 1998, 26-28.
(24) Kende, A. S.; Mendoza, J . S. Tetrahedron Lett. 1990, 31, 7105-
7108.
(33) Habermann, A.-K.; J ulia, M.; Verpeaux, J .-N.; Zhang, D. Bull.
Soc. Chim. Fr. 1994, 131, 965-972.
(34) Lima, C. D.; J ulia, M.; Verpeaux, J .-N. Synlett 1992, 133-134.
(35) Kocienski, P.; Barber, C. Pure Appl. Chem. 1990, 62, 1933-
1940.
(25) Barton, D. H. R.; J aszberenyi, J . C.; Tachdjian, C. Tetrahedron
Lett. 1991, 32, 2703-2706.
(36) Knochel, P.; Normant, J . F. Tetrahedron Lett. 1986, 27, 1039-
(26) Lee, G. H.; Lee, H. K.; Choi, E. B.; Kim, B. T.; Pak, C. S.
Tetrahedron Lett. 1995, 36, 5607-5608.
1043.
(37) Hutchins, R. F. N.; Thompson, M. J .; Svoboda, J . A. Steroids
1970, 15, 113-130.
(27) Wakefield, B. J . Organomagnesium Methods in Organic Chem-
istry; Academic Press: San Diego, 1995.
(38) J ung, M. E.; J ohnson, T. W. Tetrahedron 2001, 57, 1449-1481.
(39) Nagano, H.; Matsuda, M.; Yajima, T. J . Chem. Soc., Perkin
Trans. 1 2001, 174-182.
(28) Daub, I.; Hebermann, A.-K.; Hobert, A.; J ulia, M. Eur. J . Org.
Chem. 1999, 163-165.
(29) Gai, Y.; J ulia, M.; Verpeaux, J .-N. Bull. Soc. Chim. Fr. 1996,
133, 805-816.
(40) Spencer, T. A.; Li, D.; Russel, J . S. J . Org. Chem. 2000, 65,
1919-1923.
(30) Engman, L. J . Org. Chem. 1984, 49, 3559-3563.
(31) Hoffmann, R. W.; Knopff, O.; Kusche, A. Angew. Chem., Int.
Ed. Engl. 2000, 39, 1462-1464.
(41) Steele, J . A.; Mosettig, E. J . Org. Chem. 1963, 28, 571-572.
(42) Wechter, W. J . U.S Patent 3,152,152; Chem. Abstr. 1964, 61,
16135g.
(32) Nakamura, E.; Kubota, K.; Sakata, G. J . Am. Chem. Soc. 1997,
119, 5457-5458.
(43) Structure of 2 has been confirmed by X-ray analysis; details
will be published elsewhere.

6996 J . Org. Chem., Vol. 66, No. 21, 2001
Kurek-Tyrlik et al.
Sch em e 3
Sch em e 4
dimethyl sulfone or lithiated methyl phenyl sulfone
afforded the expected olefination product 3a (Table 1,
entries 1 and 2). However, even a slight increase in the
sulfone steric bulk resulted in concomitant formation of
addition and fragmentation products. Thus, the reaction
of 2 with lithium derivatives of diethyl sulfone or ethyl
phenyl sulfone gave 3b along with ca. 10% of 4 (Table 1,
entries 3 and 7). In the reactions of 2 with lithium
derivatives of phenyl undecyl sulfone and 3-methylbutyl
phenyl sulfone, the fragmentation product 4 predomi-
nated (Table 1, entries 10 and 12). Treatment of 2 with
lithiated phenyl isopropyl sulfone afforded compound 4
in a 95% yield (Table 1, entry 20). The reaction of less
hindered tosylhydrazone 6 (Scheme 4) with lithium
derivatives of diisopropyl or phenyl isopropyl sulfones
consistently afforded a mixture of addition and fragmen-
tation products 7a and 8, respectively (Table 2, entries
1 and 4). It is noteworthy that the reaction of tosylhy-
drazone 2 with butyllithium (THF-hexane, -20 °C)
proceeds almost instantly to give the reductive alkylation
product 9 (86% yield, Scheme 5).
Rea ction of Ar ylsu lfon ylh yd r a zon es w ith Or ga -
n om a gn esiu m Rea gen ts. We commenced our studies
with an evaluation of relative reactivity of a Grignard
reagent, dialkylmagnesium, and R-magnesio sulfones
toward tosylhydrazones. Tosylhydrazone 2 in THF at
room temperature was treated with 3 molar equiv of
i-PrMgCl. After 24 h, the reagent excess was destroyed,
and organic material was isolated and shown to comprise
unchanged 2 (70%) and a newly formed product (14%
yield), which was assigned as the nitrile 1044 (Scheme
5). Base-induced transformation of an aldehyde tosylhy-
drazone into the corresponding nitrile has previously
been recorded.10,13 The treatment of 2 in THF-hexane
with Bu2Mg at room temperature for 22 h gave the
reductive alkylation product 9 (Scheme 5) in a 28% yield
along with starting material (48% yield). Remarkably,
when i-PrMgCl (3 molar equiv) was added to a mixture
of tosylhydrazone 2 and diethyl sulfone (3 molar equiv),
the olefination products 3b could be detected (TLC)
almost instantly. After the reaction was complete, 3b was
obtained in a 86% yield.
The foregoing experiments revealed important differ-
ences in the reaction of tosylhydrazones with the orga-
nometallic reagents: R-magnesio sulfones undergo smooth
olefination in those cases where the R-lithio sulfones
induce fragmentation. Moreover, the high reactivity of
tosylhydrazones toward R-magnesio sulfones contrasts
sharply with the sluggishness of their reaction with
alkylmagnesiums.
