A versatile route to 3-benzoheteroepines containing group 15 and 16 heavier elements involving several novel ring systems, and their thermal stabilities.

Article abstract of DOI:10.1248/cpb.51.1283

The C-unsubstituted 3-benzoheteroepines (2a-g) containing group 15 (P, As, Sb, and Bi) and group 16 (S, Se, and Te) heavier elements were prepared by the reaction of the corresponding metal reagents with (Z,Z)-o-bis(beta-lithiovinyl)benzene (5) which was derived in two steps from a common o-phthalaldehyde (3). The heteroepines (2) thus obtained were thermally labile towards heteroatom extrusion, and their half-lives on heating estimated from (1)H-NMR spectral analysis showed that the 3-benzoheteroepines (2) were far less stable than the corresponding 1-benzoheteroepines (1). The 2,4-bis(trimethylsilyl)-3-benzoheteroepines (17) containing Sb, Bi, and Te were also prepared from o-diiodobenzene (9) in 6 steps and were found to be more stable than the corresponding C-unsubstituted heteroepines (2).

Full text of DOI:10.1248/cpb.51.1283

November 2003
Chem. Pharm. Bull. 51(11) 1283—1288 (2003)
1283
A Versatile Route to 3-Benzoheteroepines Containing Group 15 and 16
Heavier Elements Involving Several Novel Ring Systems, and Their
Thermal Stabilities
Shuji YASUIKE, Tsutomu KIHARADA, Takashi TSUCHIYA, and Jyoji KURITA*
Faculty of Pharmaceutical Sciences, Hokuriku University; Kanagawa-machi, Kanazawa 920–1181, Japan.
Received June 19, 2003; accepted August 6, 2003
The C-unsubstituted 3-benzoheteroepines (2a—g) containing group 15 (P, As, Sb, and Bi) and group 16 (S,
Se, and Te) heavier elements were prepared by the reaction of the corresponding metal reagents with (Z,Z)-o-
bis(b-lithiovinyl)benzene (5) which was derived in two steps from a common o-phthalaldehyde (3). The het-
eroepines (2) thus obtained were thermally labile towards heteroatom extrusion, and their half-lives on heating
1
estimated from H-NMR spectral analysis showed that the 3-benzoheteroepines (2) were far less stable than the
corresponding 1-benzoheteroepines (1). The 2,4-bis(trimethylsilyl)-3-benzoheteroepines (17) containing Sb, Bi,
and Te were also prepared from o-diiodobenzene (9) in 6 steps and were found to be more stable than the corre-
sponding C-unsubstituted heteroepines (2).
Key words 3-benzoarsepine; 3-benzostibepine; 3-benzobismepine; 3-benzoselenepine; valence isomerization; thermal decom-
position
We have already reported the syntheses of the 1-benzo- the C-unsubstituted group 15 and 16 3-benzoheteroepines
heteroepines (1) containing group 15 (P, As, Sb, and Bi) and (2a—g) and 2,4-bis(trimethylsilyl) substituted heteroepines
group 16 (S, Se, and Te) heavier elements as well as those (17c, d, g), all of which can be isolated at room temperature
comprising group 14 (Si, Ge, and Sn) elements by three dif- except for 3-benzobismepine (2d), and on the thermal stabili-
ferent routes.1—9) For instance, 1-benzophosphepine (1a) and ties of these novel heterocyclic systems.20) In the present
1-benzarsepine (1b) have been prepared by thermal valence studies, most of the C-unsubstituted heteroepines (2b, e, f)
isomerization of the corresponding 2a,7b-dihydrocyclobuta- and C-substituted heteroepines (17c, d, g) are the first iso-
[b]-1-benzoheteroles1,2) and the 2-alkyl derivatives of group lated examples of heteroepines, and their thermal stabilities
16 1-benzoheteroepines have been obtained by intramolecu- were evaluated by use of their half-lives (t1/2 at 50 °C) esti-
lar cyclization of o-(but-1-en-3-ynyl)phenylheterols.3—7) In mated by 1H-NMR analysis.
addition, all 1-benzoheteroepines (1a—h) could be synthe-
sized from (Z,Z)-1-bromo-4-(o-bromophenyl)buta-1,3-diene, Results and Discussion
via its dilithium intermediate.8,9) With regard to 3-benzo-
Synthesis of C-Unsubstituted 3-Benzoheteroepines
heteroepines, the phosphepine (2a),10) tellurepine (2g),11) and (2a—g) In the preceding papers,8,9) we have shown that the
stannepine (2h)12,13) could be prepared by the reaction of o- 1,6-dilithium intermediate, (Z,Z)-1-lithio-4-(o-lithiophenyl)-
diethynylbenzene with phenylphosphane, sodium telluride, 1-trimethylsilylbuta-1,3-diene, generated from (Z,Z)-1-
and dialkylstannanes, respectively. It has also been reported bromo-4-(o-bromophenyl)-1-trimethylsilylbuta-1,3-diene by
that the 3-alkyl derivatives of the 3-benzostibepine are ther- treatment with tert-butyllithium (t-BuLi), reacts with elec-
mally labile and can be isolated only at low temperature,14) trophilic metal regents (M or MX2: Mϭgroup 14, 15 and 16
and the C-unsubstituted arsepine (2a)10) and thiepine (2e)15,16) heavier elements) to give the corresponding 2-trimethylsilyl-
have also been known to be too thermally unstable to be iso- 1-benzoheteroepines which readily afford C-unsubstituted 1-
lated, although the 3-benzothiepines having alkoxycarbonyl benzoheteroepines (1) by detrimethylsilylation with tetra-
groups in the 2- and/or 4-positions are stable and can be iso- butylammonium fluoride. This result led us to examine the
lated at room temperature.15—19) While it was considered in reaction of (Z,Z)-o-bis(b-lithiovinyl)benzene (5) which
heteroepine chemistry that most of heteroepines were rela- would be generated from the corresponding dibromo com-
tively unstable and difficult to isolate, we were interested in pound (4) with the metal reagents, with the aim of obtaining
the synthesis of 3-benzoheteroepines under mild reaction the title 3-benzoheteroepines (2).
