Stereoselective [2 + 2 + 2] cocyclotrimerization of oxa-and azabenzonorbornadienes ? with alkynes catalyzed by nickel complexes: First transition metal-mediated synthesis of isobenzofuran and isoindole precursors

Article abstract of DOI:10.1039/a907654i

Oxabenzonorbornadiene (1a) reacted with various alkynes in the presence of Ni(PPh₃)₂Cl₂, PPh₃ and zinc powder in toluene to give two common products 2a and 2b regardless of the alkyne used. The formation of 2a a

Full text of DOI:10.1039/a907654i

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Stereoselective [2 ؉ 2 ؉ 2] cocyclotrimerization of oxa-
and azabenzonorbornadienes† with alkynes catalyzed by
nickel complexes: first transition metal-mediated synthesis
of isobenzofuran and isoindole precursors
1
Thota Sambaiah, Daw-Jen Huang and Chien-Hong Cheng*
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30043
Received (in Cambridge, UK) 22nd September 1999, Accepted 29th October 1999
Oxabenzonorbornadiene (1a) reacted with various alkynes in the presence of Ni(PPh3)2Cl2, PPh3 and zinc powder
in toluene to give two common products 2a and 2b regardless of the alkyne used. The formation of 2a and 2b are
proposed to be from the Diels–Alder reaction of 1a and isobenzofuran. The latter is generated from the retro
Diels–Alder reaction of [2 ϩ 2 ϩ 2] cycloadducts of 1a and alkynes catalyzed by the nickel system. A series of
nickel-catalyzed [2 ϩ 2 ϩ 2] cycloadducts (4a–j and 5a–d) of oxa- and azabenzonorbornadienes (1a–d) with
terminal alkynes were isolated at temperatures Ϫ5–18 ЊC. Similarly, hepta-1,6-diyne and octa-1,7-diyne reacted with
1a and 1d to give novel pentacyclic [2 ϩ 2 ϩ 2] cycloadducts 6a–d in 62–75% yields. These products are convenient
isobenzofuran and isoindole precursors that react with various dienophiles to afford the corresponding Diels–Alder
adducts. In addition, the [2 ϩ 2 ϩ 2] cycloadducts may be used as precursors for the synthesis of aromatic
compounds. For example, the reaction of 1a with methyl but-2-ynoate catalyzed by the nickel system provided
aromatic compound 3 in 94% yield. In this reaction, 1a is a ‘masked acetylene’ providing an acetylene moiety to 3.
with alkynes. The cocyclotrimerization products may be used as
Introduction
convenient new precursors for isobenzofurans and isoindoles
Isobenzofuran and its derivatives have attracted considerable
and for substituted aromatic compounds. Moreover, the
attention in recent years in organic synthesis. They have been
reaction is an excellent method for constructing multiple fused
widely used as dienes in the Diels–Alder reactions1 to provide
rings by the cycloaddition of oxa- and azabenzonorborn-
adienes with diynes. Herein we report a detailed study of this
substituted 7-oxabicyclo[2.2.1]heptanes, which are key inter-
mediates in natural products synthesis.2 Recently, Padwa and
nickel-catalyzed cocyclotrimerization reaction. Preliminary
co-workers have synthesised the Erythrinane alkaloid skeleton3
results of these studies have appeared in a communication.17
and a variety of 1-hydroxy-4-aminonaphthalene derivatives4
using isobenzofuran derivatives as key intermediates. In add-
Results and discussion
Reaction of oxabenzonorbornadiene (1a) with alkynes
ition, isobenzofurans and isoindoles are important building
blocks for the syntheses of a variety of fascinating polycyclic
unnatural products.5,6 However, isobenzofurans and isoindoles
are generally highly reactive undergoing polymerization even at
low temperature. Several precursors for isobenzofurans7 and
isoindoles8 have been developed, but most are very unstable
and difficult to handle. The search for new and viable pre-
cursors to conveniently generate isobenzofurans and isoindoles
continues.
Compound 1a reacted with various alkynes (see Table 1) at 25–
90 ЊC in the presence of Ni(PPh3)2Cl2 (5 mol%), PPh3 and zinc
powder in toluene to give two common products 2a and 2b
(Scheme 1) regardless of the alkyne used. These two unusual
Transition metal-catalyzed [2 ϩ 2 ϩ 2] cocyclotrimerization
is a powerful method for the construction of cyclic compounds
in a chemo- and regioselective manner.9,10 Cocyclotrimerization
of three acetylenes has been extensively studied by using differ-
ent metal catalysts with different unsaturated compounds.11
The [2 ϩ 2 ϩ 2] cycloaddition of two acetylenes and an alkene
has been less well explored.12 In general, this cocyclotrimeriz-
ation requires a high ratio of alkene to alkyne in order to
suppress the competing trimerization of alkynes.13 Recently,
we reported a novel one step synthesis of cyclohexadiene
derivatives of C60 via a nickel-catalyzed cycloaddition of C60
with diynes.14 In addition, we15 and Ikeda et al.16 independently
reported the [2 ϩ 2 ϩ 2] cocyclotrimerization of α,β-unsatur-
ated carbonyl compounds with mono alkynes and diynes
mediated by nickel complexes. In the pursuit for new active
alkenes for [2 ϩ 2 ϩ 2] cocyclotrimerization, we observed the
cocyclotrimerization of oxa- and azabenzonorbornadienes
Scheme 1
stereoisomers are readily distinguished in the 1H and 13C NMR
spectra (see the Experimental section). A key difference
between these two compounds is that 2a exhibits a pair of
resonances at 4.69 and 5.32 ppm for the four bridgehead pro-
tons, while 2b shows only one resonance at 5.46 ppm for
bridgehead protons. The symmetries of these two structures are
† The IUPAC name for benzonorbornadiene is 1,4-dihydro-1,4-
methanonaphthalene.
J. Chem. Soc., Perkin Trans. 1, 2000, 195–203
This journal is © The Royal Society of Chemistry 2000
195

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Table 1 Formation of products 2a and 2b from oxabenzonorbornadiene (1a) and various alkynes catalyzed by NiCl2(PPh3)2–PPh3–Zna
Product yield (%)b
Entry
[1a]/M
[Acetylene]/M
[NiCl2(PPh3)2–PPh3]/M
Temp/ЊC
(2a)
(2b)
᎐
1
2
3
4
5
6
0.40
0.40
0.50
0.50
0.50
0.5
HC᎐C(CH2)4CH3
0.020/0.32
0.020/0.32
0.025/0.40
0.025/0.40
0.025/0.0
80
25
30
30
90
70
46
58
65
25
52
43
25
40
31
36
26
26
᎐
(0.40)
᎐
HC᎐CPh
᎐
(0.80)
᎐
MeCH᎐CHCOOMe
(0.60)
TMSCH᎐CHCOOEt
᎐
᎐
᎐
(0.60)
᎐
᎐
HC᎐C(CH2)4C᎐CH
᎐
᎐
(0.50)
᎐
N(H2CC᎐CH)3
0.025/0.40
᎐
(0.50)
a Each reaction was carried out in toluene solution (2.0 ml) in the presence of the reagents shown in Table 1 and Zn metal (2.75 mmol) at the
temperature specified for 24 h. b The yields of 2a and 2b were determined by 1H NMR integration using norbornene as internal standard.
primarily responsible for the number of NMR peaks observed.
