Synthesis and conformations of [2.n]metacyclophan-1-ene epoxides and their conversion to [n.1]metacyclophanes

Article abstract of DOI:10.1039/c7ob00400a

A series of syn- and anti-[2.n]metacyclophan-1-enes have been prepared in good yields by McMurry cyclizations of 1,n-bis(5-tert-butyl-3-formyl-2-methoxyphenyl)alkanes. Significantly, acid catalyzed rearrangements of [2.n]metacyclophan-1-enes afforded [n.1]metacyclophanes in good yield. The ratios of the products are strongly regulated by the number of methylene bridges present. The percentages of the rearrangement products increase with increasing length of the carbon bridges. Characterization and the conformational studies of these products are described. Single crystal X-ray analysis revealed the adoption of syn- and anti-conformations. DFT calculations were carried out to estimate the energy-minimized structures of the synthesized metacyclophanes.

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Synthesis and conformations of [2.n]metacyclophan-1-ene
epoxides and their conversion to [n.1]metacyclophanes
Thamina Akther,a Md. Monarul Islam,a,b Shofiur Rahman,c Paris E. Georghiou,c Taisuke
Matsumoto,d Junji Tanaka,d Carl Redshawe and Takehiko Yamato*a
Received 00th January 2016,
Accepted 00th January 2016
DOI: 10.1039/x0xx00000x
A series of synꢀ and antiꢀ[2.n]metacyclophanꢀ1ꢀenes have been prepared in good yields by McMurry cyclizations of 1,nꢀ
bis(5ꢀtertꢀbutylꢀ3ꢀformylꢀ2ꢀmethoxyphenyl)alkanes. Significantly, acid catalyzed rearrangements of [2.n]metacyclophanꢀ1ꢀ
enes afforded [n.1]metacyclophanes in good yield. The ratios of the products are strongly regulated by the number of
methylene bridges present. The percentages of the rearrangement products increase with increasing length of the carbon
bridges. Characterization and the conformational studies of these products are described. Single crystal Xꢀray analysis
revealed the adoption of synꢀ and antiꢀconformations. DFT calculations were carried out to estimate the energyꢀminimized
structures of the synthesized metacyclophanes.
www.rsc.org/
Introduction
Cyclophanes1 have been wellꢀstudied in organic chemistry and
have been found to adopt unusual chemical conformations due
to the buildꢀup of strain. Although the parent
Recently, we have reported the formation of 1,2ꢀ
dimethyl[2.n
]MCPꢀ1ꢀenes11 by employing the reductive
coupling of carbonyl compounds by lowꢀvalent titanium, i.e.
deploying the McMurry reaction12–16 as a key step. In this
[2.2]metacyclophane (MCP
= metacyclophane) was first
reported as early as 1899 by Pellegrin,2 the synthesis of syn
ꢀ
paper, we report the synthesis of [2.
McMurry cyclization reaction and subsequent conversion to
1,2ꢀepoxy[2. ]MCP. The latter compounds were further
modified to [ .1]MCPs by an acid catalyzed rearrangement.
Conformational studies of these MCPs which can adopt anti
n]MCPꢀene using the
[2.2]MCP was only realized 85 year later. Mitchell et al.3
efficiently prepared synꢀ[2.2]MCP at low temperature using
(arene)chromiumcarbonyl complexation to influence the
stereochemistry. Later, Itô et al.4 also isolated and characterized
synꢀ[2.2]MCP, and it can be noted that synꢀ[2.2]MCP
isomerizes conveniently to its antiꢀisomer above 0 °C. On the
other hand, Boekelheide5 and Staab6 successfully synthesized
the intraꢀannularly substituted synꢀ[2.2]MCPs. However,
n
n
ꢀ
and/ synꢀconformations (as represented in Fig. 1), both in
solution and the solid state are also described.
Results and discussion
reports on the synthesis and reaction chemistry of syn
[2. ]MCP have not thus far been published.
ꢀ
n
The starting compounds 1,6ꢀbis(5ꢀtertꢀbutylꢀ3ꢀformylꢀ2ꢀ
On the other hand, Merz et al.7 reported the stereospecific methoxy phenyl)hexane 1a and 1,8ꢀbis(5ꢀtertꢀbutylꢀ3ꢀformylꢀ2ꢀ
epoxidation of (
E
)ꢀ and (
Z
)ꢀstilbene crown ethers with
mꢀ
methoxy phenyl)octane 1b are easily prepared from 1,6ꢀbis(5ꢀ
chloroperbenzoic acid to afford the epoxy crown ethers. Oda et tertꢀbutylꢀ2ꢀmethoxyphenyl)hexane and 1,8ꢀbis(5ꢀtertꢀbutylꢀ2ꢀ
al.8 also published the epoxidation of transꢀdiethylstilbestrol methoxyphenyl)octane, respectively according to our previous
with
diethylstilbestrol oxide. Thus, there is considerable interest in titanium tetrachloride (TiCl4), a regioselective FriedelꢀCrafts
synthesizing the [2.
]MCPꢀ1ꢀenes and their conversion to 1,2ꢀ acylation reaction20, 21 at the meta positions of 1,6ꢀbis(5ꢀtert
epoxy[2. ]MCP, which can enforce the synꢀconformation, butylꢀ2ꢀmethoxyphenyl)hexane and 1,8ꢀbis(5ꢀtertꢀbutylꢀ2ꢀ
whilst restricting the flexibility resulting from ring inversion.
Although [ .1]MCPs have been prepared by various workers,
m
ꢀchloroperbenzoic acid to afford the racemic trans
ꢀ
synthetic route.17–19 In the presence of dichloromethyl ether and
n
ꢀ
n
n
these previous synthetic routes were too tedious for practical
application. Vögtle9 reported the first synthesis of both [4.1]
and [5.1]MCP by the application of a new method, namely
sulfone pyrolysis. Later, Lin et al.10 succeeded in preparing the
lower [3.1]homologue by implementing
a photochemical
method. However, it was quite difficult to obtain sufficient
amounts of the products for any subsequent studies by
following such a route.
Fig. 1 Possible configurations of [n.1]MCPs.
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Scheme
dimethyl[2.6]MCPꢀ1ꢀene 4a and 5,19ꢀdiꢀtertꢀbutylꢀ8,22ꢀdimethoxyꢀ
1,2ꢀdimethyl[2.8]MCPꢀ1ꢀene 4b 1,2ꢀdimethyl[2.8]MCPꢀ1ꢀene 4b
2
Synthesis of 5,17ꢀdiꢀtertꢀbutylꢀ8,20ꢀdimethoxyꢀ1,2ꢀ
Scheme 1 Synthesis of 1,6ꢀbis(3ꢀacetylꢀ5ꢀtertꢀbutylꢀ2ꢀmethoxyphenyl)
hexane 3a and 1,8ꢀbis(3ꢀacetylꢀ5ꢀtertꢀbutylꢀ2ꢀmethoxyphenyl)octane
3b.
.
