Medium-sized cyclophanes. Part 58. Synthesis and conformational studies of [2.n]metacyclophan-1-enes and [n.1]metacyclophanes

Article abstract of DOI:10.1039/b010075g

A series of syn- and anti-[2.n]metacyclophan-1-enes and [2.n]metacyclophane-1,2-diols are prepared in good yields by a McMurry cyclization of 1,n-bis(5-acetyl-2-methoxyphenyl)alkanes. Interestingly, in the same coupling reaction in the absence of pyridine the pinacol rearrangement of [2.n]metacyclophane-1,2-diols to afford [n.1]metacyclophanes is observed, attributable to the TiCl₄ or acids generated from the McMurry reagent occurring during the cyclization reaction. In fact, protic acid- or Lewis-acid induced pinacol rearrangements of [2.n]metacyclophane-1,2-diols afford [n.1]metacyclophanes in good yield. The [2.n]metacyclophan-1-ene-to-[n.1]metacyclophane ratio of the products is strongly governed by the number of the methylene bridges. The proportion of the rearrangement product increases with increasing length of the bridge. Conformational studies of [n.1]metacyclophanes as well as of [2.n]metacyclophan-1-enes in both solution and solid state are also described.

Full text of DOI:10.1039/b010075g

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Medium-sized cyclophanes. Part 58.1 Synthesis and conformational
studies of [2.n]metacyclophan-1-enes and [n.1]metacyclophanes
Takehiko Yamato,*a Koji Fujitaa and Hirohisa Tsuzukib
1
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: ϩ81 0952 28 8591
b Tohwa Institute for Science, Tohwa University, 1-1-1 Chikushigaoka, Minami-ku,
Fukuoka-shi, Fukuoka 815-8510, Japan
Received (in Cambridge, UK) 13th December 2000, Accepted 27th June 2001
First published as an Advance Article on the web 13th August 2001
A series of syn- and anti-[2.n]metacyclophan-1-enes and [2.n]metacyclophane-1,2-diols are prepared in good yields by
a McMurry cyclization of 1,n-bis(5-acetyl-2-methoxyphenyl)alkanes. Interestingly, in the same coupling reaction in
the absence of pyridine the pinacol rearrangement of [2.n]metacyclophane-1,2-diols to afford [n.1]metacyclophanes
is observed, attributable to the TiCl4 or acids generated from the McMurry reagent occurring during the cyclization
reaction. In fact, protic acid- or Lewis-acid induced pinacol rearrangements of [2.n]metacyclophane-1,2-diols afford
[n.1]metacyclophanes in good yield. The [2.n]metacyclophan-1-ene-to-[n.1]metacyclophane ratio of the products is
strongly governed by the number of the methylene bridges. The proportion of the rearrangement product increases
with increasing length of the bridge. Conformational studies of [n.1]metacyclophanes as well as of
[2.n]metacyclophan-1-enes in both solution and solid state are also described.
acetyl chloride at 20 ЊC led to an ipso-acylation reaction,12
Introduction
affording the desired 1,n-bis(5-acetyl-2-methoxyphenyl)alkanes
Although [n.1]MCPs (MCP = metacyclophane) have been pre-
2 in good yield (Scheme 1).13
pared by various workers, the synthetic routes used in previous
methods were too long for practical purposes. Vögtle2 reported
the first synthesis of both [4.1]- and [5.1]MCP3 by use of the
sulfone pyrolysis method. Later, Lin et al. succeeded in prepar-
ing the lower [3.1]homologue by a photochemical method.4
However, it was quite difficult to obtain sufficient amounts for
further studies by this route.