Although common products 2a and 2b were observed, the
yields of these two species are different with different alkynes
used. The results of these reactions are shown in Table 1. In
addition to the common products, aromatic compounds were
also observed in the reaction mixtures of 1a and alkynes. As an
example, the reaction of 1a and methyl but-2-ynoate at 30 ЊC
(entry 3) gave aromatic compound 3 in 92% yield in addition to
products 2a and 2b.
ates. In view of the fact that no such products were isolated at
temperatures between 40–90 ЊC, the reactions of 1a and alkynes
were carried out at lower temperatures. Thus, treatment of 1a
with pent-1-yne in the presence of Ni(PPh3)2Cl2 (5 mol%), PPh3
and zinc powder in toluene at 18 ЊC for 24 h gave a mixture of
two cyclohexadiene derivatives 4a and 5a in 91% combined
yield (Scheme 3). Mass spectral data show that these two
The formation of 2a, 2b and aromatic compounds may be
explained in terms of a nickel-catalyzed [2 ϩ 2 ϩ 2] cocyclo-
trimerization of 1a and alkyne to give intermediate I. This
cyclohexadiene intermediate is thermally unstable and readily
undergoes retro Diels–Alder cycloaddition to give an aromatic
product and isobenzofuran. Diels–Alder reaction of isobenzo-
furan with 1a affords the observed products 2a and 2b. A
summary of the reaction pathway is shown in Scheme 2. The
driving force for the retro Diels–Alder reaction of intermediate
I is the formation of a low energy aromatic product.
Scheme 3
products are isomers having the same molecular weight. The
structures of these two regioisomers are assigned based on the
1H NMR coupling patterns. The individual yields of 4a and 5a
were determined from the 1H NMR spectrum of the mixture as
22% and 69% respectively. Control reactions revealed that no
desired product was formed in the absence of either Ni(PPh3)2-
Cl2 or zinc metal. Additional PPh3 was essential to stabilize
Ni(0) and to achieve higher yields of products. Similarly, hex-1-
yne and hept-1-yne reacted with 1a to give 4b and 5b (1:2.1),
and 4c and 5c (1:8.7) in 91 and 68% combined yields, respect-
ively. In contrast, the reaction of phenylacetylene and ethyn-1-
ylcyclohex-1-ene with 1a afforded only 1,3-isomers 4e and 4g,
in high yields, respectively (Table 2). It should be noted that
temperature control is important for the success of isolation of
cocyclotrimerization products. The reactions of pent-1-yne,
hex-1-yne, hept-1-yne and ethyn-1-ylcyclohex-1-ene with 1a
were controlled at 18 ЊC, while the reaction of phenylacetylene
with 1a was performed at Ϫ5 ЊC.
Scheme 2
Isolation of [2 ؉ 2 ؉ 2] cocyclotrimerization adducts
To support the pathway proposed in Scheme 2, an attempt was
made to isolate the [2 ϩ 2 ϩ 2] cocyclotrimerization intermedi-
In the same manner, methoxy substituted oxabenzonor-
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Table 2 Cocyclotrimerization of oxa- and azabenzonorbornadienes with terminal alkynes
3
3
Product yield (%)a
᎐
Entry
Alkene
Temp/ЊC
R C᎐CH (R )
᎐
1
2
3
4
5
6
7
8
9
1a
1a
1a
1d
1a
1d
1a
1d
1b
1c
18
18
18
18
Ϫ5
10
18
10
0
CH3(CH2)2
CH3(CH2)3
CH3(CH2)4
CH3(CH2)2
Ph
4a (22) ϩ 5a (69)
4b (29) ϩ 5b (62)
4c (7) ϩ 5c (61)
4d (26) ϩ 5d (64)
4e (95)
Ph
4f (93)
–C6H9–
–C6H9–
Ph
4g (95)
4h (90)
4i ϩ 4iЈ (72)
4j (74)
10
0
Ph
a Yields are measured by 1H NMR integration method using norbornene as internal standard.
bornadienes (1b, c) undergo cocyclotrimerization with alkynes
in the presence of Ni(PPh3)2Cl2, PPh3, and zinc powder. The
reaction of 1b with phenylacetylene afforded two regio
products 4i and 4iЈ in 72% combined yields, while treatment of
1c with phenylacetylene gave 4j in 74% yield. Similar to sub-
strate 1a–c, azabenzonorbornadiene (1d) reacted with terminal
alkynes hex-1-yne, phenylacetylene and ethyn-1-ylcyclohex-1-
ene under similar reaction conditions to afford cocyclotrimer-
ization products 4d and 5d, 4f and 4h in fair to excellent yields
(Table 2).
cocyclotrimerization with 1a and 1e, the [2 ϩ 2 ϩ 2] cyclo-
addition adducts cannot be isolated at temperatures above
Ϫ10 ЊC due to thermal instability of these adducts (vide infra).
Attempts to isolate tetrasubstituted [2 ϩ 2 ϩ 2] adducts from 1a
and disubstituted alkynes such as diphenylacetylene and methyl
3-phenylpropiolate did not succeed either.
The nickel-catalyzed [2 ϩ 2 ϩ 2] cocyclotrimerization is suc-
cessfully extended to bisalkynes. Thus, hepta-1,6-diyne and
octa-1,7-diyne reacted with 1a and 1d to give novel pentacyclic
adducts 6a–d in 62–75% yields (Scheme 4). The facile formation
In the present [2 ϩ 2 ϩ 2] cocyclotrimerization, the nickel
system selectively catalyzes the cotrimerization of an oxa- or
azabenzonorbornadiene and two alkyne moieties. Only a trace
of the trimerization product of alkyne was observed in each
reaction. The replacement of 1 by a less reactive olefin such as
hex-1-ene, 2,3-dihydro-2H-pyran or cyclohexene did not give
the expected [2 ϩ 2 ϩ 2] cotrimerization product.
All of the [2 ϩ 2 ϩ 2] cocyclotrimerization products of 1a–d
with terminal alkynes and bisalkynes are completely stereo-
selective giving only exo cyclohexadiene products. No corre-
sponding endo products were observed in all of these reactions.
The exo stereochemistry was established on the basis of the
coupling constant of bridgehead proton and endo cyclohexa-
diene proton. It is well known that for norbornene and its
derivatives, the coupling constant between an endo and a
bridgehead proton is nearly zero, while the value between an exo
and bridgehead proton is ca. 3 Hz and can be clearly observed.18
In the present cyclohexadiene derivatives, all bridgehead
protons appeared as singlets in the 1H NMR spectra indicating
these derivatives have exo stereochemistry.
