Reaction of a cyclic oxosulfonium ylide with acetates of the Baylis-Hillman adducts: Tandem Michael - Intramolecular Corey-Chaykovsky reactions

Article abstract of DOI:10.1021/ol990069f

(equation presented) The reaction of the five-membered cyclic oxosulfonium ylide 2 with α-methylene-β-acetoxy ketones in the presence of two equimolar amounts of base afforded the cycloheptene oxide derivatives with stereoselectivity in 19-74% yield via a

Full text of DOI:10.1021/ol990069f

ORGANIC
LETTERS
1999
Vol. 1, No. 3
427-430
Reaction of a Cyclic Oxosulfonium Ylide
with Acetates of the Baylis-Hillman
Adducts: Tandem
Michael−Intramolecular
Corey-Chaykovsky Reactions
Hitoshi Akiyama, Tetsuya Fujimoto,* Katsuyoshi Ohshima, Kenji Hoshino, and
Iwao Yamamoto
Department of Functional Polymer Science, Faculty of Textile Science and Technology,
Shinshu UniVersity, Ueda, Nagano 386-8567, Japan
Ryozo Iriye
Department of Bioscience and Biotechnology, Faculty of Agriculture,
Shinshu UniVersity, Minowa, Kami-ina, Nagano 399-4598, Japan
tfujimo@giptc.shinshu-u.ac.jp
Received May 3, 1999
ABSTRACT
The reaction of the five-membered cyclic oxosulfonium ylide 2 with r-methylene-â-acetoxy ketones in the presence of two equimolar amounts
of base afforded the cycloheptene oxide derivatives with stereoselectivity in 19−74% yield via a Michael-type addition of the ylide followed by
elimination of the acetoxy group and an intramolecular Corey-Chaykovsky reaction.
The reaction of a five-membered cyclic phosphonium ylide
with enones,1 enoates,2 and R,â-unsaturated thioesters3
provides cycloheptene or hydroazulene derivatives by tandem
Michael-intramolecular Wittig reactions. These tandem
reactions proceed via a rigid phosphabicyclic or phospha-
tricyclic intermediate so that the products form with stereo-
selectivity.
In the present work, we attempted to develop novel tandem
reactions employing a cyclic oxosulfonium ylide via the
above tandem reactions of the cyclic phosphonium ylide.
The Corey-Chaykovsky reaction of oxosulfonium ylides
has provided a useful method for the synthesis of cyclopro-
pane derivatives4-6 by Michael-type addition of the ylide to
the activated carbon-carbon double bond. The reaction has
also been used for the synthesis of epoxide4a,7 and aziridine4c,8
(4) (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 867.
(b) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 3782. (c)
Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353.
(5) (a) Clive, D. L. J.; Daigneault, S. J. Chem. Soc., Chem. Commun.
1989, 332. (b) Okuma, K.; Ikari, K.; Ono, M.; Sato, Y.; Kuge, S.; Ohta,
H.; Machiguchi, T. Bull. Chem. Soc. Jpn. 1995, 68, 2313. (c) Cativiela, C.;
D´ıaz-de-Villegas, M. D.; Jime´nez, A. I. Tetrahedron 1995, 51, 3025.
(6) For a review of the reaction of oxosulfonium ylides see: Gololobov,
Y. G.; Nesmeyanov, A. N.; Lysenko, V. P.; Boldeskul, I. E. Tetrahedron
1987, 43, 2609.
(7) Childers, W. E.; Furth, P. S.; Shih, M.-J.; Robinson, C. H. J. Org.
Chem. 1988, 53, 5947.
(8) Garc´ıa-Ruano, J. L.; Ferna´ndez, I.; Hamdouchi, C. Tetrahedron Lett.
1995, 36, 295.
(1) (a) Fujimoto, T.; Takeuchi, Y.; Kai, K.; Hotei, Y.; Ohta, K.;
Yamamoto, I. J. Chem. Soc., Chem. Commun. 1992, 1263. (b) Fujimoto,
T.; Uchiyama, Y.; Kodama, Y.; Ohta, K.; Yamamoto, I.; Kakehi, A. J.
Org. Chem. 1993, 58, 7322.
(2) Fujimoto, T.; Kodama, Y.; Yamamoto, I.; Kakehi, A. J. Org. Chem.
1997, 62, 6627.
(3) Manuscript submitted for publication.
10.1021/ol990069f CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/23/1999