In the course of further investigations, Bu2Mg or
i-PrMgCl was used to generate magnesium derivatives
of sulfones. Deuterium labeling experiments indicated
that primary sulfone metalation occurs in 30-45 min at
room temperature when Bu2Mg is used (1 molar equiv)
and in 1-1.5 h with i-PrMgCl (1 molar equiv). In all
reactions, an excess of a metalated sulfone was used to
account for an exchange of the tosylhydrazone proton for
the metal cation. Preliminary experiments showed that
an excess of sulfone is needed to achieve complete
consumption of arylsulfonylhydrazone. The best results
were obtained when an arylsulfonylhydrazone was treated
in THF at room temperature with a sulfonyl anion
prepared from 3 molar equiv of a sulfone and 3 molar
equiv of Bu2Mg. Under these conditions, the reaction of
tosylhydrazone 2 with unhindered sulfones was typically
completed within 4 h. Upon generation of the sulfonyl
anion with 0.5 molar equiv of Bu2Mg, lower yields of
alkylation products were obtained and the reaction was
slower (approximately 16 h were needed for consumption
of the tosylhydrazone). Alternatively, the sulfonyl anion
was generated from a sulfone and 3 molar equiv of
i-PrMgCl. The reactions of 2 with diethyl sulfone (Table
1, entries 4-6) are illustrative for various methods of
anion generation.
The reactions of tosylhydrazone 2 with magnesium
derivatives of representative sulfones were examined.
Unbranched primary alkyl sulfones and the γ-branched
sulfone afforded uniformly excellent yields of the respec-
tive olefination products (Table 1, entries 4-6, 8, 9, 11,
and 13). Phenyl cyclopropylmethyl sulfone afforded the
product 3e in 94% or 89% yields (Table 1, entries 14 and
(44) Khripach, V. A.; Zhabinskii, V. N.; Kotyatkina, A. I. Zh. Org.
Khim. 1993, 29, 1569-1572.

Novel Olefin Synthesis
J . Org. Chem., Vol. 66, No. 21, 2001 6997
Ta ble 1. Rea ction of Tosylh yd r a zon e 2 w ith r-Meta lo
Ta ble 2. Rea ction of Tosylh yd r a zon e 6 w ith r-Meta lo
Su lfon esa Accor d in g to Sch em e 4 (P r oced u r e A, w ith
Isola tion of 6; P r oced u r e B, w ith ou t Isola tion of 6, Yield s
fr om Ald eh yd e 5)
Su lfon esa Accor d in g to Sch em e 3
a
R-Metalo sulfones were generated from sulfones and 1 molar
b
equiv of butyllithium or the alkylmagnesium regents. Isomer
ratios were determined by GC, first is given isomer with shorter
tR.
Sch em e 5
a
R-Metalo sulfones were generated from sulfones and 1 molar
b
equiv of butyllithium or the alkylmagnesium regents. Isomer
ratios were determined by GC, except where otherwise indicated.
d
c 0.5 molar equiv of dibutylmagnesium was used. Isomer ratio
was determined from 1H NMR spectra.
15). The reactions of 2 with â-branched sulfones were
markedly slower, requiring 16 h for consumption of the
starting material. Nevertheless, when the reaction was
carried out with strict preclusion of air and using freshly
distilled isobutyl phenyl sulfone, product 3f was obtained
in an 85% yield (Table 1, entry 16). Cyclohexylmethyl
phenyl sulfone gave 3g in a 68% yield (Table 1, entry
17). The reaction of 2 with benzyl phenyl sulfone gave
the derivative 3h in 60% yield (Table 1, entry 18). Lower
yields of alkenes 3f, 3g, and 3j presumably reflect the
combined effect of steric hindrance in both reactants, the
respective sulfone and the tosylhydrazone 2. Indeed,
reaction of the magnesium derivative of isobutyl phenyl
sulfone with unhindered tosylhydrazone 6 was completed
within 4 h to afford olefin 7b in 81% yield (Table 2, entry
8). Reactions of tosylhydrazones 2 or 6 with isopropyl
sulfones proceeded smoothly to give the corresponding
trisubstituted olefins 3i or 7a (Table 1, entries 19 and
21; Table 2, entries 2, 3 5).
The foregoing observations on the relative rates of the
reaction of isopropyl sulfone and isobutyl sulfone were
verified in a competition experiment. Thus, a mixture of
isopropyl and isobutyl phenyl sulfones, 0.3 mmol of each,
in THF was treated with 0.6 mmol of Bu2Mg in hexane,
followed by tosylhydrazone 2 (ca. 0.1 mmol). A mixture
of products 3f and 3i was obtained in a ratio of 1:20 (by
GC), respectively. An analogous experiment with tosyl-
hydrazone 6 yielded olefins 7a and 7b in a ratio of 10:1.
These experiments suggest that branching in the R-posi-
tion of the sulfone has less effect on the reaction (cf. Table
1, entries 8 and 21) than branching in the â-position (cf.
Table 1, entries 11 and 16). The reaction of 2 with sec-
butyl phenyl sulfone afforded 3j in a 50% yield (Table 1,
entry 22).

6998 J . Org. Chem., Vol. 66, No. 21, 2001
Kurek-Tyrlik et al.
Ta ble 3. Rea ction s of Ar ylsu lfon ylh yd r a zon es 11b or 11c
w ith r-Ma gn esio Su lfon es Gen er a ted fr om 3 Mola r Equ iv
of Su lfon e a n d 3 Mola r Equ iv of Or ga n om a gn esiu m
Rea gen t
Sch em e 6
hydrazone sulfone
base
products yield (%) ratioa
1
4
5
6
7
11b
11c
11c
11c
11c
Me2SO2
Me2SO2
Me2SO2
PhSO2Me i-PrMgCl 12a /13
PhSO2Et i-PrMgCl 12b/13
Bu2Mg
Bu2Mg
i-PrMgCl 12a /13
12a /13
12a /13
50-60b
91
92
89
76
2:1
9:1
30:1
9:1
1:4
a
b
Determined by GC. 20% of unreacted 11b was recovered.
and yielded mixtures of olefination and fragmentation
products 12a and 13 (a mixture of E and Z isomers, Table
3, entry 1). Since 2,4,6-triisopropylbenzenesulfonyl-
hydrazones show higher reactivity than the correspond-
ing tosylhydrazones,46-48 it was of interest to compare
the reaction outcome for the trisylhydrazone 11c. The
reaction of 11c with the reagents prepared from dimethyl
sulfone or methyl phenyl sulfone and i-PrMgCl afforded
the olefination product 12a in high yield, contaminated
with only a small amount of fragmentation product 13
(Table 3, enties 4-6). However, the magnesio derivative
of ethyl phenyl sulfone gave a mixture of 12b and 13, in
which the latter was the predominant product (Table 3,
entry 7).
