Preparation of alkynylcyclopropanes by the titanocene(II)-promoted reaction of 1,1-bis(phenylthio)-2-alkynes with 1-alkenes

Article abstract of DOI:10.1016/S0040-4039(02)01134-6

The desulfurization of 1,1-bis(phenylthio)-2-alkynes with the titanocene(II) species Cp₂Ti[P(OEt)₃]₂ in the presence of 1-alkenes produced 1-alkyn-1-ylcyclopropanes in good yields.

Full text of DOI:10.1016/S0040-4039(02)01134-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5641–5644
Preparation of alkynylcyclopropanes by the
titanocene(II)-promoted reaction of 1,1-bis(phenylthio)-2-alkynes
with 1-alkenes
Takeshi Takeda,* Shuichi Kuroi, Kenjirou Yanai and Akira Tsubouchi
Department of Applied Chemistry, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Received 9 May 2002; accepted 7 June 2002
Abstract—The desulfurization of 1,1-bis(phenylthio)-2-alkynes with the titanocene(II) species Cp2Ti[P(OEt)3]2 in the presence of
1-alkenes produced 1-alkyn-1-ylcyclopropanes in good yields. © 2002 Elsevier Science Ltd. All rights reserved.
Vinylcyclopropanes are useful synthetic intermediates
and are easily transformed into cyclopentenes or dienes
by thermal-, transition-metal catalyzed-, or photo-iso-
merization.1 Therefore, synthetic routes to these com-
pounds have been extensively studied. Their
counterparts, alkynylcyclopropanes, are of interest as
synthetic intermediates2 and are found in structures of
certain biologically active substances.3 However, their
synthetic utility is largely restricted because of the
difficulty in preparing these compounds. Although sev-
eral reports on the synthesis of alkynylcyclopropanols4
and alkynylcyclopropanes possessing an additional
alkenyl5 or alkynyl6 substituent have appeared, only a
limited number of methods for the preparation of
unfunctionalized alkynylcyclopropanes have been
reported. For example, cyclopropylacetylene is pre-
pared from cyclopropyl methyl ketone via the forma-
tion of the corresponding gem-dichloride.7 The
cyclopropanation of pent-3-en-1-yne with diazo-
methane gives the corresponding alkynylcyclo-
propane.8 The yields of these reactions, however, were
not satisfactory for synthetic purposes. Synthesis of
various alkynylcyclopropanes by the thermal reaction
of tetrachlorocyclopropene with 1-alkenes and the suc-
cessive treatment of the resulting 1-chloro-1-
(trichlorovinyl)cyclopropanes with butyllithium and
electrophiles was studied by de Meijere and coworkers.9
During the course of our study on the desulfurization
of organosulfur compounds with titanocene(II) spe-
cies,10 we found that alkenylcyclopropanes were pro-
duced by treatment of thioacetals of a,b-unsaturated
aldehydes or 1,3-bis(phenylthio)-1-alkenes with the low-
valent titanium species Cp2Ti[P(OEt)3]2 1 in the pres-
ence of 1-alkenes.11 The organotitanium species formed
in the above reaction is assumed to be vinylcarbene
complexes of titanium. We further studied the prepara-
tion of analogous alkynylcarbene complexes from 1,1-
bis(phenylthio)-2-alkynes 2. In this communication, we
describe a facile method for the preparation of alkynyl-
cyclopropanes 3 by the titanocene(II) 1-promoted reac-
tion of 2 with terminal olefins 4 (Scheme 1).
Cp2Ti[P(OEt)3]2
SPh
R2
1
SPh
R1
R1
R2
2
3
4
Scheme 1.
OEt
PhSH / AlCl3
1) BuLi / THF-HMPA
2) R1X
OEt
OEt
2
OEt
THF
R1
Scheme 2.
Keywords: cyclopropanation; olefins; organosulfur compounds; titanocene(II).
* Corresponding author. Tel.: +81 42 388 7034; fax: +81 42 388 7034; e-mail: takeda-t@cc.tuat.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01134-6