conditions. We report here on a versatile synthetic route to
The key starting compound, (Z,Z)-o-bis(b-bromovinyl)-
benzene (4), was obtained stereoselectively in high yield
(90%) by a double Wittig reaction of o-phthalaldehyde (3)
with bromomethylenetriphenylphosphorane,21,22) generated in
situ by the reaction of bromomethyltriphenylphosphonium
bromide with potassium tert-butoxide in tetrahydrofuran at
Ϫ80 °C. The (Z)-stereostructure of the vinyl function in 4
1
was confirmed by its H-NMR spectral data, in which two
vinyl proton signals appeared at d 6.55 (2H, d, Jϭ10.8 Hz,
b-H) and 7.11 (2H, d, Jϭ10.8 Hz, a-H), indicating that the
two vinyl groups are cis-form.
Fig. 1
The dibromo compound (4) was treated with excess t-
To whom correspondence should be addressed. e-mail: j-kurita@hokuriku-u.ac.jp
© 2003 Pharmaceutical Society of Japan

1284
Vol. 51, No. 11
BuLi in anhydrous diethyl ether at Ϫ80 °C under argon at- species (5) in the present reaction. When 5 was treated with
mosphere, and then with an electrophilic metal reagent selenium or tellurium tetrachloride, the corresponding 3,3-
[PhPCl2, PhAsCl2, PhSbCl2, PhBiBr2, (PhSO2)2S, SeCl4 or dichloro compounds (7f, g) might be initially formed, and
TeCl4] to result in ring closure, giving rise to the desired 3- then dechlorination with excess t-BuLi would take place to
benzoheteroepines (2a—g) in the yields shown in Table 1. give 2f and 2g. However, all attempts to isolate the interme-
However, most heteroepines obtained here, except for diate (7f, g) failed. It would also be possible that the dichloro
phosphepine oxide (2a؅) are thermally labile towards het- compounds (7f, g) thus formed may further react with the
eroatom extrusion and gradually decomposed to naphthalene starting dilithium compound (5) to afford spiro-dimer (8),
during isolation by column chromatography, which is the but the formation of 8 could not be observed in the reaction
main reason for the relatively low yields in the isolation of 2 mixture. The phosphepine (2a) was susceptible to air oxida-
by the present reaction. When deuterium oxide was used in- tion and thus was isolated as its P-oxide (2a؅),10) which was,
stead of the metal reagents in the present reaction, it afforded however, readily deoxygenated back to 2a by treatment with
(Z,Z)-dideuterio compound (6) in 45% yield. This result trichlorosilane.2)
clearly gives evidence for the intermediacy of the 1,6-dianion
Synthesis of 2,4-Bis(trimethylsilyl)-3-benzoheteroepines
(17c, d, g) The 3-benzobismepine (2d) thus obtained was
extremely thermally unstable and could not be isolated, al-
1
though it was detected at Ϫ20 °C by H-NMR spectroscopy.
It is well known that the stability of monocyclic heteroepines
is enhanced by introduction of a bulky substituent such as a
tert-butyl group on the a-positions on the heteroepine
ring.15,16,23—27) 1-Benzoheteroepines having a bulky tri-
methylsilyl group on the 2-position are also much more sta-
ble than the corresponding C-unsubstituted heteroepines
(1).8,9) In this context, we next performed the synthesis of
the 2,4-bis(trimethylsilyl)-3-benzoheteroepines (17) which
would be more stable than the corresponding C-unsubstituted
ones.