.
the opposite aromatic ring. The structure of the synꢀconformer
is also easily evaluated from the chemical shift of the methoxy
methoxyphenyl)octane was achieved at room temperature to
afford the required 1a and 1b in 68 and 74% yield,
respectively. To a solution of methylmagnesium iodide in Et2O
protons at
observed at higher field, viz
effect of the aromatic ring. The aromatic protons of syn
reported at much higher field ( 6.64 and 6.77 ppm) than those
of compound anti 4a. These data confirm the assigned antiꢀ and
synꢀstructures for both two 4a conformers.
The Xꢀray structure of anti 4a (CCDC 1526807) in Fig. 2
δ
3.67 ppm. Here, the tertꢀbutyl proton of syn
1.11 ppm, due to the shielding
4a are
ꢀ4a is
δ
was added
a solution of compounds 1a and 1b in
ꢀ
tetrahydrofuran (THF) dropwise under relatively mild
conditions (refluxing for 12 h) to afford 1,6ꢀbis(5ꢀtertꢀbutylꢀ3ꢀ
(1ꢀhydroxyethyl)ꢀ2ꢀmethoxy phenyl)hexane 2a and 1,8ꢀbis(5ꢀ
tertꢀbutylꢀ3ꢀ(1ꢀhydroxyethyl)ꢀ2ꢀmethoxyphenyl)octane 2b in
74 and 77% yield, respectively.
δ
ꢀ
ꢀ
clearly reveals that it is the antiꢀconformer in the solid state and
that the two methoxy groups lie on the correlative side of the
inner ring, which consists of a long bridging C16–C21 chain
pointing outwards to minimize the steric repulsion with the
bridge chain. The bond lengths of C21–C20 and C22–C21 in
the hexamethylene chains and C2–C24 and C1–C5 in the
ethylenic chains have standard values at 1.53, 1.50, 1.50 and
1.49 Å, respectively. The length of the double bond in C1–C2 is
1.34 Å, which is like that of ethylene. The bond angles defined
by C1–C2–C24 and C2–C1–C5 are 123.3(2)° and 122.7(2)°,
Oxidations22 of 2a and 2b were carried out in acetone by
adding them dropwise to
a
solution of pyridinium
chlorochromate (PCC) in acetone and stirring at room
temperature for 24 h; 1,6ꢀbis(3ꢀacetylꢀ5ꢀtertꢀbutylꢀ2ꢀmethoxy
phenyl)hexane 3a and 1,8ꢀbis(3ꢀacetylꢀ5ꢀtertꢀbutylꢀ2ꢀmethoxy
phenyl)octane 3b in 69 and 62% yields, were produced
respectively as shown in Scheme 1.23–29 Elemental analysis and
spectral data were used to resolve the structures of compounds
2
and 3 2 and 3 were also
. Furthermore, the 1H NMR signals of
unambiguously assigned. The compounds 3a and 3b were
subjected to reductive coupling by the McMurry reaction
following the upgraded Grützmacher's procedure30 (Scheme 2).
showing that compound antiꢀ4a displays a nonꢀdistorted
conformation. The two benzene rings of 4a slightly deviate
from planarity. The intramolecular distances of C5–C24, C6–
C23, C9–C29, C10–C25, C7–C22, C8–C27 are 2.97, 3.45,
8.08, 5.18, 4.69 and 6.11 Å.
Thus, the reductive coupling reaction of
3 was carried out by
using TiCl4ꢀZn in the presence of pyridine in refluxing THF
under high dilution conditions to afford the required
compounds antiꢀ and synꢀ5,17ꢀdiꢀtertꢀbutylꢀ8,20ꢀdimethoxyꢀ
1,2ꢀdimethyl [2.6]MCPꢀ1ꢀene 4a in 23 and 13% yields,
The 1H NMR (CDCl3, 300 MHz) spectrum of anti
possesses a singlet at 3.52 ppm for the methoxy protons, and
a singlet at 1.28 ppm for the tertꢀbutyl protons. For the
aromatic protons, a pair of doublets was observed at 6.86 and
7.01 ( = 2.4 Hz) ppm which are in the deshielding region of
ꢀ4b
δ
δ
respectively and anti
ꢀ
and synꢀ5,19ꢀdiꢀtertꢀbutylꢀ8,22ꢀ
δ
dimethoxyꢀ1,2ꢀdimethyl[2.8] MCPꢀ1ꢀene 4b in 21 and 64%
yields, respectively. This result was different from that of the
related McMurry cyclization of 1,3ꢀbis(5ꢀacetylꢀ2ꢀmethoxyꢀ
phenyl)propane, which afforded the corresponding [3.1]MCP
by TiCl4 or acid induced pinacol rearrangement.31
J
the bridged double bond. Thus, the methoxy protons experience
an upfield shift due to the ring current of the opposite aromatic
ring. From the chemical shift of the methoxy protons at
ppm, the structure of the synꢀconformer is confirmed. Also, the
tertꢀbutyl proton of syn 4b occurs to higher field, i.e. 1.12
ppm, due to the shielding effect of the benzene ring. The
aromatic protons of syn 4b are observed at much higher field (
6.74 and 6.82 ppm) than those of anti 4b. These data allow for
the assignment of the anti and syn structures of the two
conformers of 4b
The Xꢀray structure of anti
δ 3.69
The structures of 4a and 4b were elucidated on the basis of
their elemental analyses and spectral data. In particular, the
mass spectral data for 4a and 4b (M+ = 462.4 for 4a and 490.4
for 4b) fully support the cyclic structure. The conformations of
ꢀ
δ
ꢀ
δ
ꢀ
1
4a and 4b were readily apparent from their H NMR spectrum.
The 1H NMR spectrum of anti
δ
ꢀ
4a in CDCl3 exhibits a singlet at
3.34 ppm for the methoxy protons, a singlet at 1.31 ppm for
the tertꢀbutyl protons and a pair of doublets at 6.89 and 7.04
= 2.7Hz) ppm for the aromatic protons, which are in the
.
δ
δ
ꢀ
4b (CCDC 1526816) in Fig. 2
clearly demonstrates that the antiꢀconformer is adopted in the
solid state and that the two methoxy groups lie on the
correlative side of the inner ring, which contains the long
(
J
deshielded region of the bridged double bond. Thus, the
methoxy protons appear upfield because of the ring current of
2 | J. Name., 2012, 00, 1-3
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Top view
Side view
Scheme 3 Synthesis of 5,17ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀdimethylꢀ8,20ꢀ
dimethoxy[2.6]MCP 5a and 5,19ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀdimethylꢀ
8,22ꢀdimethoxy[2.8]MCP 5b
.
The protons of the hexamethylene bridge gave rise to a
complicated signal pattern, as would be expected for a rigid
synꢀ[2.6]MCP. The protons of the benzylic CH2 group were
Top view
Side view
observed as two multiplets centered at
δ 2.28 and 2.49 ppm
which were further split by coupling with the protons of the
other CH2 groups. The peak pattern ascribed to twelve
chemically distinct protons of the alkane bridge was evidence
Fig.