In cyclophane chemistry the reductive coupling of carbonyl
compounds by low-valent titanium, the McMurry reaction,5
has been used before by Mitchell et al.6 to synthesize
cyclophanes with glycol units as bridges, by Tanner and
Wennerström,7 and recently by Hopf8 and Grützmacher et al.9
for a cyclization of suitable dialdehydes to yield unsaturated
cyclophanes. On the other hand, it is well known that acid-
catalyzed pinacol rearrangement of 1,2-glycols affords the
corresponding ketones;10 e.g., 2,3-diaryl-2,3-dihydroxybutanes
afford 3,3-diarylbutan-2-ones or 1,2-diaryl-2-methylpropan-1-
ones via aryl or methyl shift, respectively. Thus, there is sub-
stantial interest in the systematic investigation of the pinacol
rearrangement of [n.2]cyclophanes with glycol units at the
ethylene bridges to afford either [n.1]cyclophanes by ring
contraction or [n.2]cyclophane ketones.
Scheme
1
Reagents and conditions: i, MeCOCl, AlCl3–MeNO2,
CH2Cl2 room temp. for 1 h.
1,2-Bis(5-acetyl-2-methoxyphenyl)ethane 2a13 was subjected
to reductive coupling by the McMurry reaction following
Grützmacher’s procedure9 (Scheme 2). Although none of the
desired [2.2]MCP-1-ene 3a was observed, the dimer 6a was
obtained in 11% yield.
In this paper, we describe a new preparative route for a series
of anti-[2.n]MCP-1-enes and [2.n]MCP-1,2-diols using the
low-valent-titanium-induced McMurry reaction. The latter
compounds were further converted to [n.1]MCPs by pinacol
rearrangement. Conformational studies of [n.1]MCPs as well as
of [2.n]MCP-1-enes in both solution and solid state are also
described.
Interestingly, when pyridine was used in the present cycliz-
ation reaction, [2.2]MCP-1,2-diol 4a was obtained in 10% yield,
but the formation of the desired [2.2]MCP-1-ene 3a was again
not observed. This finding seems to be due to the much more
strained structure of 3a than that of diol 4a containing the
larger ring during formation of the unsaturated C᎐C linkage.
᎐
Thus, during the McMurry reaction the intramolecular
cyclization to afford 3a might be quite difficult. Interestingly,
when the reductive coupling reaction of 2a was carried out
in the presence of pyridine at room temperature, the yield of
[2.2]MCP-1,2-diol 4a increased from 10% to 30% along with
trace amount of dimer 6a. Results of the McMurry reaction for
substrates 2a–e are presented in Table 1.
Results and discussion
1,n-Bis(5-tert-butyl-2-methoxyphenyl)alkanes 1 have been pre-
pared according to our previous papers.11 The AlCl3–MeNO2-
catalyzed acetylation of compounds 1 with acetic anhydride or
DOI: 10.1039/b010075g
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097
This journal is © The Royal Society of Chemistry 2001
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Table 1 McMurry reaction of 1,n-bis(5-acetyl-2-methoxyphenyl)alkanes 2
Run
Substrate
Number of methylene units, n
Conditionsa
Products (% yield)b
1
2
3
4
5
6
7
8
9
2a
2a
2a
2b
2b
2c
2c
2d
2d
2e
2
2
2
3
3
4
4
5
5
6
Ac
B
3a (0)
4a (0)
4a (10)
4a (30)
4b (0)
4b (7)
4c (13)
4c (15)
4d (0)
4d (8)
4e (0)
5a (0)
5a (0)
5a (0)
5b (0)
5b (0)
5c (0)
5c (0)
5d (34)
5d (4)
5e (60)
3a (0)
Bd
Ac
B
3a (0)
3b (70)
3b (80)
3c (69)
3c (83)
3d (45)
3d (77)
3e (19)
A
B
A
B
10
A
a Reaction conditions: A; The reaction was carried out in the absence of pyridine. B; The reaction was carried out in the presence of pyridine.
b Isolated yields. c The dimers 6a and 6b were obtained in 11% and 2% yield, respectively. d The reaction was carried out at room temperature.