Scheme 4
As proposed in Scheme 2, the [2 ϩ 2 ϩ 2] cocyclotrimeriz-
ation products 4–6 are thermally unstable and undergo retro
Diels–Alder reaction to give isobenzofurans or isoindoles and
aromatic compounds. The stability of the [2 ϩ 2 ϩ 2] cocyclo-
trimerization products depends greatly on the substituents
of products 6a–d demonstrates that the present [2 ϩ 2 ϩ 2]
cocyclotrimerization is a powerful method for the construction
of multiple rings. Although methyl but-2-ynoate also undergoes
J. Chem. Soc., Perkin Trans. 1, 2000, 195–203
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Table 3 Effect of nickel catalysts on the [2ϩ2ϩ2] cocyclotrimerization
of oxabenzonorbornadiene with phenylacetylenea
Products yield (%)b
Entry Ni catalyst/mmol
4e 2a 2b
7
1
2
3
4
5
NiBr2 (0.10), Zn (3.0)
Ni(COD)2 (0.10)
Ni(PPh3)4 (0.050)
—
—
—
—
—
58 40
—
—
41
14
—
—
—
NiCl2(PPh3)2 (0.05), PPh3 (0.8), Zn (3.0) 18 44 26
NiCl2(PnBu3)2 (0.05), Zn (3.0)
—
—
—
a Reaction conditions: oxabenzonorbornadiene (0.50 mmol), phenyl-
acetylene (1.0 mmol) and nickel catalyst (see Table 3) in toluene (1.25
ml) at ambient temperature. b Yields are based on oxabenzonorborn-
adiene.
present on the exo cyclohexadiene ring. The products with alkyl
substituents on the exo cyclohexadiene ring are most stable and
can be stored at room temperature for a few days in solution
and in the solid state for a long time. Compounds 4g and 4h
with a cyclohex-1-enyl substituent are stable in solution for only
a few hours at room temperature. The products with phenyl
substituents 4e and 4f can be observed only at temperatures
below Ϫ5 ЊC. On the other hand, no [2 ϩ 2 ϩ 2] adduct was
observed from methyl but-2-ynoate at Ϫ5–30 ЊC.
Scheme 6
Effect of ligand on cocyclotrimerization
The [2 ϩ 2 ϩ 2] cocyclotrimerization depends greatly on the
phosphine ligand19 used (Table 3). Ni(PPh3)2Cl2–PPh3–Zn and
Ni(PPh3)4 were found to be the catalysts of choice for the
present [2 ϩ 2 ϩ 2] cocyclotrimerization (Table 3, entries 3, 4).
The highly basic ligand n-Bu3P strongly retards the reaction
(entry 5). The replacement of Ni(PPh3)2Cl2 and Ni(PPh3)4 by
Ni(COD)2 and NiBr2–Zn (entries 1 and 2) led to no reac-
tion between 1a and phenylacetylene, but instead gave homo
[2 ϩ 2] dimerization of oxabenzonorbornadiene (1a) to yield 7
(Scheme 5).20
indicates that coordination of the carbon–carbon double bond
of oxa- or azabenzonorbornadienes to the nickel center is
exclusively via the exo face. Exo selectivity has been observed
for palladium or nickel-catalyzed addition of aryl groups to
oxa- and azabenzonorbornadienes.24 The regioselectivity of the
diene moiety of [2 ϩ 2 ϩ 2] cycloadducts is determined at the
formation of metallacycle 8 and is clearly affected by the sub-
stituent of the terminal alkynes used. Alkynes with a linear
alkyl group favor the formation of 1,4-substituted metallacycle
and thus 1,4-substituted cycloadducts, whereas for alkynes with
a bulkier aryl or a cyclohexenyl substituent, 1,3-substituted
metallacycle and cycloadducts predominate. The unfavorable
formation of 1,4-substituted metallacycle for alkynes with an
aryl or a cyclohexenyl substituent is likely due to steric conges-
tion arising from these bulkier substituents with the nickel
moiety.
Scheme 5
Mechanism of [2 ؉ 2 ؉ 2] cocyclotrimerization
Based on the well established organometallic chemistry of
nickel complexes and observed regio- and stereoselectivity of
cotrimerization products, a reasonable reaction mechanism
for the Ni(0)-catalyzed [2 ϩ 2 ϩ 2] cocyclotrimerization of an
oxabenzonorbornadiene and two alkynes is depicted in Scheme
6. The reduction of Ni() species to Ni(0) species is followed by
coordination of two molecules of alkynes and oxidative cyclo-
metallation to yield a nickelacyclopentadiene intermediate
8.21,22 Coordination of an oxabenzonorbornadiene (1a) and
subsequent insertion into a Ni()–carbon bond produces
nickelacycloheptadiene intermediate 9. Reductive elimination
of 9 affording product 4 and regenerating Ni(0) completes the
catalytic cycle. Alternatively, a mechanism which involves the
coordination of an oxa- or azabenzonorbornadiene and an
alkyne to Ni(0) to produce a nickelacyclopentene intermediate23
8Ј followed by insertion of another alkyne into the nickel–
carbon bond to give nickelacycloheptadiene intermediate 9 can
not be excluded.
Synthetic application of the [2 ؉ 2 ؉ 2] cycloadducts
In addition to an efficient method for constructing multiple
fused rings (Scheme 4), the present [2 ϩ 2 ϩ 2] cycloaddition
has two other synthetic applications. First, these products are
convenient isobenzofuran and isoindole precursors. For
example, heating 6c and 6d with 1a led to the isolation of the
Diels–Alder cycloadduct of isoindole 10 in 70% yield. Treat-
ment of 6a with cyclohex-2-en-1-one, dimethyl acetylenedicarb-
oxylate and N-methoxycarbonyl-7-azabenzonorbornadiene,
respectively, in toluene at 60 ЊC afforded the corresponding
It is clear from Scheme 6 that the stereochemistry of
[2 ϩ 2 ϩ 2] cycloadducts is determined completely by the
coordination of oxa- and azabenzonorbornadienes to the nickel
center. The observation of only exo [2 ϩ 2 ϩ 2] cycloadducts
198
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Diels–Alder cycloadducts 11 and 12 (ca. 1:1), 13, and 14 and
15 (ca. 1:1) in 77, 60 and 68% combined yields respectively
(Scheme 7). Second, the present [2 ϩ 2 ϩ 2] cycloaddition can
adducts at low temperatures and have demonstrated that these
nickel-catalyzed [2 ϩ 2 ϩ 2] cycloaddition reactions are very
useful in the construction of multiple rings, synthesis of pre-
cursors of isobenzofurans and isoindoles and regioselective
synthesis of substituted aromatic compounds.
Experimental
All reactions were conducted under a nitrogen atmosphere on a
dual-manifold Schlenck line by using purified deoxygenated
solvents and standard inert atmosphere techniques, unless
otherwise stated. 1H and 13C NMR spectra were recorded
in CDCl3 using Me4Si as internal standard. Alkyl- and
aryl-substituted alkynes were used as purchased without
further purification. NiCl2(PPh3)2,26 oxabenzonorbornadienes
1a–c N-methoxycarbonyl and N-p-tolylsulfonyl-7-azabenz-
onorbornadienes27 were synthesized according to the reported
procedures.
Reaction of methyl but-2-ynoate with oxabenzonorbornadiene
(1a) to give 2a, 2b and 3
To a 50 ml round-bottomed side-arm flask was added 1a (0.144
g, 1.00 mmol), NiCl2(PPh3)2 (0.0325 g, 0.0500 mmol), PPh3
(0.210 g, 0.801 mmol) and zinc powder (0.180 g, 2.75 mmol).
The system was evacuated and purged with nitrogen gas three
times. To the system was added freshly distilled toluene (2.0 ml)
and methyl but-2-ynoate (0.118 g, 1.20 mmol). The reaction
mixture was stirred at room temperature for 24 h. The solution
was filtered through Celite and silica gel, and the filtrate was
concentrated. The residue was separated on a silica gel column
using hexanes–dichloromethane as eluent to afford 2a (0.076 g),
2b (0.052 g) and 3 (0.245 g) in 58, 40 and 92% yields, respec-
tively. The TLC Rf values of 2a, 2b and 3 are 0.62, 0.50 and
0.45, respectively, using hexane–ethyl acetate (v/v = 4/1) as the
eluent. Important spectral data of these products are listed below.