The olefination procedure, as described above, involves
two steps: transformation of an aldehyde into the cor-
responding tosylhydrazone and the reaction of the latter
with R-magnesio sulfones. In principle, condensation of
an aldehyde with arylsulfonyl hydrazide should provide
the product quantitatively. However, sterically unhin-
dered tosylhydrazones such as 6 are often isolated in
rather low yields, due to their instability.45 A one-pot
olefination procedure omitting tosylhydrazone isolation
would present an advantage in such cases. To this end,
it was found that the treatment of aldehyde 5 in THF at
room temperature with 1 molar equiv of p-toluenesulfonyl
hydrazide followed (after 45 min) by treatment with the
reagent prepared from isopropyl phenyl sulfone (3 molar
equiv) and dibutylmagnesium (3 molar equiv) afforded
alkene 7a in a 94% yield (Table 2, entry 7). Under similar
conditions, 5 was transformed into alkenes 7b or 7c in
85% and 68% yields, respectively (Table 2, entries 9 and
12), without isolation of 6. It is noteworthy that water
generated in the condensation step had no effect on the
overall outcome of the reaction.
The results presented above allow for some comments
on the stereochemistry of the alkenylation reaction. The
differences in the reactions of lithio and magnesio sul-
fones with tosylhydrazone 2 are apparent: the lithium
derivative of diethyl and ethyl phenyl sulfones gave
predominantly E products (although in low yields, Table
1, entries 3 and 7), whereas magnesium derivatives favor
formation of Z-products (Table 1, entries 4, 5, 8, and 9).
Magnesio sulfones with a longer unbranched alkyl chain
or a side chain branched in the â position (Table 1, entries
11 and 13) gave mixtures of (E)- and (Z)-alkenes with
low selectivity. Branching at the â-position resulted in
predominant formation of an (E)-alkene (only one ex-
ample was examined; Table 1, entry 22). The highest
E-selectivity was observed for sulfones in which the alkyl
group was branched at the â position (Table 1, entries
16 and 17). However, cyclopropylmethyl phenyl sulfone
afforded a product consisting of E- and Z-isomers in a
ratio of 1:3 with Bu2Mg (Table 1, entry 14) and in a ratio
of 1:1.2 with i-PrMgCl (Table 1, entry 15). Reactions of
hydrazone 6 (E- and Z-isomers, 3:1) afforded olefins as
mixtures of geometric isomers with low selectivity.
The results obtained in olefination of aldehydes via
their tosylhydrazones prompted us to examine olefination
of ketones in an analogous way. Cyclododecanone 11a
(Scheme 6) was chosen as a model. The reaction of
cyclodecanone tosylhydrazone 11b with the reagent
generated from Bu2Mg and dimethyl sulfone was slow
The pattern of higher reactivity for R-magnesio sul-
fones than Bu2Mg, in addition to the tosylhydrazone Cd
N bond, contradicts the expectations based upon reac-
tivity of the CdO bond. One possible explanation of the
observed discrepancy is illustrated in Scheme 7. The
reaction of tosylhydrazone i with dibutylmagnesium
affords the proton-metal exchange product ii (for clarity
of drawings Mg is localized on the sulfamidic nitrogen).
The addition of an external nucleophile to the CdN bond
in intermediate ii providing iii is retarded. On the other
hand, the reaction of i and R-magnesio sulfone may
generate two derivatives, ii and v. The latter may
undergo a 1,4-metalate rearrangement, which is facili-
tated by charge stabilization in the migrating group (CH2-
SO2R) and concomitant fragmentation of the intermedi-
ate vi.
In conclusion, a novel and efficient synthesis of olefins
from aldehydes and sulfones based upon the reaction of
aldehyde tosylhydrazone with R-magnesio sulfone has
been developed. The utility of this method stems from
its operational simplicity (one or two step procedures),
mildness of the reaction conditions, and use of a phenyl-
sulfonyl group that by virtue of inertness is easy to
handle in syntheses of polyfunctional subunits. Reactions
involving â-branched primary sulfones afford (E)-alkenes
with significant stereoselectivity.
Exp er im en ta l Section 49
(E)-Tosylh yd r a zon e of 3r,5-Cyclo-23,24-d in or -6â-m eth -
oxy-5r-ch ola n -24-a l 2. To a stirred solution of 1 (2.24 g, 6.5
mmol) in 96% EtOH (20 mL) was added p-toluenesulfonyl
hydrazide (1.21 g, 6.5 mmol) at 0 °C. The mixture was set aside
at room temperature for 4 h, and then solid K2CO3 (2 g) was
(46) Cusack, N. J .; Reese, C. B.; Risius, A. C.; Roozpeikar, B.
Tetrahedron 1976, 32, 2157-2162.
(47) J iricny, J .; Orere, D. M.; Reese, C. B. J . Chem. Soc., Perkin
Trans. 1 1980, 1487-1492.
(45) Bertz, S. H.; Dabbagh, G. J . Org. Chem. 1983, 48, 116-119.
(48) Chamberlin, A. R. J . Org. Chem. 1978, 43, 147-154.

Novel Olefin Synthesis
J . Org. Chem., Vol. 66, No. 21, 2001 6999
Sch em e 7
added and stirring was continued for 2 h. The solid was filtered
off, and the solvent was evaporated. The residue was chro-
matographed on SiO2 (90 g, hexane-EtOAc, 8:2) to give 2 (2.94
g, 91%) as a crystalline mass. A sample was recrystallized from
mmol) at -20 °C. After 10 min, the starting material was
consumed (TLC). The reaction was quenched with MeOH (0.1
mL). The product was isolated with hexane and chromato-
graphed on SiO2 (5 g, hexane-EtOAc, 98:2) to give 9 (29 mg,
86%).