2
ORTEP drawings of Top: antiꢀ5,17ꢀdiꢀtertꢀbutylꢀ8,20ꢀ
dimethoxyꢀ1,2ꢀdimethyl[2.6]MCPꢀ1ꢀene 4a; and Bottom: antiꢀ5,19ꢀdiꢀ
tertꢀbutyl8,22ꢀdimethoxyꢀ1,2ꢀdimethyl[2.8]MCPꢀ1ꢀene 4b Thermal
ellipsoids are drawn at the 50% probability level. All hydrogen atoms
are omitted for clarity.
.
for the absence of a anti
ꢀanti interconversion which would
exchange the HA and HB protons of each CH2 group.
1
The H NMR spectrum of syn
aromatic proton at 7.11 ( = 2.4 Hz) ppm in addition to the
resonances at 6.84 ppm for the other two protons of the
ꢀ5b revealed a doublet for the
bridging C16–C23 chain pointing outwards to keep the steric
repulsion with the bridge chain to a minimum. The bond
lengths of C23–C22 and C24–C23 in the octamethylene chains
and C2–C26 and C1– C5 in the ethylenic chains have standard
values at 1.44, 1.43, 1.45 and 1.45 Å, respectively. The length
of the double bond in C1–C2 is 1.34 Å, which is similar to that
of ethylene. The bond angles defined by C1–C2–C26 and C2–
C1–C5 are 121.4(2)° and 121.3(2)°, showing that compound 4b
displays a nonꢀdistorted conformation. The two benzene rings
of 4b moderately deviate from planarity. The intramolecular
distances of C5–C26, C6–C25, C9–C31, C10–C27, C7–C24,
C8–C29 are 2.86, 3.70, 6.29, 5.80, 4.89 and 4.85 Å.
δ
J
δ
aromatic rings. These observations suggest that the structure
consists exclusively of the synꢀconformation. These estimations
strongly suggest that the exoꢀepoxide structure of syn
synꢀepoxidation from exoꢀattack at the double bond of syn
which is formed at the time of the ring inversion of synꢀ4b
might be sterically favourable.
The protons of the octamethylene bridge gave rise to a
complex signal pattern, again as expected for a rigid syn
[2.8]MCP. The protons of the benzylic CH2 group were
observed as two multiplets centered at 2.21 and 2.91 ppm
ꢀ5b and
ꢀ
4
ꢀ
The epoxidation32 of 4a and 4b with
in the presence of dichloromethane at room temperature for 40
h afforded the desired 1,2ꢀepoxy[2. ]MCP 5a and 5b in 55 and
67% yields, respectively, as colourless prisms (Scheme 3). The
1H NMR for the benzene proton at
7.38 ppm ( = 2.4 Hz) in
addition to resonances at 6.95 and 7.29 ppm for the other two
protons of the aromatic rings. These observations strongly
m
ꢀchloroperbenzoic acid
δ
which were further split by coupling with the protons of the
CH2 groups. The peak pattern ascribed to sixteen chemically
n
distinct protons of the alkane bridge proved the absence of syn
syn interconversion which would exchange HA and HB of each
CH2 group. These findings suggest a rigid structure for syn 4b
at this temperature. This result suggests that the introduction of
an oxirane ring into the ethano bridge can strongly reduce the
flexibility arising from ring inversion.
ꢀ
δ
J
ꢀ
δ
suggest that the structure corresponds exclusively to the anti
conformation. These findings strongly suggest that the exo
ꢀ
ꢀ
Compound antiꢀ5,17ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀdimethylꢀ
epoxide structure of 5a and the synꢀepoxidation resulting from
exoꢀattack at the double bond of syn 5a formed during the ring
inversion of anti 5a might be sterically favourable (Table 1).
However, several attempts of preparing syn 5a by epoxidation
of anti 4a failed and only an intractable mixture of products
resulted.
ꢀ
Table 1 Conformational analysis of [n.2]MCPꢀenes 5a, b.
ꢀ
Products yield [%]a
Number of
ꢀ
Compound
ꢀ
methylene units [n]
antiꢀ5
55
synꢀ5
0
antiꢀ4a
antiꢀ4b
6
8
0
67
a Isolated yields are shown in parentheses.
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The crystal structure (CCDC 1526822) shows that the
conformation adopted by synꢀ5,19ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀ
dimethylꢀ8,22ꢀdimethoxy[2.8]MCP 5b is the synꢀconformation,
in which two aromatic rings are part of a nonꢀplanar chain (Fig.
3). Here, the bond lengths of C16–C17 and C16–C7 in the
octamethylene chains and C5–C1 and C26–C2 in the ethylenic
chains have typical values at 1.54, 1.51, 1.50 and 1.51 Å,
respectively. The bond angles defined by C25–C26–C2 and
C1–C5–C6 are 121.6 and 122.8 Å, showing that 5b displays a
slightly distorted conformation. The two benzene rings of 5b
slightly deviate from planarity. The intramolecular distances of
C5–C26, C1–C6, C7–C24, C9–C28 are 3.08, 4.41, 5.88 and
4.95 Å. Both methoxy groups on the benzene rings of 5b point
outwards, away from the decamethylene bridge chain. This
contributes to the lack of steric crowding with the hydrogens
and carbons of the bridge chains. Thus, it is a meso compound.
In the case of the treatment of compounds 5a and 5b with
BF3ꢀEt2O as catalyst in CH2Cl2, the desired acid catalyzed
rearrangement33 products [6.1]MCP 6a and [8.1]MCP 6b were
obtained as the main products in 51 and 41% yields,
respectively (Table 2). No formation of dehydration product(s)
or ringꢀcleavage product(s) was observed. The yields of the
Fig. 3 ORTEP drawings of Top: antiꢀ5,17ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀ
dimethylꢀ8,20ꢀdimethoxy[2.6]MCP 5a; and Bottom: synꢀ5,19ꢀdiꢀtert
ꢀ
rearrangement products
methylene bridges. This result might be attributed to the
decrease of carbon ring strain in the [ .1]MCPs.
Similarly, the conformation of the [ .1]MCPs 6a and 6b were
6 decrease with the number of the
butylꢀ1,2ꢀepoxyꢀ1,2ꢀdimethylꢀ8,22ꢀdimethoxy[2.8]MCP 5b Thermal
.
ellipsoids are drawn at the 50% probability level. All hydrogen atoms
are omitted for clarity.
n
n
1
8,20ꢀdimethoxy[2.6]MCP
5a
crystallized
in
the
readily apparent from their H NMR spectra. For example, in
1
centrosymmetric space group P21/a (CCDC 1526819). There
are independent molecules (Z = 4) at general positions in the
asymmetric unit of the crystal structure. It is clear that antiꢀ5a
the H NMR spectrum of [6.1]MCP 6a in CDCl3 upfield shifts
and different chemical shifts for the internal aromatic protons at
δ
7.25 and 7.28 ppm due to the ring current of the opposite
adopt the anti- conformation in which two benzene rings are in
a nonꢀplanar chain form (Fig. 3). The measured torsional angles
between the planes C6–C8–C10–C7, C4–C5–C6 and C8–C3–
C7 planes, and those of C22–C27–C25–C24 with C27–C28–
C29 and C24–C25–C26 are 116.9°, 121.1°, 117.1° and 120.9°,
respectively, showing that this molecule has an asymmetrical
strain between the ‘top’ and ‘bottom’ rings, and that the amount
of strain is much greater at the internal carbons than at the
external carbons. The C6–C5–C1–C3 and C4–C2–C26–C25
planes are twisted out of coplanarity and have a dihedral angle
of 5.2°, and thus the two carbonyl groups, C6–O2 and C25–O3
do not lie in the same plane where the adjacent two carbon
atoms are included.
aromatic ring were observed. This data strongly suggests that
the structure of 6a is the antiꢀconformer.