Scheme 7
be employed to synthesize aromatic compounds. The cyclo-
addition of 1a and 1e with methyl but-2-ynoate in the presence
of the nickel catalyst demonstrates both applications. The reac-
tion of 1a with methyl but-2-ynoate produced aromatic
compound 3 regioselectively and the Diels–Alder cycloadducts
2a and 2b. Whereas, the reaction of 1e with methyl but-
2-ynoate provided 3 and exclusively 16 in 94 and 72% yields,
respectively. Compounds 1a and 1e, which provide an acetylene
moiety to each aromatic compound, serve as ‘masked acetylene’
in the reactions. All new products were characterized by the 1H,
13C NMR, and low and high resolution mass spectral data
(see the Experimental section).
In most of the regioselective cotrimerization of alkynes to
arenes catalyzed by cobalt complexes, a diyne was used as one
component and bistrimethylsilyl acetylene as the other. This
generally led to the formation of a mixture of isomers when
sterically less-hindered monoalkynes were used.25 The present
[2 ϩ 2 ϩ 2] cycloaddition reactions provide a highly regio-
selective, and exo selective new alternative method for the
construction of arenes by employing masked acetylenes.
(1R*,3R*,10S*,12S*)-19,20-Dioxahexacyclo[10.6.1.13,10.-
02,11.04,9.013,18]icosa-4,6,8,13,15,17-hexaene 2a. 1H NMR (300
MHz, CDCl3): δ 7.27 (m, 4 H, benzo), 7.08 (m, 4 H, benzo),
5.32 (dd, J = 3.4 Hz, J = 1.8 Hz, 2 H, bridgehead), 4.69 (s, 2 H,
bridgehead), 2.80 (dd, J = 3.4 Hz, J = 1.8 Hz, 2 H); 13C NMR
(75 MHz, CDCl3): δ 146.97 (s), 143.64 (s), 127.03 (d), 126.42
(d), 119.93 (d), 119.35 (d), 80.21 (d, O–C, bridgehead), 51.00
(d), 50.10 (d); MS: [m/z, (%)] 262 (Mϩ, 59.0), 233 (91.1), 215
(91.0), 118 [(C8H6O)ϩ, 100]; HRMS: calcd for C18H14O2
262.0995, found 262.0970.
(1R*,3S*,10R*,12S*)-19,20-Dioxahexacyclo[10.6.1.13,10.-
02,11.04,9.013,18]icosa-4,6,8,13,15,17-hexaene 2b. 1H NMR (300
MHz, CDCl3): δ 7.21 (dd, J = 5.2 Hz, J = 3.0 Hz, 4 H, benzo),
7.67 (dd, J = 5.3 Hz, J = 3.0 Hz, 4 H, benzo), 5.46 (s, 4 H,
bridgehead), 2.06 (s, 2 H); 13C NMR (75 MHz, CDCl3): δ
146.48 (s), 126.57 (d), 119.08 (d), 81.31 (d, O–C, bridgehead),
51.22 (d); MS: [m/z, (%)] 262 (Mϩ, 7.2), 233 (5.5), 215 (29.0),
202 (22.7), 189 (8.2), 165 (6.9), 118 [(C8H6O)ϩ, 100]; HRMS:
calcd for C18H14O2 262.0995, found 262.000.
1
Dimethyl 2,4-dimethylisophthaloate 3. H NMR (300 MHz,
CDCl3): δ 7.78 (d, J = 8.0 Hz, 1 H, aromatic H), 7.06 (d, J = 8.0
Hz, 1 H, aromatic H), 3.90 (s, 3 H, COOCH3), 3.85 (s, 3 H,
COOCH3), 2.47 (s, 3 H, CH3), 2.28 (s, 3 H, CH3); 13C NMR (75
Conclusion
We have observed unusual nickel-catalyzed reactions of oxa-
and azabenzonorbornadiene with various alkynes to give
common products 2a, 2b, and aromatic compounds. These
results may be rationalized based on a [2 ϩ 2 ϩ 2] cocyclo-
trimerization of two alkyne and one oxabenzonorbornadiene
molecules. The [2 ϩ 2 ϩ 2] cycloadducts undergo retro Diels–
Alder reaction to give aromatic products and isobenzofuran.
The latter is then trapped by oxabenzonorbornadiene to give
products 2a, 2b. We have isolated various [2 ϩ 2 ϩ 2] cyclo-
MHz, CDCl ): δ 171.56 (C᎐O), 170.11 (C᎐O), 167.63 (s), 138.72
᎐
᎐
3
(s), 136.31 (d), 136.22 (d), 128.04 (s), 127.34 (d), 52.11 (q), 51.88
(q) 19.71 (q), 17.98 (q); MS: [m/z, (%)] 222 (Mϩ, 47.2), 207
[(M Ϫ CH3)ϩ, 79.7], 191 [(M Ϫ OCH3)ϩ, 100], 162 [(M Ϫ
COOCH3)ϩ, 45.5]; HRMS: calcd for C12H14O4 222.0893, found
222.0897.
The reaction of 1a and various alkynes in the presence of
NiCl2(PPh3)2, PPh3 and zinc powder also led to the formation
J. Chem. Soc., Perkin Trans. 1, 2000, 195–203
199

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of 2a and 2b. The reaction conditions and the yields are listed in
Table 1.
benzo), 5.46 (br s, 2 H, cyclohexadiene), 5.16 (s, 2 H, O–CH,
bridgehead), 2.61 (br s, 2 H, ᎐CH, endo cyclohexadiene), 2.11 (t,
᎐
A similar procedure was employed for the reaction of 1e with
methyl but-2-ynoate to give 3 and 16 in 94 and 72% yields,
respectively. The spectral data of compound 16 follow.
J = 8.0 Hz, 4 H, CH2, pentyl), 1.35 (m, 12 H, CH2), 0.9 (t, 6 H,
J = 9.0 Hz, CH3); 13C NMR (75 MHz, CDCl3): δ 146.00 (s),
135.97 (s), 125.55 (d), 121.08 (d), 118.92 (d), 86.80 (d, O–C,
bridgehead), 41.05 (d), 32.29 (t), 31.89 (t), 29.00 (t), 22.61 (t),
14.11 (q); MS: [m/z, (%)] 336 (Mϩ, 0.8), 279 [(M Ϫ C4H8)ϩ,
16.0], 218 [(M Ϫ C8H6O)ϩ, 27], 118 (C8H6Oϩ, 100); HRMS:
calcd for C24H32O 336.2455, found 336.2451.
(1R*,3R*,10S*,12S*)-5,8,14,17-Tetramethyl-19,20-dioxa-
hexacyclo[10.6.1.13,10.02,11.04,9.013,18]icosa-4,6,8,13,15,17-hexaene
16. 1H NMR (300 MHz, CDCl3): δ 6.91 (s, 2 H, benzo), 6.77 (s,
2 H, benzo), 5.40 (dd, J = 2.97 Hz, J = 1.8 Hz, 2 H, bridgehead),
4.67 (s, 2 H, bridgehead), 2.76 (dd, J = 3.01 Hz, J = 1.7 Hz,
2 H), 2.39 (s, 6 H, 2 × CH3), 2.23 (s, 6 H, 2 × CH3); 13C NMR
(125 MHz, CDCl3): δ 144.99 (s), 141.89 (s), 128.28 (d), 127.77
(d), 126.29 (s), 125.81 (s), 78.98 (d, O–C, bridgehead), 76.04
(d, O–C, bridgehead), 49.61 (d), 18.20 (q), 17.95 (q); MS (FAB):
[m/z, (%)] 319 (M ϩ 1, 10.1), 173 (C12H13O, 88.3), 146 (C10H10O,
100); HRMS (M ϩ 1): calcd for C22H23O2 319.1698, found
319.1674.