derivatives by nucleophilic addition of the ylide to carbonyl
and imine functionalities. However, only limited examples
of the reaction using cyclic oxosulfonium ylides have been
thus far reported.9
Cyclic oxosulfonium salt 1 was prepared by arylation10
of tetramethylene sulfide using diphenyliodonium salt fol-
lowed by oxidation of the resulting S-phenyl sulfonium salt
using m-CPBA11 (Scheme 1). At first, the reaction of
Therefore, we considered that substrates suitable for the
desired tandem reactions would be those in which no enolate
anion generated after an initial Michael addition remains.13
The reaction of the oxosulfonium ylide 2 with 4-acetoxy-
3-methylene-2-butanone (5a), which was prepared from the
corresponding Baylis-Hillman adduct,14 was then attempted
in the presence of two equimolar amounts of LHMDS.
Consequently, the cycloheptene oxide derivative 6a was
obtained in 23% yield with stereoselectivity (Scheme 3). This
Scheme 1
Scheme 3
oxosulfonium ylide 2, generated from 1 using LHMDS as a
base, with 4-hexen-3-one was examined. If the regeneration
of the ylide after Michael-type addition followed by an
intramolecular Corey-Chaykovsky reaction proceeds in a
manner similar to a cyclic phosphonium ylide, the cyclo-
heptene oxide derivative 4 would be obtained. However,
cyclopropane derivative 312 was formed in 98% yield via
the addition of the ylide and the elimination of the oxosul-
fonium group (Scheme 2). These results indicated that the
Scheme 2
reaction would proceed via a Michael-type addition of the
ylide 2 followed by elimination of the acetoxy group and an
intramolecular Corey-Chaykovsky reaction of the regenerated
ylide. Although the intramolecular Michael-type addition of
the regenerated ylide is also possible, the compound stem-
ming from the reaction was not isolated. The structure and
stereochemistry of cycloheptene oxide derivative 6a was
1
determined by H NMR, 13C NMR, and NOESY spectra.
Especially in the NOESY spectrum, the correlation between
the proton in the oxirane ring and Me and between Me and
the aromatic protons of the phenyl sulfinyl group was
observed. Accordingly, it was clarified that 6a has a trans
relationship between the phenyl sulfinyl group and the
oxirane ring, as shown in Scheme 3. Moreover, no peaks
intramolecular nucleophilic substitution of the enolate anion
would be preferred to the regeneration of the ylide for the
reaction of cyclic oxosulfonium ylide with enone.
(11) (a) Mori, M.; Takeuchi, H.; Minato, H.; Kobayashi, M.; Yoshida,
M.; Matsuyama, H.; Kamigata, N. Phosphorus, Sulfur Silicon Relat. Elem.
1990, 47, 157. (b) Takeuchi, H.; Minato, H.; Kobayashi, M.; Yoshida, M.;
Matsuyama, H.; Kamigata, N. Phosphorus, Sulfur Silicon Relat. Elem. 1990,
47, 165.
(9) (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1964, 86, 1640.
(b) Moody, C. J.; Taylor, R. J. Tetrahedron 1990, 46, 6525.
(10) (a) Crivello, J. V.; Lam, J. H. W.J. Org. Chem. 1978, 43, 3055. (b)
1-Phenylthiolanium salt was synthesized from ω-bromoalkyl sulfide with
silver perchlorate10c or from the reaction of ω-phenylthio alcohol with
trimethylsilyl iodide.10d (c) Yano, Y.; Ishihara, M.; Tagaki, W. Int. J. Sulfur
Chem. A 1972, 2, 169. (d) Cere´, V.; Pollicino, S.; Fava, A. Tetrahedron
1996, 52, 5989.
(12) Although the 13C NMR spectrum indicated that the product 3 was
a single stereoisomer, the stereochemistry was not determined.
(13) Smith, A. B., III; Wexler, B. A.; Slade, J. S. Tetrahedron Lett. 1980,
21, 3237.
(14) (a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653. (b)
Fort, Y.; Berthe, M. C. Tetrahedron 1992, 48, 6371. (c) Basavaiah, D.;
Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001.
428
Org. Lett., Vol. 1, No. 3, 1999