Furthermore, the two methoxy groups exhibit different
chemical shifts at
four external aromatic protons were also observed as different
chemical shifts at 7.05 ( = 2.4 Hz) and 7.12 ( = 2.4 Hz)
δ 3.29 and 3.41 ppm, each as a singlet. The
δ
J
J
ppm; the latter proton is in a strongly deshielding region of the
oxygen atom of the acetyl group on the methylene bridge. The
compound 6a exhibits a splitting pattern for the benzyl protons
as two multiplets centred at
CH2 groups were also observed as two multiplets centred at
0.88 and 1.32 ppm. These findings suggest a regioꢀselective
δ 2.25 and 2.41 ppm. The central
δ
1
formation of [6.1]MCP 6a at this temperature.
NMR spectrum of [8.1]MCP 6b in CDCl3 upfield shifts and
different chemical shifts for the aromatic protons at 6.86 and
In the H
δ
6.87 ppm strongly suggest that the structure of 6b is the syn
ꢀ
conformer.
Table 2 Conformational analysis of [n.1]MCPꢀenes 6a, b.
Products yield [%]a
Number of
Compound
methylene units [n]
antiꢀ6
synꢀ6
antiꢀ5a
synꢀ5b
6
8
51
0
0
Scheme 4 Synthesis of 13ꢀacetylꢀ9,16ꢀdiꢀtertꢀbutylꢀ12,19ꢀdimethoxyꢀ13ꢀ
methyl[6.1]MCP 6a and 15ꢀacetylꢀ11,18ꢀdiꢀtertꢀbutylꢀ14,21ꢀdimethoxyꢀ
15ꢀmethyl[8.1]MCP 6b.
41
a Isolated yields are shown in parentheses.
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Fig. 5 DFT geometryꢀoptimized structures of anti
ꢀ5a (top left), synꢀ5b
Fig. 4 (a) Chromatogram of antiꢀ13ꢀacetylꢀ9,16ꢀdiꢀtertꢀbutylꢀ12,19ꢀ
dimethoxyꢀ13ꢀmethyl[6.1]MCP 6a (HPLC on chiral column). Daicel
(top right), anti 6a (bottom left) and syn 6b (bottom right). Colour
ꢀ
ꢀ
code: carbon = dark and light grey, and oxygen = red. Hydrogen atoms
omitted for clarity.
chiralpak ADeH. Eluent: hexanes. (b) CD spectra of
Pꢀ and Mꢀ
enantiomers of inherently chiral MCP antiꢀ13ꢀacetylꢀ9,16ꢀdiꢀtertꢀbutylꢀ
12,19ꢀdimethoxyꢀ13ꢀmethyl [6.1]MCP 6a
.
(chloroform) with the B3LYP/6ꢀ31G(d) basis set.35 The DFTꢀ
geometry optimized B3LYP/6ꢀ31G(d) energies in both the gasꢀ
phase or with the solvent correction term for all four compound
shifts for the aromatic protons at
δ
6.86 and 6.87 ppm strongly
suggest that the structure of 6b is the synꢀconformer.
Furthermore, the two methoxy groups appear as a singlet with
6a
, 6b, 5a, 5b is given in Fig.5.
chemical shift
protons as two multiplets centred at
exhibited for this compound. The CH2 groups were also
observed as two multiplets centred at 0.78 and 1.59 ppm.
These findings suggest a rigid structure of [8.1]MCP 6b at this
temperature and this one is a meso compound.
δ
3.71 ppm. A splitting pattern for the benzyl
The trend for the stabilities of
6
and 5 could tentatively be
δ
2.30 and 2.89 ppm was
rationalized on the basis of the antiꢀconformations of 6a and 5a
vs the synꢀconformations of 6b and 5b. However, the geometryꢀ
optimized energy of the synꢀstructure is sufficiently higher than
that of the antiꢀstructure. Both the single crystal and DFTꢀ
δ
optimized structures of 5a indicate that it adopts an anti
ꢀ
The chiral properties of the compound anti
were investigated by chromatographic resolution using a chiral
column. Interestingly, anti 6a exhibits two well resolved peaks
in the ratio of 50:50 for the ꢀ and ꢀenantiomers. This finding
strongly suggests that the resolution of racemic anti 6a could
be accomplished by chromatographic separation using a chiral
column. In fact, we have succeeded in resolving each ꢀ and
ꢀ6a in solution
conformation and that the methoxy groups are positioned
opposite to the benzene rings (Fig. 3 and 5).
The greater activity may be attributed to the higher solubility
of the compounds. We have calculated the energies of the
HOMO and LUMO orbitals in Table 3. The difference between
the energy levels of the HOMO and LUMO (the HOMO–
ꢀ
P
M
ꢀ
P
Mꢀ
LUMO gap, ∆E) shows the stability or reactivity of the
enantiomers. The circular dichroism (CD) spectra of the
separated enantiomer with precise mirror images are shown in
Fig. 4. Indeed, we have succeeded in generating inherent
chirality in the metacyclophane system containing two aromatic
molecules, such as, pointing out the possible electronꢀrich or
electronꢀdeficient regions in the structures.
Table
3 DFT geometryꢀoptimized computed energies for the
rings
by
the
regioꢀselective
.
rearrangement
of
compounds
5–6
generated from the solidꢀstate Xꢀray coordinates.
[6.1]metacyclophane 6a
Energy (kJ molꢀ1)
Density functional theory (DFT) computational studies were
carried out to demonstrate the geometryꢀoptimized energies of
compounds 5–6. The starting structures were generated with the
Compound
Gasꢀphase
ꢀ3866698.72
ꢀ3866688.48
ꢀ4073149.44
ꢀ4073145.22
HOMO
ꢀ553.98
ꢀ545.05
ꢀ15.75
LUMO
5.25
∆E
antiꢀ5a
synꢀ5b
antiꢀ6a
synꢀ6b
548.73
538.01
13.12
10.50
initial geometries based upon their own Xꢀray crystal structures.
The DFT level of theory using the prominent B3LYP (Becke,
7.04
2.63
threeꢀparameter,
LeeꢀYangꢀParr)34
exchangeꢀcorrelation
ꢀ13.13
2.63
functional with the 6ꢀ31G(d) basis set. By using Gaussianꢀ09,
the individual geometryꢀoptimized structures of these
molecules were first conducted in the gas phase and after that in
solvent
a Based on DFT using the B3LYP/6ꢀ31G(d) basis setꢀup.
