Reaction of tertiary cyclopropyl silyl ethers with diethylaminosulfur trifluoride: The effects of substituents on the cleavage of the cyclopropane ring

Article abstract of DOI:10.1016/j.tetlet.2003.09.089

The reaction of tertiary cyclopropanol silyl ethers with diethylaminosulfur trifluoride usually causes ring opening to produce allylic fluorides. However, cyclopropyl silyl ethers bearing a strong electron-donating substituent at C1 or an electron-withdra

Full text of DOI:10.1016/j.tetlet.2003.09.089

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8513–8518
Reaction of tertiary cyclopropyl silyl ethers with
diethylaminosulfur trifluoride: the effects of substituents on the
cleavage of the cyclopropane ring
Masayuki Kirihara,a,* Hiroko Kakuda,b Makoto Tsunooka,a Akihiro Shimajiri,a Tomofumi Takuwac
and Akihiko Hatanoa
aDepartment of Materials Science, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa, Fukuroi, Shizuoka 437-8555,
Japan
bLaboratory of Chemistry, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
cFaculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Received 9 July 2003; revised 1 September 2003; accepted 5 September 2003
Abstract—The reaction of tertiary cyclopropanol silyl ethers with diethylaminosulfur trifluoride usually causes ring opening to
produce allylic fluorides. However, cyclopropyl silyl ethers bearing a strong electron-donating substituent at C1 or an
electron-withdrawing substituent at C2 do not afford allylic fluorides but fluorocyclopropanes. It has also been proved that an
electron-donating substituent at C2 of the tertiary cyclopropanol silyl ethers promotes ring opening in the reaction with
diethylaminosulfur trifluoride.
© 2003 Elsevier Ltd. All rights reserved.
Tertiary cyclopropyl systems (1) are important syn-
thetic intermediates due to their high reactivity.1 Sev-
eral methods have been developed to achieve specific
cleavage at bond ‘a’ or ‘b’.2,3 The methods of bond
cleavage at both ‘a’ and ‘b’ have been reported by
Rubottom4 and ourselves.5 We have also reported that
the reaction of 1 with diethylaminosulfur trifluoride
(DAST)6 causes ring fragmentation at bond ‘c’ to
provide allylic fluorides.7 Allylic bromides or chlorides
have been synthesized from the reaction of tertiary
cyclopropoxy sulfonates with metal halides (magnesium
bromide etc.) by Kulinkovich (Scheme 1).8†
strong electron-donating substituent at C1 only gave a
fluorocyclopropane (3).9 In this case, the strong elec-
tron-donating substituent stabilized the cyclopropyl
cation (B) derived from 1, and hence B could survive
long enough to react with the fluoride ion.
The plausible mechanism of the reaction of DAST with
1 is shown in Scheme 2. This reaction proceeds through
allylic cations (A and A%) which are produced by the
elimination of the oxygen functionality from 1.
In most cases, 1 reacted with DAST to afford allylic
fluorides (2 and/or 2%), whereas substrates bearing a
* Corresponding author. Tel.: +81-538-45-0166; fax: +81-538-45-0110;
e-mail: kirihara@ms.sist.ac.jp
† Some stereochemical and kinetic studies of ‘c’ bond cleavage of 1
have been reported by several groups.1b
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.089

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M. Kirihara et al. / Tetrahedron Letters 44 (2003) 8513–8518
Scheme 2.
Scheme 3.

M. Kirihara et al. / Tetrahedron Letters 44 (2003) 8513–8518
8515
We further examined the reaction of several kinds of 1
dency for the cleavage of
a
cyclopropane ring
with DAST and found that the electronic property of
the substituents on the cyclopropane ring of 1 influ-
enced the reactivity for the cleavage of cyclopropane
ring. We would now like to report the results of this
study.
decreased further with an increase in the electron
donating ability of the substituent on C1. For exam-
ple, (1b) having the phenyl group, which is a relatively
weak electron releasing group, afforded only an allylic
fluoride (2b) (entry 2). On the other hand, 1e having
the 2,4-dimethoxyphenyl group, which is a strong elec-
tron releasing group, furnished only fluorocyclo-
propane (3e) (entry 5). The compound (1c) bearing the
2-methoxyphenyl group, whose electron donativity is
between phenyl and 2,4-dimethoxyphenyl, produced a
mixture of allylic fluoride (2c) and fluorocyclopropane
(3c) (entry 3).
First, we investigated the effect of the C1 substituent
of 1 on the reaction. Tertiary cyclopropylsilylethers
(1a–g) were treated with DAST in dichloromethane
and the results are shown in Table 1. In all cases,
allylic fluorides and/or fluorocyclopropanes were effec-
tively obtained. The difference in yield mainly depends
on the stability of the products during the silica-gel
column chromatography. As we expected, the ten-
We then examined the reaction of DAST with 1 hav-
ing an electron-withdrawing substituent (CO2Et) at
C2. We summarized these results in Table 2 and also
showed the results of the reaction with 1 having no
substituent at C2 for comparison. Interestingly, fluoro-
cyclopropanes are the only products for 1 having the
CO2Et group at C2 (entries 2, 4, 6, 8, 10 and 12).‡
These results are in sharp contrast to the reaction of
DAST with tertiary cyclopropylsilylethers which have
no substituents at C2 (entries 1, 3, 5 and 9). The
reaction of 1 containing an electron-attracting group
at C2 with DAST must be a good method to synthe-
size the fluorocyclopropanes. As noted in entry 12, the
cis-isomer (1m) gave a mixture of the cis- and trans-
fluorocyclopropanes (3m). This result confirms that the
reaction proceeds through a cyclopropyl cation inter-
mediate.
Table 1.
We next investigated the reaction of DAST toward 1
bearing an electron-releasing substituent (Me or Ph) at
C2 and found that allylic fluorides were obtained in all
cases (Table 3).‡ Even if 1 had a strong electron-
releasing group at C1, no fluorocyclopropane was pro-
duced (entries 2, 3 and 6). These results are contrary
to the results of 1 having an electron-withdrawing
substituent.
Our results suggest that the electronic property of the
substituents at C2 strongly affects the reactivity of the
cyclopropane ring in 1. We depicted the plausible reac-
tion mechanism of 1 containing a substituent at C2 in
Scheme 3. Since the electron-donating group at C2 can
stabilize the allylic cation (A), the cleavage of the
cyclopropane ring is stimulated. On the other hand,
the electron-accepting group at C2 destabilizes the
allylic cation (A), and the cyclopropyl cation can sur-
vive long enough to react with the fluoride ion. Fur-
ther details of this reaction are currently under
investigation.
‡ Since some products (2, 3) were unstable to silica gel column
chromatography, the isolated yields of the products were very low
in some cases. The unstable compounds easily decomposed to
afford complex mixtures. We measured the 1H NMR of the crude
products and confirmed that the desired products (2, 3) were
effectively obtained.

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M. Kirihara et al. / Tetrahedron Letters 44 (2003) 8513–8518
Table 2.
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