CH2Cl2-hexane: mp 162-164 °C; FTIR (KBr) 3193 (NH) cm-1
;
1H NMR 7.79 (d, J ) 8.2 Hz, 2H), 7.71 (s, 1H, NH), 7.27 (d, J
) 8.2 Hz, 2H), 6.98 (d, J ) 7.3 Hz, 1H), 3.29 (s, 3H), 2.74 (t, J
) 2.6 Hz, 1H), 2.40 (s, 3H) overlapping 2.42-2.20 (m, 1H),
0.98 (s, 3H), 0.98 (d, J ) 6.6 Hz, 3H), 0.61 (s, 3H), 0.41 (dd, J
) 7.9, 5.1 Hz, 1H)(in other spectra of this compound the NH
signal appeared between 8.1 and 7.3 ppm); 13C NMR 157.7,
143.9, 135.2, 129.4, 127.9, 82.2, 56.5, 56.1, 53.5, 47.9, 43.3, 42.9,
39.8, 39.5, 35.1, 35.0, 33.3, 30.3, 27.1, 24.8, 24.1, 22.6, 21.5,
21.4, 19.2, 17.3, 13.0, 12.4; HRMS calcd for C30H45O3N2S
513.31509 (M+), found 513.31749.
b. Rea ction of 2 w ith Bu 2Mg. To a solution of 2 (100 mg,
0.195 mmol) in THF (0.5 mL) was added Bu2Mg (1 M in
heptane, 0.5 mL, 0.5 mmol) at room temperature. The mixture
was stirred for 22 h, and the reaction was quenched with
aqueous NH4Cl. The product was isolated with ether and
chromatographed on SiO2 to give 9 (21 mg, 28%) and un-
changed 2 (49 mg, 49%).
9: 1H NMR 3.31 (s, 3H), 2.76 (br t, J ) 2.7 Hz, 1H), 1.01 (s,
3H), 0.91-0.82 m, 6H), 0.71 (s, 3H); 13C NMR 82.43, 56.52,
56.31, 48.03, 43.37, 42.75, 40.29, 35.91, 35.76, 35.29, 35.04,
33.35, 32.40, 30.47, 28.31, 25.79, 24.97, 24.18, 22.77, 21.50,
(E)- a n d (Z)-Tosylh yd r a zon es of 3r,5-Cyclo-6â-m eth -
oxy-5r-ch ola n -24-a l 6. To a stirred solution of methyl 3R,5-
cyclo-6â-methoxy-5R-cholan-24-oate42 (250 mg, 0.62 mmol) in
toluene (1.5 mL) was added DIBALH (1.2 M in toluene, 0.62
mL, 0.74 mmol) dropwise at -78 °C. The mixture was stirred
-78 °C for 45 min, and then the reaction was quenched with
a mixture of Et2O-AcOH-H2O (10:4:1, 0.35 mL). The product
was isolated with Et2O and chromatographed on SiO2. Alde-
hyde 542 was obtained (214 mg, 92% yield): 1H NMR 9.77 (s,
1H), 3.32 (s, 3H), 2.79 (m, 1H), 2.41 (m, 2H), 1.02 (s, 3H), 0.94
(d, J ) 6.1 Hz, 3H), 0.72 (s, 3H). To a stirred solution of the
aldehyde 5 (742 mg, 2.00 mmol) in 96% EtOH (20 mL) was
added p-toluenesulfonyl hydrazide (459 mg, 2.47 mmol) at -20
°C. The mixture was allowed to warm to room temperature
over 2 h and then set aside for 4 h. Solid K2CO3 (0.5 g) was
added; the suspension was stirred for 2 h and filtered. The
solvent was evaporated at room temperature, and the residue
was chromatographed on SiO2 (45 g, hexane-EtOAc, 8:2) to
give 6 as a foam (1.05 g, 90% yield): 1H NMR, major isomer,
7.88-7.76 (m, 2H), 7.5 (br. s, 1H, NH), 7.36-7.27 (m, 2H), 7.14
(t, J ) 5.6 Hz, 1H, CHdN), 3.32 (s, 3H), 2.77 (t, J ) 2.8 Hz,
1H), 2.43 (s, 3H), 1.02 (s, 3H), 0.85 (d, J ) 6.6 Hz, 3H), 0.65
(s, 3H), 0.43 (dd, J ) 8.1, 5.1 Hz, 1H); minor isomer 7.64 (br
s, 1H), 6.70 (t, J ) 5.2 Hz, 1H, CHdN), 0.68 (s, 3H); 13C NMR
(major isomer, diagnostic signals) 153.3, 143.7, 129.4, 127.7.
Isomer ratio 3:1 was determined from CHdN signals in the
1H NMR spectrum. This product was further used immediately
after preparation.
19.29, 18.69, 14.15, 13.06, 12.25; HRMS calcd for C27H46
O
386.35487 (M+), found 386.35442.
Rea ction of 2 w ith i-P r MgCl. 20(S)-6â-Meth oxy-3,5-
cyclo-5r-p r egn a n e-20-ca r bon itr ile 10. To a solution of 2
(205 mg, 0.4 mmol) in THF (1.4 mL) was added i-PrMgCl (2M
in THF, 0.6 mL, 1.2 mmol), and the mixture was stirred at
room temperature for 24 h. The reagent excess was quenched
with aqueous NH4Cl. The product was isolated with Et2O and
chromatographed on SiO2 to give unchanged 2 (143 mg, 70%)
and nitrile 10 (19 mg, 14%): FTIR (film) 2237 cm-1; 1H NMR
0.78 (s, 3H), 1.03 (s, 3H), 1.35 (d, J ) 7.1 Hz, 3H), 2.65 (quintet,
J ) 7.1 Hz, 1H), 2.78 (m, 1H), 3.33 (s, 3H); MS m/e 341 (M+);
in agreement with those reported.44
Gen er a l P r oced u r e for Rea ction of Tosylh yd r a zon e
2 w ith Meta la ted Su lfon es. a . With Use of Bu Li. To a
solution of sulfone (0.53 mmol) in THF (3 mL), stirred under
argon at 0 °C, was added BuLi (2.2 M in hexane, 0.26 mL,
0.572 mmol). The cooling bath was removed, and after 15 min,
a solution of tosylhydrazone 2 (90 mg, 0.176 mmol) in THF (1
mL) was added dropwise. The mixture was set aside for 16 h,
and then saturated aqueous NH4Cl (3 mL) was added. The
product was extracted with Et2O. The organic extract was
dried with Na2SO4, and the solvent was evaporated. The
residue was chromatographed on a silica gel column. Yields
of the products are given in Table 1.
b. With Use of Bu 2Mg. To a solution of sulfone (0.53 mmol)
in THF (3 mL), stirred under argon at room temperature, was
added Bu2Mg (1.0 M in heptane, 0.55 mL, 0.55 mmol). After
45 min, a solution of tosylhydrazone 2 (90 mg, 0.176 mmol) in
THF (1 mL) was added dropwise. Progress of the reaction was
monitored by TLC. After consumption of the hydrazone (ca.
