Transformation of thioacetals to cyclopropanes

Article abstract of DOI:10.1016/j.tetlet.2004.12.017

Cyclopropanes were obtained by the titanocene(II)-promoted reaction of thioacetals with vinyl pivalate. It was also found that vinycyclopropanes were produced by a similar treatment of thioacetals with the titanocene(II) species in the presence of 1,3-dienes.

Full text of DOI:10.1016/j.tetlet.2004.12.017

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 775–778
Transformation of thioacetals to cyclopropanes
*
Takeshi Takeda, Koutaro Arai, Hirohisa Shimokawa and Akira Tsubouchi
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Received 15 November 2004;revised 3 December 2004;accepted 6 December 2004
Available online 18 December 2004
Abstract—Cyclopropanes were obtained by the titanocene(II)-promoted reaction of thioacetals with vinyl pivalate. It was also
found that vinycyclopropanes were produced by a similar treatment of thioacetals with the titanocene(II) species in the presence
of 1,3-dienes.
Ó 2004 Elsevier Ltd. All rights reserved.
Small ring compounds such as cyclopropanes are useful
synthetic intermediates because of their ring-opening
and ring-enlargement reactions using their strain re-
1
leases as driving forces. Therefore a variety of methods
2
have been developed for their preparation. We found
that alkenylcyclopropanes were produced by the reac-
tion of terminal olefins with titanium alkenylcarbene
complexes generated by the treatment of b,c-unsatu-
rated thioacetals or 1,3-bis(phenylthio)-1-alkenes with
Scheme 1.
3
the titanocene(II) species Cp Ti[P(OEt) ] (1). A similar
2
3 2
cyclopropanation also proceeds with alkynylcarbene
4
complexes. In contrast to the reactions of alkenyl-
Two types of side reactions are probable in the above
cyclopropanation (Scheme 2). The first one is a metath-
esis-type degradation of the titanacycle 5 giving a termi-
and alkynyl-carbene complexes, the major reaction of
titanocene alkylidene complexes 2, prepared from satu-
rated thioacetals 3, with terminal olefins is olefin metath-
5
nal olefin 8. If the regioisomeric titanacycle 9 is
5
esis and no cyclopropane derivative is obtained.
produced, its b-elimination affords a terminal olefin 10
with two-carbon homologation via the allyltitanium spe-
cies 11. Therefore we anticipated that the choice of the
leaving group (X) was of crucial importance for the
selective formation of the cyclopropanes 7.
The transformation of thioacetals into cyclopropanes is
of great value as a reductive cyclopropanation of syn-
thetic equivalents of aldehydes. In order to substantiate
such transformation, we examined the reaction of the
titanocene-alkylidenes 2 with heteroatom-substituted
olefins 4. Our approach is outlined in Scheme 1;forma-
tion of the titanacyclobutane intermediate 5 and subse-
We initially examined the titanocene(II)-promoted reac-
tion of the thioacetal 3a with various heteroatom-substi-
tuted olefins 4 (Table 1). The reactions of 3a with phenyl
vinyl sulfone 4a and tert-butyl vinyl ether 4b exclusively
produced the terminal olefin with one-carbon homolo-
gation 8a via the metathesis-type degradation of the
titanacyclobutane 5. Although the cyclopropane 7a
was obtained in moderate yield by the use of vinyl bro-
mide 4c, a substantial amount of the terminal olefin 10a
was produced as a by-product. The reaction of 3a with
vinyl acetate 4d also gave the cyclopropane 7a along
with the vinyl ether, 4-benzyl-2-ethenyloxy-5-phenyl-
pent-2-ene, which was formed by the olefination of the
quent
intramolecular
substitution
afford
the
cyclopropyltitanocene 6, which is then hydrolyzed to
produce a cyclopropane 7.
Keywords: Cyclopropanation;Titanocene(II) reagent;Thioacetals;
Vinyl pivalate;1,3-Dienes.
*
Corresponding author. Tel./fax: +81 42 388 7034;e-mail: takeda-t@
cc.tuat.ac.jp
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.12.017

