Medium-sized cyclophanes. Part 57. Synthesis, conformations and stereodynamics of [2.n] metacyclophan-1-enes and their conversion to [2.n] metacyclophan-1-ynes

Article abstract of DOI:10.1039/b010205i

anti- and syn-[2.8]Metacyclophan-1-enes 3a, which are both conformationally rigid structures, were prepared in good yields by a McMurry cyclization of 1,8-bis(5-tert-butyl-3-formyl-2-methoxyphenyl)octane 2a. Similarly, McMurry cyclization of 1,10-bis(5-te

Full text of DOI:10.1039/b010205i

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Medium-sized cyclophanes. Part 57.¤ Synthesis, conformations and
stereodynamics of [2.n]metacyclophan-1-enes and their conversion to
[2.n]metacyclophan-1-ynes
Takehiko Yamato,*a Koji Fujita,a Takao Abea and Hirohisa Tsuzukib
a Department of Applied Chemistry, Faculty of Science and Engineering, Saga University,
Honjo-machi 1, Saga-shi, Saga, 840-8502, Japan. E-mail: yamatot=cc.saga-u.ac.jp
Fax: ] 81 0952 28 8591
b T ohwa Institute for Science, T ohwa University, 1-1-1 Chikushigaoka, Minami-ku, Fukuoka-shi,
Fukuoka 815-8510, Japan
Received (in Montpellier, France) 18th December 2000, Accepted 22nd February 2001
First published as an Advance Article on the web 23rd April 2001
anti- and syn-[2.8]Metacyclophan-1-enes 3a, which are both conformationally rigid structures, were prepared in
good yields by a McMurry cyclization of 1,8-bis(5-tert-butyl-3-formyl-2-methoxyphenyl)octane 2a. Similarly,
McMurry cyclization of 1,10-bis(5-tert-butyl-2-methoxy-3-formylphenyl)decane 2b a†orded (E)- and (Z)-[2.10]-
metacyclophan-1-enes 3b in good yields. The assignment of the E and Z structures was conÐrmed by 1H-NMR
analyses and single crystal X-ray di†raction studies. Bromination of (E)- and (Z)-3b with benzyltrimethyl-
ammonium tribromide a†ords exclusively the cis-adduct 4b to the bridged double bond. When treated with
potassium tert-butoxide in reÑuxing HOBut at 80 ¡C for 3 h, bromine adduct meso-4b gave the dehydrobrominated
product [2.10]metacyclophan-1-yne 6b in 93% yield, along with 1-bromo[2.10]metacyclophan-1-ene 5b in 7%
yield; the same reaction with the bromine adduct dl-4b gave 29% 6b along with 5b in 71% yield. Similarly, anti-
and syn-[2.8]metacyclophan-1-ynes 6a were also prepared by bromination of syn-[2.n]metacyclophan-1-ene syn-3a,
followed by the dehydrobromination of the bromine adduct. The characterization and the reaction pathway of
these products are discussed. The dynamics of the ring inversion and UV spectra are also presented.
Cyclophanes belong to one of the remarkable compound
classes that has attracted extensive studies.2 In 1982, Psiorz
and Hopf reported the identiÐcation of elusive strained
paracyclophyne intermediates, which were indirectly con-
Ðrmed by their giving DielsÈAlder adducts with dienophiles or
trimerizing to the hexaphenyl benzene derivatives.3 Later, the
groups of Meijere4a,b and Wong4c,d reported the existence of
strained cyclophynes as intermediates, which was established
by a trapping method. Ramming and Gleiter described the
syntheses of [n]MCP-diynes (MCP \ metacyclophane) and
the transformation of the propargylic moieties into allenic
groups, as well as reactions with strong bases.5 Recently,
compounds by low-valent titanium, the McMurry reaction,8
has been used before by Mitchell and Weerawana9 to synthe-
size cyclophanes with glycol units as bridges, by Tanner and
Wennerstrom,10 and recently by Hopf and Mlynek11 and
Grutzmacher and Neumann,12 for the cyclization of suitable
dialdehydes to yield unsaturated cyclophanes.
The starting compounds, 1,8-bis(5-tert-butyl-2-methoxy-
phenyl)octane 1a and 1,10-bis(5-tert-butyl-2-methoxyphenyl)-
decane 1b13 are easily prepared in three steps from anisole by
using the tert-butyl group as a positional protective group on
the aromatic ring.14 The cross-coupling reactions15 of 5-tert-
butyl-2-methoxyphenylmagnesium bromide with 1,8-dibromo-
octane and 1,10-dibromodecane have been carried out in the
presence of cuprous bromide as a catalyst in a mixture of
hexamethylphosphoric triamide (HMPA) and tetrahydrofuran
at reÑux temperature to give the desired 1a and 1b in 87 and
81% yields, respectively.
Kawase and co-workers reported the synthesis of [2 ]MCP-n-
n
ynes by bromination-dehydrobromination of the correspond-
ing MCP-n-enes, which are considerably strained with bent
triple bonds.6 Although we have attempted to prepare [2.3]-
and [2.4]MCP-1-ynes by dehydrobromination of the corre-
sponding 1,2-dibromo[2.n]MCPs,7 formation of the desired
[2.n]MCP-ynes was not observed; instead, only 1-bromo[2.n]
MCP-1-enes along with [2.n]MCP-1-ones were obtained. No
reports of the synthesis of [2.n]MCP-ynes have yet been
published. In this paper, we describe the Ðrst preparation of
[2.n]MCP-1-enes using the low-valent titanium-induced
McMurry reaction and their conversion to [2.n]MCP-1-ynes.
Formylation of 1a and 1b13 with dichloromethyl methyl
ether in the presence of titanium tetrachloride in dichloro-
methane for 2 h yields the corresponding 2a and 2b in 73 and
70% yields, respectively (Scheme 1).
1,8-Bis(5-tert-butyl-3-formyl-2-methoxyphenyl)octane
2a
was subjected to reductive coupling by the McMurry reaction
following GrutzmacherÏs procedure (Scheme 2).12,16 The
desired [2.8]MCP-1-ene 3a was obtained in 61% yield. The
1H-NMR spectrum of 3a shows two kinds of methoxy
protons, each as a singlet. By careful column chromatography
(silica gel, Wako C-300), two isomers, anti-3a and syn-3a, were
separated in 13 and 48% yield, respectively. They are ther-
mally stable and do not interconvert at 180 ¡C in DMSO
solution and at 400 ¡C in the solid state.
Results and discussion
Syntheses and structural determinations
In cyclophane chemistry, the reductive coupling of carbonyl
¤ For part 56, see: ref. 1.
The structures of products anti-3a and syn-3a were deter-
mined on the basis of their elemental analyses and spectral
728
New J. Chem., 2001, 25, 728È736
DOI: 10.1039/b010205i
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

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The 1H-NMR spectrum of (E)-3b in CDCl shows a singlet at
3
d 7.44 for the oleÐnic protons and a doublet (J 2.4 Hz) at d
7.30 for one aromatic proton, which is in the strongly
deshielding region of the bridged double bond. In contrast,
the 1H-NMR spectrum of (Z)-3b in CDCl shows a singlet at
3
d 6.67 for the oleÐnic protons and a set of doublets (J 2.4 Hz)
at d 6.77 and 6.87. Also, the tert-butyl protons of (Z)-3b are
observed at higher Ðeld, d 1.05, due to the strong shielding
e†ect of the benzene ring. The syn conformation is also by the
chemical shift of the methoxy proton peaks, at d 3.71 for (E)-
3b and 3.59 for (Z)-3b. These data strongly support the assign-
ed E and Z conÐgurations for 3b, along with the syn confor-
mation for both (E)-3b and (Z)-3b.