1.5 h with unbranched sulfones and ca. 16 h with â branched
ones), saturated aqueous NH4Cl (3 mL) was added. The
product was isolated with Et2O. Yields are given in Table 1.
c. With Use of i-P r MgCl. To a solution of sulfone (0.53
mmol) in THF (3 mL), stirred under argon at room tempera-
ture was added i-PrMgCl (1.9 M in THF, 0.289 mL, 0.55
mmol). After 1 h, a solution of tosylhydrazone 2 (90 mg, 0.176
mmol) in THF (1 mL) was added dropwise. The mixture was
set aside for 16 h, and then saturated aqueous NH4Cl (3 mL)
was added. The product was isolated with Et2O. Yields are
given in Table 1.
3,5-Cyclo-6â-m eth oxy-27-n or -5r-ch olesta n e 9. a . Rea c-
tion of 2 w ith Bu Li. To a solution of 2 (45 mg, 0.09 mmol) in
THF (3 mL) was added BuLi (2.25 M in hexane, 0.12 mL, 0.27
(49) General experimental conditions are described elsewhere.50
NMR spectra were recorded at 200 MHz (1H) and 50 MHz (13C) unless
otherwise indicated. Dibutylmagnesium (1 M in heptane), isopropyl-
magnesium chloride (2 M in THF), and butyllithium (2.2 M in hexane)
were purchased from Aldrich. Concentrations of these solutions were
determined by titration with s-butanol using 1,10-phenanthroline51 or
N-phenyl-1-naphthylamine52 as an indicator. Sulfones were obtained
from commercial suppliers or prepared by the usual methods, com-
mercial reagents were distilled before the use. Olefination reactions
were carried out under argon containing less than 0.5 ppm of oxygen
and less than 1.4 ppm of water. 3R,5-Cyclo-23,24-dinor-6â-methoxy-
5R-cholane-24-al37 1 was prepared from stigmasterol following the
literature procedures. Methyl 3R,5-cyclo-6â-methoxy-5R-cholane-24-
oate was prepared from methyl 3â-hydroxy-chol-5-en-24-oate using
1
P r od u ct Id en tifica tion . H NMR spectra were in agree-
reported method.42 GC were performed in
Hewlett-Packard HP-5MS column at programmed temperature 70-
300 °C.
a GC-MS unit, with
ment with those reported, and HRMS confirmed the structures
for the following compounds: 6â-methoxy-3,5-cyclo-24-nor-5R-

7000 J . Org. Chem., Vol. 66, No. 21, 2001
Kurek-Tyrlik et al.
chol-22-ene 3a ,53 (E)- and (Z)-6â-methoxy-3,5-cyclo-5R-cholest-
22-ene 3d ,54 and 6â-methoxy-20-methylene-3,5-cyclo-5R-preg-
nane 4.55
GC-MS E-isomer, tR 54.04 min, Z-isomer, tR 51.76 min; HRMS
calcd for C30H42O 418.32357, found 418.324598.
6â-Meth oxy-23-m eth yl-3,5-cyclo-5r-ch ol-22-en e 3i: 1H
NMR 4.89 (br d, J ) 9.8 Hz), 3.32 (s, 3H), 2.78 (t, J ) 2.8 Hz,
1H), 1.64 (d, J ) 1.1 Hz, 3H), 1.60 (d, J ) 1.1 Hz, 3H), 1.02 (s,
3H), 0.93 (d, J ) 6.6 Hz, 3H), 0.75 (s, 3H), 0.66 (m, 1H), 0.42
(dd, J ) 8.0, 5.0 Hz, 1H); 13C NMR, 132.01, 127.49, 82.42,
56.86, 56.60, 56.54, 48.09, 43.39, 42.62, 40.21, 35.29, 35.05
(2C), 33,35, 30.47, 28.10, 25.77, 24.96, 24.12, 22.77, 21,50,
(E)- a n d (Z)-6â-m eth oxy-3,5-cyclo-5r-ch ol-22-en e 3b:
1
isomers E/Z in a ratio of 4:1 or 1:2 by GC; H NMR, selected
signals, E-isomer (from the mixture) 5.42-5.05 (m), 3.32 (s,
3H), 2.76 (t, J ) 2.8 Hz, 1H), 1.60 (d, J ) 4.8 Hz, 3H), 1.02 (s,
3H), 0.98 (d, J ) 6.6 Hz), 0.72 (s, 3H), 0.64 (m), 0.42 (dd, J )
5.0, 8.0 Hz); Z-isomer 5.45-5.05 (m), 0.95 (d, J ) 6.6 Hz), 0.76
(s); decoupling experiment: at irradiation at d 1.6 ppm,
multiplet at 5.45-5.05 ppm collapsed to q AB, 5.32, 5.21 ppm,
J ) 16 Hz, overlapping d 5.28 ppm, J ) 10.3 Hz, and dd 5.16
ppm, J ) 10.3 and 9.4 Hz; 13C NMR, E-isomer 138.04, 121,67,
82.39, 56.60, 56.55, 56.09, 48.07, 43.40, 42.68, 40.19, 40.01,
35.32, 35.04, 33.38, 30.49, 28.63, 24.99, 24.17, 22,79, 21.54,
20.66, 19.33, 17.89, 13.10, 12.45; Z-isomer, selected signals,
137.60, 120.22; GC-MS E-isomer, tR 42.21 min, Z-isomer, tR
20.69, 19.30, 18.11, 13.07, 12.53; HRMS calcd for C26H42
370.32357, found 370.32256.