(1R*,8S*,9R*,14S*)-10,13-Dipropyl-15-[(4-methylphenyl)-
sulfonyl]-15-azatetracyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-
pentaene 5d. Yield 64%. 1H NMR (400 MHz, CDCl3): δ 7.39 (d,
J = 6.0 Hz, 2 H, tosyl), 6.97–6.90 (m, 6 H, benzo tosyl), 5.38
(br s, 2 H, cyclohexadiene), 4.79 (s, 2 H, N–CH, bridgehead),
2.55 (br s, 2 H, ᎐CH, endo cyclohexadiene), 2.26 (s, 3 H, CH ),
᎐
3
2.05 (m, 4 H, CH2, propyl), 1.43 (m, 4 H, CH2, propyl), 0.94 (t,
J = 9.0 Hz, 6 H, CH3); 13C NMR (100 MHz, CDCl3): δ 144.13
(s), 143.79 (s), 136.42 (s), 135.96 (s), 128.71 (d), 127.74 (d),
126.46 (d), 122.82 (d), 119.94 (d), 71.39 (d, N–C, bridgehead),
43.19 (d), 34.51 (t), 22.47 (t), 21.28 (q), 13.88 (q); MS (FAB):
[m/z, (%)] 334 (M ϩ 1, 3.6), 271 (C15H13NSO2ϩ, 100), 231
(24.8), 91 (46.1); HRMS (Mϩ1): calcd for C27H32NSO2
434.2154, found 434.2155.
General procedure for the isolation of [2 ؉ 2 ؉ 2] cocyclo-
trimerization products. To a 50 ml round-bottomed side-arm
flask was added an oxa- or azabenzonorbornadiene (1.00
mmol), NiCl2(PPh3)2 (0.0325 g, 0.0500 mmol), PPh3 (0.210 g,
0.801 mmol) and zinc powder (0.180 g, 2.75 mmol). The system
was evacuated and purged with nitrogen gas three times. To the
system was added freshly distilled toluene (2.0 ml) and an
alkyne (mono alkyne, 2.0 mmol; bisalkyne, 1.0 mmol). The
reaction mixture was stirred for 24 h at a specified temperature
as shown in Table 2. The solution was filtered through Celite
and silica gel, and the filtrate was concentrated. The residue was
separated on a silica gel column using hexanes–dichloro-
methane as eluent to afford the [2 ϩ 2 ϩ 2] products. Com-
pounds 5a–d were thus prepared following the above procedure.
The corresponding minor isomers 4a–d cannot be separated
from 5a–d completely. Due to thermal instability, no purific-
ations on silica gel column were carried out for 4e, 4i–j. The
residues from concentration of the filtrates were used directly
for spectral analysis. For compounds 6a–d, the reaction tem-
perature was 18 ЊC and the reaction time was 48 h. Selected
spectral data are listed below:
(1R*,8S*,9R*,14S*)-10,12-Diphenyl-15-oxatetracyclo-
[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 4e. Yield 95%.
1H NMR (300 MHz, CDCl3): δ 7.40 (m, 10 H, phenyl), 7.25 (m,
4 H, benzo), 6.70 (br s, 1 H, cyclohexadiene), 6.05 (d, J = 3.6
Hz, 1 H, cyclohexadiene), 5.41 (s, 1 H, O–CH, bridgehead),
5.22 (s, 1 H, O–CH, bridgehead), 3.36 (d, J = 11 Hz, 1 H, endo
cyclohexadiene), 3.10 (dd, J = 11 Hz, J = 3.6 Hz, 1 H, ᎐CH,
᎐
endo cyclohexadiene); 13C {1H} NMR (75 MHz, CDCl3):
δ 146.10 (s), 145.20 (s), 140.80 (s), 135.52 (s), 132.50 (s), 132.48
(s), 129.10 (d), 128.71 (d), 128.25 (d), 128.24 (d), 127.51 (d),
127.48 (d), 127.00 (d), 126.10 (d), 125.90 (d), 125.20 (d), 122.26
(d), 122.10 (d), 118.75 (d), 118.31 (d), 86.62 (d, O–C, bridge-
head), 85.52 (d, O–C, bridgehead), 42.60 (d), 42.25 (d); MS:
[m/z, (%)] 262 [(M Ϫ C18H14)ϩ, 57.9], 230 [(M ϪC8H6O)ϩ, 100],
183 (28.2), 152 (20.9), 118 (C8H6Oϩ, 53.2).
(1R*,8S*,9R*,14S*)-10,13-Dipropyl-15-oxatetracyclo-
[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 5a. Yield 69%.
1H NMR (300 MHz, CDCl3): δ 7.24 (m, 2 H, benzo), 7.14 (m, 2
H, benzo), 5.47 (br s, 2 H, cyclohexadiene), 5.17 (s, 2 H, O–CH,
(1R*,8S*,9R*,14S*)-10,12-Diphenyl-15-[(4-methylphenyl)-
sulfonyl]-15-azatetracyclo[6.6.102,7.09,14]pentadeca-2,4,6,10,12-
pentaene 4f. Yield 93%. 1H NMR (300 MHz, CDCl3): δ
7.57–7.31 (m, 12 H, phenyl tosyl), 7.15–6.93 (m, 4 H, benzo),
6.92 (d, J = 8.14 Hz, 2 H, tosyl), 6.57 (s, 1 H, cyclohexadiene),
5.94 (d, J = 4.21 Hz, 1 H, cyclohexadiene), 5.04 (s, 1 H, N–CH,
bridgehead), 4.87 (s, 1 H, N–CH, bridgehead), 3.24 (d,
J = 11.31 Hz, 1 H, endo cyclohexadiene), 3.02 (dd, J = 11.35 Hz,
bridgehead), 2.62 (br s, 2 H, ᎐CH, endo cyclohexadiene), 2.08
᎐
(t, J = 8.0 Hz, 4 H, CH2, propyl), 1.46 (m, 4 H, CH2, propyl),
0.96 (t, J = 9.0 Hz, 6 H, CH3); 13C NMR (75 MHz, CDCl3):
δ 146.12 (s), 135.64 (s), 126.53 (d), 121.28 (d), 118.88 (d), 86.80
(d, O–C, bridgehead), 41.08 (d), 34.45 (t), 22.26 (t), 13.85 (q);
MS: [m/z, (%)] 280 (Mϩ, 0.5), 237 [(M Ϫ C3H7)ϩ, 3.5], 162 [(M
Ϫ C8H6O)ϩ, 17.5], 133 (54.4), 118 (C8H6Oϩ, 100); HRMS: calcd
for C20H24O 280.1828, found 280.1802.
J = 4.25 Hz, 1 H, ᎐CH, endo cyclohexadiene), 2.26 (s, 3 H,
᎐
CH3); 13C NMR (75 MHz, CDCl3): δ 144.67 (s), 143.88 (s),
142.75 (s), 140.66 (s), 140.15 (s), 136.35 (s), 136.01 (s), 135.96
(s), 129.15 (d), 128.85 (d), 128.80 (d), 128.76 (d), 128.49 (d),
128.41 (d), 127.79 (d), 127.73 (d), 127.39 (d), 127.22 (d), 126.90
(d), 126.08 (d), 125.87 (d), 125.66 (d), 123.61 (d), 121.32 (d),
120.43 (d), 120.21 (d), 119.60 (d), 71.46 (d, N–C, bridgehead),
69.40 (d, N–C, bridgehead), 43.81 (d), 43.64 (d), 21.33 (q); MS
(FAB): [m/z, (%)] 502 [(Mϩ 1)ϩ, 4.8], 271 (C15H13NSO2ϩ, 100),
231 (32.9), 91 (C7H7ϩ, 45.4); HRMS (M ϩ 1): calcd for C33H28
NSO2 502.1841, found 502.1815.