Single crystal X-ray di†raction structures of (E)-3b and (Z)-
3b, recrystallized from hexane, are illustrated in Fig. 1 and 2,
with the atom numbering system. Compound (E)-3b crys-
tallized in the centrosymmetric triclinic space group P1 (no. 2).
In contrast, compound (Z)-3b crystallized in the centro-
Scheme 1
data. The 1H-NMR spectrum of anti-3a in CDCl shows a
singlet at d 3.53 for methoxy protons, a singlet at d 6.61 for
3
oleÐnic protons and a pair of doublets (J 2.4 Hz) at d 6.94,
7.29 for aromatic protons, which are in the deshielding region
of the bridged double bond. Thus, the methoxy protons
should show an upÐeld shift due to the ring current of the
opposite aromatic ring.2,17 The structure of the syn confomer
is also readily assigned from the chemical shift of the methoxy
protons at d 3.69. Also, the tert-butyl proton of syn-3a is
observed at higher Ðeld, d 1.12, due to the shielding e†ect of
the benzene ring. The aromatic protons of syn-3a are observed
at much higher Ðeld (d 6.79, 6.89) than those of anti-3a. These
data conÐrm the assigned anti and syn structures of the two
3a conformers.
asymmetric orthorhombic space group P2 2 2 (no. 19). Both
1 1 1
compounds were located at general positions in the asym-
metric unit of the crystal structure. The X-ray crystallographic
analyses of (E)-3b and (Z)-3b clearly show that both com-
pounds also adopt the syn conformation in the solid state. In
addition, the two methoxy groups are obviously located on
the same side of the 18-membered inner ring, which contains
the long bridging C1È10 chain toward the outer direction, and
the double bond adopts the E or Z conÐguration in the two
compounds. These results seem to indicate that the double
bond in (E)-3b and (Z)-3b plays an important role in Ðxing the
conformation in the solid state.
Similarly, 1,10-bis(5-tert-butyl-2-methoxyphenyl)decane 2b
was subjected to reductive coupling by the McMurry reaction
(Scheme 2). The novel [2.10]MCP-1-ene 3b was obtained in
almost quantitative yield. The 1H-NMR spectrum of 3b also
shows two kinds of methoxy protons, each as a singlet. By
careful column chromatography (silica gel, Wako C-300), two
isomers, (E)-3b and (Z)-3b, were isolated in 52 and 42% yield,
respectively.
In (E)-3b the bond distance C17ÈC18 is 1.33 A, which is
almost the same as that in ethylene. The bond distances C15È
The structures of products (E)-3b and (Z)-3b were also
determined on the basis of their elemental analyses and spec-
tral data. 1H-NMR signals of the oleÐnic protons for E- and
Z-oleÐns should be observed at d [ 7.4 (E) and \6.9 (Z).18
Fig. 1 X-Ray structure of (E)-5,21-di-tert-butyl-8,24-dimethoxy-
[2.10]metacyclophan-1-ene (E)-3b. Thermal ellipsoids are drawn at
the 50% probability level. For clarity, all hydrogen atoms are omitted.
Fig. 2 X-Ray structure of (Z)-5,21-di-tert-butyl-8,24-dimethoxy-
[2.10]metacyclophan-1-ene (Z)-3b. Thermal ellipsoids are drawn at
the 50% probability level. For clarity, all hydrogen atoms are omitted.
Scheme 2
New J. Chem., 2001, 25, 728È736
729

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C17 and C18ÈC19 are 1.46 and 1.47 A, respectively, which are
slightly shorter than C1ÈC23 (1.51 A) and C10ÈC11 (1.50 A).
This might be due to some conjugation e†ects through the
ethylenic bond. The dihedral angles between the plane formed
by the bridging alkyl chain and the bridging double bond
(C1ÈC2ÈC3ÈC4ÈC5ÈC6ÈC7ÈC8ÈC9ÈC10ÈC17ÈC18) and the
planes of the benzene rings (C11ÈC12ÈC13ÈC14ÈC15ÈC16
and C19ÈC20ÈC21ÈC22ÈC23ÈC24) have di†erent values, 30.2
and 56.6¡, respectively, showing that the aromatic rings adopt
an asymmetrical conformation in the molecule. This reÑects
the bond angles in the ethylenic bridge chain; the bond angles
C15ÈC17ÈC18 and C17ÈC18ÈC19 have di†erent values, 129.7
and 122.7¡.
In (Z)-3b, the bond distance C17ÈC18 is 1.28 A, which is
slightly shorter than that in ethylene. The bond distances
C15ÈC17 and C18ÈC19 are 1.47 and 1.49 A, respectively,
almost equal to those of C1ÈC23 (1.50 A) and C10ÈC11 (1.48
A). The conjugation e†ects through the ethylenic bond are
similar in (Z)-3b and (E)-3b. The dihedral angles between the
planes
C1ÈC2ÈC3ÈC4ÈC5ÈC6ÈC7ÈC8ÈC9ÈC10ÈC17ÈC18,
C11ÈC12ÈC13ÈC14ÈC15ÈC16 and C19ÈC20ÈC21ÈC22ÈC23È
C24 are 43.3 and 63.3¡, respectively. These values are much
larger than in the case of (E)-3b. This suggests that the aro-
matic rings of (Z)-3b adopt a tighter conformation than in (E)-
3b to avoid steric repulsion. The bond angles C15ÈC17ÈC18
and C17ÈC18ÈC19 are also di†erent, 125.5 and 129.1¡, respec-
tively. One of the two angles is much larger than in the case of
(E)-3b, showing that (Z)-3b is a more strained compound than
(E)-3b.
Interestingly, when (E)-3b was irradiated using a high pres-
sure Hg lamp in cyclohexane at room temperature for 2 h,
photo-induced isomerization occurred to a†ord (Z)-3b in
quantitative yield. In contrast, irradiation of (Z)-3b under the
same reaction conditions gave only recovery of the starting
compound. Thus, one-way photoisomerization is observed in
this system, as has been reported for normal cycloalkene
systems.19
Attempted bromination of anti-5,19-di-tert-butyl-8,22-
dimethoxy[2.8]MCP-1-ene (anti-3a) with 1.1 equiv. of
bromine carried out in dichloromethane solution at room
temperature for 1 h led to the expected trans adduct anti-4a
(endo-endo-Br) in 60% yield, along with 40% of the starting
compound. Bromination of anti-3a carried out with an equi-
molar amount of benzyltrimethylammonium tribromide
Scheme 3
larly, the 1H-NMR spectrum of syn-4a in CDCl shows a
singlet at d 6.07 for the methine protons and a doublet (J 2.0
Hz) at d 7.46 for the two aromatic protons, which are in the
strongly deshielding region of the endo-Br atom on the ethyl-
ene bridge. Thus, the two Br atoms are both endo and there-
fore, syn-4a is found to be the cis adduct at the bridged double
bond.