O
(E)- a n d (Z)-23,24-d im eth yl-6â-m eth oxy-3,5-cyclo-5r-
1
1
ch ol-22-en e 3j: isomers E/Z in a ratio of 4:1 by H NMR, H
NMR (500 MHz) E-isomer (from the mixture) 4.89 (dq, J )
9.7, 1.3 Hz, 1H), 3.32 (s, 3H), 2.76 (t, J ) 2.8 Hz, 1H), 1.60 (d,
J ) 1.4 Hz, 3H), 1.03 (s, 3H), 0.962 (t, J ) 7.5 Hz, 3H), 0.932
(d, J ) 6.6 Hz, 3H), 0.752 (s, 3H), 0.65 (m, 1H), 0.43 (dd, J )
8.0, 5.0 Hz, 1H); Z-isomer, selected signals 4.86 (br d, J ) 9.5
Hz), 1.63 (d, J ) 1.3 Hz), 0.966 (t, J ) 7.5 Hz), 0.937 (d, J )
6.6 Hz), 0.747 (s) NOE measurements: at irradiation at d 1.60
ppm (the major isomer signal) increase of integration of the
signal 2.5 ppm (assigned to C-20 by a COSY experiment) and
no increase of integration of the vinylic proton signal at 4.89
ppm was recorded; at irradiation at δ 1.63 ppm increase of
integration of the signals at 4.86 ppm was observed. These
measurements indicate trans relationship of the vinylic methyl
group and the vinylic proton in the major isomer (E configu-
ration of the double bond). 13C NMR, selected signals E-isomer
133.04, 130.51; Z-isomer 133.16; 131.76; HRMS calcd for
42.32 min; HRMS calcd for C25H40
356.30780.
O 356.30792, found
(E)- a n d (Z)-24-n on yl-6â-m eth oxy-3,5-cyclo-5r-ch ol-22-
en e 3c: isomers E/Z in a ratio of 1:1 by 1H NMR, selected
signals, 5.35-5.05 (m, 2H), 3.32 (s, 3H), 2.76 (t, J ) 2.5 Hz,
1H), 1.02 (s, 3H), 0.97 (d, J ) 6.6 Hz, 1.5 H), 0.95 (d, J ) 6.6
Hz, 1.5 H), 0.88 (t, J ) 6.7 Hz, 3H), 0.75 (s, 1.5 H), 0.72 (s, 1.5
H); 13C NMR, selected signals, 136.87, 136.56, 127.55, 126.64;
HRMS calcd for C34H58O 482.44877, found 482.44700.
(E)- a n d (Z)-23-cyclop r op yl-6â-m eth oxy-3,5-cyclo-24-
n or -5r-ch ol-22-en e 3e: isomers E/Z in a ratio of 1:3 or 1:1.2
by GC; 1H NMR, selected signals, E-isomer (from the mixture)
5.31 (dd, J ) 15.3, 8.4 Hz, 1H), 4.86 (dd, J ) 15.3, 8.6 Hz,
1H), 3.317 (s, 3H), 2.76 (t, J ) 2.8 Hz, 1H), 1.01 (s, 3H)
overlapping 0.99 (d, J ) 6.6 Hz, 3H), 0.71 (s, 3H), 0.32-0.22
(m, 2H); Z-isomer 5.06 (t, J ) 10.5 Hz, 1H), 4.54 (t, J ) 10.5
Hz), 3.322 (s, 3H), 1.03 (s, 3H) overlapping 1.01 (d, J ) 6.6
Hz), 0.77 (s, 3H); 13C NMR, selected signals, E-isomer 134.65,
130.85, Z 135.12, 130.64; GC-MS E-isomer, tR 46.91 min,
Z-isomer, tR 46.61 min; HRMS calcd for C27H42O 382.32357,
found 382.32362.
(E)- a n d (Z)-6â-m eth oxy-24,24-d im eth yl-5r-ch ol-22-en e
3f: isomers E/Z in a ratio of 7:1 by GC; 1H NMR, E-isomer
(from the mixture) 5.26 (part A of ABXY system, J ) 15.3, 6.0
Hz, 1H), 5.16 (part B, 15.3, 7.5 Hz, 1H), 3.32 (s, 3H), 2.75 (t,
J ) 2.6 Hz, 1H), 1.02 (s, 3H), 0.99 (d, J ) 6.6 Hz, 3H), 0.94 (d,
6.8 Hz, 6H), 0.72 (s, 3H), 0.64 (m, 1H), 0.42 (dd, J ) 8.0, 5.0
Hz, 1H); 13C NMR, selected signals E-isomer 134.72, 133.63;
GC-MS E-isomer, tR 43.61 min, Z-isomer, tR 43.26 min; HRMS
calcd for C27H44O 384.33922, found 384.33939.
(E)- a n d (Z)-23-cycloh exyl-6â-m eth oxy-24-n or -5r-ch ol-
22-en e 3g: isomers E/Z in a ratio of 12:1 by GC; 1H NMR,
E-isomer (from the mixture) 5.26 (part A of an ABXY system,
J ) 15.4, 5.8 Hz, 1H), 5.16 (part B, 15.4, 7.2 Hz, 1H), 3.32 (s,
3H), 2.75 (t, J ) 2.6 Hz, 1H), 1.02 (s, 3H), 0.99 (d, J ) 6.6 Hz,
3H), 0.72 (s, 3H), 0.64 (m, 1H), 0.42 (dd, J ) 8.0, 5.0 Hz); 13C
NMR, E-isomer, selected signals 134.22, 133.58; GC-MS
E-isomer, tR 52.11 min, Z-isomer, tR 51.14 min; HRMS calcd
for C30H48O 424.37052, found 424.36978.
C
27H44O 384.33922, found 384.34103.
Gen er a l P r oced u r e for Rea ction of Tosylh yd r a zon e
6 w ith Meta la ted Su lfon es. Reactions were carried out as
described above for 2, using a sulfone (0.26 mmol) in THF (1.5
mL), BuLi (2.0 M in hexane, 0.15 mL, 0.30 mmol), or Bu2Mg
(1 M in heptane, 0.3 mL, 0.30 mmol) and tosylhydrazone 6
(47 mg, 0.087 mmol) in THF (0.5 mL). Yields are given in Table
2.
Olefin a tion Rea ction s In volvin g in Situ P r ep a r a tion
of Tosylh yd r a zon e 6. To a solution of aldehyde 5 (0.33 mmol)
in THF (0.5 mL) was added p-toluenesulfonyl hydrazide (0.33
mmol) in THF (0.5 mL) (solution A). In parallel, a solution of
sulfone (1 mmol) in THF (4 mL) was treated with Bu2Mg (1
M in heptane, 1 mL, 1 mmol) (solution B). After 45 min,
solution A was carefully added to solution B. Progress of the
reaction was monitored by TLC. After consumption of the
hydrazone (ca. 1.5 h with unbranched sulfones and ca. 16 h
with â branched ones) saturated aqueous NH4Cl (3 mL) was
added, and the product was isolated with Et2O. Yields are
given in Table 2.