o-Diiodobenzene (9) was coupled with trimethylsilylacety-
lene (2.5 eq) in benzene in the presence of diethylamine and
a catalytic amount of a mixture of bis(triphenylphosphine)-
palladium dichloride and copper(I) iodide to afford o-
bis(trimethylsilylethynyl)benzene (10) in 67% yield.28) How-
ever, treatment of 10 with diisobutylaluminum hydride
(DIBAL-H) and N-bromosuccinimide (NBS) gave only a
complex mixture, and the expected key starting compound,
(Z,Z)-o-bis(b-bromo-b-trimethylsilylvinyl)benzene (14)
could not be obtained. Therefore, each of the iodine moieties
on 9 was transformed to a b-bromo-b-trimethylsilylvinyl
group one by one to obtain 14. Namely, diiodobenzene (9)
was coupled with one equivalent of trimethylsilylacetylene
giving rise to o-iodo(trimethylsilylethynyl)benzene (11). The
ethynylbenzene (11) was hydraluminated with DIBAL-H in
hexane,29—31) and then brominated with NBS8,9,32,33) to afford
(Z)-b-bromo-o-iodo-b-trimethylsilylstyrene (12) stereoselec-
Chart 1
Table 1. 3-Benzoheteroepines 2 and 17
HR-MS (m/z: Mϩ)
Yielda)
(%)
Appearance
Formula
Compound
M
Metal reagent
(mp/°C)
Found
Required
2ab)
2b
2c
2d
2e
2f
2g
17c
17d
17g
PPh
AsPh
SbPh
BiPh
S
Se
Te
SbPh
BiPh
Te
PhPCl2
PhAsCl2
PhSbCl2
PhBiBr2
(PhSO2)2S
SeCl4
13b)
20
25
20
15
12
12
7
85—87c,d)
Oil
C16H13P
236.0757
280.0123
326.0061
414.0755
160.0483
207.9661
257.9652
470.0432
558.1551
402.1485
236.0755
280.0234
326.0054
414.0761
160.0347
207.979
257.9695
470.0845
558.1545
402.5376
C16H13As
C16H13Sb
C16H13Bi
C10H8S
C10H8Se
C10H8Te
C22H29SbSi2
C22H29BiSi2
C22H29Si2Te
76—78c)
Oil
Oil
Oil
Oil
TeCl4
PhSbCl2
PhBiBr2
TeCl4
95—97.5c)
Oil
10
11
Oil
a) Isolated yields. b) Its 3-oxide 2a؅ initially formed was deoxygenated by treatment with trichlorosilane to 2a (see Experimental), and the yield of 2a was calculated from
4 used. c) Recrystallized from MeOH. d) Lit.,10) mp 86—88 °C.

November 2003
1285
Chart 2
Table 2. 1H-NMR Spectral Data for the 3-Benzoheteroepines 2a—g
d (CDCl3, 400 MHz)
tively. The remaining iodine moiety on 12 was converted to a
bromotrimethylsilylethenyl group by the same procedure via
13 to afford 14 in 39% yields from 12. The stereochemistry
of the vinyl functions for the compounds 12 and 14 was elu-
cidated to be Z configuration by their 1H-NMR spectral
analyses; an NOE was observed between vinyl and TMS pro-
tons in the both compounds.
Comp.
M
1(5)-H
(2H, d)
2(4)-H
(2H, d)
J1,2(4,5)
Hz
/
Ar-H
(m)c)
2a
2b
2c
2d
2e
2f
PPh
AsPh
SbPh
BiPh
S
6.64a)
7.16
7.54
8.92
6.72
7.16
7.62
5.74b)
6.20
6.52
7.59
5.89
6.31
6.79
12.0
11.4
12.1
11.2
9.5
6.90—7.62
7.73—8.21
7.22—7.73
7.00—8.20
7.10—7.18
7.16—7.25
7.16—7.28
The dibromo compound (14) was treated with t-BuLi in
anhydrous diethyl ether, then with water forming o-bis(b-
1
trimethylsilylvinyl)benzene (16). In the H-NMR spectrum
Se
Te
9.2
9.9
of 16, two vinyl protons appeared at d 6.36 (2H, d, Jϭ19.1
Hz, b-H) and 7.23 (2H, d, Jϭ19.1 Hz, a-H), indicating not
only that the stereochemistry of the vinyl groups on 16 is
2g
a) Double doublet,
JP, 1(5)-Hϭ12.0 Hz. b) Double doublet,
JP, 2(4)-Hϭ21.2 Hz.
trans, but also that the vinyl function in parent 14 is (Z)- c) Each 9H for 2a—d and each 4H for 2e—g.
form, and the 1,6-dilithium compound (15) is clearly formed.
These results encouraged us to perform the reaction of 15
with electrophilic reagents. Treatment of 15, generated in
situ, with the electrophilic metal reagents (PhSbCl2, PhBiBr2,
and TeCl4) resulted in ring closure to give 2,4-bis(trimethyl-
silyl)-3-benzoheteroepines (17c, d, g) in the yields shown
in Table 1. As expected, the heteroepines (17) having
trimethylsilyl groups are much more stable than the corre-
sponding C-unsubstituted heteroepines (2), and the bis-
mepine (17d) could be isolated under the usual handling at
room temperature. It should be noted that the reaction of 15
with the other metal reagents [PhPCl2, PhAsCl2, (PhSO2)2S,
or SeCl4] did not give any cyclized products. These results
might be attributable to the difference in the covalent bond
radii of each metal, the bond length between the metals and
the carbon atoms newly formed by ring closure being in-
creased when the metal became heavier.
2,4-bis(trimethylsilyl)heteroepines (17c, d, g) are the first iso-
lated examples of 3-benzoheteroepines. These novel com-
pounds were characterized mainly by their high resolution
(HR)-MS and H-NMR spectral analyses summarized in Ta-
bles 1 and 2, respectively.
1
The chemical shifts of the heteroepine ring protons on the
3-benzoheteroepines (2) are sensitive to a change in the het-
eroatoms in analogy with 1-benzoheteroepines (1)8,9) and 1-
benzoheteroles.32,33) For all 3-benzoheteroepines (2), the
chemical shift of the proton at the 1(4)-position is higher
than that of the proton at the 2(5)-position, and that of both
protons is observed at lower field when the metal became
heavier in the same group heteroepines; the chemical shifts
(d) of these protons increase in the order 2a (P)Ͻ2b
(As)Ͻ2c (Sb)Ͻ2d (Bi) and 2e (S)Ͻ2f (Se)Ͻ2g (Te). It is
also apparent that the coupling constants J1,2(4,5) of the group
15 heteroepines (2a—d) are somewhat larger than those of
the group 16 heteroepines (2e—g).