3
(BTMABr ) in dichloromethane, which was recently found to
3
be a convenient solid brominating agent,20 a†orded the same
bromine adduct anti-4a in 71% yield (Scheme 3). Interestingly
reaction of syn-3a with 1.1 equiv. of BTMABr in dichloro-
3
methane at room temperature for 2 h led to the cis adduct
syn-4a (endo-endo-Br) in 54% yield. In contrast, bromination
Previously, we reported that bromination of anti-[2.3]
MCP-1-ene with bromine a†orded exclusively the cis adduct
and the cis addition of anti-[2.4]MCP-1-ene with bromine
competed with trans addition due to the decrease of strain of
the nonclassic bromonium ion intermediate A.19 In the
present system, in which the number of methylene units in the
polymethylene bridge is increased from four to eight, bromine
addition to the bridging double bond proceeds exclusively via
trans addition, as has been reported for bromine addition in
normal alkene systems.19
In contrast, the fact that the cis adduct syn-4a (endo-endo-
Br) is exclusively obtained indicates the steric e†ect of the
internal methoxy groups for the exo-Br addition, as well as
the presence of a four-membered transition state B22 rather
than the nonclassic bromonium ion intermediate A19 in the
bromination process7. The absence of A might be a result of
the strain in this intermediate.
of (Z)- and (E)-5,21-di-tert-butyl-8,24-dimethoxy[2.10]MCP-
1-ene (3b) with 1.1 equiv. of BTMABr in dichloromethane at
3
room temperature for 5 min a†orded stereoselectively the cis
adducts, meso-4b (endo-endo-Br) and dl-4b (endo-exo-Br) in 54
and 88% yields, respectively (Scheme 3).
The structures of the products obtained in the present work
were determined from their elemental analyses and spectral
data. We previously assigned21 the 1H-NMR signals of 1-exo-
5,13-trichloro-8,16-dimethyl[2.2]MCP, and we have assigned
the 1H-NMR signals of anti-4a and syn-4a in a similar
fashion. On the basis of the spectral data, anti-4a and syn-4a
are assigned the structures, anti-15,16-dibromo- and syn-15,
16-dibromo-11,19-di-tert-butyl-14,22-dimethoxy[8.2]MCP,
respectively. The 1H-NMR spectrum of anti-4a in CDCl
3
shows a singlet at d 5.96 for the methine protons and a
doublet (J 2.2 Hz) at d 7.46 for the two aromatic protons
which are in the strongly deshielding region of the endo-Br
atom on the ethylene bridge. These data strongly support the
endo arrangement for both Br atoms and therefore, anti-4a is
found to be a trans adduct at the bridged double bond. Simi-
When treated with potassium tert-butoxide in reÑuxing
HOBut at 50 ¡C for 1 h, bromine adduct meso-4b gave the
monodehydrobrominated product 1-bromo[2.10]MCP-1-ene
5b in 92% yield, along with 1% of [2.10]MCP-1-yne 6b
730
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Table 1 Dehydrobromination of 1,2-dibromo[2.10]MCPs 4b
Product yielda (%)
(E)-5b
Substrate
T /¡C
Time/h
6b
Recovery
meso-4b
meso-4b
meso-4b
meso-4b
dl-4b
20
50
80
80
50
80
1
1
1
3
1
3
22
95(85)b
52
7
12
0
1
78
7
0
0
88
0
48
93(80)b
0
dl-4b
71
29
a Yields determined by 1H-NMR spectrometry. b Isolated yields are shown in parentheses.
(Scheme 4). Prolonged reaction (to 3 h) and a higher reaction
temperature (to 80 ¡C) furnished the doubly dehydrobrominat-
ed product 6b in 93% yield, along with 7% of 5b (Table 1).
Similar treatment of the bromine adduct dl-4b under the same
reaction conditions gave 6b in 29% yield along with 5b in
71% yield. Interestingly, similar dehydrobromination of the
bromine adduct syn-4a carried out in HOBut at 80 ¡C for 12 h
a†orded [2.8]MCP-1-yne as a mixture of two isomers, anti-6a
and syn-6a, in the ratio of 65 : 35 (Scheme 4). This Ðnding
strongly suggests that the ring inversion to the thermodynami-
cally more stable anti conformation is possible in 6a, as in
[2.2]paracyclophan-ynes23 and [n.2]MCPs.24
In contrast, attempts at dehydrobromination of the
bromine adduct anti-4a with potassium tert-butoxide to a†ord
anti-[2.8]MCP-1-yne under the various reaction conditions
failed. Only the starting compound anti-4a could be recov-
ered. Due to the fact that elimination of HBr should be anti-
periplanar and that the rigid molecular frameworks restrict
CÈC bond rotation, anti-4a (endo-endo-Br) should react much
more slowly than syn-4a, whose exo-H and endo-Br on the
ethylene bridge can adopt a trans-arrangement.4d
failed. anti-6a and syn-6a are both thermally stable and do not
interconvert at 180 ¡C in DMSO solution and at 400 ¡C in the
solid state. The 1H-NMR spectra of anti-6a and syn-6a show
almost the same chemical shifts for the aromatic protons (d
7.07, 7.18 for anti-6a and 7.02, 7.20 for syn-6a) and the tert-
butyl protons (d 1.31 for anti-6a and 1.28 for syn-6a); only the
methoxy proton singlets are observed at signiÐcantly di†erent
chemical shifts, d 3.58 and 3.85, respectively. Consequently,
the 1H-NMR spectrum of dimethoxy[2.8]MCP-1-yne 6a
shows that it is present as a mixture of two isomers, anti-6a
and syn-6a, in the ratio 65 : 35 in CDCl .
