The formation of cyclopropane derivatives bearing 1,2-dicarbonyl groups through tandem Michael-Favorskii-type reactions with (E) -β-styrylselenonium triflate

Article abstract of DOI:10.1002/ejoc.200400756

A novel tandem Michael-Favorskii-type reaction is described. Treatment of active methylene carbanions, prepared by the reaction of NaH and active methylene compounds, with (E)-β-styrylselenonium triflate in DMF at 70°C for 3 h gave cyclopropane derivatives bearing 1,2-dicarbonyl groups in moderate to good yields. On the other hand, the carbanions derived from malonates reacted with the selenonium salt to afford 1,1-dicarbonylcyclopropane compounds in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400756

SHORT COMMUNICATION
The Formation of Cyclopropane Derivatives Bearing 1,2-Dicarbonyl Groups
through Tandem Michael–Favorskii-Type Reactions with
(E)-β-Styrylselenonium Triflate
Shin-ichi Watanabe,*[a] Ippei Nakayama,[a] and Tadashi Kataoka*[a]
Keywords: Selenium / Domino reactions / Michael addition / Rearrangement/ Ring contraction
A novel tandem Michael–Favorskii-type reaction is de-
scribed. Treatment of active methylene carbanions, prepared
by the reaction of NaH and active methylene compounds,
with (E)-β-styrylselenonium triflate in DMF at 70 °C for 3 h
gave cyclopropane derivatives bearing 1,2-dicarbonyl
groups in moderate to good yields. On the other hand, the
carbanions derived from malonates reacted with the sele-
nonium salt to afford 1,1-dicarbonylcyclopropane com-
pounds in good yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
a useful compound. We now report tandem Michael–Favor-
skii-type reactions of β-styrylselenonium salts with 1,1-di-
carbonyl compounds, through which 1,2-dicarbonylcyclo-
propane derivatives are formed.
Introduction
The versatility of carbonylcyclopropane compounds has
made them regarded as useful synthons in organic chemis-
try.[1] In particular, the efficient behavior of dicarbonylcy-
clopropanes as good Michael acceptors[2] and important
precursors of bioactive derivatives may be cited.[3] Treat-
ment of an α,β-unsaturated carbonyl compound with a
chalcogenonium ylide derived from the corresponding chal-
cogenonium salt is known as a typical procedure for the
preparation of cyclopropane derivatives bearing electron-
withdrawing groups.[4] Although it is familiar that the beta-
ine intermediate – the key compound for the cyclopropane
ring formation – can be generated by the reaction of elec-
tron-deficient olefins with β-oxo-onium ylides,[5] betaine
elaboration from an alkenylchalcogenonium salt and a nu-
cleophile has hardly been reported.[6] On the other hand,
Kuwajima reported a cyclopropane synthesis using vinyl se-
lenones as the Michael acceptors and active methylene or
active methylidyne carbanions, and prepared various types
of carbonylcyclopropane compounds.[7]
Recently, we developed a new Michael-type reaction of
alkynylselenonium salts as Michael acceptors with nucleo-
philes.[8] In particular, the tandem Michael addition–cycli-
zation route between alkynylselenonium salts and active
methylene carbanions afforded highly functionalized furan
derivatives.[9] These interesting results prompted us to inves-
tigate a tandem reaction of an alkenylselenonium salt in-
volving multiple carbon–carbon bond formation to afford
Results and Discussion
We first examined the reaction of (E)-β-styrylselenonium
triflate (1)[10] with an active methylene carbanion generated
from benzoylacetone and a base (Table 1). The use of so-
dium hydride as a base gave 1-(2-benzoyl-3-phenylcyclopro-
pyl)ethanone (2a) with a trace amount of its diastereo-
isomer 3a after 24 h at room temperature (Entry 1). The
yields of the desired compounds were improved under re-
flux for 3 h, to afford 2a and 3a in 66% and 8% yields,
respectively (Entry 2). However, the use of a different base,
potassium tert-butoxide or DBU, did not improve the yield
obtained with sodium hydride (Entries 3 and 4) under the
conditions of Entry 2. When DMF was used at 70 °C for
3 h, the cyclopropane derivatives were obtained in 81%
yield (Entry 5). The stereochemistry of compounds 2a and
3a was determined by comparison with known com-
pounds;[11] in particular, NOE measurements of 2a[12]
showed the relative configuration of the cyclopropane ring
to be (1R*,2S*,3R*).
Secondly, to broaden the scope of this transformation, a
variety of active methylene compounds were allowed to re-
act with alkenylselenonium salt 1 under these reaction con-
ditions (Table 2). A series of cyclopropanes 2, with anti rela-
tionships between the phenyl group and the other func-
tional groups, were prepared as the main products in mod-
erate to good yields from active methylene compounds pos-
sessing at least one ketone group by application of this new
[a] Gifu Pharmaceutical University,
6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Fax: +81-58-237-5979
E-mail: kataoka@gifu-pu.ac.jp
watanabe@gifu-pu.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
1
methodology (Entries 1–5). The H and 13C NMR spectra
Eur. J. Org. Chem. 2005, 1493–1496
DOI: 10.1002/ejoc.200400756
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S. Watanabe, I. Nakayama, T. Kataoka
SHORT COMMUNICATION
Table 1. Cyclopropane formation from alkenylselenonium salt 1
and benzoylacetone.
Table 2. Cyclopropane formation from alkenylselenonium salt 1
with various active methylene compounds.
[a] Inseparable mixtures.
[a] The yield was obtained after 20 h at 70 °C.
of products 2b and 2c[13] demonstrated highly symmetrical
skeletons. The relative configurations of minor products
were determined by the coupling constants in their 1H
NMR spectra. On the other hand, the reaction with diethyl
malonate, which has no ketone group, afforded a good yield
of diethyl 2-phenylcyclopropane-1,1-dicarboxylate (4a),[14]