NMR time-scale above this temperature. However, in dimer 6a
even at Ϫ60 ЊC in CDCl3–CS2 (1 : 3) the singlet signal of the
ArCH2CH2Ar ethylene protons remains unsplit. These obser-
vations indicate the flexible structure of 6a, similar to that of
[24]MCP in spite of the introduction of two additional double
bonds of the ethylene bridge.17
Similar McMurry cyclization of 1,3-bis(5-acetyl-2-methoxy-
phenyl)propane 2b carried out under the same reaction
conditions afforded the desired [2.3]MCP-1-ene 3b in 70% yield
along with a trace amount of dimer 6b. When pyridine was
used in the present cyclization reaction, the yield of 3b
increased to 80%.The same results were obtained in the case of
the longer diacetyldiphenylbutane 2c except for the formation
of [4.2]MCP-11,12-diol 4c. Interestingly, the coupling reaction
of 1,5-bis(5-acetyl-2-methoxyphenyl)pentane 2d with low-
valent titanium (TiCl4/Zn) in the absence of pyridine led to the
intramolecular cyclization affording 1,2-dimethyl[2.5]MCP-1-
ene 3d along with the [5.1]MCP 5d in 34% yield. The formation
of the corresponding 1,2-diol 4d was not observed. This finding
suggests that the pinacol rearrangement of 1,2-diol 4d catalyzed
by TiCl4 or acids generated from the McMurry reagent
occurred during the cyclization reaction. In fact, when the same
reaction was carried out in the presence of an excess of
Scheme 2 (see Table 1). Reagents and conditions: i, TiCl4–Zn–pyridine,
THF, reflux for 60 h.
pyridine, the corresponding 1,2-diol 4d was obtained in 8%
yield. In the case of 1,6-bis(5-acetyl-2-methoxyphenyl)hexane
2e the preference for formation of the rearrangement product
The structures of products, diol 4a and dimer 6a were
5e was observed. Thus, the [2.n]MCP-to-[n.1]MCP ratio of
determined on the basis of their elemental analyses and
products is strongly governed by the number of methylene
spectral data. Thus, Griffin et al. reported14 the structure of
bridges. The portion of the rearrangement product increases
with increasing length of the bridge. To the best of our know-
ledge the present rearrangements of [2.n]MCPs to the smaller-
1,2-dimethyl[2.2]MCP and assigned the exo-endo-arrange-
1
ment. We have assigned the H NMR signals of 4a in a simi-
1
lar fashion. In the H NMR spectrum of 4a in CDCl3 upfield
ring-size [n.1]MCPs by a ring contraction are the first such case
shifts and the different chemical shifts for internal aromatic
in cyclophane chemistry. In fact Grützmacher et al. reported18
a
protons at δ 4.36 and 4.83 due to the ring current of the
opposite aromatic ring were observed.15,16 These data strongly
suggest that the structure of 4a is the anti-conformer. Further-
more, the two methyl groups show different chemical shifts at
δ 1.30 and 1.83 each as a singlet. The four external aromatic
protons were also observed as different chemical shifts at
δ 6.81, 6.88, 7.13 and 7.40; the latter proton is in a strongly
deshielding region of the oxygen atom of the endo-OH on the
ethylene bridge. In contrast, one of the two internal aromatic
protons was observed at lower field (δ 4.83) attributable to
being in a strongly deshielding region of the oxygen atom of
the exo-OH on the ethylene bridge. These data strongly sup-
port the suggestion that the two OH groups are in an endo-
and exo-arrangement and, therefore, anti-4a is found to be
the trans-diol.
similar acid-catalyzed rearrangement of [2.1.2.1]paracyclo-
phane-1,2-diol to afford the corresponding ketones by a pinacol
rearrangement. No ring contraction was observed in spite of
the much larger ring size than the present [2.n]MCP-1,2-diols
(see Scheme 3).
The mass spectral data for dimer 6a (Mϩ = 588) strongly sup-
port a cyclic dimeric structure. In the 1H NMR spectrum of the
tetramethoxy[24]MCP 6a, protons of methyl groups, methoxy
groups and ArCH2CH2Ar methylene protons each appear as a
singlet at 27 ЊC. This behaviour indicates that the rate of con-
formational ring flipping of macrocycle 6a is faster than the
Scheme 3 Reagents and conditions: i, H2SO4.