3
The 1H-NMR spectrum of 6b shows two internal methoxy
protons as a singlet at d 3.80, and two aromatic protons as a
set of doublets at d 7.08 and 7.27 (J 2.4 Hz). The presence of
the signal due to the methoxy protons in the normal aromatic
methoxy proton region strongly supports that the structure of
6b is the syn conformer. A deshielded aromatic proton is
observed in the NMR spectrum of 6b at d 7.27, which is in the
strongly deshielding region due to the p-electrons of the triple
bond. While the chemical shifts of the 1H- and 13C-NMR
signals arising from the benzene rings of 6a and 6b are compa-
rable to those of the acyclic compound 12, which was pre-
pared from 4-tert-butyl-2-formyl-6-methylanisole in 3 steps
using the same procedure as for [2.n]MCP-1-ynes 6, the
signals of the acetylenic carbons (Table 2) are observed at con-
siderably lower Ðeld than those of 12. This reÑects the appre-
ciable strain in the triple bonds due to bending. In particular,
the chemical shift of the sp carbon in anti-6a is to consider-
ably lower Ðeld than that of 12 and has almost the same value
The structures of products 6a and 6b were determined on
the basis of their elemental analyses and spectral data. From
the 1H-NMR spectrum of 6a the products were found to be a
mixture of two conformers, anti-6a and syn-6a. However,
attempted separation of the mixture by careful column chro-
matography (silica gel, Wako C-300) or recrystallization
as that of [2 ]MCP-1,9,17-triyne (d 99.86),6c but is at lower
3
Ðeld than that of [2 ]MCP-1,9,17,25-tetrayne(d 92.20) or 1,5-
4
cyclooctadiyne (d 95.8).25
The single-crystal X-ray di†raction structure of the
[2.10]MCP-1-yne 6b recrystallized from methanol is shown in
Fig. 3 with the atom numbering system. Compound 6b crys-
tallized in the centrosymmetric triclinic space group P1 (no. 2)
Table 2 Spectral data of [2.n]MCP-1-ynes 6 and reference com-
pound 12 at 270 MHz in CDCl
3
1H NMR, d
13C NMR, d
C3 C
Aromatic
OMe
anti-6a
syn-6a
6b
7.07, 7.18
7.02, 7.20
7.08, 7.27
7.21, 7.37
3.58
3.85
3.80
3.99
99.02
97.52
92.86
89.52
12
Scheme 4
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Table 3 The coalescence temperatures and energy barriers of ring
inversion in [10.2]MCP 13 and [2.10]MCPs 3bÈ6ba
T /¡C
*l/Hz
k
*GE/kcal mol~1
c
c
13
[20
20
40
90
[50
È
È
11.9
13.8
14.8
17.3
10.5
(Z)-3b
(E)-3b
(E)-5b
6b
135.7
140.7
139.9
112.3
301.4
312.3
310.7
249.4
a T and *GE were determined in 1 : 3 CDCl ÈCS or CDBr using
c
c
3
2
3
SiMe as reference.
4
solution is increased, the individual peaks of the benzyl
protons merge and eventually a single peak is observed above
40 ¡C. The energy barrier to the conformational ring Ñipping
estimated from the coalescence temperature (T ) is 14.8 kcal
c
mol~1. Similarly, (Z)-3b exhibits conformational Ñipping with
a coalescence temperature of 20 ¡C (*GE \ 13.8 kcal mol~1).
c
This 1.0 kcal mol~1 di†erence indicates a more Ñexible struc-
ture for (Z)-3b than for (E)-3b, in spite of them both having
the same ring size, which might be attributed to the di†erent
available space for conformational ring Ñipping. Interestingly,
in the case of (E)-5b substitution of Br atoms at the double
bond increases the energy barrier of the conformational ring
Fig. 3 X-Ray structure of 5,21-di-tert-butyl-8,24-dimethoxy[2.10]-
metacyclophan-1-yne 6b. Thermal ellipsoids are drawn at the 50%
probability level. For clarity, all hydrogen atoms are omitted.
Ñipping to 17.3 kcal mol~1 (T \ 90 ¡C). Thus, the solution
c
conformation of [2.n]MCP-1-enes is sensitive not only to the
conÐguration of the double bond but also to the substituents
at the double bond.
at the general position (Z \ 2). The X-ray structure of 6b
clearly indicates that it is also the syn conformer in the solid
state and that the two methoxy groups lie on the same side of
the 18-membered inner ring, which contains the long bridging
C1È10 chain toward the outer direction to avoid steric repul-
sion with the bridge chain as in (E)-3b and (Z)-3b. The bond
distance C17ÈC18 is 1.19 A, which is almost equal to that in
acetylene. The bond distances C15ÈC17 and C18ÈC19 are
both 1.44 A, which is much shorter than C1ÈC23 and C10È
C11 (1.51 A). This might be attributed to conjugation e†ects
through the acetylenic bond. Interestingly, the acetylene-
containing bridge does not adopt the linear structure seen in
reference compound 12; the bond angles C15ÈC17ÈC18 and
C17ÈC18ÈC19 have unusual values of 170.4 and 169.5¡. This
clearly shows that 6b is signiÐcantly bent and explains the
lower Ðeld shifts of the signals of the acetylenic carbons in its
13C-NMR spectrum.
The energy barrier to conformational ring Ñipping for
[2.10]MCP-1-yne 6b, estimated from the coalescence tem-
perature, is 10.5 kcal mol~1. A lower ring inversion barrier
was observed for the [2.10]MCP-1-yne than that for the
[2.10]MCP-1-ene, in spite of the smaller ring size due to the
substitution of a triple bond for the alkene bridge. The barrier
to ring inversion in the [2.10]MCP-1-yne corresponds to a
decrease in the rigidity of the system by about 3.3È4.2 kcal
mol~1 in CDCl . The decreased rigidity of 6b may be due to
3
the distorted bond angles of the bridged triple bond.
The UV spectra of the [2.n]MCP-1-ynes 6a and 6b, along
with that of the reference compound 1,2-bis(5-tert-butyl-2-
methoxy-3-methylphenyl)ethyne 12, in cyclohexane are shown
in Fig. 4. The UV spectra of the [2.n]MCP-1-ynes 6a and 6b
show di†erent absorption curves compared to that of the
Ring inversion and transannular interaction
Recently, we have found7,15b,c,24b that the solution conforma-
tion of [n.2]MCPs is sensitive to the chain length of the
bridges. The ring inversion barriers determined by variable
temperature 1H-NMR decrease with increasing length of the
bridges. Thus, [n.2]MCPs are conformationally rigid for
[7.2]- and [8.2]MCP below 140 ¡C, but [10.2]MCP exhibits
conformational Ñipping above [20 ¡C (*GE \ 11.9 kcal
c
mol~1).7
The conformations of dimethoxy[2.8]MCP-1-enes and -1-
ynes, such as anti-3a, syn-3a and anti-6a, syn-6a that have
been prepared in the present work, are rigid in solution and
the signals of the methylene bridge do not coalesce below
150 ¡C. The energy barriers to Ñipping are greater than 25 kcal
mol~1. However, (E)- and (Z)-dimethoxy[2.10]MCP-1-enes 3b
and [2.10]MCP-1-yne 6b seem to have sufficient space for
conformational ring Ñipping, as demonstrated by molecular
models. Therefore, we have studied the ring inversion of these
systems by using variable temperature 1H-NMR spectroscopy
(Table 3). The 1H-NMR spectrum of (Z)-3b and (E)-3b in
Fig. 4 UV absorption spectra of [2.8]MCP-1-yne 6a and
[2.10]MCP-1-yne 6b in cyclohexane, along with that of the reference
compound 12.
CDCl at room temperature exhibits a split pattern for the
3
benzyl protons. For (E)-3b, as the temperature of a CDBr
3
732
New J. Chem., 2001, 25, 728È736

View Article Online
model acyclic compound 12. The lack of an acetylene-type
chromophore in the UV spectra of the MCP-ynes conÐrms
the non-planarity of the aromatic ring and triple bond.
Bathochromic shifts were observed for 6a and 6b, which are
ascribed to a transannular interaction between the two
benzene rings and an increase in the strain of these systems.26
When the length of the methylene bridge is decreased by two
carbons, a small red shift from 290 nm (log e \ 4.29) to 297
nm (log e \ 3.92) was observed. This Ðnding seems to support
the notion that the strain in the [2,n]MCP-1-ynes increases as
the length of the methylene bridge decreases.