(1R*,8S*,9R*,14S*)-10,13-Dibutyl-15-oxatetracyclo-
[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 5b. Yield 62%.
1H NMR (300 MHz, CDCl3): δ 7.24 (m, 2 H, benzo), 7.16 (m, 2
H, benzo), 5.47 (br s, 2 H, cyclohexadiene), 5.16 (s, 2 H, O–CH,
bridgehead), 2.62 (br s, 2 H, ᎐CH, endo cyclohexadiene), 2.11 (t,
᎐
J = 8.0 Hz, 4 H, CH2, butyl), 1.39 (m, 8 H, CH2, butyl), 0.93 (t,
J = 9.0 Hz, 6 H, CH3); 13C NMR (75 MHz, CDCl3): δ 146.09
(s), 135.90 (s), 126.53 (d), 121.10 (d), 118.90 (d), 86.79 (d, O–C,
bridgehead), 41.05 (d), 31.99 (t), 31.49 (t), 22.60 (t), 14.06 (q);
MS: [m/z, (%)] 308 (Mϩ, 0.6), 190 [(M Ϫ C8H6O)ϩ, 29.5], 147
(16.8), 118 (C8H6Oϩ, 100), 105 (68.4); HRMS: calcd for
C22H28O 308.2142, found 308.2143.
(1R*,8S*,9R*,14S*)-10,12-Di(cyclohex-1-enyl)-15-oxatetra-
cyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 4g. Yield
95%. 1H NMR (300 MHz, CDCl3): δ 7.32 (m, 2 H, benzo), 7.18
(m, 2 H, benzo), 6.30 (br s, 1 H, cyclohexadiene), 6.01 (br t,
J = 3.9 Hz, 1 H, cyclohexenyl), 5.92 (br t, J = 3.9 Hz, 1 H,
cyclohexenyl), 5.74 (d, J = 2.8 Hz, 1 H, cyclohexadiene), 5.33 (s,
1 H, O–CH, bridgehead), 5.28 (s, 1 H, O–CH, bridgehead), 2.89
(1R*,8S*,9R*,14S*)-10,13-Dipentyl-15-oxatetracyclo-
[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 5c. Yield 61%. 1H
NMR (300 MHz, CDCl3): δ 7.25 (m, 2 H, benzo), 7.16 (m, 2 H,
(s, 1 H, endo cyclohexadiene), 2.88 (d, J = 2.8 Hz, 1 H, ᎐CH,
᎐
endo cyclohexadiene), 2.25 (m, 8 H, –CH2–, cyclohexenyl), 1.66
200
J. Chem. Soc., Perkin Trans. 1, 2000, 195–203

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(m, 8 H, CH2, cyclohexenyl); 13C NMR (75 MHz, CDCl3):
δ 146.74 (s), 145.25 (s), 135.95 (s), 135.27 (s), 135.23 (s), 135.04
(s), 126.68 (d), 126.64 (d), 124.41 (d), 123.07 (d), 119.36 (d),
118.32 (d), 118.24 (d), 117.47 (d), 87.51 (d, O–C, bridgehead),
86.72 (d, O–C, bridgehead), 42.56 (d), 40.71 (d), 26.40 (t), 26.22
(t), 25.78 (t), 22.95 (t), 22.38 (t), 22.25 (t); MS (FAB): [m/z, (%)]
356 [(M Ϫ H)ϩ, 17.9], 255 (87.9), 238 [(M Ϫ C8H6O)ϩ, 100], 118
(C8H6Oϩ, 76.4); HRMS (M Ϫ 1): calcd for C26H27O 355.2064,
found 355.2058.
MHz, CDCl3): δ 7.26 (m, 2 H, benzo), 7.15 (m, 2 H, benzo),
5.52 (br s, 2 H, ᎐CH, cyclohexadiene), 5.16 (s, 2 H, O–CH,
᎐
bridgehead), 2.69 (br s, 2 H, endo cyclohexadiene), 2.34 (m, 4 H,
2 × CH2), 1.77 (m, 1 H), 1.62 (m, 1 H); 13C NMR (75 MHz,
CDCl3): δ 146.22 (s), 139.65 (s), 126.54 (d), 118.89 (d), 115.37
(d), 86.62 (d, O–C, bridgehead), 42.03 (d), 31.38 (t), 24.48 (t);
MS (FAB): [m/z, (%)] 236 (Mϩ, 5.1), 154 (16.6), 136 (15.1), 118
[(C8H6O)ϩ, (C9H10)ϩ, 100]; HRMS: calcd for C17H16O 236.1201,
found 236.1198.
(1S*,2R*,11S*,12R*)-19-Oxapentacyclo[10.6.1.02,11.04,9.-
(1R*,8S*,9R*,14S*)-10,12-Di(cyclohex-1-enyl)-15-[(4-meth-
ylphenyl)sulfonyl]-15-azatetracyclo[6.6.1.02,7.09,14]pentadeca-
2,4,6,10,12-pentaene 4h. Yield 90%. 1H NMR (300 MHz,
CDCl3): δ 7.42 (d, J = 8.1 Hz, 2 H, tosyl), 7.11–6.85 (m, 6 H,
benzo tosyl), 6.24 (s, 1 H, cyclohexadiene), 5.99 (br s, 1 H, cyclo-
hexenyl), 5.81 (br s, 1 H, cyclohexenyl), 5.58 (br s, 1 H,
cyclohexenyl), 4.84 (s, 1 H, N–CH, bridgehead), 4.76 (s, 1 H,
1
0
13,18]nonadeca-3,9,13,15,17-pentaene 6b. Yield 70%. H NMR
(300 MHz, CDCl3): δ 7.22 (m, 2 H, benzo), 7.13 (m, 2 H,
benzo), 5.39 (br s, 2 H, ᎐CH, cyclohexadiene), 5.15 (s, 2 H, O–
᎐
CH, bridgehead), 2.62 (br s, 2 H, endo cyclohexadiene), 2.26 (m,
4 H, 2 × CH2), 1.57 (m, 4 H, 2 × CH2); 13C NMR (75 MHz,
CDCl3): δ 146.09 (s), 133.59 (s), 126.54 (d), 119.95 (d), 118.89
(d), 86.63 (d, O–C, bridgehead), 41.28 (d), 29.83 (t), 23.13 (t);
MS (FAB): [m/z, (%)] 250 (Mϩ, 9.4), 233 (22.3), 132
[(M Ϫ C8H6O)ϩ, 8.2], 118 [(C8H6O)ϩ, 100]; HRMS: calcd for
C18H18O 250.1357, found 250.1363.