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Table 2 Pinacol rearrangement of [2.n]MCP-1,2-diols 4c–e
Run
Substrate
Number of methylene units, n
Conditionsa
Products (% yield)b
1
2
3
4
5
6
4c
4c
4d
4d
4e
4e
4
4
5
5
6
6
A
B
A
B
A
B
5c (45) 7c (5), 8c (7), 2c (8)
5c (33)c
5d (65)
5d (62)
5e (95)
5e (96)
a Reaction conditions: A; I2–HOAc, 1,4-dioxane, reflux for 30 min. B; BF3ؒEt2O, CH2Cl2, room temperature for 30 min. b Isolated yields. c Intractable
mixture was also obtained.
As mentioned previously, synthesis of [n.1]MCPs have not
been commonplace due to the lack of a general method such as
that developed by Boekelheide for the [2.2]MCPs.19 As men-
tioned previously, Vögtle2 reported the first synthesis of both
[4.1]- and [5.1]-MCP by use of the sulfone pyrolysis method.
Later, Lin et al. succeeded in preparing the lower [3.1]homo-
logue by a photochemical method.4 However, the synthesis of
[n.1]MCPs has not been established so far due to both the low-
yield preparation and the unsuccessful attempts to prepare the
lower [3.1]homologue except by photochemical synthesis. On
the other hand, substituent effects on the pinacol rearrange-
ment have been reported.10,20 Thus, there is substantial interest
in pinacol rearrangement of [n.2]cyclophanes with glycol units
at the ethylene bridge to afford either [n.1]cyclophanes by ring
contraction or [n.2]cyclophane ketones. From the above
results, the present pinacol rearrangement could be used for the
preparation of novel [n.1]MCPs.
The structures of pinacol rearrangement products 5c–e and
dehydration products 7c, 8c were determined on the basis of
their elemental analyses and spectral data. In particular, in the
case of [4.1]- and [2.4]-systems, for example, the mass spectral
data for 5c (Mϩ = 338) and 7c, 8c (Mϩ = 338 and 320) strongly
support a cyclic structure. The reaction pathway in which the
rearrangement products 5 would be formed via the protic-acid-
catalyzed rearrangement of the 1,2-diols 4 is the same as that of
the rearrangement of 4-methoxyacetophenone pinacol.10b
However, in the case of [2.2]MCP-1,2-diol 4a and [3.2]MCP-
10,11-diol 4b with BF3ؒEt2O in dichloromethane the formation
of the desired pinacol rearrangement products [2.1]MCP 5a
and [3.1]MCP 5b was not observed under the reaction condi-
tions used. Only the transannular cyclization products 9a and
9b were obtained, along with a large amount of a mixture of
intractable products. When CF3SO3H was used in the present
reaction, the transannular cyclization products 9a and 9b were
obtained in almost quantitative yields (Scheme 5). These results
An attempted pinacol rearrangement of [4.2]MCP-11,12-
diol 4c with I2–HOAc10b,21 in 1,4-dioxane under reflux for 3 h
led to the desired [4.1]MCP 5c in 45% yield along with the
dehydration products 7c and 8c in 5 and 7% yield (Scheme 4,
Scheme 5 Reagents and conditions: i, CF3SO3H, CH2Cl2, room
temperature for 30 min.
are consistent with the results obtained from the anti-[2.2]- and
-[2.3]MCP-1-enes, which undergo transannular cyclization
reactions under the acidic conditions or photoirradiation
attributable to the proximity of the intra-annular positions and
the release of the considerable strain energy.9a,9b,22
Deacetylation of ketone 5c with molten potassium hydroxide
gave the bridge-methyl-substituted [n.1]MCP 10c in 91% yield.