125 mmol) and Zn powder (18 g, 275 mmol) in 500 mL of dry
THF, under nitrogen. A solution of 2b (4.72 g, 9 mmol) in dry
THF (250 mL) was added over 60 h to the black McMurry
reagent mixture by using a high-dilution technique with con-
tinuous reÑuxing and stirring. The reaction mixture was
reÑuxed for an additional 8 h, cooled to room temperature,
and hydrolyzed with aqueous 10% K CO (500 mL) at 0 ¡C.
2
3
The reaction mixture was extracted with CH Cl (300
2
2
mL ] 3). The combined extracts were washed with water,
dried with Na SO and concentrated. The residue was chro-
2
4
matographed over silica gel (Wako C-300, 500 g) with
hexaneÈbenzene (2 : 1) as eluent to give (E)-3b and (Z)-3b as
colorless solids. Recrystallization from hexane a†orded (E)-3b
(2.30 g, 52%) and (Z)-3b (1.85 g, 42%), Compounds anti-3a
and syn-3a were similarly prepared in 13 and 48% yields,
respectively.
Conclusions
We have synthesized, for the Ðrst time, two conformers,
anti-6a and syn-6a, of [2.8]MCP-1-yne in the MCP-1-yne
systems. The dehydrobromination of bromine adducts of
[2.n]MCP-1-enes with base will also open up new mechanistic
aspects for cyclophane chemistry. Further studies on the
(E)-5,21-Di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-
1-ene, (E)-3b. (E)-3b was obtained as colorless prisms (hexane),
mp 160È162 ¡C; l
(KBr)/cm~1: 2952, 2853, 1479, 1458,
chemical properties of [2.n]MCP-1-ynes
progress.
6 are now in
max
1362, 1290, 1207, 1021, 870, 649; d (CDCl ): 1.32 (18 H, s),
H
3
0.86È3.10 (20 H, m), 3.71 (6 H, s), 6.96 (2 H, d, J 2.4), 7.30 (2 H,
d, J 2.4), 7.44 (2 H, br s); m/z: 490 (M`). Anal. calc. for
Experimental
All melting points (Yanagimoto MP-S1) and boiling points
are uncorrected. NMR spectra were determined at 270 MHz
with a Nippon Denshi JEOL FT-270 NMR spectrometer with
C
H
O (490.8): C, 83.21; H, 10.27; found: C, 83.01; H,
34 50
2
10.67%.
(Z)-5,21-Di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-
1-ene, (Z)-3b. (Z)-3b was obtained as colorless prisms (hexane),
SiMe as an internal reference: J values are given in Hz. IR
mp 95È96 ¡C; l
(KBr)/cm~1: 2912, 1474, 1362, 1217, 1018,
4
max
spectra were measured for samples as KBr pellets or a liquid
881, 744; d (CDCl ): 1.05 (18 H, s), 0.99È1.21 (4 H, m), 1.31È
H
3
Ðlm on NaCl plates in a Nippon Denshi JIR-AQ2OM spec-
trophotometer. UV spectra were measured on a Shimadzu 240
spectrophotometer. Mass spectra were obtained on a Nippon
Denshi JMS-01SA-2 spectrometer at 75 eV using a direct-inlet
system through a GLC. Elemental analyses were performed
on a Yanaco MT-5.
1.36 (4 H, m), 1.95È3.12 (2 H, br s), 3.59 (6 H, s), 6.67 (2 H, br
s), 6.77 (2 H, d, J 2.4), 6.87 (2 H, d, J 2.4); m/z: 490 (M`).
Anal. calc. for C
C, 83.34; H, 10.56%.
H
O (490.8): C, 83.21; H, 10.27; found:
34 50
2
anti-5,19-Di-tert-butyl-8,22-dimethoxy[2.8]metacyclophan-
1-ene, anti-3a. anti-3a was obtained as colorless prisms
(MeOH), mp 200È202 ¡C; l
(KBr)/cm~1: 2917, 1474, 1255,
Syntheses
max
1097, 1010, 881, 871; d (CDCl ): 0.80È1.19 (4 H, m), 1.20È1.60
H
3
1,8-Bis(5-tert-butyl-2-methoxyphenyl)octane 1a and 1,10-bis(5-
tert-butyl-2-methoxyphenyl)decane 1b were prepared from
anisole according to the reported procedure.13 The prep-
(8 H, m), 1.35 (18 H, s), 2.32È2.44 (2 H, m), 2.69È2.82 (2 H, m),
3.53 (6 H, s), 6.61 (2 H, s), 6.94 (2 H, d, J 2.4), 7.29 (2 H, J 2.4);
m/z: 462 (M`). Anal. calc. for C
H, 10.02; found: C, 82.98; H, 9.71%.
H
O (462.72): C, 83.06;
32 46
2
aration of 4-tert-butyl-2-methylanisole
described.27
7 was previously
syn-5,19-Di-tert-butyl-8,22-dimethoxy[2.8]metacyclophan-
1-ene, syn-3a. syn-3a was obtained as a colorless oil; l
max
H
1,10-Bis(5-tert-butyl-3-formyl-2-methoxyphenyl)decane, 2b.
To a solution of 1b13 (12.57 g, 27 mmol) and Cl CHOCH
(NaCl)/cm~1: 2962, 1479, 1327, 1215, 1019, 883, 810; d
(CDCl ): 0.88È1.20 (8 H, m), 1.12 (18 H, s), 1.22È1.36 (2 H, m),
2
3
3
(6.84 mL, 75.6 mmol) in CH Cl (60 mL) was added a solution
1.38È1.45 (2 H, m), 2.15È2.25 (2 H, m), 2.72È2.82 (2 H, m), 3.69
2
2
of TiCl (18.0 mL, 163.5 mmol) in CH Cl (60 mL) at 0 ¡C.
(6 H, s), 6.79 (2 H, d, J 2.4), 6.89 (2 H, d, J 2.4), 6.88 (2 H, s);
4
2 2
After stirring the reaction mixture at room temperature for 2
h, it was poured into a large volume of ice water (400 mL) and
extracted with CH Cl (200 mL ] 2). The combined extracts
m/z: 462 (M`). Anal. calc. for C
H, 10.02; found: C, 82.81; H, 10.04%.
H
O (462.72): C, 83.06;
32 46
2
2
2
were washed with water, dried with Na SO and concen-
2
4
trated. The residue was chromatographed over silica gel
(Wako C-300, 500 g) with benzene as eluent to give crude 2b.
Recrystallization from hexane gave 9.06 g (64%) of 2b as pale
General procedure for the bromination of 3 with BTMABr .
3
To a solution of (Z)-3b (253 mg, 0.52 mmol) in CH Cl (50
2
2
mL) was added BTMABr (223 mg, 0.57 mmol) at room
3
yellow prisms, mp 82È84 ¡C; l (KBr)/cm~1: 1683 (C2O);
temperature. After stirring the reaction mixture at room
max
d (CDCl ): 1.31 (18 H, s), 1.20È1.40 (12 H, m), 1.50È1.70 (4 H,
temperature for 5 min, it was poured into a large volume
of ice water (50 mL) and extracted with CH Cl (50 mL
H
3
m), 2.66 (4 H, t, J 7.9), 3.87 (6 H, s), 7.48 (2 H, d, J 2.4), 7.69 (2
H, d, J 2.4), 10.36 (2 H, s); m/z: 522 (M`). Anal. calc. for
2
2
] 2). The combined extracts were washed with water,
C
H
O (522.8): C, 78.12; H, 9.64; found: C, 78.14; H,
dried with Na SO and concentrated. The residue was
34 50
4
2
4
9.72%.
recrystallized
(54%) of
from
hexane
gave
182
mg
1,8-Bis(5-tert-butyl-3-formyl-2-methoxyphenyl)octane,
Compound 2a was synthesized in the same manner as
described above for 2b and obtained in 70% yield as a pale
2a.
