A new route to alkenylcyclobutenes

Article abstract of DOI:10.1016/j.tetlet.2008.08.085

Reaction of titanium cyclobutylidene complexes, prepared by the desulfurizative titanation of 1,1-bis(phenylthio)cyclobutanes with Cp₂Ti[P(OEt)₃]₂, with alkynes gave 1-(alk-1-enyl)cyclobutenes.

Full text of DOI:10.1016/j.tetlet.2008.08.085

Tetrahedron Letters 49 (2008) 6426–6428
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A new route to alkenylcyclobutenes
*
Shigeki Oishi, Tomohiro Shono, Takehiro Nagasawa, Takafumi Inoue, Akira Tsubouchi, Takeshi Takeda
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of titanium cyclobutylidene complexes, prepared by the desulfurizative titanation of 1,1-
bis(phenylthio)cyclobutanes with Cp2Ti[P(OEt)3]2, with alkynes gave 1-(alk-1-enyl)cyclobutenes.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 11 July 2008
Revised 22 August 2008
Accepted 25 August 2008
Available online 28 August 2008
Keywords:
Alkenylcyclobutenes
Titanocene(II)
Alkynes
Carbene complexes
Alkenylcyclobutenes are interesting synthetic intermediates for
organic synthesis because of their unique structure and reactivity.
Especially, the Diels–Alder reaction using these compounds as
dienes has been investigated as a convenient tool for the prepara-
tion of benzocyclobutenes.1 A variety of methods for the prepara-
tion of alkenylcyclobutenes have been reported.1,2 They include,
for example, addition of vinylmagnesium bromide to cyclobuta-
none and subsequent dehydration,1a,d Pd(0)-catalyzed coupling
between 1-cyclobutenylmetals and alkenyl halides,2g decarboxyla-
R2
R2
Cp2Ti[P(OEt)3]2
SPh
SPh
5
2
R1
R1
R1
TiCp2
- Cp2Ti(SPh)2
4
3
R2
R1
TiCp2
R2
- Cp2Ti
R2
R2
6
1
tive dehydration of b,c-unsaturated d-hydroxy acids having a
Scheme 1.
cyclobutane substructure,2e Pt(II) chloride-catalyzed intramolecu-
lar cycloisomerization of allenynes,2j and the Grubbs II-catalyzed
1,5-enyne metathesis.2k All these reactions, however, suffer serious
limitations: they are only applicable to the preparation of specific
alkenylcyclobutenes, and the starting materials are not readily
accessible.
The treatment of the thioacetal 4a with 5 at room temperature
for 15 min in THF generated the carbene complex 3a, which was
further treated with the alkyne 2a at reflux for 2 h to produce
the alkenylcyclobutene 6a. The cyclobutene 6a was found to be
unstable under air, and gradually decomposed during workup.
The difficulty in isolation was overcome by the use of a trace
amount of hydroquinone as a stabilizing agent, and thus 6a was
isolated in 71% yield (Table 1, entry 1). The reaction was com-
pletely stereoselective: the substituents (R2) originated from the
alkyne 2a were found to be cis to each other. Similarly, the sym-
metrical alkyne 2b also gave the alkenylcyclobutene 6b in good
yield (entry 2).
Although the alkenylcyclobutene 6c was obtained by the reac-
tion of the alkyne 2c having ether linkages, the reaction of the
propargyl ether 2d predominantly gave the vinylvinylidenecyclo-
butane 7 along with a small amount of the alkenylcyclobutene 6
(entry 4). The formation of 7 is attributable to the preferential
elimination of an alkoxy group of the titanacyclobutene intermedi-
ate 8 prior to b-hydride elimination as depicted in Scheme 2.
Recently, we reported the first synthesis of titanacyclobutenes
with a spiro-bonded cyclopropane.3 It is of interest that these
strained titanacycles were thermally stable and could be isolated.
In connection with this study, we examined the preparation of
titanacyclobutenes having a cyclobutane substructure 1 by the
reaction of internal alkynes 2 with titanium cyclobutylidene com-
plexes 3, generated by the reductive titanation of cyclobutanone
diphenyl thioacetals 4 with the titanocene(II) reagent Cp2Ti-
[P(OEt)3]2 5.4 Unlike the titanacyclobutenes bearing a cyclopropane
ring, the spirocyclic titanacyclobutenes 1 were thermally unstable
and readily decomposed to produce alkenylcyclobutenes 6 through
the b-hydride elimination5 (Scheme 1).
* Corresponding author. Tel./fax: +81 42 388 7034.
E-mail address: takeda-t@cc.tuat.ac.jp (T. Takeda).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.085