N–CH, bridgehead), 2.82 (br s, 2 H, ᎐CH, endo cyclohexa-
᎐
diene), 2.28 (s, 3 H, CH3), 2.23 (m, 8 H, –CH2–, cyclohexenyl),
1.66 (m, 8 H, CH2, cyclohexenyl); 13C NMR (75 MHz, CDCl3):
δ 145.20 (s), 138.18 (s), 136.92 (s), 135.98 (s), 135.55 (s), 134.45
(s), 128.77 (d), 127.91 (d), 126.72 (d), 124.22 (d), 123.08 (d),
120.31 (d), 119.14 (d), 118.36 (d), 117.51 (d), 71.55 (d, N–C,
bridgehead), 70.26 (d, N–C, bridgehead), 43.17 (d), 41.87 (d),
26.32 (t), 26.21 (t), 25.81 (t), 22.93 (t), 22.88 (t), 22.30 (t), 22.27
(t), 21.38 (q); MS (FAB): [m/z, (%)] 509 (Mϩ, 2.1), 271
(C15H13NSO2ϩ, 91.6), 91 (C7H7)ϩ; HRMS (FAB): calcd for
C33H35NSO2 509.2388, found 509.2398.
(1S*,2R*,10S*,11R*)-18-[(4-Methylphenyl)sulfonyl]-18-
azapentacyclo[9.6.1.02,10.04,8.012,17]octadeca-3,8,12,14,16-
pentaene 6c. Yield 71%. 1H NMR (300 MHz, CDCl3): δ 7.40 (d,
J = 8.23 Hz, 2 H, tosyl H), 6.99–6.91 (m, 6 H, aromatic), 5.43
(br s, 2 H, ᎐CH, cyclohexadiene), 4.78 (s, 2 H, N–CH, bridge-
᎐
head), 2.61 (br s, 2 H, endo cyclohexadiene H), 2.31 (m, 4 H,
2 × CH2), 2.27 (s, 3 H, CH3), 1.76 (m, 1 H), 1.64 (m, 1 H); 13
C
(1S*,8R*,9S*,14R*)-10,12-Diphenyl-3-methoxy-15-oxatetra-
NMR (75 MHz, CDCl3): δ 144.39 (s), 142.64 (s), 140.43 (s),
136.05 (s), 128.75 (d), 127.82 (d), 126.56 (d), 119.86 (d), 114.59
(d), 70.90 (d, N–C, bridgehead), 42.87 (d), 31.41 (t), 24.54 (t),
21.36 (q); MS (FAB): [m/z, (%)] 390 (M ϩ 1, 6.7), 271
(C15H13NSO2ϩ, 100), 155 (25.4), 91 (45.4); HRMS (Mϩ1): calcd
for C24H24NSO2 390.1528, found 390.1518.
cyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene
4i
and
(1S*,8R*,9S*,14R*)-10,12-diphenyl-6-methoxy-15-oxatetra-
cyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene 4iЈ. Com-
bined yield 72%. The following two sets of spectral data are for
1
compounds 4i and 4iЈ. H NMR (300 MHz, CDCl3): δ 7.50–
6.80 (m, 13 H, phenyl, benzo), 6.70 (s, 1 H, cyclohexadiene),
6.02 (d, J = 4.5 Hz, 1 H, cyclohexadiene), 5.60 (s, 1 H, O–CH,
bridgehead), 5.24 (s, 1 H, O–CH, bridgehead), 3.86 (s, 3 H,
OCH3), 3.31 (d, J = 11.5 Hz, 1 H, endo cyclohexadiene), 3.11
(1S*,2R*,11S*,12R*)-19-[(4-Methylphenyl)sulfonyl]-19-aza-
pentacyclo[10.6.1.02,11.04,9.013,18]nonadeca-3,9,13,15,17-pentaene
6d. Yield 75%. 1H NMR (300 MHz, CDCl3): δ 7.43 (d, J = 8.27
Hz, 2 H, tosyl H), 7.01–6.92 (m, 6 H, aromatic), 5.32 (br s, 2 H,
(dd, J = 11.5 Hz, J = 4.5 Hz, 1 H, ᎐CH, endo cyclohexadiene);
᎐
MS (FAB): [m/z, (%)] 337 [(M ϩ 1)ϩ, 15.0], 361 [(M Ϫ O)ϩ,
16.8], 307 (13.63).
᎐CH, cyclohexadiene), 4.79 (s, 2 H, N–CH, bridgehead), 2.57
᎐
(br s, 2 H, endo cyclohexadiene H), 2.28 (s, 3 H, CH3), 2.25 (m, 4
H, 2 × CH2), 1.59 (m, 4 H, 2 × CH2); 13C NMR (75 MHz,
CDCl3): δ 144.62 (s), 142.65 (s), 135.61 (s), 134.38 (s), 128.76
(d), 127.76 (d), 126.54 (d), 119.83 (d), 119.06 (d), 70.88 (d, N–C,
bridgehead), 42.08 (d), 29.77 (t), 23.03 (t), 21.34 (q); MS (FAB):
[m/z, %)] 404 (M ϩ 1, 3.3), 271 (C15H13NSO2ϩ, 100), 155 (23.5),
91 (47.7); HRMS (Mϩ1): calcd for C25H26NSO2 404.1684,
found 404.1675.
1H NMR (300 MHz, CDCl3): δ 7.50–6.80 (m, 13 H, phenyl,
benzo), 6.75 (s, 1 H, cyclohexadiene), 6.10 (d, J = 4.5 Hz, 1 H,
cyclohexadiene), 5.52 (s, 1 H, O–CH, bridgehead), 5.38 (s, 1 H,
O–CH, bridgehead), 3.86 (s, 3 H, OCH3), 3.31 (d, J = 11.5 Hz,
1 H, endo cyclohexadiene), 3.04 (dd, J = 11.5 Hz, J = 4.5 Hz, 1
H, ᎐CH, endo cyclohexadiene); MS (FAB): [m/z, (%)] 337
᎐
[(M ϩ 1)ϩ, 15.0], 361 [(M Ϫ O)ϩ, 16.8], 307 (13.63).
(1S*,8R*,9S*,14R*)-3,6-Dimethoxy-10,12-diphenyl-15-oxa-
tetracyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,10,12-pentaene
4j.
Diels–Alder cycloaddition of in situ generated isobenzofuran
or isoindole with 1a. To a 50 ml round-bottomed side-arm flask
consisting of 6c (or 6d) (0.0720 mmol) and 1a (0.0104 g, 0.0720
mmol) was added freshly distilled xylene (5.0 ml). The system
was evacuated and purged with nitrogen gas three times. The
reaction mixture was then heated at 90 ЊC for 7.5 h. The solvent
was removed under vacuum and the resulting solid was purified
by silica gel column using a mixture of hexanes–ethyl acetate
(v/v = 7/3) as eluent to give 10 in 70% yield.
1
Yield 74%. H NMR (300 MHz, CDCl3): δ 7.40 (m, 10 H,
phenyl), 6.79 (s, 1 H, cyclohexadiene), 6.71 (br s, 2 H, dimeth-
oxybenzo), 6.09 (d, J = 4.4 Hz, 1 H, cyclohexadiene), 5.58 (s, 1
H, O–CH, bridgehead), 5.50 (s, 1 H, O–CH, bridgehead), 3.83
(s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 3.32 (d, J = 11.6 Hz, 1 H,
endo cyclohexadiene), 3.11 (dd, J = 11.6 Hz, J = 4.4 Hz, 1 H,
᎐CH, endo cyclohexadiene); 13C NMR (75 MHz, CDCl3):
᎐
δ 146.69 (s), 146.46 (s), 141.72 (s), 141.11 (s), 139.42 (s), 135.67
(s), 135.47 (s), 134.98 (s), 128.74 (d), 128.52 (d), 128.35 (d),
127.34 (d), 127.19 (d), 126.05 (d), 125.82 (d), 125.49 (d), 122.52
(d), 121.89 (d), 85.15 (d, O–C, bridgehead), 84.08 (d, O–C,
bridgehead), 56.16 (q, OCH3), 56.01 (q, OCH3), 42.84 (d), 41.96
(d); MS: [m/z, (%)] 408 (Mϩ, 0.1), 230 [(M Ϫ C18H14)ϩ, 100], 178
[(C10H10O3)ϩ, 1.16]; HRMS: calcd for C28H24O3 408.1725,
found 408.1717.