776
T. Takeda et al. / Tetrahedron Letters 46 (2005) 775–778
Scheme 2.
Table 1. Titanocene(II)-promoted reaction of the thioacetal 3a with
a
heteroatom-substituted olefins 4
(120 mg) were placed in a flask and dried by heating
with a heat gun under reduced pressure (2–3 mmHg).
After cooling, THF (2 mL) and P(OEt)3 (0.41 mL,
Entry
4
X
Time (h)
Product/yield (%)
2
2
.4 mmol) were added successively with stirring at
5 °C under argon. After 3 h, 3a (128 mg, 0.3 mmol) in
7
a
8a
10a
1
2
3
4a
4b
4c
4d
4e
4e
SO
t
2
Ph
2
Overnight
—
—
45
34
60
76
45
46
—
—
—
—
—
7
O Bu
Br
OCOMe
2
2
2
2
15
3
a
b
Table 2. Cyclopropanation of thioacetals 3
4
t
5
OCO Bu
t
OCO Bu
2
Entry
Thioacetal 3
Cyclopropane 7 (yield/%)
c
6
2
a
All reactions were carried out using 1 (3 equiv) and 4 (3 equiv) at
1
25 °C.
b
c
4
4
-Benzyl-2-ethenyloxy-5-phenylpent-2-ene was obtained in 27% yield.
equiv of 1 were used.
b
3a
7a (76)
c
6
2
ester carbonyl. In order to suppress the carbonyl olefin-
ation, we employed commercially available vinyl piva-
late 4e and found that the cyclopropane 7a was
selectively produced in 60% yield. The yield was further
increased by increase of the titanocene(II) reagent to
accelerate the desulfurization of the thioacetal 3a.
3b
3c
3d
7b (71)
7c (72)
7d (73)
7e (49)
7f (60)
3
4
5
6
In a similar fashion, the titanocene(II)-promoted reac-
tion of various thioacetals 3 with vinyl pivalate 4e was
performed and the corresponding cyclopropanes 7 were
obtained. As shown in Table 2, the yield of 7 is depen-
dent on the steric bulkiness of the thioacetal employed.
The reaction of the thioacetals 3 possessing an a-substi-
tuent gave the cyclopropanes 7 in good yields. The use
of less hindered thioacetals, however, led to the decrease
of the yields of 7 due to the concomitant formation of
the terminal olefin 10. In such cases, the pure cyclopro-
pane was isolated after treatment of a crude product
mixture with MCPBA. These results imply that the reg-
ioselectivity of the titanacycle formation (5 vs 9) is deter-
mined by the extent of the steric repulsion between the
substituent of the carbene complex (R) and pivaloyloxyl
group of 4e.
3
3
e
f
In order to confirm the proposed pathway for the for-
mation of the cyclopropanes 7, the reaction of 3a with
vinyl pivalate 4e was quenched with D O, and the
2
trans-deuterated cyclopropane 12 (85% deuterium incor-
7
poration) was isolated in 72% yield (Scheme 3). The
formation of 12 indicates that the reaction proceeds
via the formation of the cyclopropyltitanocene interme-
diate 6 as expected.
7
8
3
3
g
h
7g (46)
7h (43)
a
b
c
All the reactions were performed with a similar procedure as
described in the text, unless otherwise noted.
Obtained as a mixture of 7a and 10a. The yield was determined by
NMR analysis.
The typical experimental procedure is as follows: Mag-
nesium turnings (32 mg, 1.3 mmol;purchased from Nac-
alai Tesque Inc. Kyoto, Japan), Cp TiCl (299 mg,
2
2
1
.2 mmol), and finely powdered molecular sieves 4 A
3.5 equiv of 1 were used.

T. Takeda et al. / Tetrahedron Letters 46 (2005) 775–778
777
be formed by the reaction of titanocene-alkylidenes 2
with 14 (Scheme 4). As expected, the treatment of thio-
acetals 3 with titanocene(II) reagent 1 in the presence of
1
,3-butadiene 14a or isoprene 14b gave the vinylcyclo-
8
propanes 13 as single stereoisomers (Table 3). The
NOE measurement of 13b indicated that it had trans-
configuration.
Scheme 3.
9
THF (1 mL) was added and the mixture was stirred for
1
Takai et al. reported the preparation of cyclopropylsil-
anes by the chromium(II)-promoted reaction of
0 min. After addition of 4e (0.13 mL, 0.9 mmol), stir-
ring was continued for 2 h. The reaction was quenched
by addition of 1 M NaOH, and the insoluble materials
were filtered off through Celite and washed with ether.
The organic materials were extracted with ether, and
the extract was dried (Na SO ). After removal of the
1
0
diiodomethyltrimethylsilane with terminal olefins.
Recently the low-valent titanium-mediated reaction of
the silane with 1,3-dienes giving (2-vinylcyclopropyl)sil-
1
1
anes was also reported. These reactions are suggested
to proceed via the formation of metallacyclobutane
intermediate and subsequent reductive elimination simi-
larly to the above cyclopropanation of dienes with thio-
acetals 3.
2
4
solvent, the residue was purified by PTLC (hexane–
AcOEt = 99:1) to give a mixture of 7a and 10a
(55 mg). The yield of 7a (76%) was determined by
NMR analysis.
Since aldehydes are easily converted to thioacetals, the
titanocene(II)-promoted reactions of thioacetals with
vinyl pivalate and 1,3-dienes provide convenient tools
for the transformation of aldehydes to cyclopropanes.
The transformation of thioacetals 3 into vinylcyclopro-
panes 13 was also achieved by their treatment with the
titanocene(II) reagent 1 in the presence of conjugated
dienes 14. As noted above, alkenylcyclopropanes were
produced by the reaction of alkenylcarbene complexes
3
with terminal olefins. Since it was assumed that the
Acknowledgements
cyclopropanation proceeds through the reductive elimi-
nation of 2-alkenyltitanacyclobutane, we anticipated
that the similar titanacyclobutane intermediate 15 would
This research was supported by a Grant-in-Aid for Sci-
entific Research (No. 14340228) from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan. This work was carried out under the 21st
Century COE program of ÔFuture Nano-materialsÕ in
Tokyo University of Agriculture and Technology.
a
Table 3. Transformation of thioacetals 3 to vinylcyclopropanes 13
Entry
Thioacetal 3
Diene 14
Vinylcyclopropane
1
3 (yield/%)
1
3a
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4a
4b
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Scheme 4.

778
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4
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˚
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(128 mg, 0.3 mmol) in THF (1 mL) was added to the
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3
5
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1
3
) spectral data for 13b: d 0.20
(ddd, J = 8.6, 5.0, 5.0 Hz, 1H), 0.56 (ddd, J = 8.6, 4.6,
4.6 Hz, 1H), 0.65–0.78 (m, 1H), 0.96 (ddd, J = 8.4, 4.6,
4.6 Hz, 1H), 1.25–1.40 (m, 1H), 1.48 (s, 3H), 2.66 (dd,
J = 6.2, 3.3 Hz, 4 H), 4.47 (s, 1H), 4.56 (s, 1H), 7.10–7.30
(m, 10H).
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6
7
8
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