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Journal Name
7.11 (2H, d,
H
J
= 2.4 Hz, Arꢀ
H
) and 7.27 (2H, d,
J = 2.4 Hz, Arꢀ
Conclusions
) ppm. 13C NMR (100 MHz, CDCl3):
δ
= 23.94, 29.77, 30.07,
In conclusion, a new synthesis of [2.n]MCPꢀ1ꢀenes 4a and 4b
by McMurry cyclization has been developed. Acid catalysed
rearrangements of 5a and 5b the corresponding epoxides
31.11, 34.31, 61.76, 65.76, 120.74, 126.29, 134.58, 137.50,
146.81 and 153.25 ppm. MS (EI): m/z found 499 [M+]. Anal.
calcd. for C32H50O4 (498.7) C, 77.06; H, 10.10, found C, 77.23;
H, 10.41.
formed with
.1]MCPs 6a and 6b, respectively. 1H NMR spectroscopy and
Xꢀray analysis of compounds and confirmed that they
mꢀCPBA can be applied toward the synthesis of
[
n
5
6
Preparation of 1,8-bis(5-tert-butyl-3-(1-hydroxyethyl)-2-
adopted different antiꢀ and synꢀconformation both in solution
and in the solid state. The results from DFT calculations were
consistent with the observed experimental results. Further
studies based on this type of novel ring contraction of
[2.n]cyclophanes is being extended with glycol units at the
ethylene bridge to afford [n.1]cyclophanes, are now in progress.
methoxyphenyl)octane 2b.
Compound 2b was synthesized in the same manner as
described above for 2a and obtained (8.48 g, 77%) as colourless
prisms. M.p. 107–108 °C. IR (KBr): υmax = 3313, 2915, 1469,
1295, 1174, 1115, 1000 and 879 cm–1. H NMR (300 MHz,
1
CDCl3):
(6H, d,
2), 2.59–2.63 (4H, m, C
bs, O ), 7.12 (2H, d, = 2.4 Hz, Arꢀ
Hz, Arꢀ
) ppm. 13C NMR (100 MHz, CDCl3):
28.87, 29.65, 30.49, 31.03, 34.16, 61.22, 65.12, 120.03, 125.91,
134.58, 136.84, 146.55 and 152.69 ppm. MS (EI): m/z found
527 [M+]. Anal. calcd. for C34H54O4 (526.9) C, 77.52; H, 10.33,
found C, 76.17; H, 10.29.
δ
= 1.30 (18H, s,
= 6.6 Hz, C 2), 1.58–1.69 (6H, m, C
2), 3.77 (6H, s, OC
) and 7.27 (2H, d,
= 23.51,
t
Bu), 1.36–1.45 (4H, m, C
3), 2.33 (4H, s,
3), 5.20 (2H,
= 2.4
H2), 1.52
J
H
H
Experimental
C
H
H
H
H
J
H
J
All melting points were uncorrected. Proton nuclear magnetic
resonance (1H NMR) spectra were recorded on a Nippon
Denshi JEOL FTꢀ300 spectrometer and Varianꢀ400MRꢀvnmrs
H
δ
400 spectrometer. Chemical shifts are reported as
δ values
(ppm) relative to internal Me4Si. The IR spectra were obtained
as KBr pellets on a Nippon Denshi JIRꢀAQ2OM spectrometer.
Mass spectra were obtained on a Nippon Denshi JMSꢀHX110A
Ultrahigh Performance Mass Spectrometer at 75 eV using a
directꢀinlet system. Elemental analyses were performed with a
Yanaco MTꢀ5 analyser. Elemental analyses were performed by
Yanaco MTꢀ5. Gas–liquid chromatograph (GLC) analyses were
performed by Shimadzu gas chromatograph, GCꢀ14A; silicone
OVꢀ1, 2 m; programmed temperature rise, 12 °C minꢀ1; carrier
gas nitrogen, 25 mL minꢀ1.
Preparation
of
1,6-bis(3-acetyl-5-tert-butyl-2-methoxy
phenyl)hexane 3a.
To a solution of pyridinium chlorochromate, C5H5NH+CrO3Clꢀ
(31.0 g, 144 mmol) in acetone (300 mL) was added a solution
of
1,6ꢀbis(5ꢀtertꢀbutylꢀ3ꢀ(1'ꢀhydroxyethyl)ꢀ2ꢀmethylphenyl)ꢀ
hexane 2a (10.62 g, 21.3 mmol) in acetone (100 mL) dropwise
at 0 °C. The reaction mixture was stirred at room temperature
for 24 h. The reaction mixture was filtered and the filtrate was
concentrated. The residue was subjected to silicaꢀgel (Wako, Cꢀ
300; 500 g) column chromatography using as eluent CHCl3 to
afford 1,6ꢀbis(3ꢀacetylꢀ5ꢀtertꢀbutylꢀ2ꢀmethoxyphenyl) hexane
3a (7.27 g, 69%) as colourless prisms (Hexane). M.p. 127–128
°C. IR (KBr): υmax = 2848, 1676, 1472, 1362, 1222, 1126 and
Materials
1,6ꢀBis(5ꢀtertꢀbutylꢀ3ꢀformylꢀ2ꢀmethoxyphenyl)hexane 1a and
1,8ꢀbis(5ꢀtertꢀbutylꢀ3ꢀformylꢀ2ꢀmethoxyphenyl)octane 1b were
prepared according to the literature procedures.17
1004 cm–1. 1H NMR (300 MHz, CDCl3):
δ
= 1.30 (18H, s,
2), 1.61–1.72 (4H, m,
3), 3.73 (6H, s, OC 3), 7.33 (2H, d,
= 2.4 Hz, Arꢀ
) ppm. 13C
= 29.65, 30.08, 30.50, 30.98,
tBu),
1.42–1.50 (4H, m, C
2), 2.63 (6H, s, C
2.4 Hz, Arꢀ
NMR (100 MHz, CDCl3):
H
2), 1.45 (4H, s, CH
Preparation of 1,6-bis(5-tert-butyl-3-(1-hydroxyethyl)-2-
methoxylphenyl)hexane 2a.
C
H
H
H
J =
H) and 7.41 (2H, d,
J
H
δ
To a solution of methylmagnesium iodide [prepared from
methyl iodide (14.40 g, 101 mmol) and magnesium (2.05 g,
84.3 mmol)] in Et2O (45 mL) was added a solution of 1a (8.85
g, 20.9 mmol) in tetrahydrofuran (100 mL) dropwise under the
conditions of gentle reflux. After the reaction mixture was
refluxed for an additional 5 h, it was quenched with 10%
ammonium chloride (100 mL) and extracted with Et2O (3 × 100
mL). The extract was washed with water (2 × 100 mL), dried
over MgSO4, and concentrated in vacuo. The residue was
recrystallized from hexane to afford 1,6ꢀbis(5ꢀtertꢀbutylꢀ3ꢀ(1ꢀ
hydroxyethyl)ꢀ2ꢀmethoxyphenyl)hexane 2a (7.71 g, 74%) as
colourless prisms. M.p. 125–126 °C. IR (KBr): υmax = 3308,
2963, 2856, 2827, 1480, 1463, 1429, 1363, 1282, 1231, 1202,
1172, 1119, 1074, 1011 and 879 cmꢀ1. 1H NMR (300 MHz,
31.43, 34.51, 62.81, 124.30, 131.13, 133.06, 136.04, 146.84,
155.27 and 201.92 ppm. MS (EI): m/z found 495 [M+]. Anal.
calcd. for C32H46O4 (494.7) C, 77.69; H, 9.37, found C, 77.91;
H, 9.36.