Structures and Thermal Stabilities of 2 and 17 Al-
though 3-benzophosphepine (2a),10) 3-benzotellurepine
(2g),11) and 3-alkyl- and 3-chloro-3-benzostibepine14) have
been reported, the other 3-benzoheteroepines (2b, d—f) and
As noted in the introductory paragraphs, most het-
eroepines were relatively unstable and difficult to isolate. We

1286
Vol. 51, No. 11
Table 3. Half-lives of 1, 2 and 17 at 50 °C in Toluene
tions; all experimental manipulation to prepare them being
carried out at below room temperature. The results showed
that 2,4-bis(trimethylsilyl)-substituted bismepine could be
isolated at room temperature, although C-unsubstituted bis-
mepine was far more unstable to isolate. The half-lives deter-
mined by 1H-NMR spectral analysis revealed that the stabili-
ties of the group 16 heteroepines increase in the order
SϽSeϽTe, but there is no such pattern relative to the stabili-
ties of the group 15 heteroepines BiϽAsϽSbϽP.
Compound
t1/2
Compound
t1/2
2a (P)
2b (As)
2c (Sb)
2d (Bi)
2e (S)
82 h
1a (P)
28 h
180 min
48 h
18 min
44 min
110 min
133 min
4 min
45 min
Ͻ1 min
1 min
1b (As)
1c (Sb)
1d (Bi)
1e (S)
2f (Se)
2g (Te)
17c (Sb)
17d (Bi)
4 min
48 min
190 h
1f (Se)
1g (Te)
Experimental
34 min
Melting points were determined on a Yanagimoto micro melting point hot
stage apparatus and are uncorrected. Infra red spectra were recorded on a
Hitachi 270-30 spectrometer. All mass spectra including high-resolution
1
mass spectra were recorded on a JEOL JMP-DX300 instrument. H-NMR
spectra were recorded on a JEOL JNM-GSX-400 (400 MHz) spectrometer,
and spectral assignments were confirmed by spin-decoupling and nuclear
Overhouser effect (NOE) analyses. All column chromatography was per-
formed on Silica gel 60N (Kanto Chemical Co., Inc. Japan). The metal
reagents, PhAsCl2,34) PhSbCl2,35) PhBiBr2,36) and (PhSO2)2S37) were prepared
according to the literature method, and the others were purchased from
Wako Pure Chemical Industries, Ltd. Japan, and were used without further
purification.
(Z,Z)-o-Bis(b-bromovinyl)benzene (4) (Bromomethyl)triphenylphos-
phonium bromide (27.5 g, 63 mmol) was added in small portions to a stirred
solution of potassium tert-butoxide (7.09 g, 63 mmol) in THF (100 ml) at
Ϫ80 °C under argon atmosphere, and the mixture was warmed slowly to
Ϫ30 °C. The mixture was cooled again to Ϫ80 °C, then a solution of o-ph-
thalaldehyde (3, 2.01 g, 15 mmol) in THF (10 ml) was added dropwise to the
mixture with stirring. The reaction mixture was allowed to warm slowly to
room temperature and stirred overnight. The mixture was diluted with water
(100 ml) and the whole was extracted with CH2Cl2 (200 mlϫ2). The com-
bined extracts were washed with brine, dried over anhydrous sodium sulfate,
and concentrated in vacuo. The resulting residue was purified with silica gel
chromatography using hexane as an eluent to give 4 as a colorless oil (3.8 g,
87%). 1H-NMR (CDCl3) d: 6.55 (2H, d, Jϭ10.8 Hz, b-H), 7.11 (2H, d,
Jϭ10.8 Hz, a-H), 7.37—7.68 (4H, m, Ar-H). Electron impact (EI-MS) m/z:
286 (Mϩ). HR-MS m/z: 285.9016 (Calcd for C10H8Br2: 285.8994).
Chart 3
next studied the thermal reaction of heteroepines (2) and
(17), most of which are thermally labile towards heteroatom
extrusion and gradually decomposed to naphthalenes during
isolation as noted earlier. The half-lives (t1/2) of 2 and 17 esti-
1
mated from H-NMR spectral analysis are listed in Table 3,
along with those of 1-benzoheteroepines (1).8,9)
(Z,Z)-o-Bis(b-deuteriovinyl)benzene (6) A solution of t-BuLi (1.5 M
solution in pentane, 10 ml, 15 mmol) in anhydrous ether (20 ml) was added
dropwise to a stirred solution of 4 (577 mg, 2 mmol) in anhydrous ether
(20 ml) at Ϫ80 °C under argon atmosphere. After stirring the solution for
15 min, D2O (99.8%, 2 ml) was added to the solution with stirring at
Ϫ80 °C, and the mixture was allowed to warm to room temperature. The
mixture was diluted with water (50 ml) and the whole was extracted with
pentane (100 mlϫ3). The combined extracts were washed with brine, dried
over anhydrous sodium sulfate, and evaporated in vacuo. The resulting
The 3-benzoheteroepines (2) are far less stable than the
corresponding 1-benzoheteroepines (1) except for the
phosphepine (2a) which is much more stable than the others.