ascribed to other possible stereoisomers were observed in
1
the H and 13C NMR spectra. Therefore, the reaction was
Table 2. Reaction of R-Methylene-â-acetoxy Ketone with 2
considered to proceed via the rigid thiabicyclic intermediate
7, which is similar to that proposed in the reaction of the
cyclic phosphonium ylide. The effect of bases on this reaction
was examined for the sake of the enhancement of the yield
(Table 1). Surprisingly, the same reactions using NaH or
Table 1. Reaction of R-Methylene-â-acetoxy Ketone with 2
The correlation between the vinylic proton and the methyl
group bonded to the oxirane ring was observed, but no
correlation between methylene protons in the ethyl group
and the methyl group was found. Therefore, the resulting
product was determined to be the cycloheptene oxide
derivative which has the geometry as shown in Figure 1.
t-BuOK did not afford the cycloheptene oxide derivative 6a.
In addition, the reactions under various reaction conditions,
the amount of base, the order of addition of reactants, and
solvents, did not bring about an improvement in the yield
for the reaction with 4-acetoxy-3-methylene-2-butanone (5a).
However, the reaction of 4-acetoxy-3-methylene-8-pentanone
(5b) using t-BuOLi as a base for 1 h at room temperature
provided the corresponding cycloheptene oxide derivative
6b in 56% yield.
Figure 1.
To elucidate the versatility of this reaction, the reaction
of the ylide 2 with some R-methylene-â-acetoxy ketones
5c-e was examined under the same reaction conditions.
Consequently, cycloheptene oxide derivatives 6c-e were
obtained in 66-74% yield (Table 2). Although the existence
of the further two isomers relevant to the geometry of exo-
methylene was possible in 6b-e, any peaks ascribed to other
possible isomers were not observed in the 1H and 13C NMR
spectra. To clarify the geometry of the exo-trisubstituted
olefin, the NOESY spectrum of compound 6c15 was analyzed.
It has been reported that the SN2′ addition of a hydride
ion or a carbanion to acetates of the Baylis-Hillman adducts
from acrylate produces an E-trisubstituted olefin16 because
of steric interaction in the transition state for elimination of
the acetoxy group. Therefore, the E-trisubstituted enone
intermediate was considered to be generated by the initial
SN2′ addition of the cyclic oxosulfonium ylide into R-me-
thylene-â-acetoxy ketone via the same transition state.
7.5 Hz, 3H), 1.21-1.28 (m, 1H), 1.29 (s, 3H), 1.55-1.62 (m, 2H), 1.66-
1.74 (m, 1H), 2.05-2.12 (m, 2H), 2.30-2.34 (m, 1H), 2.36-2.39 (m, 1H),
2.50-2.55 (m, 1H), 2.84-2.87 (m, 1H), 5.46 (t, J ) 7.4 Hz, 1H), 7.57-
7.70 (m, 5H); 13C NMR (125.76 MHz, acetone-d6) δ 14.13, 20.73, 22.71,
24.97, 25.98, 29.08, 60.97, 62.69, 65.38, 125.35, 129.83, 131.53, 132.23,
(15) Typical Procedure for the Reaction of the Cyclic Oxosulfonium
Ylide 2 Using 5c. To a solution of five-membered oxosulfonium salt (0.10
g, 0.31 mmol) in dry THF (2 mL) was added dropwise a solution of lithium
tert-butoxide (2.05 equiv) (in 1 M THF solution, 0.63 mL, 0.63 mmol),
and the mixture was stirred at room temperature for 10 min. A solution of
5c (0.05 g, 0.31 mmol) in dry THF (2 mL) was then added dropwise to the
mixture, and the resulting solution was stirred for 1 h. The mixture was
quenched with water and extracted with ether. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by flash column chromatography on silica
gel using AcOEt as an eluent to give 6c (0.0589 g, 66% yield) as a white
136.33, 144.33; IR (KBr) 1090 (oxirane), 1030 (SdO), 860 (CdC) cm-1
;
HRMS (70 eV) calcd for C17H22O2S (M+) m/z 290.1340, found (M+)
290.1334.
(16) (a) Hoffmann, H. M. R.; Rabe, J. J. Org. Chem. 1985, 50, 3849.
(b) Basavaiah, D.; Sarma, P. K. S. J. Chem. Soc., Chem. Commun. 1992,
955. (c) Basavaiah, D.; Sarma, P. K. S.; Bhavani, A. K. D. J. Chem. Soc.,
Chem. Commun. 1994, 1091. (d) Beltaˆıef, I.; Amri, H. Synth. Commun.
1994, 24, 2003. (e) Basavaiah, D.; Krishnamacharyulu, M.; Hyma, R. S.;
Sarma, P. K. S.; Kumaragurubaran, N. J. Org. Chem. 1999, 64, 1197.
1
solid: mp 92-94 °C; H NMR (500.13 MHz, acetone-d6) δ 0.78 (t, J )
Org. Lett., Vol. 1, No. 3, 1999
429

Consequently, the (E)-exo-methylene cycloheptene oxide
derivative would be obtained by the subsequent intra-
molecular reaction.
In conclusion, we have developed novel tandem reactions
of cyclic oxosulfonium ylide with acetates of the Baylis-
Hillman adducts for the stereoselective synthesis of cyclo-
heptene oxide derivatives. Further studies on the reaction
mechanism and application of this method to the synthesis
of other complex molecules are currently underway.
Ministry of Education, Science, Sports and Culture of Japan.
We thank Miss M. Mizu of the Faculty of Agriculture,
Shinshu University, for the 500 MHz NMR measurements
and Yoshitomi Pharmaceutical Co., Ltd., for the mass
spectrum measurements.
Supporting Information Available: 1H and 13C NMR
spectra for compounds 3 and 6a-e. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was supported in part by
a Grant-in-Aid for COE Research (10CE2003) by the
OL990069F
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Org. Lett., Vol. 1, No. 3, 1999