17,18-di-endo-bromo-13,21-di-tert-butyl-16,24-
dimethoxy[10.2]metacyclophane, meso-4b as colorless prisms,
mp 134È135 ¡C; l (KBr)/cm~1: 2928, 1858, 2824, 1458,
max
yellow oil; l
(NaCl)/cm~1: 1692 (C2O); d (CDCl ): 1.32
1427, 1363, 1204, 1115, 1008, 810, 449; d (CDCl ): 1.16 (18 H,
max
H
3
H
3
(18 H, s), 1.32È1.42 (8 H, m), 1.58È1.70 (4 H, m), 2.65È2.71 (4
H, m), 3.87 (6 H, s), 7.47 (2 H, d, J 2.4), 7.70 (2 H, d, J 2.4),
s), 0.75È1.78 (16 H, m), 2.19È2.35 (2 H, m), 2.62È2.80 (2 H, m),
3.65 (6 H, s), 5.95 (2 H, s), 7.00 (2 H, d, J 2.4), 7.23È7.60 (2 H,
10.36 (2 H, s); m/z: 494 (M`). Anal. calc. for C
(494.72): C, 77.69; H, 9.37. found: C, 77.37; H, 9.18%.
H
O
br d); m/z: 648, 650, 652 (M`). Anal. calc. for C
(650.6): C, 62.77; H, 7.75; found: C, 63.05; H, 8.01%.
H
O Br
32 46
4
34 50
2
2
17-endo,18-exo-Dibromo-13,21-di-tert-butyl-16,24-dimethoxy
[10.2]metacyclophane, dl-4b. Compound dl-4b was synthe-
sized in the same manner as described above for meso-4b and
General procedure for the McMurry coupling reaction of 2.
The McMurry reagent was prepared from TiCl (13.75 mL,
4
New J. Chem., 2001, 25, 728È736
733

View Article Online
obtained in 88% yield as colorless prisms (hexane), mp 199 ¡C;
(KBr)/cm~1: 2900, 2863, 1484, 1477, 1463, 1363 1247,
metacyclophane-1-yne, syn-6a in a ratio of 65 : 35 determined
from the 1H-NMR spectrum.
l
max
1231, 1212, 1013, 1003; d (CDCl ): 0.43È0.62 (2 H, br m),
5,19-Di-tert-butyl-8,22-dimethoxy[2.8]metacyclophane-1-yne,
6a. 6a was obtained as colorless prisms (MeOH), mp 117È
H
3
0.73È1.59 (14 H, m), 1.20 (18 H, s), 2.15È2.28 (2 H, m), 2.64È
2.80 (2 H, br m), 3.71 (6 H, s), 5.99 (2 H, s), 6.84 (2 H, d, J 1.95),
7.24 (2 H, br d); m/z: 648, 650, 652 (M`). Anal. calc. for
119 ¡C; l (KBr)/cm~1: 2916, 1471, 1363, 1261, 1221, 1104,
max
1008, 875; (anti-6a) d (CDCl ): 0.75È1.68 (12 H, m), 1.31 (18
H
3
C
H
O Br (650.6): C, 62.77 ; H, 7.75; found: C, 63.32; H,
H, s), 2.29È2.43 (2 H, br m), 2.77È2.98 (2 H, br m), 3.58 (6 H, s),
7.07 (2 H, d, J 2.4), 7.18 (2 H, d, J 2.4); d (CDCl ): 26.14,
34 50
2
2
7.88%.
C
3
- anti-15,16-Di-endo-bromo-11,19-di-tert-butyl-14,22-dimethoxy
[8.2]metacyclophane, anti-meso-4a. Compound anti-meso-4a
was synthesized in the same manner as described above for
meso-4b and obtained in 71% yield as colorless prisms
29.13, 29.41, 30.04, 30.20, 31.10, 31.57, 32.77, 34.29, 59.95, 99.02
(acetylenic C), 116.43, 123.76, 127.36, 134.23, 145.96, 160.64;
(syn-6a) d (CDCl ): 0.75È1.68 (12 H, m), 1.28 (18 H, s), 2.29È
H
3
2.43 (2 H, br m), 2.77È2.98 (2 H, br m), 3.85 (6 H, s), 7.02 (2 H,
d, J 2.4), 7.20 (2 H, d, J 2.4); d (CDCl ): 26.55, 29.13, 29.41,
(hexane), mp 134È135 ¡C; l (KBr)/cm~1: 2928, 1858, 2824,
max
C
3
1458, 1427, 1363, 1204, 1115, 1008, 810, 449; d (CDCl ): 0.70È
29.75, 30.57, 31.10, 31.49, 32.77, 33.15, 61.47, 97.52 (acetylenic
H
3
1.02 (6 H, m), 1.07È1.43 (6 H, m), 1.27 (18 H, s), 2.16È2.38 (2 H,
m), 2.58È2.72 (2 H, m), 3.64 (6 H, s), 5.96 (2 H, s, CHBr), 6.95 (2
H, d, J 2.2), 7.46 (2 H, d, J 2.2); m/z: 620, 622, 624 (M`). Anal.
C), 117.22, 124.67, 127.27, 134.81, 145.96, 158.70; m/z: 460
(M`). Anal. calc. for C
found: C, 83.68; H, 9.51%.
H
O (460.71): C, 83.43; H, 9.63;
32 44
2
calc. for C
61.91; H, 7.12%.
H
O Br (622.52): C, 61.74; H, 7.45; found: C,
32 46
2
2
4-tert-Butyl-2-formyl-6-methylanisole, 8. To a solution of
4-tert-butyl-2-methylanisole 727 (6.38 g, 35.76 mmol) and
Cl CHOCH (4.52 mL, 150 mmol) in CH Cl (40 mL) was
syn-15,16-Di-endo-bromo-11,19-di-tert-butyl-14,22-dimethoxy
[8.2]metacyclophane, syn-meso-4a. Compound syn-meso-4a
was synthesized in the same manner as described above for
meso-4b and obtained in 54% yield as a colorless oil;
2
3
2 2
added a solution of TiCl (12.0 mL, 108.4 mmol) in CH Cl
4
2 2
(40 mL) at 0 ¡C. After stirring the reaction mixture at room
temperature for 2 h, it was poured into a large volume of ice
water (400 mL) and extracted with CH Cl (200 mL ] 2). The
l
(NaCl)/cm~1: 2923, 1463, 1169, 1037, 809, 667;
max
H
d (CDCl ): 0.78È0.94 (2 H, m), 0.97È1.39 (8 H, m), 1.17 (18 H,
3
2 2
s), 1.48È1.67 (2 H, m), 2.19È2.35 (2 H, br m), 2.62È2.79 (2 H, br
m), 3.68 (6 H, s), 6.07 (2 H, s, CHBr ), 6.94 (2 H, d, J 2.0), 7.55
(2 H, d, J 2.0); m/z: 620, 622, 624 (M`). Anal. calc. for
combined extracts were washed with water, dried with
Na SO and concentrated. The residue was chromatographed
over silica gel (Wako C-300, 500 g) with hexane as eluent to
2
4
C
H
O Br (622.53): C, 61.74; H, 7.45; found: C, 62.01; H,
give 8 (5.93 g, 80%) as a yellow oil; l (NaCl)/cm~1: 1683
32 46
2
2
max
7.25%.