The widely accepted mechanism of the heteroatom extrusion
in heteroepines involves valence isomerization of the seven-
membered ring to the corresponding norcaradiene intermedi-
ate and following irreversible loss of the heteroatom moi-
ety.15,16) The differences in thermal stability between 1 and 2
residue was purified by silica gel column chromatography using pentane as
1
may be explained by comparison of the easiness toward the an eluent to give 6 as a colorless oil (118 mg, 45%). H-NMR (CDCl3) d:
5.29 (2H, d, Jϭ10.8 Hz, b-H), 6.99 (2H, dt, Jϭ10.8 and 2.6 Hz, a-H),
7.22—7.43 (4H, m, Ar-H). HR-MS m/z: 132.1002 (Calcd for C10H8D2:
132.0908)
transformation of the heteroepines 1 and 2 into the corre-
sponding norcaradiene intermediates 18 and 19, respectively.
The valence isomerization of 2 into intermediary o-xylylene
system 19 should be easier than that of 1 into bicyclo-octate-
traene system 18.15,16) The stabilities of the group 16 het-
eroepines (2e—g) increase in the expected order 2e (S)Ͻ2f
(Se)Ͻ2g (Te), but there is no such pattern relative to the sta-
bilities of the group 15 heteroepines (2a—d).
The bismepine (17d) having bulky trimethylsilyl groups in
both of the a-positions is far more stable (t1/2ϭ34 min at
50 °C) than the corresponding C-unsubstituted bismepine
(2d: t1/2ϭϽ1 min at 50 °C), as are the monocyclic 2,7-di(tert-
butyl)-thiepines23—26) and -selenepines,27) either of which are
relatively stable and can be isolated although their unsubsti-
tuted derivatives are too unstable to be isolated.
General Procedure for the Synthesis of 3-Benzoheteroepines (2a—g)
A solution of 4 (576 mg, 2 mmol) in anhydrous ether (30 ml) was added
dropwise over 10 min to a stirred solution of t-BuLi (1.5 M solution in pen-
tane, 10 ml, 16 mmol) in anhydrous ether (20 ml) at Ϫ80 °C under argon at-
mosphere. After stirring the solution for 10 min, a solution of an elec-
trophilic metal reagent, (PhPCl2 or PhAsCl2: 4 mmol, 2 eq) in anhydrous
ether (20 ml) or a reagent [PhSbBr2, PhBiBr2, (PhSO2)2S, SeCl4 or TeCl4:
3—4 mmol; they are insoluble in ether], was added dropwise or in small por-
tions over 15 min with vigorous stirring at Ϫ80 °C. The mixture was allowed
to warm slowly to Ϫ10 °C and stirred for an additional 3 h, and then diluted
with pentane (100 ml) and water (100 ml). The insoluble substances were re-
moved by suction filtration and the filtrate was separated. The aqueous layer
was extracted with pentane (100 mlϫ2) and the combined organic layer was
washed with brine, dried over anhydrous sodium sulfate, and evaporated in
vacuo. The resulting residue was purified by silica gel column chromatogra-
phy with pentane as an eluent to give the heteroepine (2). In the case for the
preparation of phosphepine (2a), no 2a was obtained, and elution of the col-
umn with a mixture of CH2Cl2–acetone (5 : 1) afforded 3-phenyl-3-ben-
zophosphepine 3-oxide (2a؅) in 38% yield. The 3-benzoheteroepines (2)
In conclusion, we have demonstrated the first versatile
synthesis of novel C-unsubstituted 3-benzoheteroepines con-
taining group 15 and 16 heavier elements, most of which
were new heterocyclic systems, under mild reaction condi- thus obtained are listed together with the reagent used, yields, and HR-MS

November 2003
1287
analytical data in Table 1. 1H-NMR spectral data are collected in Table 2.
was washed with water, dried over anhydrous sodium sulfate, and evaporated
in vacuo. The resulting residue was purified by silica gel column chromatog-
raphy with hexane as an eluent to give 13 as a pale yellow oil (17.9 g,
3-Phenyl-3-benzophosphepine 3-Oxide (2a؅) Colorless prisms, mp
1
155—156 °C (acetonitrile) (lit.,10) 155—156 °C). H-NMR (CDCl3) d: 6.44
1
86.2%), bp 138—142 °C (3 mmHg). IR lmax (film) cmϪ1: 2164 (C¤C). H-
(2H, dd, Jϭ11.4 and 12.8 Hz, 2- and 4-H), 7.54 (2H, dd, Jϭ11.4 and 34.4
Hz, 1- and 5-H) 7.75—7.45 (9H, m, Ar-H). EI-MS m/z: 252 (Mϩ). Anal.
Calcd for C16H13OP: C, 76.18; H, 5.19. Found: C, 76.26; H, 5.16.
NMR (CDCl3, CH2Cl2, d 5.30 as an internal standard) d: 0.26 and 0.31
(each 9H, each s, SiMe3), 7.61 (1H, s, a-H), 7.32—8.04 (4H, m, Ar-H). EI-
MS m/z: 350 (Mϩ). HR-MS m/z: 350.0524 (Calcd for C16H23BrSi2:
350.0522).
Reduction of 3-Phenyl-3-benzophosphepine 3-Oxide (2a؅) with
Trichlorosilane All solvents employed in this reaction were deaerated by
stirring the solvents over 15 min under reduced pressure (20—100 mmHg)
on cooling, and then by filling with argon at atmospheric pressure. To a solu-
tion of 2a؅ (252 mg, 1 mmol) in benzene (40 ml) was added a benzene solu-
tion of SiHCl3 (1.4 M, 1.9 ml, 2.7 mmol), and the mixture was heated at
80 °C for 1 h under argon atmosphere. The reaction mixture was diluted with
benzene (40 ml) and stirred with aqueous 8% NaOH (10 ml) for 5 min in an
ice bath. The separated benzene layer was washed with brine, dried over an-
hydrous sodium sulfate, and concentrated in vacuo. The resulting residue
was passed through a short silica gel column with hexane–benzene (10 : 1)
as an eluent to give the phosphepine (2a: 80 mg, 34%). The spectral data for
the phosphepine (2a) are listed in Table 1 and Table 2.