S. Oishi et al. / Tetrahedron Letters 49 (2008) 6426–6428
6427
Table 1
Preparation of alkenylcyclobutenesa
Entry
1
Thioacetal 4
Alkyne 2
Alkenylcyclobutene 6b (Yield/%)c
SPh
6a (71)
6b (75)
SPh
2a
4a
Ph
Ph
O
Ph
2
3
4a
4a
4a
Ph
2b
Ph
O
Ph
6c (69)
7 (53)
O
Ph
Ph
Ph
O
2c
O
Ph
4d
O
O
Ph
2d
Ph
SPh
SPh
5
2b
2c
6d (89)
6e (69)
Ph
4b
O
Ph
O
Ph
6
4b
4b
Ph
Ph
7
Ph
6fe
2e
,
e
6f
79% (6f : 6f’ = 55 : 45)
SPh
SPh
Ph
8
9
2a
6g (67)
4c
Ph
Ph
Ph
4c
4c
2b
6h (91)
6i (81)
Ph
Ph
Ph
Ph
Ph
Ph
10
2f
a
All reactions were performed with a similar procedure as described in the text, unless otherwise noted.
The stereochemistry was determined by NOE experiment.
Isolated yield based on 2.
The reaction was carried out at 25 °C for 2 h.
The stereochemistry of both isomers was estimated by analogy with the other examples.
b
c
d
e
The titanium carbene complexes were also generated from the
6f and 6f0 (entry 7). These cyclobutenes were rather stable as com-
pared with the alkenylcyclobutenes with no alkyl substituent on
the cyclobutene ring. In contrast to the above results, no alkenyl-
cyclobutene was obtained when terminal alkynes, such as phenyl-
acetylene, were employed.
thioacetals of substituted cyclobutanones 4b and 4c, and their
reactions with alkynes 2 gave the alkenylcyclobutenes 6d–i (en-
tries 5–10).6 When the unsymmetrical alkyne 2e was employed,
the reaction produced an almost 1:1 mixture of the regioisomers