Preparation
of
1,8-bis(3-acetyl-5-tert-butyl-2-methoxy
phenyl)octane 3b.
Compound 3b was synthesized in the same manner as
described above for 3a and obtained (6.91 g, 62%) as colourless
prisms (MeOH). M.p. 58–59 °C. IR (KBr): υmax = 2944, 2848,
1682 (C=O), 1476, 1369, 1266, 1222 and 1008 cm–1. H NMR
1
(300 MHz, CDCl3):
2), 1.55–1.68 (4H, m, C
OC 3), 7.34 (2H, d, = 2.4 Hz, Arꢀ
Hz, Arꢀ
) ppm. 13C NMR (100 MHz, CDCl3):
δ
= 1.30 (18H, s,
2), 2.63 (6H, s, C
) and 7.41 (2H, d,
= 29.49,
t
Bu) ,1.37–1.46 (12H, m,
3), 3.73 (6H, s,
= 2.4
C
H
H
H
H
J
H
J
CDCl3):
(6H, d,
(4H, m, C
δ
J
= 1.30 (18H, s,
= 6.6 Hz, C 3), 2.26–2.36 (4H, m, C
2), 3.77 (6H, s, OC 3), 5.16–5.25 (2H, bs, OH
t
Bu), 1.51–1.70 (6H, m, C
2), 2.58–2.68
),
H2), 1.52
H
δ
H
H
29.75, 29.96, 30.43, 30.91, 31.35, 34.44, 62.72, 124.17, 131.04,
H
H
6 | J. Name., 2012, 00, 1-3
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ARTICLE
132.97, 136.04, 146.74, 155.18 and 201.88 ppm. MS (EI): m/z (6H, s, C
H
2), 2.59–2.70 (2H, m, C
= 2.4 Hz, Arꢀ ) and 7.01 (2H, d,
ppm. 13C NMR (100 MHz, CDCl3):
= 22.25, 24.41, 25.89,
H
2), 3.52 (6H, s, OC
H3), 6.86
found 522 [M+]. Anal. calcd. for C34H50O4 (522.7) C, 78.12; H, (2H, d,
J
H
J
= 2.4 Hz, Arꢀ
H)
6.94, found C, 77.88; H, 9.60.
δ
27.45, 28.96, 31.44, 34.02, 59.76, 124.93, 125.59, 129.90,
132.92, 136.42, 143.74 and 152.44 ppm. MS (EI): m/z found
The McMurry reagent was prepared from TiCl4 (13.75 mL, 125 490.4 [M+]. Anal. calcd. for C34H50O2 (490.8) C, 83.21; H,
mmol) and Zn powder (18.0 g, 275 mmol) in dry THF (500 10.27, found C, 83.52; H, 10.18.
McMurry coupling reaction of 3.
mL), under nitrogen. A solution of 1,6ꢀbis(3ꢀacetylꢀ5ꢀtert
butylꢀ2ꢀmethoxylphenyl)hexane 3a (3.4 g, 6.8 mmol) and described above for syn
pyridine (22.8 mL, 0.20 mol) in dry THF (250 mL) was added colourless prisms (MeOH). M.p. 104–105 °C. IR (KBr): υmax
within 60 h to the black mixture of the McMurry reagent by 2944, 2856, 1472, 1454, 1362, 1214, 1015, 875 and 801 cm–1.
using a highꢀdilution technique with continuous refluxing and 1H NMR (300 MHz, CDCl3):
= 0.94–1.12 (6H, m, C 2), 1.12
stirring. The reaction mixture was refluxed for additional 8 h, (18H, s, Bu), 1.27–1.36 (6H, m, C 2), 2.13–2.23 (2H, m,
cooled to room temperature, and hydrized with aqueous 10% 2), 2.20 (6H, s, C 3), 2.73–2.85 (2H, m, C 2), 3.69 (6H, s,
K2CO3 (200 mL) at 0 °C. The reaction mixture was extracted OC 3), 6.74 (2H, d, = 2.4 Hz, Arꢀ ) and 6.82 (2H, d, = 2.4
with CH2Cl2 (3 × 200 mL). The combined extracts were Hz, Arꢀ = 20.62,
ꢀ
Compound syn
ꢀ
4b was synthesized in the same manner as
ꢀ
4a and obtained (2.14 g, 64%) as
=
δ
H
t
H
C
H
H
J
H
H
H
J
H
) ppm. 13C NMR (100 MHz, CDCl3):
δ
washed with water, dried with MgSO4 and concentrated in 26.92, 27.62, 29.24, 30.40, 31.57, 33.93, 60.02, 125.58, 126.14,
vacuo. The residue was chromatographed over silica gel (Wako 131.40, 134.06, 136.16, 144.25 and 153.48 ppm. MS (EI): m/z
Cꢀ300, 300 g) with hexane–toluene (1:1) and toluene as eluents found 490 [M+]. Anal. calcd. for C34H50O2 (490.8) C, 83.21; H,
to give anti
were recrystallized from hexane to afford anti
23%) and syn 4a (410 mg, 13%), respectively. antiꢀ5,17ꢀDiꢀ
tertꢀbutylꢀ8,20ꢀdimethoxyꢀ1,2ꢀdimethyl[2.6]metacyclophanꢀ1ꢀ
ene (anti 4a) was obtained as colourless prisms (MeOH). M.p. (6 mg, 0.082 mmol) in toluene (2 mL) was added
ꢀ
4a and syn
ꢀ
4a as a colourless solid. Each eluents 10.27, found C, 83.82; H, 10.18.
ꢀ
4a (724 mg,
General procedure for epoxydation of 4 with
To a suspension of anti 4a (20 mg, 0.044 mmol) and NaHCO3
ꢀCPBA
m-CPBA.
ꢀ
ꢀ
ꢀ
m
183–184 °C. IR (KBr): υmax = 2944, 2856, 1469, 1358, 1233, (20.5 mg, 0.082 mmol) and the mixture was stirred for 40 h.