(Z,Z)-o-Bis(b-bromo-b-trimethylsilylvinyl)benzene (14) from 13
A
solution of DIBAL-H in hexane (0.93 M, 78 ml, 72 mmol) was added drop-
wise to a stirred solution of 13 (3.15 g, 9 mmol) in hexane (50 ml) under an
argon atmosphere at room temperature, and the solution was stirred for addi-
tional 10 h. NBS (13.0 g, 72 mmol) was added to the solution in small por-
tions over 15 min with vigorous stirring in a methanol-ice bath (ca. Ϫ20 °C),
then the stirring was continued for a further 7 h in the bath. The reaction
mixture was diluted with hexane (200 ml) and water (50 ml), and the insolu-
ble substances were removed by suction filtration. The filtrate was separated
and the aqueous layer was extracted with hexane (150 ml). The combined
extracts were washed with brine, dried over anhydrous sodium sulfate, and
evaporated in vacuo. The resulting residue was purified by silica gel column
chromatography with hexane as an eluent to give 14 as a yellow oil (1.8 g,
45%). 1H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal standard) d: 0.29
(18H, s, SiMe3), 7.24 (2H, s, a-H), 7.34—7.60 (4H, m, Ar-H). EI-MS m/z:
430 (Mϩ). HR-MS m/z: 429.9758 (Calcd for C10H24Br2Si2: 429.9784).
(E,E)-o-Bis(b-trimethylsilylvinyl)benzene (16) A solution of 14 (650
mg, 1.52 mmol) in anhydrous ether (30 ml) was added dropwise over 10 min
to a stirred solution of t-BuLi (1.57 M solution in pentane, 5.8 ml, 9.12
mmol) in anhydrous ether (20 ml) at Ϫ80 °C under argon atmosphere. After
stirring for a further 10 min, the reaction mixture was quenched with water
(5 ml). The mixture was allowed to warm to room temperature, and then di-
luted with pentane (100 ml) and water (50 ml). The mixture was separated,
and the organic layer was washed with brine, dried over anhydrous sodium
sulfate, and evaporated in vacuo. The resulting residue was purified by silica
gel column chromatography with pentane as an eluent to give 16 as a color-
less oil (213 mg, 52%). 1H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal
standard) d: 0.18 (18H, s, SiMe3), 6.35 (2H, d, Jϭ19.1 Hz, b-H), 7.23 (2H,
Jϭ19.1 Hz, a-H), 7.18—7.47 (4H, m, Ar-H). EI-MS m/z: 274 (Mϩ). HR-
MS m/z: 274.1579 (Calcd for C16H26Si2: 274.1573).
o-Bis(trimethylsilylethynyl)benzene (10) from 9 Bis(triphenylphos-
phine)palladium dichloride (480 mg, 0.68 mmol), copper(I) iodide (410 mg,
3.75 mmol), and trimethylsilylacetylene (21 ml, 150 mmol, 2.5 eq) were suc-
cessively added to a stirred solution of o-diiodobenzene (9: 20 g, 60 mmol)
and diethylamine (15 ml) in benzene (90 ml) in an ice-bath. The mixture was
stirred for 30 min in the bath and for a further 15 h at room temperature.
After concentration of the reaction mixture in vacuo, the resulting residue
was diluted with water (100 ml) and the whole was extracted with CH2Cl2
(150 mlϫ3). The combined extracts were washed with water (150 mlϫ3),
dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue
was purified by silica gel column chromatography with hexane as an eluent
to give 10 as a yellow oil (11.0 g, 67%), bp 141—144 °C (5 mmHg). IR lmax
1
(film) cmϪ1: 2164 (C¤C). H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal
standard) d: 0.28 (18H, s, SiMe3), 7.24 and 7.46 (4H, m, Ar-H). EI-MS m/z:
270 (Mϩ). HR-MS m/z: 270.5247 (Calcd for C16H22Si2: 270.5244).
o-Iodo(trimethylsilylethynyl)benzene (11) Bis(triphenylphosphine)-
palladium dichloride (1.55g, 2.2 mmol), copper(I) iodide (3.72 g, 34 mmol),
and trimethylsilylacetylene (31 ml, 205 mmol, 1.2 eq) were successively
added to a solution of o-diiodobenzene (9: 56 g, 170 mmol) and diethyl-
amine (35 ml) in benzene (100 ml) with stirring in an ice bath. The mixture
was stirred for 30 min in the bath and for a further 15 h at room temperature.
After concentration of the reaction mixture in vacuo, the residue was diluted
with water (150 ml) and the whole was extracted with CH2Cl2 (150 mlϫ3).
