Formation of titanacyclobutenes with a spiro-bonded cyclopropane

Article abstract of DOI:10.1039/b804930k

The reaction of titanium cyclopropylidene complexes, prepared by the reductive titanation of 7,7-dichlorobicyclo[4.1.0]heptanes, with alkynes produced air and moisture stable titanacyclobutenes with a spiro-bonded cyclopropane. The Royal Society of Chemistry.

Full text of DOI:10.1039/b804930k

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Formation of titanacyclobutenes with a spiro-bonded cyclopropanew
Tomohiro Shono,a Takehiro Nagasawa,a Akira Tsubouchi,a Keiichi Noguchib
and Takeshi Takeda*a
Received (in Cambridge, UK) 25th March 2008, Accepted 24th April 2008
First published as an Advance Article on the web 30th May 2008
DOI: 10.1039/b804930k
The reaction of titanium cyclopropylidene complexes, prepared
by the reductive titanation of 7,7-dichlorobicyclo[4.1.0]heptanes,
with alkynes produced air and moisture stable titanacyclo-
butenes with a spiro-bonded cyclopropane.
Metallacycles fused with a small ring are an interesting class of
Scheme 2
compounds because of their unique structure and reactivity. A
variety of metallacycles with spiro-bonded cyclopropane rings
have been prepared by the reaction of alkylidenecyclopro-
panes, transition metal complexes and unsaturated com-
pounds, such as alkenes and alkynes.1 However, the
preparation of metallacyclobutenes linked to a cyclopropane
in a spirocyclic manner has not been reported, and hence their
reactivity and stability are not yet known.
4a was confirmed by an X-ray diffraction study, as shown in
Fig. 1.3 The stereochemistry of 4a indicates that the cis-fused
cyclohexane ring shields the most reactive allylic carbon–
titanium bond of 4a. The molecular structure of 4a also
suggests that the titanacycles 4 would be formed through the
approach of alkynes from the less sterically-hindered side of
cyclopropylidene complexes 1.
Recently, we reported that titanium cyclopropylidene com-
plexes 1 are readily prepared by the reductive titanation of 1,1-
Hydrolysis of the isolated titanacyclobutenes 4a–c produced
synthetically useful alkenylcyclopropanes 6a–c as single iso-
mers in good yields (Table 1). The stereochemistry of titana-
dichlorocyclopropanes
2 with the titanocene(II) reagent
Cp2Ti[P(OEt)3]2 (3).2 This finding prompted us to investigate
the preparation of spirocyclic organotitanium compounds 4
by the reaction of 1 with alkynes 5 (Scheme 1).
cyclobutenes
4
are integrally reflected in those of
alkenylcyclopropanes 6. The two substituents (R3) originating
from the alkynes were found to be cis to each other. In
addition, the NOE experiments of 6a and 6b indicated that
the alkenyl group of the cyclopropane ring was trans with
respect to the six-membered ring. Therefore, the protonation
of 4 should proceed with the retention of stereochemistry of
the carbon–carbon double bond and the cyclopropane ring.
Treatment of the titanium cyclopropylidene complex 1a,
prepared by the reductive titanation of 7,7-dichlorobicy-
clo[4.1.0]heptane (2a) with the titanocene(II) reagent 3, with
diphenylacetylene (5a) gave spirocyclic titanacyclobutene 4a
as an air and moisture stable brownish-red solid (Scheme 2).z
The titanacyclobutenes having a bicyclo[4.1.0]heptane moiety,
4b and 4c, were also found to be unsusceptible to air and
moisture, and could be isolated. The titanacyclobutenes 4
(R2 = H) having a substituent on their cyclopropane ring
were, however, unstable under atmospheric circumstances,
and gradually hydrolyzed during isolation. The structure of
Scheme 1
a Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, Koganei, Tokyo
184-8588, Japan. E-mail: takeda-t@cc.tuat.ac.jp;
Fax: +81 42 388 7034; Tel: +81 42 388 7034
b Instrumentation Analysis Center, Tokyo University of Agriculture
and Technology, Koganei, Tokyo 184-8588, Japan
w Electronic supplementary information (ESI) available: Experimental
procedure for the hydrolysis of 4 and characterization data for all
compounds.