Similar treatment of ketones 5d and 5e afforded the desired
products 10d and 10e in 95 and 68% yield, respectively (Scheme
6).
Scheme 4 (see Table 2). Reagents and conditions: i, I2–HOAc, 1,4-
dioxane, reflux for 30 min; BF3ؒEt2O, CH2Cl2 room temperature for
30 min.
Table 2). Furthermore, the ring cleavage at the 1,2-diol moiety
occurred to form 1,4-bis(5-acetyl-2-methoxyphenyl)butane 2c
in 8% yield under the conditions used. The same reaction
carried out in the presence of BF3ؒEt2O afforded the
rearrangement product 5c in 33% yield along with a mixture of
intractable products. In contrast, in the case of treatment
of [5.2]MCP-12,13-diol 4d and [6.2]MCP-13,14-diol 4e with
I2–HOAc in 1,4-dioxane the desired pinacol rearrangement
products [5.1]MCP 5d and 5e were the main products, obtained
in 65, 95% yield, respectively. No formation of dehydration
product or ring-cleavage product was observed. Similar results
were also obtained in the presence of BF3ؒEt2O as a catalyst.
The yields of the rearrangement products 5 increase with the
number of the methylene bridges. This result might be
attributed to the decrease of ring strain in [n.1]MCPs.
Scheme 6 Reagents and conditions: i, KOH, 180 ЊC for 3 h.
Although the preparations of [n.1]MCPs were reported by
various research groups,2–4 we have accomplished the first
successful, convenient preparation of a series of [n.1]MCPs by
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097
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Table 3 Coalescence temperature (T c) and ∆G‡c for conformational
ring inversion of [2.n]MCP-1-enes 3, and [n.1]MCPs 5 and 10
Number of
methylene units, n
∆G‡c
a
Compd.
T c/ЊCa
(kcal molϪ1
)
3b
3c
3
4
5
4
5
4
5
70
Ϫ30
<Ϫ100
90
<Ϫ100
90
<Ϫ100
15.6
10.7
3d
5c
5d
10c
10d
17.3
17.3
Fig. 1 Possible conformations of [2.n]MCP-1-enes.
pinacol rearrangement via ring contraction of [n.2]MCPs 4
having a 1,2-diol unit on the ethylene bridge.
a T c and ∆Gc‡ were determined in CDCl3–CS2 (1 : 3) or CDBr3, using
SiMe4 as a reference.
[2.n]MCP-1-enes adopt either a ‘stair-case’ anti conform-
ation or a syn conformation with overlaying aromatic rings
(Fig. 1).9b,15,23 Depending on the size of the bridges and on the
presence of intra-annular substituents, the interconversion
between the syn and anti conformers occurs by ring flipping.24
The conformation of 1,2-dimethyl[2.n]MCP-1-enes 3 was
readily apparent from their 1H NMR spectrum. Thus, the
internal aromatic proton shows an upfield shift (δ 5.69–6.77)
due to the ring current of the opposite benzene ring.15,16 The 1H
NMR spectrum of 1,2-dimethyl[2.3]MCP-1-ene 3b at 27 ЊC
showed a broad singlet of the intra-annular proton Hi at δ 5.69,
apart from those at δ 6.72 and 7.03 for the other two protons on
the aromatic rings. The methyl protons at the bridged double
bond and the methoxy protons were observed each as a singlet
at δ = 2.19 and 3.83, respectively, and the protons of the tri-
methylene bridge generate a complicated signal pattern as
expected for a rigid anti-[2.3]MCP-1-ene. The protons of the
benzylic CH2 group were observed as two multiplets centred at
δ 1.95 and 2.92, which are further split by coupling with the
protons of the central CH2 group. This central CH2 group was
also observed as a multiplet centred at δ 1.69. This peak pattern
ascribed to six chemically distinct protons of the propano
bridge confirms the absence of an anti-anti interconversion
which would exchange HA and HB of each CH2 group. As the
temperature of the solution of 3b in CDBr3 is increased, the
individual peaks of the benzyl protons merge and eventually a
single peak is observed above 70 ЊC. This observation indicates
that the rate of conformational ring flipping of 3b is faster than
the NMR time-scale at this temperature. The energy barrier to
the conformational ring flipping estimated from the coalescence
temperature (Tc) is 15.6 kcal molϪ1.†
shifts for internal aromatic protons at δ 6.33 and 6.56 due to the
ring current of the opposite aromatic ring were observed.15,16
These data strongly suggest that the structure of 5c is the
anti-conformer. Furthermore, the two methoxy groups show
different chemical shifts at δ 3.80 and 3.81, each as a singlet.