P r odu ct Iden tification . 6â-Meth oxy-3,5-cyclo-5r-ch olest-
24-en e 7a : mp 62-64 °C (acetone); 1H NMR 5.51 (tt, J ) 5.7,
2.7 Hz, 1H), 3.32 (s, 3H), 2.76 (t, J ) 2.7 Hz, 1H), 1.68 (s, 3H),
1.59 (s, 3H), 1.02 (s, 3H), 0.93 (d, J ) 6.7 Hz, 3H), 0.71 (s,
3H), 0.66-0.62 (m, 1H), 0.45-0.39 (m, 1H), in agreement with
that reported.57
1
6â-Meth oxy-3,5-cyclo-5r-ch ol-23-en e 8: H NMR (diag-
nostic signals from mixture 7 and 8) 5.16-4.90, 3.31, 2.76,
(E)- a n d (Z)-6â-m eth oxy-23-p h en yl-3,5-cyclo-24-n or -5r-
ch ol-22-en e 3h : isomers E/Z in a ratio of 2:1 by GC; 1H NMR
(500 MHz) E-isomer (from the mixture) 7.36-7.15 (m, 5H),
6.33 (d, J ) 15.8 Hz, 1H), 6.10 (dd, J ) 15.8, 8.7 Hz, 1H), 3.35
(s, 3H), 2.79 (t, J ) 2.8 Hz, 1H), 1.15 (d, J ) 6.6 Hz, 3H), 1.06
(s, 3H), 0.81 (s, 3H), 0.64 (m, 1H), 0.42 (dd, J ) 8.0, 5.0 Hz,
1H); Z-isomer, selected signals 6.28 (d, 11.7 Hz), 5.47 (dd, J )
11.7, 10.6 Hz), 3.33 (s), 1.14 (d, J ) 6.6 Hz), 1.04 (s), 0.69 (s);
1.01, 0.92, 0.71.
(E)- a n d (Z)-6â-m eth oxy-3,5-cyclo-24-h om o-5r-ch olest-
24(24a )-en e 7b: isomers E/Z in a ratio of 1.5:1 by GC; 1H NMR
(500 MHz) E-isomer (from the mixture) 5.32-5.23 (m, 8 lines,
2H), 3.25 (s, 3H), 2.70 (t, J ) 2.6 Hz), 2.15 (m, 1H), 0.95 (s,
3H), 0.89 (d, J ) 6.8 Hz, 6H), 0.85 (d, J ) 6.6 Hz, 3H), 0.643
(s, 3H), 0.58 (m, 1H), 0.36 (dd, J ) 8, 5 Hz); Z-isomer, selected
signals, 5.17-5.06 (m, 2H), 2.52 (m, 1H), 0.88 (d, 6.8 Hz, 6H),
0.87 (d, J ) 6.6 Hz, 3H), 0.649 (s, 3H); 13C NMR (125 MHz),
E-isomer, selected signals, 137.27, 127.69; Z-137.29, 127.87;
1H NMR in C6D6 (500 MHz) selected signals, E-isomer, 5.52-
5.43 (m), Z-isomer 5.41-5.35 (m, 1H), 5.33-5.28 (m, 1H);
Signals of the E-and Z-isomers were assigned from the
(50) Marczak, S.; Michalak, K.; Urbanczyk-Lipkowska, Z.; Wicha,
J . J . Org. Chem. 1998, 63, 2218-2223.
(51) Watson, S. C.; Eastham, J . F. J . Organomet. Chem. 1967, 9,
165-168.
(52) Bergbreiter, D. E.; Pendegrass, E. J . Org. Chem. 1981, 46, 219-
220.
(53) Posner, J . P.; Ourisson, G. J . Chem. Soc., Perkin Trans. 1 1974,
2061-2066.
(54) Lang, R. W.; Djerassi, C. J . Org. Chem. 1982, 47, 625-633.
(55) Dasgupta, S. K.; Gut, M. J . Org. Chem. 1975, 40, 1475-1477.
(56) Dasgupta, S. K.; Crump, D. R.; Gut, M. J . Org. Chem. 1974,
39, 1658-1662.
(57) Giner, J . L.; Margot, C.; Djerassi, C. J . Org. Chem. 1989, 54,
2117-2125.

Novel Olefin Synthesis
J . Org. Chem., Vol. 66, No. 21, 2001 7001
decoupling experiment: at irradiation at d 2.1 ppm (C-23 H
according to the COSY spectrum) multiplet 5.33-5.28 ppm
collapsed to 5.34 (dd, J ) 10.8, 7.9 Hz), multiplet 5.41-5.35
collapsed to 5.42 (dt, J ) 10.8, 2.2 Hz) and multiplet 5.52-
5.43 collapsed to distorted AB quartet, 5.51 (J ) 15.5 Hz); GC-
drazide47 (1.19 g, 5 mmol), and Et2O (25 mL) was stirred at
room temperature for 16 h. The solvent was evaporated in a
stream of dry nitrogen to ca. 1/3 of the mixture volume. The
remainder was set aside at -20 °C for 1.5 h, and crystalline
material was filtered off and washed with cold Et2O. Trisyl-
hydrazone 11c was obtained: 1.60 g (69%); mp 136-138 °C
dec; 1H NMR 7.34 (br. s, 1H), 7.16 (s, 2H), 4.19 (sept., J ) 6.6
Hz, 2H), 2.90 (sept., J ) 7.0 Hz), 2.28-2.08 (m, 4H), 1.65-
1.47 (m, 4 H), 1.32-1.05 (m, 14H) overlapping 1.27 (d, J )
6.6 Hz, 12H), 1.25 (d, J ) 7.0 Hz, 6H); 13C NMR 158.9, 153.0,
131.3, 123.4, 34.2, 31.8, 30.1, 28.2, 25.7, 25.6, 24.9, 24.6, 23.6,
23.3, 23.1, 23.0, 22.7, 22.6, 22.2. Anal. Calcd for C27H46N2O2S
(462.74) C, 70.08; H, 10.02; N, 6.05; S, 6.92. Found: C, 70.05;
H, 10.19; N, 6.02; S, 7.06.