(C2O); d (CDCl ): 1.31 (9 H, s), 2.34 (3 H, s), 3.86 (3 H, s),
H
3
7.47 (1 H, d, J 2.1), 7.70 (1 H, d, J 2.1), 10.37 (1 H, s); m/z: 206
(M`). Anal. calc. for C
found: C, 75.52; H, 8.72%.
H
O (206.29): C, 75.69; H, 8.8;
13 18
2
Dehydrobromination of 4b with KOBut. To a solution of
meso-4b (180 mg, 0.28 mmol) in HOBut (24 mL) was added
KOBut (1.18 g, 10.5 mmol) at room temperature. After stirring
the reaction mixture at 50 ¡C for 1 h, it was poured into a
large amount of ice water (50 mL) and extracted with CH Cl
McMurry coupling reaction of 8 (Scheme 5). The McMurry
reagent was prepared from TiCl (13.75 mL, 125 mmol) and
4
Zn powder (18 g, 275 mmol) in 300 mL of dry THF, under
2
2
(100 mL ] 2). The combined extracts were washed with water,
nitrogen. A solution of 8 (5.37 g, 25.95 mmol) and pyridine
(22.8 mL, 200 mmol) in dry THF (100 mL) was added over 1 h
to the black McMurry reagent mixture by using a high-
dilution technique with continuous reÑuxing and stirring. The
reaction mixture was reÑuxed for an additional 12 h, cooled to
room temperature, and hydrolyzed with aqueous 10% K CO
dried with Na SO and concentrated. The residue was rec-
2
4
rystallized from methanol gave 136 mg (85%) of (E)-1-bromo-
5,21-di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-1-ene,
(E)-5b as colorless prisms, mp 89È90¡C; l (KBr)/cm~1:
max
2899, 2866, 2830, 1469, 1427, 1363, 1295, 1235, 1210, 1114,
2
3
1008; d (CDCl ): 0.92 (9 H, s), 1.27 (9 H, s), 1.10È1.65 (16 H,
(500 mL) at 0 ¡C. The reaction mixture was extracted with
H
3
br m), 1.95È3.06 (4 H, br m), 3.63 (3 H, s), 3.88 (3 H, s), 6.42 (1
H, d, J 2.4), 6.92 (1 H, d, J 2.4), 7.06 (1 H, d, J 2.4), 7.31 (1 H,
s), 7.38 (1 H, d, J 2.4); m/z: 568, 570 (M`). Anal. calc. for
CH Cl (300 mL ] 3). The combined extracts were washed
2
2
with water, dried with Na SO and concentrated. The residue
2
4
was chromatographed over silica gel (Wako C-300, 500 g)
with hexane, 3 : 1 hexaneÈbenzene and 4 : 1 benzeneÈEtOAc
as eluents to give (E)-10 (1.58 g, 32%), (Z)-10 (507 mg, 10%)
and 9 (1.82 g, 34%), respectively.
C
H
O Br (569.7): C, 71.69; H, 8.67; found: C, 71.62; H,
34 49
2
8.39%.
Similary, compound meso-4b was treated with KOBut in
HOBut at 80 ¡C for 3 h to a†ord 5,21-di-tert-butyl-8,24-
dimethoxy[2.10]metacyclophan-1-yne, 6b (80%) as colorless
1,2-Bis(5-tert-butyl-2-methoxy-3-methylphenyl)ethane-1,2-diol,
9. 9 was obtained as a yellow oil; l (NaCl)/cm~1: 3407
max
prisms (methanol), mp 137 ¡C; l (KBr)/cm~1: 2949, 2853,
(OH); d (CDCl ): 1.29 (18 H, s), 2.27 (2 H, s), 2.30 (6 H, s),
max
H
3
2822, 2210, 1479, 1459, 1363, 1237, 1200, 1023, 873;
3.78 (6 H, s), 4.70 (2 H, s), 7.14 (2 H, d, J 2.4), 7.18 (2 H, d, J
d (CDCl ): 1.30 (18 H, s), 0.82È1.58 (16 H, br m), 2.61È2.68 (4
2.4); m/z: 414 (M`). Anal. calc. for C
75.32; H, 9.24; found: C, 75.05; H, 9.34%.
H
O (414.59): C,
H
3
26 38
4
H, t, J 6.1), 3.80 (6 H, s), 7.08 (2 H, d, J 2.4), 7.27 (2 H, d, J
2.4); m/z: 488 (M`). Anal. calc. for C
83.55; H, 9.90; found: C, 83.60; H, 10.14%.
H
O
(488.8): C,
(Z)-1,2-Bis(5-tert-butyl-2-methoxy-3-methylphenyl)ethene,
(Z)-10. (Z)-10 was obtained as colorless oil;
(NaCl)/cm~1: 2928, 1478, 1362, 1210, 1118, 1015, 810;
34 48
2
a
l
max
d (CDCl ): 1.05 (18 H, s), 2.28 (6 H, s), 3.78 (6 H, s), 6.81 (2 H,
Dehydrobromination of syn-4a with KOBut. To a solution of
syn-4a (285 mg, 0.458 mmol) in THF (20 mL) was added
KOBut (513 mg, 4.58 mmol) at room temperature. After stir-
ring the reaction mixture under reÑux for 12 h, it was poured
into a large volume of ice water (50 mL) and extracted with
CH Cl (100 mL ] 2). The combined extracts were washed
H
3
s), 6.92 (2 H, d, J 2.4), 7.01 (2 H, d, J 2.4); m/z: 380 (M`).
Anal. calc. for C
C, 81.86; H, 9.52%.
H
O (380.58): C, 82.06; H, 9.53; found:
26 36
2
(E)-1,2-Bis(5-tert-butyl-2-methoxy-3-methylphenyl)ethene,
(E)-10. (E)-10 was obtained as colorless prisms (MeOH), mp
2
2
with water, dried with Na SO and concentrated. The residue
148È150 ¡C; l (KBr)/cm~1: 2958, 1483, 1428, 1368, 1248,
2
4
max
was chromatographed over silica gel (Wako C-300, 500 g)
with hexane as eluent to give crude 6a as a colorless solid. The
solid was recrystallized from methanol to a†ord a mixture of
anti- (anti-6a) and syn-5,19-di-tert-butyl-8,22-dimethoxy[2.8]
1205, 1111, 1003, 870; d (CDCl ): 1.34 (18 H, s), 2.32 (6 H, s),
H
3
3.76 (6 H, s), 7.25 (2 H, br s), 7.40 (2 H, s), 7.48 (2 H, br s); m/z:
380 (M`). Anal. calc. for C
9.53; found: C, 82.22; H, 9.30%.
