Regioselective ring opening of alkylidenecyclopropanone silyl acetals

Article abstract of DOI:10.1016/j.tetlet.2004.09.002

Alkylidenecyclopropanone silyl acetals have been prepared from an iodonium salt via an alkylidenecarbene. Three different C-C bonds of the cyclopropane ring can be selectively cleaved with appropriate reagents. Alkylidenecyclopropanone silyl acetals are readily available from the reaction of an alkylidenemethyliodonium salt and ketene silyl acetals in the presence of triethylamine. The three different C-C bonds of the cyclopropane ring can be selectively cleaved with HCl, Lewis acid, or fluoride. The alkylideneallyl cation formed via the cleavage of C2-C3 bond with Lewis acids shows further selectivity in reacting with a nucleophile.

Full text of DOI:10.1016/j.tetlet.2004.09.002

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8023–8026
Regioselective ring opening of alkylidenecyclopropanone
silyl acetals
Morifumi Fujita,* Koji Fujiwara, Hiroshi Mouri, Yutaka Kazekami and
Tadashi Okuyama*
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo, Kamigori, Hyogo 678-1297, Japan
Received 31July 2004; revised 31August 2004; accepted 1September 2004
Available online 16 September 2004
Abstract—Alkylidenecyclopropanone silyl acetals are readily available from the reaction of an alkylidenemethyliodonium salt and
ketene silyl acetals in the presence of triethylamine. The three different C–C bonds of the cyclopropane ring can be selectively cleaved
with HCl, Lewis acid, or fluoride. The alkylideneallyl cation formed via the cleavage of C2–C3 bond with Lewis acids shows further
selectivity in reacting with a nucleophile.
Ó 2004 Elsevier Ltd. All rights reserved.
Alkylidenecyclopropanes1 undergo ring-opening reac-
tions promoted by Brønsted2,3 and Lewis acids4,5 as well
as by transition metal complexes,1a,6 and are employed
as synthetic building blocks. Reactivity is controlled
by a functional substituent on the cyclopropane ring.
For example, 1,1-dialkoxy-2-methylenecyclopropanes
are in equilibrium with the trimethylenemethane forms,
Scheme 1. Preparation of alkylidenecyclopropanone silyl acetals.
and undergo [3+2] cycloaddition to olefins.7 Regioselecti-
vity of the bond cleavage of the cyclopropane ring is also
an attractive point of interest in these reactions.5b,6f
the presence of amine in an aprotic solvent owing to
the high acidity of the a-hydrogen11,12 and the excellent
nucleofugality13 of the positive iodonio group. The
The present communication describes regioselective
unsaturated carbene10 must be a key intermediate in
ring-opening reactions of alkylidenecyclopropanone
silyl acetals. The cyclopropane ring contains three differ-
ent carbon–carbon bonds, and each of these bonds can
be cleaved selectively with an appropriate reagent.
the cyclopropanation of the ketene silyl acetal.
The reactions of 3a and 3b with anhydrous hydrogen
chloride (20mM) in dichloromethane at 0°C immedi-
ately gave allylcarboxylates 4a and 4b in 95% and 78%
yield, respectively (top of Scheme 2). Yields of the prod-
ucts were determined by GC14 and the structures were
determined by NMR and MS of the isolated products.
We propose that cleavage of the C1–C2 bond of the
cyclopropane ring of 3 occurs in this reaction, initiated
by protonation of the olefinic moiety of 3, to give I1,
the positive charge of which is stabilized by the a-cyclo-
propyl group. In the ring-opening reaction of I1, C1–C2
cleavage is preferred to C2–C3 cleavage because of sta-
bilization of the positive charge by the a-oxy groups in
the resulting cation I01. Similar regioselective bond
cleavage is observed in the ring-opening reactions
Reaction of the alkylidenemethyliodonium salt 18
(10mM) with triethylamine (16mM) in chloroform con-
taining ketene silyl acetal 2a (100mM) at ambient tem-
perature gave alkylidenecyclopropanone silyl acetal 3a
in 43% yield (Scheme 1). A diastereomeric mixture
(3:1) of 3b was obtained in 31% yield from an E/Z (3/1)
mixture of 2b.9 The alkylidenemethyliodonium salt 1
readily gives the corresponding alkylidenecarbene10 in
Keywords: Alkylidenecyclopropane; Allyl cation; Alkylidenecarbene;
Iodonium salt.
*
Corresponding authors. Tel.: +81 791 58 0170; fax: +81 791 58 0115
(M.F.); tel.: +81 791 58 0169; fax: +81 791 58 0115 (T.O.); e-mail
addresses: fuji@sci.u-hyogo.ac.jp; okuyama@sci.u-hyogo.ac.jp
of
1-alkoxy-2-cyclohexylidenecyclopropanes.2
The
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.002