(1S*,3S*,10R*,12R*)-20-[(4-Methylphenyl)sulfonyl]-19-oxa-
20-azahexacyclo[10.6.1.13,10.02,11.04,9.013,18]icosa-4,6,8,13,15,17-
hexaene 10. 1H NMR (300 MHz, CDCl3): δ 7.34 (d, J = 7.6 Hz,
2 H, tosyl H), 7.12 (m, 4 H, benzo), 7.07 (m, 4 H, benzo), 6.94
(d, J = 6.4 Hz, 2 H, tosyl H), 5.07 (br s, 2 H, O–CH, bridge-
head), 4.66 (s, 2 H, N–CH, bridgehead), 2.95 (br s, 2 H), 2.27 (s,
3 H, CH3); 13C NMR (75 MHz, CDCl3): δ 146.13 (s), 142.84 (s),
141.24 (s), 136.26 (s), 129.85 (d), 128.92 (d), 127.82 (d), 127.35
(d), 126.87 (d), 126.67 (d), 120.43 (d), 118.94 (d), 77.69 (d, C–O,
(1S*,2R*,10S*,11R*)-18-Oxapentacyclo[9.6.1.02,10.04,8.012,17]-
1
octadeca-3,8,12,14,16-pentaene 6a. Yield 62%. H NMR (300
J. Chem. Soc., Perkin Trans. 1, 2000, 195–203
201

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bridgehead), 65.42 (d, N–C, bridgehead), 49.26 (d), 21.33
(q); MS (FAB): [m/z, (%)] 416 [(M ϩ 1)ϩ, 28.8], 272 (85.9),
271 (100), 245 (72.5), 91(75.2); HRMS (M ϩ 1): calcd for
C25H22NSO3 416.1320, found 416.1352.
Similarly, 11 and 12, 13 and 14 and 15 were prepared by
reacting 6a with cyclohex-2-en-1-one, dimethyl acetylenedicarb-
oxylate and N-methoxycarbonyl-7-azabenzonorborndiene at
60 ЊC in toluene for 3 h. The combined yields of these products
is 77, 60 and 68%. Selected spectral data of these products
follow.
References
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δ 189.53 (C᎐O, s), 145.33 (s), 144.43 (s), 126.86 (d), 126.77 (d),
᎐
119.27 (d), 118.99 (d), 84.27 (d, C–O, bridgehead), 81.91 (d,
C–O, bridgehead), 51.97 (d), 42.38 (d), 38.98 (t), 27.92 (t),
20.59 (t).
(1S*,2R*,7S*,8R*)-15-Oxatetracyclo[6.6.1.02,7.09,14]penta-
deca-9,11,13-trien-3-one 12. 1H NMR (300 MHz, CDCl3):
δ 7.26–7.15 (m, 4 H, benzo), 5.59 (d, J = 5.5 Hz, 1 H, O–CH,
bridgehead), 5.33 (d, 1 H, J = 4.9 Hz, O–CH, bridgehead), 3.15
(m, 1 H, CH), 2.99 (m, 1 H, CH), 2.06 (m, 1 H, CH), 2.00 (m,
1 H), 1.49–1.29 (m, 2 H, CH2), 0.91 (m, 1 H), 0.67 (m, 1 H); 13
C
NMR (75 MHz, CDCl ): δ 189.5 (C᎐O, s), 143.75 (s), 143.19 (s),
᎐
3
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127.05 (d), 126.68 (d), 121.81 (d), 120.98 (d), 83.24 (d, C–O,
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38.49 (d), 24.38 (t), 20.24 (t).
Dimethyl
11-oxatricyclo[6.2.1.02,7]undeca-2,4,6,9-tetraene-
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δ 162.78 (C᎐O, s), 151.19 (s), 146.12 (s), 126.12 (d), 121.48 (d),
᎐
84.79 (d, C–O, bridgehead), 52.38 (d).
11 N. E. Schore, Chem. Rev., 1988, 88, 1081; B. M. Trost, Science, 1996,
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Methyl (1S*,2S*,3S*,10R*,11R*,12R*)-19-oxa-20-azahexa-
cyclo[10.6.1.13,10.02,11.04,9.013,18]icosa-4,6,8,13,15,17-hexaene-20-
carboxylate 14. H NMR (300 MHz, CDCl3): δ 7.20 (m, 4 H,
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1
benzo), 7.04 (m, 4 H, benzo), 5.38 (dd, J = 3.5 Hz, J = 1.9 Hz,
2 H, O–CH, bridgehead), 4.67 (s, 2 H, N–CH, bridgehead), 3.68
(s, 3 H, OCH3), 2.69 (dd, J = 3.4 Hz, J = 1.9 Hz, 2 H); 13C NMR
(75 MHz, CDCl ): δ 154.68 (C᎐O, s), 147.27 (s), 145.72 (s),
᎐
3
13 R. Grigg, R. Scott and P. Stevenson, J. Chem. Soc., Perkin Trans. 1,
1988, 1365; Z. Zhou, L. P. Battaglia, G. P. Chiusoli, M. Costa,
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127.40 (d), 126.63 (d), 119.65 (d), 119.32 (d), 81.09 (d, C–O,
bridgehead), 62.58 (d, C–N, bridgehead), 52.12 (d), 51.82 (q);
MS (FAB): [m/z, (%)] 319 (Mϩ, 8.3), 320 (M ϩ 1, 68.3), 245
(41.8), 175 (100), 118 (C8H6O, 40.8); HRMS (M ϩ 1): calcd for
C20H18NO3 320.1286, found 320.1273.
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pentadiene complex, see: Y. Wakatsuki, O. Nomura, K. Kitaura,
Methyl (1R*,2S*,3S*,10R*,11R*,12S*)-19-oxa-20-azahexa-
cyclo[10.6.1.13,10.02,11.04,9.013,18]icosa-4,6,8,13,15,17-hexaene-20-
carboxylate 15. H NMR (300 MHz, CDCl3): δ 7.23 (m, 4 H,
1
benzo), 7.03 (m, 4 H, benzo), 5.25 (s, 2 H, O–CH, bridgehead),
4.57 (s, 2 H, N–CH, bridgehead), 3.19 (s, 3 H, OCH3), 1.97 (s,
2 H); 13C NMR (75 MHz, CDCl ): δ 153.64 (C᎐O, s), 146.20
᎐
3
(s), 145.48 (s), 127.22 (d), 126.42 (d), 120.23 (d), 119.49 (d),
80.21 (d, C–O, bridgehead), 50.72 (d, C–N, bridgehead), 51.03
(q), 49.62 (d); MS (FAB): [m/z, (%)] 320 (M ϩ 1, 68.3), 176
(96.40), 175 (100), 118 (C8H6O, 40.5); HRMS (M ϩ 1): calcd
for C20H18NO3 320.1286, found 320.1268.
Acknowledgements
We are grateful to the National Science Council of the Republic
of China for financial support of this research (NSC 87-2811-
M-007-0042). TS thanks NSC for a Post Doctoral fellowship.
202
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Paper a907654i
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