The four external aromatic protons were also observed as dif-
ferent chemical shifts at δ 6.66, 6.72, 6.91 and 7.21; the latter
proton is in a strongly deshielding region of the oxygen atom of
the acetyl group on the methylene bridge. Thus, 5c adopts a
‘stair-case’ anti conformation as known for other [2.3]MCP-1-
enes9b,23e and [3.2]MCPs24 having the same 11-membered ring.
1
The H NMR spectrum of 5c in CDCl3 at room temperature
exhibits a split pattern for the benzyl protons as two multiplets
centred at δ 2.34 and 2.7. The central CH2 group was also
observed as two multiplets centred at δ 0.95 and 1.69. These
findings suggest a rigid structure of [4.1]MCP 5c at this tem-
perature. However, as the temperature of the solution in CDBr3
is increased, a pair of multiplets of the benzyl protons merged
into a single peak above 90 ЊC. The energy barrier to conform-
ational ring flipping estimated from the coalescence temper-
ature (Tc) is 17.3 kcal molϪ1. The energy barrier for the
[4.1]-system 10c was also estimated to be the same [17.3
(Tc = 90 ЊC) kcal molϪ1]. This energy is much lower than that of
25,26
the rigid [2.2]MCP (>27 kcal molϪ1
)
and is similar to that
for the homologous [3.2]MCPs (15.8–19.1 kcal molϪ1).27 This
finding indicates a more rigid structure for [4.1]MCP 5c and
10c (ca. 6.6 kcal molϪ1) than that for [2.4]MCP-1-ene 3c
(∆G‡c = 10.7 kcal molϪ1) attributable to the one methylene
decrease. It was also found that the solution conformation of
[n.1]MCPs is sensitive to the chain length of the bridges. The
Similar findings were also observed in the 1H NMR spectrum
of 1,2-dimethyl[2.4]MCP-1-ene 3c at 27 ЊC, but the protons of
the butane bridge give rise to two multiplets centered at δ 1.57
and 2.47, respectively, providing a fast interconversion of the
two anti conformations of 3c by ring flipping. However, as the
temperature of the solution in CDCl3–CS2 (1 : 3) is decreased, a
single peak for the benzyl protons splits into a pair of doublets
below Ϫ30 ЊC. The energy barrier to the conformational ring
flipping estimated from the coalescence temperature (Tc) is 10.7
kcal molϪ1. This finding indicates a more flexible structure for
3c than of 3b, attributable to the larger cyclophane ring size. In
spite of a decrease in temperature to Ϫ100 ЊC in CDCl3–CS2
(1 : 3), no change in the spectrum is observed for the [2.5]-
system 3d. The solution conformation of 1,2-dimethyl-
[2.n]MCP-1-enes 3 is sensitive to the chain length of the bridge.
The ring-inversion barriers determined by variable-temperature
1H NMR decrease with increasing length of the bridges. Values
for coalescence temperature and ring-flipping energy barriers
are given in Table 3
1
ring-inversion barriers determined by variable-temperature H
NMR dramatically decrease with increasing length of the
bridge by one unit.