8024
M. Fujita et al. / Tetrahedron Letters 45 (2004) 8023–8026
Scheme 2. Regioselective cleavage of the cyclopropane ring of 3.
ring-opening reaction initiated by protonation at
the carbon–carbon double bond is well known for
the
acid-mediated
ring
opening
of
simple
alkylidenecyclopropanes.3
When Lewis acids TiCl4 or SnCl4 were employed for the
reaction of 3, two isomeric products, 5 and 6, were ob-
tained plus 50, the enol ether related to 5 (middle of
Scheme 2).15 The yields determined by GC are summa-
rized in Table 1. The C2–C3 bond in 3 is selectively
cleaved in these reactions, although the regioselectivity
of chloride substitution (5/6) depends on the reaction
conditions. These products can be rationalized by a
reaction pathway involving the alkylideneallyl cation16
intermediate I02 formed via silyloxide elimination.17
Scheme 3. Reaction via a symmetrical allylic anion.
ring selectively to give the allylically stabilized anion
I03, which is protonated to yield a mixture of vinylcarb-
oxylates, 7a and 8a. The fluoride initiated ring-opening
reaction of the spiro substrate 3c gave a single product
9 in 95% yield as expected because of the symmetrical
structure of the allylic anion intermediate (Scheme 3).
Yet another type of ring-opening reaction was observed
in the reaction of 3a with Bu4NF (76mM) in CH2Cl2 at
ambient temperature to give a 1:1 mixture of esters 7a
and 8a in 93% yield in 5min.18 Ring cleavage occurs
at the C1–C3 bond (bottom of Scheme 2). Reaction of
3a with fluoride ion must be initiated by elimination of
the silyl group to give the anion I3. Cleavage of the
C1–C3 bond of this first-formed anion then opens the
Among these three regioselective ring-opening reactions
of 3, further consideration is warranted of the Lewis-
acid-mediated reaction involving the alkylideneallyl cat-
ion intermediate I02, which has two electrophilic centers,
the sp and sp2 carbons. The product ratio of (5+50):6 de-
pends on the reaction conditions. Exclusive formation of
5 (50) is observed in the reaction of 3a with SnCl4 (entries
3 and 4), but the TiCl4-induced reaction also gives 6
Table 1. Reaction of 3 with Lewis acid in CH2Cl2
Entry
Subst.a
Acid (concn, mM)
Temp (°C)
Time (min)
Yield (%)
5
50
6
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3b
3b
3b
3b
TiCl4 (9)
TiCl4 (6)
SnCl4 (7)
SnCl4 (6)
TiCl4 (5)
TiCl4 (4)
SnCl4 (5)
SnCl4 (4)
0
ꢀ78
0
2
5
16
0
51
82
85
29
6
5
0
0
ꢀ78
0
10
3
0
98
b
0
32
49
65
70
63
27
35
10
b
b
b
ꢀ78
0
3
5
ꢀ78
5
a Concentration of 3a was 2.5–4.6mM, and that of 3b was 1.2–1.5mM.
b Not determined, but must be small (less than 5% yield).

M. Fujita et al. / Tetrahedron Letters 45 (2004) 8023–8026
8025
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.tetlet.2004.09.002.
Scheme 4. Trapping of alkylideneallyl cation by methanol.
References and notes
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Although the major reaction of 3 with anhydrous HCl in
an aprotic solvent was the olefinic protonation leading
to the C1–C2 cleavage, the C2–C3 cleavage can also
be induced by HCl in a protic solvent. The reaction of
3a in methanol containing HCl (0.4M) at ambient tem-
perature gave 10 in 80% yield in 5min (Scheme 4). When
the reaction was carried out in CD3OD, deuterium was
incorporated at the vinylic position of 10, and 10 con-
tained the labeled methoxy CD3O group. This is consist-
ent with
a
reaction mechanism involving the
nucleophilic addition of methanol to I02a formed by the
proton-induced silyloxide elimination.20 The original
methoxy group must be removed during acid-induced
cleavage of the initially formed enol ether product.21
The selective nucleophilic addition at the sp2 position of
I02a agrees with the charge distribution of I02a,16,19 but is
in contrast to the chloride addition in the Lewis-acid-
mediated reaction.
In summary, alkylidenecyclopropanone silyl acetals
have been prepared for the first time, and the silyl acetal
functional group plays an important role in controlling
the regioselective cleavage of the three different C–C
bonds of the cyclopropane ring of 3. Compound 3 is a
good precursor of the alkylideneallyl cation.
Acknowledgments
We are very grateful to Professor Howard Maskill
(Newcastle upon Tyne) for reading the manuscript and
invaluable comments. This work is partially supported
by KAKENHI, and M.F. acknowledges financial sup-
port from JCCF Award in Synthetic Organic Chemistry,
Japan.
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M. Fujita et al. / Tetrahedron Letters 45 (2004) 8023–8026
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