1107, 1023, 875, 805 and 654 cm–1. 1H NMR (300 MHz, The reaction mixture was diluted with water (20 mL), and
CDCl3):
m, C 2), 1.31 (18H, s,
3), 2.52 (2H, m, C
2.7 Hz, Arꢀ ) and 7.04 (2H, d,
NMR (100 MHz, CDCl3): = 22.13, 26.56, 27.94, 29.13, dimethylꢀ8,20ꢀdimethoxy [2.6]metacyclophane
31.30, 33.90, 59.37, 124.29, 124.36, 129.44, 133.39, 135.98, colourless prisms (MeOH). M.p. 192–193 °C. IR (KBr): υmax
δ
= 0.50 (2H, m, C
Bu), 2.10 (2H, m, C
2), 3.34 (6H, s, OC 3) 6.89 (2H, d,
= 2.7 Hz, Arꢀ
) ppm. 13C give (11 mg, 55%) antiꢀ5,17ꢀdiꢀtertꢀbutylꢀ1,2ꢀepoxyꢀ1,2ꢀ
H
2), 0.83 (2H, m, C
2), 2.22 (6H, s, were washed with water (2 × 10 mL), dried with MgSO4 and
concentrated. The residue was recrystallized from methanol to
H2), 1.26 (4H, extracted with CH2Cl2 (2 × 10 mL). The combined extracts
H
t
H
CH
H
H
J =
H
J
H
δ
(
anti
ꢀ
5a
)
as
=
144.19 and 152.03 ppm. MS (EI): m/z found 462.4 [M+]. Anal. 2944, 2856, 1472, 1450, 1352, 1229, 1085, 1019, 875 and 750
calcd. for C32H46O2 (462.7) C, 83.06; H, 10.02, found C, 82.87; cm–1. 1H NMR (300 MHz, CDCl3):
H, 9.99. 2), 0.70–0.81 (4H, m, C 2), 1.30 (9H, s,
synꢀ5,17ꢀDiꢀtertꢀbutylꢀ8,20ꢀdimethoxyꢀ1,2ꢀdimethyl[2.6]ꢀ Bu), 1.73 (3H, s, C 3), 1.95 (3H, s, C 3), 2.21–2.35 (2H, m,
metacyclophanꢀ1ꢀene (syn 4a) was obtained as colourless 2), 2.44–2.53 (2H, m, C 2), 3.39 (3H, s, OC 3), 3.49 (3H, s,
prisms (MeOH). M.p. 90–91 °C. IR (KBr): υmax = 2961, 2923, OC ), 6.95 (1H, d, = 2.4 Hz,
) and 7.38 (1H, d, = 2.4
= 23.13,
2), 2.80 (2H, 27.67, 29.70, 31.79, 33.87, 60.21, 61.91, 66.77, 125.91, 126.43,
= 2.4 Hz, Arꢀ 132.48, 134.94, 145.30 and 153.58 ppm. MS (EI): m/z found
) ppm. 13C NMR (100 MHz, 478.4 [M+]. Anal. calcd. for C32H46O3 (478.7) C, 80.29; H,
= 30.7, 31.2, 32.8, 33.9, 34.3, 64.5, 70.7, 122.1, 9.69, found C, 79.90; H, 9.62.
126.9, 127.2, 127.4, 128.0, 128.6, 128.9, 129.3, 129.5, 137.3, However, several attempted epoxidations of syn
δ
= 0.25–0.35 (4H, m,
Bu), 1.31 (9H, s,
C
H
H
t
t
H
H
ꢀ
C
H
H
H
H
H
3), 6.94 (1H, d,
), 7.29 (1H, d,
J
J
= 2.4 Hz, Arꢀ
= 2.4 Hz, Arꢀ
H
H
J
1
1476, 1235 and 1026 cm–1. H NMR (300 MHz, CDCl3):
0.59 (2H, m, C 2), 0.85 (2H, m, C 2), 1.11 (18H, s,
(4H, m, C 2), 2.18 (6H, s, C 3), 2.28 (2H, m, C
m, C 2), 3.67 (6H, s, OC 3), 6.64 (2H, d,
and 6.77 (2H, d, = 2.4 Hz, Arꢀ
CDCl3):
δ
=
Arꢀ
J
H
H
t
Bu), 1.30 Hz, Arꢀ
H
) ppm. 13C NMR (100 MHz, CDCl3):
δ
H
H
H
H
H
J
H)
J
H
δ
ꢀ
5a failed.
143.6, 146.8, 146.9, 156.2 and 156.6 ppm. MS (EI): m/z found Only an intractable mixture of products resulted.
462 [M+]. Anal. calcd. for C32H46O2 (462.7) C, 83.06; H, 10.02,
Preparation
of
syn-5,19-di-tert-butyl-1,2-epoxy-1,2-
found C, 82.59; H, 10.01.
Preparation of 5,19-di-tert-butyl-8,22-dimethoxy-1,2-
dimethyl[2.8]metacyclophan-1-ene 4b.
Compound anti 4b was synthesized in the same manner as colourless prisms (MeOH). M.p. 152–153 °C. IR (KBr): υmax
described above for anti 4a and obtained (701 mg, 21%) as 2959, 2922, 2856, 1480, 1362, 1258, 1203 1111, 1011 and 801
colourless prisms (MeOH). M.p. 178–179 °C. IR (KBr): υmax = 0.71–0.97 (4H, m,
cm–1. 1H NMR (300 MHz, CDCl3):
2), 1.16 (18H, s, Bu), 1.31–1.42 (4H, m, C 2), 1.48–1.59
2), 1.12–1.33 (4H, m, C 2), 1.88 (6H, s, C 3), 2.16–2.26 (2H, m, C
Bu), 2.01–2.11 (2H, m, C 2), 2.15 2.87–2.94 (2H, m, C 2), 3.80 (6H, s, OC 3), 6.84 (2H, d,
dimethyl-8,22-dimethoxy[2.8]metacyclophane syn-5b.
Compound syn 5b was synthesized in the same manner as
described above for anti 5a and obtained (15 mg, 67%) as
ꢀ
ꢀ
ꢀ
=
ꢀ
=
δ
1
2959, 2856, 1472, 1458, 1262, 1233 and 1104 cm–1. H NMR
(300 MHz, CDCl3): = 0.79–1.95 (6H, m, C
(6H, m, C 2), 1.28 (18H, s,
C
H
t
H
δ
H
H
H
H
J
2),
=
H
t
H
H
H
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2.4 Hz, Arꢀ
H) and 7.11 (2H, d,
J = 2.4 Hz, ArꢀH
) ppm. 13C has been assisted using computing resources provided by
NMR (100 MHz, CDCl3):
δ
= 21.88, 26.03, 27.35, 28.18, Compute Compute/Calcul Canada. Dr. Grigory Shamov,
30.55, 31.44, 34.06, 60.63, 67.84, 122.93, 127.20, 131.92, Westgrid/U. Manitoba is thanked for onꢀgoing support.
133.05, 144.36 and 153.87 ppm. FABMS: m/z found 506.4
[M+]. Anal. calcd. for C34H50O3 (506.7) C, 80.58; H, 9.94,
found C, 80.58; H, 9.86.
Notes and references
a
Department of Applied Chemistry, Faculty of Science and
General procedure for the acid catalyzed rearrangement of
epoxymetacyclophane anti-5a.
Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840-
8502, Japan. Fax: (internat.) + 81(0)952/28-8548;
E-mail: yamatot@cc.saga-u.ac.jp.