MS E- 47.56 min and Z- 47.42 min; HRMS calcd for C29H48
O
412.37052, found 412.37095.
(E)- an d (Z)-6â-m eth oxy-26-m eth yl-3,5-cyclo-5r-ch olest-
24-en e 7c: isomers E/Z in a ratio of 1.7:1 by GC; 1H NMR
E-isomer (from the mixture) 5.20-5.00 (m, 1H), 3.32 (s, 3H),
2.75 (t, J ) 2.6 Hz), 1.59 (br s, 3H), 1.02 (s, 3H), 0.98 (t, J )
7 Hz, 3H), 0.92 (d, J ) 6.6 Hz, 3H), 0.71 (s, 3H), 0.64 (m, 1H),
0.42 (dd, J ) 8, 5 Hz); Z-isomer, selected signals, 1.67 (d, J )
1 Hz, 3H); 13C NMR, E-isomer, selected signals, 136.34, 123.59;
Z-136.59, 124.78; E/ Z assignments were based upon chemical
shifts of vinylic methyl group signals, with that of the isomer
E- occurring at higher field, cf. reported values for the
respective 3-hydroxy-5-enes58 and spectra of 3j; GC-MS
E-isomer 47.74 min and Z-isomer 47.53 min; HRMS calcd for
A Gen er a l P r oced u r e for Rea ction of 11b or 11c w ith
r-Ma gn esio Su lfon es. To a solution of freshly distilled
sulfone in THF (4 mL), stirred at room temperature, was added
a solution of Bu2Mg (1 M in heptane) or i-PrMgCl (2 M in
THF). After 30 min, a solution of 11b or 11c (0.33 mmol) in
THF (2 mL) was added. The mixture was stirred for 18 h, and
then aqueous NH4Cl and water were added. The product was
isolated with CH2Cl2 and chromatographed on a SiO2 (4 g).
The olefins were eluted with hexane, and then the column was
washed with hexane-acetone, 9:1, to recover unchanged
hydrazones. The olefin 12/13 ratio was determined by GC.
Yields and product composition are give in Table 3.
P r od u ct Id en tifica tion . methylene-cyclodecane 12a : 1H
NMR 4.80 (t, J ) 1.0 Hz, 2H), 2.06 (t, J ) 5.9 Hz, 4H), 1.59-
1.44 (m, 4H), 1.37-1.27 (m, 14H); 13C NMR 147.46, 110.32,
33.07 (2C), 24.47 (2C), 24.15 (2C), 23.73 (2C), 23.28 (2C), 22.63,
in agreement with those reported.
C
29H48O 412.37052, found 412.37075.
Rea ction of Tosylh yd r a zon es 2 or 6 w ith a Mixtu r e of
Isobu tyl- a n d Isop r op yl P h en yl Su lfon es. To a solution of
isopropyl phenyl sulfone (48 mg, 0.3 mmol) and isobutyl phenyl
sulfone (53 mg, 0.3 mmol) in THF (2 mL) was added Bu2Mg
(1 M in hexane, 0.6 mL, 0.6 mmol). The mixture was stirred
at room temperature for 1 h, tosylhydrazone 2 (0.09 mmol) or
6 (0.09 mmol) in (THF, 1 mL) was added, and stirring was
continued for 16 h. The reaction was quenched with water.
The product was isolated with Et2O and purified by chroma-
tography on SiO2 (hexane, hexane-EtOAc, 97:3). The composi-
tion of the mixture was determined by GC.
Reaction with tosylhydrazone 2: crude product 31 mg, 3f/
3i ) 1:20.
Reaction with tosylhydrazone 6: crude product 33 mg, 7a /
7b ) 10:1.
Tosyloh yd r a zon e of Cyclod od eca n on e 11b. A mixture
of cyclododecanone 11a (1.02 g, 5.6 mmol), p-toluenesulfonyl
hydrazide (1.10 g, 5.9 mmol), and anhydrous ethanol (10 mL)
was heated under reflux for 2 h and then set aside at room
temperature for 6 h. Crystalline material was filtered off,
washed with ethanol, and dried to give 11b: 1.76 g (90%); mp
160-161 °C dec; 1H NMR 7.82 (d, J ) 8.3 Hz, 2H), 7.74 (br.s,
1H), 7.26 (d, J ) 8.3 Hz, 2H), 2.38 (s, 3H), 2.24-2.07 (m, 4H),
1.72-0.70 (m, 18H); 13C NMR 159.35, 143.80, 135.42, 129.48
(2C), 125.12, 31.28, 28.76, 25.93, 25.84, 23.67, 23.14, 22.87,
22.64, 22.60, 21.75, 21.50, 21.44. Anal. Calcd for C19H30N2O2S
(350.53): C, 65.11; H, 8.63; N, 7.99; S, 9.15. Found: C,65.12;
H, 8.80; N, 8.02; S, 9.16.
Ethylidenecyclodecane 12b: 1H NMR from a mixture with
13, 5.40-5.20 (m), 2.20-1.90 (m), 1.60 (d, J ) 6.7 Hz), 1.50-
1.10 (m); 13C NMR 138.36, 118.81 ppm (diagnostic signals);
E/Z 13: 13C NMR 130.35 ppm (diagnostic signal).
Ack n ow led gm en t. We thank Professor Philip J .
Kocienski of the University of Leeds for helpful discus-
sions, Professor J ames R. Bull of the University of Cape
Town for assistance in idiomatic English, and Professor
Zofia Urbanczyk-Lipkowska for the X-ray structure of
compound 2. Financial support from the State Commit-
tee for Scientific Research, Grant No. 3 T09A 134 18, is
gratefully acknowledged.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 3b,c,e-j and 7b,c and 1H NMR spec-
trum of compound 6. This material is available free of charge
via the Internet at http://pubs.acs.org.
Tr isylh yd r a zon e of Cyclod eca n on e 11c. A mixture of
11a (0.91 mg, 5 mmol), 2,4,6-triisopropylbenzenesulfonyl hy-
(58) Fukuzawa, S.; Mutoh, K.; Tsuchimoto, T.; Hiyama, T. J . Org.
Chem. 1996, 61, 5400-5405.
J O015699L