Titanocene(II)-promoted cyclization of unsaturated thioacetals

Article abstract of DOI:10.1055/s-1999-2618

The low-valent titanium species-promoted transformation of unsaturated thioacetals to cyclic compounds was studied. The cyclization of thioacetals having an olefin moiety proceeded with the loss of terminal olefin carbon to produce the corresponding five-

Full text of DOI:10.1055/s-1999-2618

354
LETTER
Titanocene(II)-Promoted Cyclization of Unsaturated Thioacetals
Tooru Fujiwara, Takeshi Takeda*
Department of Applied Chemistry, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Fax 81 42 388 7034; E-mail: takeda-t@cc.tuat.ac.jp
Received 5 January 1999
Abstract: The low-valent titanium species-promoted transforma-
tion of unsaturated thioacetals to cyclic compounds was studied.
The cyclization of thioacetals having an olefin moiety proceeded
with the loss of terminal olefin carbon to produce the corresponding
five-, six-, and seven-membered cycloalkenes when they were treat-
ed with the low-valent titanium species Cp2Ti[P(OEt)3]2 in reflux-
ing THF. The similar reactions of 1-[3,3-bis(phenylthio)propoxy]-
2-(prop-1- and prop-2-enyl)benzenes gave the seven- and eight-
membered unsaturated cyclic ethers, respectively.
Key words: titanocene(II), thioacetal, cyclization, ring-closing
metathesis
Construction of cyclic molecules is of fundamental im-
Scheme 1
portance in organic synthesis, and many carbon-carbon
bond forming reactions have been employed for this pur-
pose. The transition metal catalyzed ring-closing metathe-
sis (RCM) of dienes is a useful method for the preparation
of various cyclic compounds.1 Molybdenum,2 tungsten,3
and rhenium4 complexes have been employed as catalysts
for such transformations. Since the discovery of Grubbs’
catalysts,5 syntheses of complex molecules by the rutheni-
um alkylidene-catalyzed RCM of dienes have been exten-
sively studied.6 As for the titanium methylidene-promoted
RCM, Nicolaou et al. recently reported the preparation of
cyclic ethers from unsaturated esters using the Tebbe or
Petasis reagent, in which the alkylidenetitanium having a
terminal vinyl ether moiety was suggested as an interme-
diate.7
The treatment of unsaturated thioacetal 2a with the ti-
tanocene(II) species 1 (4 equiv) in THF at room tempera-
ture for 17 h afforded the cyclopentene 5a in 14% yield
along with the methylcyclopentane 7a and methylenecy-
clopentane 8 (entry 1, Table 1). Unlike the intermolecular
reaction,9c the metathesis proceeded selectively to pro-
duce cyclopentene 5a in 71% yield as the sole product
when the reaction mixture was refluxed for 1 h after the
treatment of 2a with 1 at room temperature for 2 h (entry
2). Under similar reaction conditions, the cyclization of
the methyl group substituted homologues of 2a was stud-
ied. The unsaturated thioacetals having a 1,2-disubstituted
olefin moiety 2b also produced the cyclopentene 5a in
comparable yield (entry 3). In contrast to these results,
only 8% of 5a was produced from the thioacetal having a
trisubstituted double bond 2c. On the other hand, the reac-
tion by which a trisubstituted olefin was formed proceed-
ed smoothly giving the cyclopentene 5b in high yield
(entry 5).10
Recently we found that alkylidenetitanocenes or their
equivalents are easily formed by the desulfurization of
thioacetals with a low-valent titanium reagent 1. These ac-
tive species react with organic molecules having a carbon-
oxygen8 or carbon-carbon multiple bond.9 For example,
their reaction with trialkylallylsilanes affords the metathe-
sis products, g-substituted allylsilanes, along with the ho-
moallylsilanes which would be formed by the β-hydride
elimination from the intermediary titanacycle.9c Since
these findings clearly showed the potential synthetic util-
ity of thioacetals as starting materials for RCM, we have
studied the preparation of cycloalkenes from thioacetals
having an olefin moiety. Our new process consists of the
formation of titanium carbene complex 3 by the treatment
of unsaturated thioacetal 2 with the low-valent titanium 1,
its intramolecular reaction with the double bond to form
titanacyclobutane 4, and the subsequent elimination of the
alkylidenetitanocene 6 (Scheme 1). We also describe in
this paper the application of this method for the construc-
tion of unsaturated oxygen heterocycles.
In order to probe the intermediary of this reaction, the un-
saturated thioacetal 2b was treated with 1 for 2 h at room
temperature and then the reaction was quenched with D2O
(Scheme 2). The formation of dideuterio compound 7b
suggests that the present reaction proceeds via the titana-
cyclobutane intermediate 4. Taking into account the reac-
tion pathway depicted in Scheme 1, the substituent effect
of methyl groups observed in the above reactions of 2a, b,
and d is explained by the extent of the retrograde reaction
between the cycloalkene 5 and the alkylidenetitanocene 6.
In the case of 2c, the steric repulsion between the two ter-
minal methyl substituents of 2c and Cp rings on titanium
makes the formation of titanacycle 4 unfavorable.
Synlett 1999, No. 3, 354–356 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Titanocene(II)-Promoted Cyclization of Unsaturated Thioacetals
355
Scheme 2
Next we examined the reactions of the unsaturated thioac-
etals having a longer carbon chain 2f-g and found that the
corresponding six- and seven-membered rings were also
obtained in good yields. Similarly to the preparation of cy-
clopentenes, the trisubstituted olefins 5e and g were pro-
duced in better yields than their unsubstituted congeners
(entries 8 and 10).
Since a diphenyl thioacetal moiety is easily introduced to
organic molecules by alkylation of bis(phenylthio)meth-
ane or treatment of carbonyls with thiophenol, it is clear
that the low-valent titanium reagent promoted cyclization
of unsaturated thioacetals is a strong synthetic tool for the
construction of a variety of cyclic compounds including
heterocycles. This idea was substantiated when the
2-allyl- and 2-(prop-1-enyl)phenyl ethers 2j-l were treated
with the titanocene(II) species 1. As shown in Table 1, the
seven- and eight-membered unsaturated cyclic ethers 5h-
j were obtained in good yields. In the case of the allylben-
zene derivative 2l, the initial product 5j partially isomer-
ized to the conjugated olefin 8 when a large excess of 1
was used (see entries 13 and 14).
In summary, we have developed an intramolecular met-
athesis of titanium carbene complexes formed from unsat-
urated thioacetals. The further application of this new
methodology to the preparation of various types of carbo-
and hetero-cycles is now under investigation.
Acknowledgement
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Area No. 10125209 from the Minis-
try of Education, Science, Sports, and Culture, Japan.
References and Notes
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T. Fujiwara, T. Takeda
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Synlett 1999, No. 3, 354–356 ISSN 0936-5214 © Thieme Stuttgart · New York