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T. Takeda et al. / Tetrahedron Letters 43 (2002) 5641–5644
The starting materials 2 were prepared by the reaction
of the lithium salt of propiolaldehyde diethyl acetal
(BuLi; 1.1 equiv./THF-HMPA/−78°C/0.7–1.5 h) with
appropriate alkylating agents (1.1 equiv.) (−78°C–room
temperature/overnight, Ph(CH2)3Br; 87%, CH3-
(CH2)3OTs; 76%, CH3I; 71%) and the treatment of
Table 1. Preparation of alkynylcyclopropanesa
4
Temp
/ °C
2
Time
/ h
Product 3
(Yield / %; Ratio of stereoisomersb)
Entry
1c
(equiv)
SPh
SPh
Ph
0
3
Ph
Ph
Ph
3a (27; >99 : 1)
4a (2)
2a
Ph
Ph
5 (16; >99 : 1)
2c
3
4a (4)
4a (4)
3a (54; >99 : 1)
3a (65; >99 : 1)
2
25
25
2a
2a
3.5
Ph
4
2a
2a
25
25
3.5
3.5
Ph
Ph
4b(8)
3b (59; 68 : 32)
5
Ph
3c (58; 63 : 42)
4c (8)
4d (8)
6
2a
2a
25
3.5
Ph
3d (65; 60 : 40)
7d
25 / reflux
3 / 0.5
Ph
3e (56)
4e
SPh
SPh
Ph
4a (4)
25
25
3.5
3.5
8
3f (73; >99 : 1)
2b
2b
Ph
9c
4b (8)
3g (65; 60 : 40)
3g (77; 57 : 43)
4b (8)
4b (8)
2b
25
25
3.5
3.5
10
SPh
SPh
Ph
11c
2c
3h (58; 57 : 43)
3h (70; 56 : 44)
4b (8)
2c
25
3.5
12
aAll reactions were performed by a similar procedure as described in the text, unless otherwise noted.
bDetermined by NMR analysis.
cCarried out in the absence of additional triethyl phosphite.
dThe titanocene(II) species prepared in the presence of an equimolar amount of triethyl phosphite under ethylene
was used.
Cp2Ti
1 (2 equiv)
4
TiCp2
R2
2
3
R1
- Cp2Ti(SPh)2
- Cp2Ti
6
7
R1
Scheme 3.

T. Takeda et al. / Tetrahedron Letters 43 (2002) 5641–5644
5643
titanocene(II) species. The cyclopropane 3 would be
produced by the formation of titanacyclobutane 7 with
terminal olefin and the subsequent reductive elimina-
tion (Scheme 3).
the alkylated acetals with thiophenol (2.2 equiv.) in the
presence of aluminum chloride (2.2 equiv.) (THF/0°C–
room temperature/2 days, 2a; 70%, 2b; 72%, 2c; 97%)
(Scheme 2). When the thioacetal 2a was treated with
the low-valent titanium reagent 1 (2 equiv.) in the
presence of styrene (4a) (2 equiv.) at 0°C for 3 h, the
alkynylcyclopropane 3a was produced in 27% yield
(Table 1, entry 1). The major byproduct isolated was
the cis-alkenylcyclopropane 5, which would be pro-
duced by the further reduction of 3a with 1 via the
formation of titanacyclopropene.12 The formation of 5
was absolutely suppressed and 3a was obtained in 54%
yield by use of higher reaction temperature (entry 2). It
was found that the yield of 3a was increased when the
reaction was carried out in the presence of additional 4
equiv. of triethyl phosphite (entry 3).
Since the starting materials 2 are readily available, this
reaction provides a practical way for the synthesis of
different alkynylcyclopropanes. Further study on the
reaction of titanium–alkynylcarbene complexes is cur-
rently underway.
Acknowledgements
This research was supported by a Grant-in-Aid for
Scientific Research (No. 14340228) and a Grant-in-Aid
for Scientific Research on Priority Areas (A) ‘‘Exploita-
tion of Multi-Element Cyclic Molecules’’ (No.
14044022) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
In a similar manner, the reactions of several unsatu-
rated thioacetals 2 with terminal olefins 4 were per-
formed, and the alkynylcyclopropanes 3 were produced
in good yields using excess triethyl phosphite (see
entries 9, 10, 11, and 12). The cyclopropanes 3 were
obtained as single isomers by the reactions using sty-
rene,13 whereas mixtures of stereoisomers were pro-
duced in all the other cases examined. The
alkynylcyclopropane 3e possessing no substituent on
the cyclopropane ring was produced only in poor yield
under the reaction conditions described above. How-
ever, 3e was obtained in moderate yield when the
reaction was carried out at 25°C and then at reflux
using the titanocene(II) reagent prepared by the reduc-
tion of titanocene dichloride with magnesium in the
presence of an equimolar amount of triethyl phosphite
under ethylene (entry 7).
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The typical experimental procedure is as follows: Mag-
nesium turnings (24 mg, 1 mmol; purchased from
Nacalai Tesque Inc. Kyoto, Japan) and finely powdered
,
molecular sieves 4 A (100 mg) were placed in a flask
and dried by heating with a heat gun under reduced
pressure (2–3 mmHg). After the mixture was stirred for
15 h under argon at room temperature, Cp2TiCl2 (249
mg, 1 mmol) was added to the mixture and dried by
heating under reduced pressure. After cooling, THF (2
ml), P(OEt)3 (0.69 ml, 4 mmol), and 4a (0.23 ml, 2
mmol) were added successively with stirring at 25°C
under argon. After 3 h, 2a (187 mg, 0.5 mmol) in THF
(1.5 ml) was added to the mixture, and stirring was
continued for 3.5 h. The reaction was quenched by
addition of 1 M NaOH (10 ml), and the resulting
insoluble materials were filtered off through Celite and
washed with ether (10 ml). The organic materials were
extracted with ether (3×30 ml), and the extract was
dried (Na2SO4). After removal of the solvent, the
residue was purified by PTLC (hexane:AcOEt=98:2) to
give 3a (85 mg, 65%).
Although we have no corroborating evidence for the
reaction pathway, we tentatively assume that the
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by the desulfurization of the thioacetal 2 with the
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