H
O (380.58): C, 82.06; H,
26 36
2
734
New J. Chem., 2001, 25, 728È736

View Article Online
a large volume of ice water (100 mL) and extracted with
CH Cl (50 mL ] 2). The combined extracts were washed
2
2
with water, dried with Na SO and concentrated. The residue
2
4
was recrystallized from hexane to give 526 mg (97%) of 1,2-
dibromo-1,2-bis(5-tert-butyl-2-methoxy-3-methylphenyl)ethane,
11 as colorless prisms, mp 193È195 ¡C; l (KBr)/cm~1: 2955,
max
1482, 1361, 1249, 993, 605; d (CDCl ): 1.13 (9 H, s), 1.34 (9 H,
H
3
s), 2.10 (3 H, s), 2.33 (3 H, s), 3.82 (3 H, s), 3.93 (3 H, s), 5.30 (1
H, s), 6.15 (1 H, s), 6.84 (1 H, br d), 7.10 (1 H, br d), 7.20 (1 H,
br d), 7.45 (1 H, br d); m/z: 538, 540, 542 (M`). Anal. calc. for
C
6.46%.
H
O Br (540.38): C, 57.79; H, 6.72; found: C, 57.78; H,
26 36
2
2
Dehydrobromination of 11 with KOBut in THF. To a solu-
tion of 11 (376 mg, 0.696 mmol) in THF (62 mL) was added
KOBut (2.98 g, 26.59 mmol) at room temperature. After stir-
ring the reaction mixture at 50 ¡C for 1 h, it was poured into a
large volume of ice water (100 mL) and extracted with
CH Cl (100 mL ] 2). The combined extracts were washed
2
2
with water, dried with Na SO and concentrated. The residue
2
4
was recrystallized from methanol to give 245 mg (93%) of 1,2-
bis(5-tert-butyl-2-methoxy-3-methylphenyl)ethyne, as
12,
colorless prisms, mp 126È127 ¡C; l (KBr)/cm~1: 2358, 1227,
max
1116, 1002, 878, 651; d (CDCl ): 1.31 (18 H, s), 2.29 (6 H, s),
H
3
3.99 (6 H, s), 7.16 (2 H, d, J 2.4), 7.37 (2 H, d, J 2.4);
d (CDCl ): 15.91, 30.89, 33.72, 60.09, 89.52, 115.77, 127.59,
C
3
128.15, 129.94, 145.67, 156.64; m/z: 378 (M`). Anal. calc. for
C
9.02%.
H
O (378.56): C, 82.49; H, 9.05; found: C, 82.30; H,
26 34
2
Estimation of the activation energy of the ring Ñipping
The rate constant (k ) of the observed conformational inter-
c
conversion at the coalescence temperature (T ) can be calcu-
c
lated by using eqn. (1).28 The free energy of activation (*GE)
c
at coalescence can then be estimated by using the Eyring
equation [eqn. (2)].28
k \ n*l/21@2
(1)
(2)
c
*GE \ 2.303RT (10.32 ] log T [ log k )
c
c
c
c
Scheme 5
X-Ray crystallography
Bromination of (E)-10 with BTMABr . To a solution of (E)-
Crystallographic data and data collection details for (E)-3b,
(Z)-3b and 6b are given in Table 4. In a typical procedure, a
single crystal was mounted on a quartz Ðber and the unit cell
constants for (E)-3b were derived from a least-squares analysis
3
10 (380 mg, 1 mmol) in CH Cl (40 mL) was added BTMABr
2
2
3
(440 mg, 1.1 mmol) at room temp. After stirring the reaction
mixture at room temperature for 24 h, it was poured into
Table 4 Crystallographic data and data collection details for (E)-5,21-di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-1-ene (E)-3b, (Z)-5,21-
di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-1-ene (Z)-3b and 5,21-di-tert-butyl-8,24-dimethoxy[2.10]metacyclophan-1-yne 6b
(E)-3b
(Z)-3b
6b
Formula
FW
Crystal system
C
490.78
Triclinic
H
O
C
490.78
Orthorhombic
H
O
C
H O
34 50
2
34 50
2
34 48 2
488.76
Triclinic
Space group
P1 (no. 2)
12.554(1)
13.707(2)
10.288(1)
108.20(1)
113.805(8)
83.10(1)
1538.5(3)
2
295
4.52
6366
5694
P2 2 2 (no. 19)
P1 (no. 2)
12.1080(8)
13.949(2)
10.2097(11)
105.5138(99)
113.595(7)
84.019(8)
1522.7(3)
2
298
4.57
6198
5872
1 1 1
a/A
b/A
c/A
a/¡
14.4498(14)
21.115(2)
9.6625(7)
b/¡
c/¡
U/A
Ž
3
3152.0(4)
4
295
4.42
3203
3176
È
0.090
0.116
Z
T /K
k/cm~1
No. of reÑections
Unique reÑections
R
int
R
0.04
0.107
0.150
0.03
0.066
0.096
R a
w
a u \ 4(F )2/[(pI )2 ] 0.0016(F )4].
o
o
o
New J. Chem., 2001, 25, 728È736
735

View Article Online
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of the settings of a CAD4 FR 586 di†ractometer for 25 reÑec-
tions, in the range 29.92¡ \ h \ 31.43¡. The intensities of all
independent reÑections with 8¡ \ 2h \ 144¡ were measured
with u [ 2h scan width (0.80 ] 0.14 tan h) using Ni-Ðltered
Cu-Ka radiation (j \ 1.541 84 A). The X-ray analysis was per-
formed with the MolEN program package29 and the structure
was determined uneventfully by direct methods (SIR 88).30
The structure of 6b was determined by direct methods using
MULTAN 80.31 No corrections were made for absorption
e†ects. The 36 independent non-hydrogen atoms were reÐned
anisotropically. The 41 independent hydrogen atoms, except
for those on C26, C27 and C28, were put in calculated posi-
13 T. Yamato, J. Matsumoto, M. Sato, K. Noda and M. Tashiro, J.
Chem. Soc., Perkin T rans. 1, 1995, 1299.
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M. Tashiro, J. Chem. Soc., Perkin T rans. 1, 1992, 2675; (c) T.
Yamato, A. Miyazawa and M. Tashiro, J. Chem. Soc., Perkin
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mekpor, K. Hasegawa and M. Koike, Chem. Ber., 1993, 126,
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Chem. Express, 1990, 5, 769; (b) T. Yamato, J. Matsumoto, S. Ide,
K. Tokuhisa, K. Suehiro and M. Tashiro, J. Org. Chem., 1992, 57,
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K. Suehiro and M. Tashiro, Chem. Ber., 1992, 125, 2443.
16 (a) H.-F. Grutzmacher, E. Neumann, F. Ebmeyer, K. Albrecht
and P. Schelenz, Chem. Ber., 1989, 122, 2291; (b) H.-F.
Grutzmacher and G. Nolte, Chem. Ber., 1994, 127, 1157; (c) H.-F.
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bonded. The reÐnement was performed by full-matrix least-
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CCDC reference number 156035È156037. See http://
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17 (a) M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 4556; (b)
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