Fig. 1 Molecular structure of titanacyclobutene 4a. Principal bond
lengths (A) and angles (1): Ti1–C1 2.130(3), Ti1–C3 2.100(3), C1–C2
1.543(4), C2–C3 1.339(4); C1–Ti1–C3 71.22(12), C2–C1–Ti1
82.62(18), C1–C2–C3 117.3(3), C2–C3–Ti1 88.7(2).
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Table 1 Hydrolysis of titanacyclobutenes 4a
Table 2 Formation of alkenylcyclopropanes 6a
Entry
1
4
Product 6
Yield (%)
68
Entry
1c
2
5
Product 6
Yield (%)b
4a
Z-6a
Z-6b
E-6cb
2a 5a
E-6a (78)
2
3
4b
4c
67
86
Z-6a (trace)
2
2b 5a
E-6b (36)
Z-6b (39)
a
b
Carried out in 1 M NaOH/THF (1 : 1) under reflux for 3 h. Single
cis/trans isomer. The stereochemistry was not determined.
Alkenylcyclopropanes 6 were also obtained along with trace
amounts of by-products (alkylidenecyclopropanes 7) by the
in situ hydrolysis of titanacyclobutenes 4 without isolation
(Scheme 3). Thus, the reaction of 2a with 5b afforded the
alkenylcyclopropane 6c after an aqueous work-up (Table 2,
entry 3). Similar treatment of carbene complexes 1, generated
from several 1,1-dichlorocyclopropanes 2, with symmetrical
alkynes 5 produced alkenylcyclopropanes 6. Although no
regioselectivity was observed in the reaction of unsymmetrical
internal alkynes, the reaction of terminal alkynes proceeded
with good regioselectivity; for example, the reaction of 2a with
para-methoxyphenylacetylene (5d) gave 6g in 64% yield with a
small amount of its regioisomer 6g0 (Scheme 4). As shown in
Table 2, entries 3–6, the stereochemistry of 6, formed by the
reaction with aliphatic alkynes, is the same as that obtained by
the hydrolysis of isolated 4a–c. On the contrary, the reaction
with 5a gave either the E-isomer predominantly or a mixture
of the two stereoisomers (Table 2, entries 1 and 2). The
inversion of the double bond geometry of 6a and 6b, obtained
by the in situ hydrolysis, was associated with the inversion of
stereochemistry of the cyclopropane ring; E-6a and 6b were
proved to have a cis-configuration.
3
4
5
2a 5b
E-6c (74)d,e
2b 5b
E-6d (69)
2c 5b
E-6e (62)d,e
6
2d 5c
E-6f (46)f
a
All the reactions were performed using a similar procedure, as
It was suspected that the formation of E-6a and 6b by the
in situ hydrolysis of 4a and 4b was attributable to the action of
certain low-valent titanium species. Next, the hydrolysis of 4a
was examined in the presence of titanocene(II) species 3. After
4a was mixed with 3 in THF at 25 1C, the mixture was treated
with 1 M NaOH (Scheme 5). As expected, E-6a was exclusively
produced in 79% yield. This result clearly shows that the
formation of E-6a and 6b is due to the reaction of 4a with low-
b
c
described in ref. 4. Based on the alkyne 5 used. Carried out using
d
7 equiv. of 3. Single cis/trans isomer. The stereochemistry was not
e
determined. Contaminated with a trace amount of the alkylidene-
f
cyclopropane 7. The yield was corrected for the contaminant. trans :
cis = 89 : 11.
valent titanium species during the hydrolysis, though the
detailed reaction pathway is not clear at present.
In conclusion, we have demonstrated that titanacyclobu-
tenes having a spiro-bonded cyclopropane were produced by
the successive treatment of 1,1-dichlorocyclopropanes with a
titanocene(II) reagent and alkynes. Alkenylcyclopropanes are
useful intermediates in various organic transformations, such
as the magnification to cyclopentenes,5 and [5+2],6,7
[5+2+1]7,8 and [5+1+2+1] cycloadditions.9 Our procedure
Scheme 3
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0.30 ꢁ 0.05 mm3, monoclinic, P21/c, a = 8.3434(2), b =
15.5514(3), c = 17.7460(3) A, b = 100.736(1)1, V = 2262.26(7)
A3, Z = 4, T = 98 K, D = 1.323 g cmꢂ3, m(Cu-Ka) = 3.308
mmꢂ1, Rint = 0.0817, number of measured/independent reflec-
tions = 30475/4083, R = 0.0705 and wR = 0.1786 (all data).