The combined extracts were washed with water (150 mlϫ3), dried over an-
hydrous sodium sulfate, and evaporated in vacuo. The residue was purified
by silica gel column chromatography with hexane as an eluent to give 11 as
General Procedure for the Synthesis of 2,4-Bis(trimethylsilyl)-3-ben-
zoheteroepines (17c, d, g) A solution of 14 (650 mg, 1.52 mmol) in anhy-
drous ether (30 ml) was added dropwise over 10 min to a stirred solution of
t-BuLi (1.57 M solution in pentane, 5.8 ml, 9.12 mmol) in anhydrous ether
(20 ml) at Ϫ80 °C under argon atmosphere. After stirring the solution for 10
min at the same temperature, the electrophilic reagent (PhSbCl2, PhBiBr2 or
TeCl4: 4 mmol) was added in small portions over 15 min with vigorous stir-
ring at Ϫ80 °C. The mixture was allowed to warm slowly to room tempera-
ture and stirred for an additional 3 h. The reaction mixture was diluted with
pentane (100 ml), quenched with water (100 ml) and the insoluble sub-
stances were removed by suction filtration. The filtrate was separated and the
aqueous layer was extracted with pentane (100 mlϫ2). The combined ex-
tracts were washed with brine, dried over anhydrous sodium sulfate, and
evaporated in vacuo. The resulting residue was purified by silica gel column
chromatography with pentane as an eluent to give 17. The 3-benzo-
heteroepines (17c, d, g) thus obtained are listed together with the reagents
a yellow oil (33.1 g, 65%), bp 114—119 °C (3 mmHg). IR lmax (film) cmϪ1
:
1
2164 (C¤C). H-NMR (CDCl3, CH2Cl2: d 5.30 as an internal standard) d:
0.30 (9H, s, SiMe3), 6.89—7.89 (4H, m, Ar-H). HR-MS m/z: 299.9836
(Calcd for C11H13ISi: 299.9833).
(Z)-b-Bromo-o-iodo-b-trimethylsilylstyrene (12)
A
solution of
DIBAL-H in hexane (0.93 M, 180 ml, 167 mmol) was added dropwise to a
stirred solution of 11 (33.2 g, 110 mmol) in hexane (200 ml) at room temper-
ature under argon atmosphere, and the solution was stirred for an additional
8 h. NBS (30.0 g, 168.5 mmol) was added to the solution in small portions
over 20 min with vigorous stirring in a methanol-ice bath (ca. Ϫ20 °C), then
the stirring was continued for a further 5 h in the bath. The reaction mixture
was diluted with hexane (200 ml) and water (100 ml), and insoluble sub-
stances were removed by suction filtration. The filtrate was separated and the
aqueous layer was extracted with hexane (150 ml). The combined organic
layer was washed with brine, dried over anhydrous sodium sulfate, and evap-
orated in vacuo. The resulting residue was purified by silica gel column
chromatography with hexane as an eluent to give 12 as a pale yellow oil
1
used, yields, and HR-MS analytical data in Table 1. H-NMR spectral data
are shown below. 17c: 1H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal stan-
dard) d: 0.29 (18H, s, SiMe3), 7.93 (2H, s, 1- and 5-H), 6.81—7.01 (9H, m,
1
Ar-H). 17d: H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal standard) d:
0.29 (18H, s, SiMe3), 8.58 (2H, s, 1- and 5-H), 6.49—6.96 (9H, m, Ar-H).
17g: 1H-NMR (CDCl3, CH2Cl2, d 5.30 as an internal standard) d: 0.23 (18H,
s, SiMe3), 7.71 (2H, s, 1- and 5-H), 7.18—7.25 (4H, m, Ar-H).
Thermolysis of 3-Benzoheteroepines 2 and 17 A solution of the het-
eroepine (2a—g or 17c, d: 6—20 mg, 0.02—0.06 mmol) in d8-toluene (0.7
ml) was heated at the temperature shown below. The disappearance of the
signals for the heteroepines and the appearance of the signals for naph-
thalenes (20 or 21) were monitored by NMR integration using the signals on
undeuterated toluene (benzyl group d 2.09) contaminated in d8-toluene as an
internal standard. After the reaction was completed, the reaction mixture was
purified by silica gel column chromatography with pentane as an eluent to
give 20 or 21 almost quantitatively. The first-order rate constants obtained
1
(27.1 g, 64.5%), bp 128—133 °C (2 mmHg). H-NMR (CDCl3, CH2Cl2: d
5.30 as an internal standard) d: 0.31 (9H, s, SiMe3), 7.19 (1H, s, vinyl-H),
7.34—7.89 (4H, m, Ar-H). HR-MS m/z: 379.9098 (Calcd for C11H14BrISi:
379.9095)
(Z)-b-Bromo-b-trimethylsilyl-o-trimethylsilylethynylstyrene (13) Bis-
(triphenylphosphine)palladium dichloride (0.82 g, 1.2 mmol), copper(I) io-
dide (0.28 g, 2.6 mmol) and trimethylsilylacetylene (12.5 ml, 89 mmol) were
successively added to a stirred solution of 12 (22.5 g, 59 mmol) in diethyl-
amine (300 ml) in an ice bath. The reaction mixture was stirred for 30 min in
the bath and for a further 15 h at room temperature. After concentration of
the reaction mixture in vacuo, the residue was diluted with water (100 ml)
and the whole was extracted with CH2Cl2 (100 mlϫ3). The combined extract
are described as follows; 2a: 80.0 °C; k353ϭ1.96ϫ10Ϫ4 sϪ1
k362ϭ1.91ϫ10Ϫ4 sϪ1, 100.0 °C; k373ϭ1.86ϫ10Ϫ4 sϪ1, 2b: 22.3 °C; k295.3
2.35ϫ10Ϫ4 sϪ1 30.5 °C; k303.5ϭ2.28ϫ10Ϫ4 sϪ1 40.1 °C; k313.1ϭ2.21ϫ
10Ϫ4 sϪ1, 2c: 40.2 °C; k313.2ϭ2.21ϫ10Ϫ4 sϪ1, 50.1 °C; k323.1ϭ2.14ϫ10Ϫ4 sϪ1
, 89.0 °C;
ϭ
,
,
,

1288
Vol. 51, No. 11
60.0 °C; k333ϭ2.08ϫ10Ϫ4 sϪ1, 2e: 23.0 °C; k296ϭ2.34ϫ10Ϫ4 sϪ1, 28.2 °C;
375—386 (1970).