6428
S. Oishi et al. / Tetrahedron Letters 49 (2008) 6426–6428
W. J.; Lee, G. A. Tetrahedron Lett. 1983, 24, 241; (e) Doecke, C. W.; Garratt, P. J.;
(RO)Cp2Ti
Cp2Ti
OR
Shahriari-Zavareh, H.; Zahler, R. J. Org. Chem. 1984, 49, 1412.
2. (a) Park, J. D.; Frank, W. C. J. Org. Chem. 1964, 29, 1445; (b) Muramatsu, H.;
Inukai, K.; Ueda, T. J. Org. Chem. 1965, 30, 2546; (c) Hall, H. K., Jr.; Yancy, R. E., III
J. Org. Chem. 1974, 39, 2862; (d) Takeda, A.; Tsuboi, S.; Sakai, F.; Tanabe, M. J. Org.
Chem. 1974, 39, 3098; (e) Vogel, E.; Caravatti, G.; Franck, P.; Aristoff, P.; Moody,
C.; Becker, A.-M.; Felix, D.; Eschenmoser, A. Chem. Lett. 1987, 219; (f) Minami, T.;
Shikita, S.; So, S.; Nakayama, M.; Yamamoto, I. J. Org. Chem. 1988, 53, 2937; (g)
Negishi, E.; Liu, F.; Choueiry, D.; Mohamud, M. M.; Silveira, A., Jr.; Reeves, M. J.
Org. Chem. 1996, 61, 8325; (h) Liu, Y.; Sun, W.-H.; Nakajima, K.; Takahashi, T.
Chem. Commun. 1998, 1133; (i) Kasai, K.; Liu, Y.; Hara, R.; Takahashi, T. Chem.
Commun. 1998, 1989; (j) Matsuda, T.; Kadowaki, S.; Goya, T.; Murakami, M.
Synlett 2006, 575; (k) Debleds, O.; Campagne, J.-M. J. Am. Chem. Soc. 2008, 130,
1562.
(RO)Cp2Ti
OR
OR
or
OR
8
H2O
OR
7
Scheme 2.
3. Shono, T.; Nagasawa, T.; Tsubouchi, A.; Noguchi, K.; Takeda, T. Chem. Commun.
2008, 3537.
4. Fujiwara, T.; Iwasaki, N.; Takeda, T. Chem. Lett. 1998, 741.
5. Takeda, T.; Shimokawa, H.; Miyachi, Y.; Fujiwara, T. Chem. Commun. 1997, 1055.
In conclusion, we have established a new route to 1-(alk-1-
enyl)cyclobutenes utilizing diphenyl thioacetals of cyclobutanones
and alkynes. Since the starting materials are readily available, this
method enables us to prepare various alkenylcyclobutenes. Further
study on the unique reactivity of these strained unsaturated com-
pounds is currently underway.
6.
A typical experimental procedure is as follows: Magnesium turnings (33 mg,
1.4 mmol), finely powdered molecular sieves 4A (113 mg) and Cp2TiCl2 (280 mg,
1.1 mmol) were placed in a flask and dried by heating with a heating gun under
reduced pressure (2–3 mmHg). After cooling, THF (2.3 ml) and P(OEt)3 (0.39 ml,
2.3 mmol) were added successively with stirring at 25 °C under argon. After 3 h,
a THF (1.0 ml) solution of the thioacetal 4c (157 mg, 0.45 mmol) was added to
the mixture and stirring was continued for 15 min. After a THF (2.0 ml) solution
of 2f (53 mg, 0.30 mmol) was added dropwise over 10 min, the reaction mixture
was refluxed for 2 h. After cooling to room temperature, a few crystals of
hydroquinone were added to the mixture, and the reaction mixture was
quenched by the addition of 1 M NaOH. The insoluble materials were filtrated
off through Celite and washed with Et2O. The layers were separated, and the
aqueous layer was extracted with Et2O. After the combined organic extracts
were dried over Na2SO4 and the solvent was evaporated, the residue was
purified by silica gel column chromatography (eluted with hexane/AcOEt (98:2)
containing a trace amount of hydroquinone) to give 6i (75 mg, 81%); mp 126–
127 °C. 1H NMR d 2.65 (dd, J = 12.6, 1.9 Hz, 1H), 3.32 (dd, J = 12.7, 5.0 Hz, 1H),
3.93 (br d, 1H), 5.93 (s, 1H), 6.52 (s, 1H), 6.94–7.05 (m, 2H), 7.05–7.16 (m, 3H),
7.16–7.43 (m, 10H); 13C NMR d 38.1, 42.2, 126.2, 126.8, 126.99, 127.04, 127.3,
128.0, 128.3, 128.6, 129.2, 129.4, 133.0, 136.4, 137.2, 137.4, 143.8, 149.0; IR
(KBr) 3078, 3058, 3023, 2951, 2921, 2903, 1602, 1491, 1444, 1073, 1028, 938,
920, 841, 771, 760, 737, 712, 689 cmꢀ1. Anal. Calcd for C24H20: C, 93.46; H, 6.54.
Found: C, 93.09; H, 6.73.
Acknowledgments
This work was supported by Grant-in-Aid for Scientific Re-
search (No. 18350018) and Grant-in-Aid for Scientific Research
on Priority Areas ‘Advanced Molecular Transformations of Carbon
Resources’ (No. 19020016) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and notes
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W. J. Org. Chem. 1977, 42, 300; (c) Thummel, R. P.; Cravey, W. E.; Nutakul, W. J.
Org. Chem. 1978, 43, 2473; (d) Markgraf, J. H.; Greeno, E. W.; Miller, M. D.; Zaks,