CCDC 678446. For crystallographic data in CIF or other electro-
nic format see DOI: 10.1039/b804930k.
for the preparation of alkenylcyclopropanes is versatile and
may have wide applications, because a variety of the starting
materials are readily available through the dichlorocyclopro-
panation of alkenes with CHCl3–NaOH.10
This work was supported by a Grant-in-Aid for Scientific
Research (no. 18350018) and a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Transfor-
mations of Carbon Resources’’ (no. 19020016) from the
Ministry of Education, Culture, Sports, Science and
Technology, Japan.
4. A representative experimental procedure for the preparation of
alkenylcyclopropanes: A THF (2 cm3) solution of 2a (124 mg, 0.75
mmol) was added to a THF (3.6 cm3) solution of 3 (prepared from
magnesium turnings (44 mg, 1.8 mmol), Cp2TiCl2 (448 mg, 1.8
mmol) and P(OEt)3 (0.62 cm3, 3.6 mmol) in the presence of
molecular sieves 4A (180 mg)) at 25 1C. After the reaction mixture
had been stirred for 10 min, a THF (1 cm3) solution of 5b (79 mg,
0.3 mmol) was added, and the reaction mixture was refluxed for
5 h. After being cooled to room temperature, the reaction was
quenched by the addition of 1 M NaOH (20 cm3). The insoluble
materials were filtered off through Celite and washed with ether
(40 cm3). The layers were separated, and the aqueous layer was
extracted with ether (2 ꢁ 20 cm3). The combined organic
extracts were dried over Na2SO4. After removal of the solvent
under a reduced pressure, the residue was purified by PTLC
(hexane) to give a mixture of E-6c and 7-[5-phenyl-1-(3-phenyl-
propyl)pentylidene]bicyclo[4.1.0]heptane (7a) (84 mg; E-6c: 74%,
7a: 5%).
Notes and references
z A representative experimental procedure for the isolation of titana-
cyclobutenes: To a dry flask charged with finely powdered molecular
sieves 4A (1.00 g), magnesium turnings (0.243 g, 10.0 mmol) and
Cp2TiCl2 (2.49 g, 10.0 mmol) were added THF (20 cm3) and P(OEt)3
(3.43 cm3, 20.0 mmol), successively, with stirring, at 25 1C, under
argon. After 3 h, a THF (2 cm3) solution of 2a (0.660 g, 4.0 mmol) was
added to the reaction mixture, which was then stirred for a further 10
min. Then, a THF (2 cm3) solution of 5a (0.357 g, 2.0 mmol) was
added, and the reaction mixture was stirred for a further 16 h. After
filtration through a glass filter, the filtrate was chromatographed over
alumina gel (20 g, eluted with hexane (40 cm3)). The eluate was
evaporated to dryness in vacuo, giving a brownish-red solid. After
the solid had been washed with hexane (3 ꢁ 3 cm3), pure 4a was
obtained (0.668 g, 74%). 4a: m.p. 196–198 1C (dec.); found: C, 82.73;
H, 6.84. C31H30Ti requires C, 82.66; H, 6.71%; dH (300 MHz, CDCl3,
Me4Si) 0.85–0.99 (2 H, m), 1.10–1.31 (4 H, m), 1.73–2.06 (4 H, m), 6.11
(10 H, s), 6.58 (2 H, d, J = 7.2 Hz), 6.74 (2 H, d, J = 6.8 Hz), 6.95 (1
H, t, J = 7.2 Hz), 7.05 (2 H, dd, J = 7.5 and 7.5 Hz), 7.16 (1 H, t, J =
7.2 Hz) and 7.24 (2 H, dd, J = 7.5 and 7.5 Hz); dC (75 MHz; CDCl3);
22.2, 23.4, 24.7, 85.7, 105.0, 110.9, 124.9, 125.6, 127.6, 127.7, 127.8,
129.8, 137.5, 143.2 and 205.0; nmax/cmꢂ1 3072, 3057, 2975, 2925, 2853,
1591, 1540, 1487, 1476, 1458, 1440, 1382, 1171, 1155, 1066, 1016, 957,
838, 804, 778 and 761.
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