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
present reaction proceeds via the initial formation of an
unprecedented alkynylcarbene complex of titanium 6
by the desulfurization of the thioacetal 2 with the
10. (a) Takeda, T.; Fujiwara, T. J. Synth. Org. Chem. Jpn.
1998, 56, 1048; (b) Takeda, T.; Fujiwara, T. Rev. Het-
eroatom Chem. 1999, 21, 93.
Takeda, Takeshi