k301.2ϭ2.30ϫ10Ϫ4 sϪ1, 32.3 °C; k305.3ϭ2.27ϫ10Ϫ4 sϪ1, 2f: 22.8 °C; k295.8
ϭ
13) Ashe III A. J., Kampf J. W., Kausch C. M., Konishi H., Kristen M. O.,
Kroker J., Organometallics, 9, 2944—2948 (1990).
14) Ashe III A. J., Goossen L., Kampf J. W., Konishi H., Angew. Chem.,
Int. Ed. Engl., 31, 1642—1643 (1992).
2.34ϫ10Ϫ4 sϪ1
10Ϫ4 sϪ1, 2g: 40.3 °C; k313.3ϭ2.21ϫ10Ϫ4 sϪ1, 50.2 °C; k323.2ϭ2.14ϫ10Ϫ4 sϪ1
60.0 °C; k333ϭ2.08ϫ10Ϫ4 sϪ1, 17c: 70.0 °C; k343ϭ2.02ϫ10Ϫ4 sϪ1, 80.0 °C;
k353ϭ1.96ϫ10Ϫ4 sϪ1, 90.0 °C; k363ϭ1.91ϫ10Ϫ4 sϪ1, 17d: 30.0 °C; k303
2.29ϫ10Ϫ4 sϪ1, 40.0 °C; k313ϭ2.21ϫ10Ϫ4 sϪ1, 50.0 °C; k323ϭ2.15ϫ10Ϫ4 sϪ1
, ,
30.4 °C; k303.4ϭ2.28ϫ10Ϫ4 sϪ1 40.1 °C; k313.1ϭ2.21ϫ
,
15) Murata I., Nakatsuji K., Top. Curr. Chem., 97, 33—70 (1981).
16) Yamamoto K., Yamazaki S., “Comprehensive Heterocyclic Chemistry
II,” Vol. 9, eds. by Katritzky A. R., Rees C. W., Scriven E. F. V., Perga-
mon Press, Oxford, 1996, pp. 67—111.
17) Scott G. P., J. Am. Chem. Soc., 75, 6332—6333 (1953).
18) Dimroth K., Lenke G., Angew. Chem., 68, 519—520 (1956).
19) Dimroth K., Lenke G., Chem. Ber., 89, 2608—2616 (1956).
20) A part of this work has been published in a preliminary communica-
tion; Yasuike S., Kiharada T., Kurita J., Tsuchiya T., Chem. Commun.,
1996, 2183—2184.
ϭ
.
The half lives (t1/2) for the compounds 2a—c, e—f and 17c, d at 50 °C were
estimated based on the rate constants at 50 °C obtained by Arrhenius plot
analysis of the corresponding first-order rate constants shown above.
2,3-Bis(trimethylsilyl)naphthalene (21) Colorless oil, 1H-NMR
(CDCl3, CH2Cl2, d 5.30 as an internal standard) d: 0.43 (18H, s, SiMe3),
7.49—7.80 (4H, m, Ar-H), 8.14 (2H, m, 1- and 4-H). EI-MS m/z: 272 (Mϩ).
HR-MS m/z: 272.1425 (Calcd for C16H24Si2: 272.1416).
21) Matsumoto M., Kuroda K., Tetrahedron Lett., 21, 4021—4024 (1980).
22) Romero M. A., Fallis A. G., Tetrahedron Lett., 35, 4711—4714
(1994).
23) Nishino K., Yano S., Kohashi Y., Yamamoto K., Murata I., J. Am.
Chem. Soc., 101, 5059—5060 (1979).
24) Yamamoto K., Yamazaki S., Kohashi Y., Murata I., Kai Y., Kanehisa
N., Miki K., Kasai N., Tetrahedron Lett., 23, 3195—3198 (1982).
25) Yamamoto K., Matsukawa A., Murata I., Chem. Lett., 1985, 1119—
1122.
26) Yamamoto K., Yamazaki S., Osedo H., Murata I., Angew. Chem., Int.
Ed. Engl., 25, 635—637 (1986).
27) Hori H., Yamazaki S., Yamamoto K., Murata I., Angew. Chem., Int.
Ed. Engl., 29, 424—425 (1990).
28) Takahashi S., Kuroyama Y., Sonogashira K., Hagihara N., Synthesis,
1980, 627—630.
29) Eisch J. J., Foxton M. W., J. Org. Chem., 36, 3520—3525 (1971).
30) Zweifel G., Lewis W., J. Org. Chem., 43, 2739—2744 (1978)
31) Miller J. A., Zweifel G., J. Am. Chem. Soc., 105, 1383—1384 (1983).
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Acknowledgements This work was partly supported by a Grant-in-Aid
for Scientific Research on Priority Areas (A) ‘Exploitation of Multi-Element
Cyclic Molecules’ from the Ministry of Education, Sciences, Sports and
Technology of Japan, and Takeda Scientific Foundation. Financial support
by The Specific Research Fund of Hokuriku University is also gratefully ac-
knowledged.
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