bearing 1,1-dicarbonyl groups (Entry 6). Treatment with di-
benzyl malonate also afforded the corresponding 1,1-dicar-
bonylcyclopropane compound 4b in excellent yield (En-
try 7).
On the basis of these results, we propose a plausible
mechanism for the reactions of the alkenylselenonium salt
with active methylene carbanions (Scheme 1). Selenonium
ylides 5 are formed from the Michael addition of the carb-
anion to the alkenylselenonium salt. When the active meth-
ylene compound possesses one or more ketone group(s),
the ylide carbanion attacks the more active carbonyl group
intramolecularly to form a cyclobutane ring, which is fol-
lowed by the 1,2-migration of the endo carbon–carbon
bond with the elimination of diphenyl selenide to form a
cyclopropane derivative bearing 1,2-dicarbonyl groups
(path a). This ring contraction reaction is similar to the se-
Scheme 1. Plausible mechanism for cyclopropane formation.
mibenzylic pathway for the Favorskii rearrangement.[15] On were in equilibrium between the starting materials and cy-
the other hand, since the carbonyl groups derived from ma- clobutane intermediate 6, the reactions proceeded via the
lonates in ylide 5 are less reactive toward the ylide carban- thermodynamically stable configurations of 5 and 6, each
ion, deprotonation of an active methyne proton occurs pref- with a predominant trans configuration between a phenyl
erentially, to form another carbanion, followed by intramo- group and a carbonyl substituent. Conformer 5A, which is
lecular nucleophilic substitution to give a cyclopropane de- sterically preferred over the other 5B, cyclizes to form cyclo-
rivative bearing 1,1-dicarbonyl groups (path b).
butane 6A. The subsequent 1,2-migration of the endo car-
The stereoselectivity of the formation of cyclopropane bon–carbon bond of 6A occurs from the backside to the
compounds 2 and 3 is explained as follows (Figure 1). Since selenonio group. Consequently, compound 2 is obtained as
these reactions were examined above room temperature and a main product. Cyclopropane formation by tandem
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Formation of Cyclopropane Derivatives Bearing 1,2-Dicarbonyl Groups
SHORT COMMUNICATION
Michael addition and Favorskii rearrangement has been re- expansion process (Entry 1). On the other hand, the reac-
ported in the reaction of vinyl selenones with active methyl- tions with 1,3-cyclohexanedione derivatives did not give
ene or methylidyne compounds.[7] The reactions of alkenyl good results, and the condensed-ring compounds, obtained
selenones with α-monosubstituted β-dicarbonyl compounds in low yields, each possessed a seven-membered ring (En-
proceeded through a similar addition–rearrangement path- tries 2 and 3). This would be attributable to the difficulties
way to give 1,2-dicarbonylcyclopropanes,[7b,7c] but α-unsub- inherent in transformation to the flexible seven-membered
1
stituted β-dicarbonyl compounds did not undergo Favorskii ring. The H and 13C NMR spectra of the products indi-
rearrangement to afford 1,1-dicarbonylcyclopropanes.[7c,7d] cated that products had highly symmetrical skeletons.
It is very interesting that α-unsubstituted β-dicarbonyl com-
pounds have reacted with alkenylselenonium salt 1 to form
1,2-dicarbonylcyclopropanes, differently from the case of
selenones.
Conclusion
In conclusion, we have found the first example of a tan-
dem Michael–Favorskii-type process in reactions of alkenyl-
substituted onium salts with active methylene carbanions
bearing at least one ketone group to produce α,β-dicarbon-
ylcyclopropane derivatives. On the other hand, cyclopro-
panes bearing α,α-bis(oxycarbonyl) groups were obtained
in good yields from the reactions with malonates. It is note-
worthy that the formation of the cyclopropane skeleton de-
pends on the properties of the functional groups in active
methylene compounds. In addition, it is valuable that di-
phenyl selenide, which was recovered in these reactions,
could be reused as one of the starting materials for the
preparation of the β-styrylselenonium salt. Further applica-
tions of this strategy are currently underway in our labora-
tory.
Figure 1. 1,2-Migration from the backside of the selenonio group.
Next, we tried to construct a fused bicyclic ring system
through reactions with cyclic β-diketones (Table 3). The re-
action of 1,3-indandione with alkenyl selenonium salt 1 was
carried out under the same conditions as in Table 2 to af-
ford a 2,3-dihydro[1,4]naphthoquinone derivative 8a, fused
to a cyclopropane ring, in moderate yield through the ring
Experimental Section
General Procedure for Reactions of Alkenylselenonium Salt 1 with
Active Methylene Compounds: In a typical experiment, an active
methylene compound (0.20 mmol) was dissolved in anhydrous
DMF (3 mL), and sodium hydride (60%, 8 mg, 0.20 mmol) was
added to the solution at room temperature. After the mixture had
been stirred at the same temperature for 1 h, alkenylselenonium salt
1 (146 mg, 0.30 mmol) was added. The whole was stirred at 70 °C
for 3 h, then worked up with water and extracted with ethyl acetate.
The organic layers were combined, washed with brine, dried with
MgSO4, filtered, and concentrated. The crude product was sepa-
rated by preparative TLC (silica gel, hexane/ethyl acetate mixture)
to give cyclopropane derivatives 2–4 or 8. For spectroscopic data
for all compounds, see Supporting Information.
Table 3. Cyclopropane formation from alkenylselenonium salt 1
with cyclic β-diketones.
Acknowledgments
This research was partially supported by the Ministry of Educa-
tion, Culture, Sports, Science and Technology of Japan through a
Grant-in-Aid for Young Scientists (B), 2004, 14771246.
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Received October 23, 2004
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