To a suspension of antiꢀ5a (30 mg, 0.062 mmol) in CH2Cl2 (3
b Chemical Research Division, Bangladesh Council of Scientific and
mL) was added BF3ꢀEt2O (8.4 mg, 0.059 mmol) and the
mixture was heated to reflux for 1 h. The cooled solution was
quenched by water (5 mL), and extracted with CH2Cl2 (2 × 10
mL). The combined extracts were washed with 5% aqueous
NaHCO3 (10 mL), water (2 × 10 mL), dried with MgSO4 and
concentrated to give synꢀ13ꢀacetylꢀ9,16ꢀdiꢀtertꢀbutylꢀ12,19ꢀ
Industrial Research(BCSIR), Dhanmondi, Dhaka-1205, Bangladesh
c Department of Chemistry, Memorial University of Newfoundland,
St. John’s, Newfoundland and Labrador, Canada A1B3X7.
d
Institute of Materials Chemistry and Engineering, Kyushu
University,
6-1, Kasugakoen, Kasuga 816-8580, Japan.
e
School of Mathematics and Physical Sciences, The University of
dimethoxyꢀ13ꢀmethyl[6.1]metacyclophane (antiꢀ6a) (15 mg,
Hull, Cottingham Road, Hull, Yorkshire, HU6 7RX, UK.
51%) as colourless prisms (MeOH). M.p. 111–112 °C. IR
(KBr): υmax = 2966, 2915, 2863, 1690 (C=O), 1476, 1454,
1358, 1222, 1107, 1004, 879 and 643 cm–1. 1H NMR (300
†
Electronic Supplementary Information (ESI) available:
Details of the singleꢀcrystal Xꢀray crystallographic data and DFT
computational data and xyz files. For ESI and crystallographic
data in CIF see DOI: 10.1039/b000000x/
MHz, CDCl3):
δ
= 0.53–0.70 (2H, m, C
2), 1.30 (9H, s, Bu), 1.32 (9H, s, Bu), 1.26–1.37 (4H, m,
2), 1.71 (3H, s, C 3), 1.76 (3H, s, C 3), 2.20–2.30 (2H, m,
2), 2.34–2.47 (2H, m, C 2), 3.29 (3H, s, OC 3), 3.41 (3H, s,
), 7.12 (1H, d, = 2.4 Hz,
) and 7.28 (1H, d, = 2.4
= 26.12,
H2), 0.80–0.95 (2H, m,
CH
CH
CH
t
t
H
H
1
(a) Cyclophanes (Eds.: P. M. Keehn, and S. M. Rosenfield),
H
H
Academic Press: New York, 1983, vol. 1, chapter 6, p.
428; (b) F. Vögtle, CyclophaneꢀChemistry, Wiley:
Chichester, 1993.
M. Pelligrin, Recl. Trav. Chim. Pays-Bas Belg., 1889, 18,
458.
R. H. Mitchell, T. K. Vinod and G. W. Bushnell, J. Am.
Chem. Soc., 1985, 107, 3340.
Y. Fujise, Y. Nakasato and S. Itô, Tetrahedron Lett., 1986,
27, 2907.
OC
Arꢀ
Hz, Arꢀ
H
H
3), 7.05 (1H, d,
), 7.25 (1H, d,
J
= 2.4 Hz, Arꢀ
= 2.4 Hz, Arꢀ
H
H
J
J
J
H
) ppm. 13C NMR (100 MHz, CDCl3):
δ
2
3
4
5
26.29, 27.16, 28.72, 28.85, 29.17, 31.39, 31.55, 34.28, 61.08,
61.89, 123.67, 125.36, 125.40, 128.52, 133.27, 144.55, 144.85
and 210.26 ppm. FABMS: m/z found 478.3 [M+]. Anal. calcd.
for C32H46O3 (478.7) C, 80.29; H, 9.69, found C, 80.33; H,
9.67.
Preparation
of
syn-15-acetyl-11,18-di-tert-butyl-14,21-
(
a
) R. H. Mitchell and V. Boekelheide, J. Am. Chem. Soc.,
1974, 96, 1547; ( ) Y.ꢀH. Lai, H.ꢀL. Eu, J. Chem. Soc.,
Perkin Trans. 1, 1993, 233.
dimethoxy-15-methyl[8.1]metacyclophane syn-6b
.
b
Compound syn 6b was synthesized in the same manner as
described above for anti 6a and obtained (13 mg, 41%) as
colourless prisms (MeOH). M.p. 118–119 °C. IR (KBr): υmax
2937, 2856, 1690 (C=O), 1568, 1476, 1476, 1362, 1211, 1008,
894, 750 and 717 cm–1. 1H NMR (300 MHz, CDCl3):
= 0.70–
Bu), 1.24–1.34 (4H, s, C 2),
ꢀ
6
7
H. A. Staab, W. R. K. Riebel, and C. Krieger, Chem. Ber.,
1985, 118, 1230.
Merz, A. Karl, T. Futterer, N. Stacherdinger, O. Schneider,
J. Lex, E. Luboch and J. F. Biernat, Liebigs Ann. Chem.,
1994, 1199.
ꢀ
=
δ
0.86 (4H, m, C
1.54–1.64 (4H, m, C
3), 2.42 (3H, s, C
OC
(100 MHz, CDCl3):
H
2), 1.16 (18H, s,
t
H
8
(a) T. Kawase, N. Ueda, H. R. Darabi and M. Oda, Angew.
H
H
2), 2.25–2.35 (2H, m, C
3), 2.82–2.95 (2H, m, C
H
H
2), 2.37 (3H, s,
2), 3.71 (6H, s,
) ppm. 13C NMR
Chem., 1996, 108, 1658; Angew. Chem. Int. Ed. Engl.,
1996, 35, 1556; (b) T. Kawase, H. R. Darabi and M. Oda,
Angew. Chem., 1996, 108, 2803; Angew. Chem. Int. Ed.
CH
H
3) and 6.87 (4H, dd,
J
= 2.4 Hz, Arꢀ
H
δ
= 22.45, 25.21, 27.67, 28.72, 29.02,
Engl., 1996, 35, 2664; (
Oda, Tetrahedron Lett., 1997, 38, 6681.
F. Vögtle and P. Neumann, Synthesis, 1973, 85.
c) T. Kawase, N. Ueda and M.
29.39, 30.06, 31.44, 31.77, 34.23, 61.91, 63.61, 110.31, 125.90,
126.31, 126.58, 135.60, 144.92, 156.34 and 210.70 ppm.
FABMS: m/z found 506.3 [M+]. Anal. calcd. for C34H50O3
(506.7) C, 80.58; H, 9.94, found C, 80.66; H, 9.88.
9
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a
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c
Acknowledgements
This work was performed under the Cooperative Research
Program of “Network Joint Research Centre for Materials and
Devices (Institute for Materials Chemistry and Engineering,
Kyushu University)”. We would like to thank the OTEC at
Saga University for financial support. The computational work
7
d
3
12 (
a
b
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