Usually, parent [n.2]MCPs in which intra-annular substitu-
ents are absent preferably adopt an anti-conformation.28,29
Similarly, in the case of the [4.1]MCP 5c the anti-conformation
was found to be favorable. The conformation of 5c has also
been confirmed by X-ray crystallographic analysis. Single
colorless crystals of 6,14-dimethoxy-1,2-dimethyl[2.4]MCP-1-
ene 3c and of 11-acetyl-11-methyl-6,15-dimethoxy[4.1]MCP 5c
suitable for X-ray crystallography were both obtained by
recrystallization from methanol–chloroform (1 : 1).
The perspective ORTEP drawings of 3c and 5c are illustrated
in Figs. 2 and 3, with the atom-numbering system. Compound
3c crystallized in centrosymmetric orthorhombic space group
Pbcn (No. 60) and is located about a two-fold axis, since this
molecule has crystallographic C2 symmetry. Therefore, the
asymmetric unit contains one half of a molecule (Z = 4). Com-
pound 5c crystallized in monoclinic space group P21/c (No. 14)
(Z = 4).
Similarly, the conformation of [n.1]MCPs 5 and 10 was read-
ily apparent from their 1H NMR spectrum. For example, in the
1H NMR spectrum of 11-acetyl-11-methyl-6,15-dimethoxy-
[4.1]MCP 5c in CDCl3 upfield shifts and the different chemical
The X-ray crystallography clearly shows that both conform-
ations of 3c and 5c adopt the anti form in which two aromatic
rings are in a non-planar chain form. In 3c the selected bond
lengths of C1–C2 and C2–C3 in the tetramethylene chains and
† 1 cal = 4.184 J.
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C13–C14–C15–C16) relative to the C13–C17–C4 plane are 33.2
(3)Њ and 44.2 (3)Њ, respectively.
The UV spectra of the [n.1]MCPs 10c,d showed different
absorption curves to that of the model acyclic compound, 1,1-
bis(4-methoxyphenyl)ethane 11. A small bathochromic shift at
285 nm (log εmax = 3.55) in comparison with that of 11 at 277
nm (log εmax = 3.62) was observed for the [4.1]MCPs 10c, which
is ascribed to a transannular interaction between the two ben-
zene rings and an increase in the strain of these systems.15 The
same phenomenon is also observed in [5.1]MCP 10d but the
bathochromic shift is smaller than that of [4.1]MCPs 10c.
Tetracyanoethylene (TCNE) complexes have often been used
in studies on the relative π-base strength of various methyl-
substituted benzenes.30 The π-basicity of the donor molecules
increases with an increase in the number of substituted methyl
groups and/or stacking benzene rings and an increase in the
face-to-face overlapping between aromatic nuclei.31 A solution
of [4.1]MCP 10c and TCNE in CH2Cl2 present a purple color
and the charge-transfer band at 606 nm (log ε = 1.138) was
observed in its UV spectrum. This absorption is due to the
formation of 1 : 1 charge-transfer complex among the electron
donor, [4.1]MCP, and the electron acceptor, TCNE. The pos-
ition of the absorption maximum and the shape of the absorp-
tion curve remain unchanged when a 4–12-fold excess of TCNE
was added. However, the charge-transfer absorption band of
the reference compound, 2,4-dimethylanisole 12, with TCNE
was observed at 414 nm (log ε = 2.073). Such a red shift
could be due to the through-space electronic interaction of the
opposite uncomplexed benzene ring, which tends to work as a
π-electron donor. In contrast to [4.1]MCP 10c, which exhibits
the charge-transfer absorption band with TCNE at 606 nm (log
ε = 1.138), a mixture of TCNE and [5.1]MCP 10d exhibits an
absorption peak at 510 nm (log ε = 1.716), while that of
[6.1]MCP 10e is shifted to 501 nm (log ε = 0.931). Introduction
of the one methylene inert to the tetramethylene bridge of 10c
causes a larger blue shift as indicated by the 96 nm shift for the
CT-band of 10d due to the decreased transannular π-electron
donation from the non-complexed benzene ring to the com-
plexed benzene ring.
Fig. 2 X-Ray structure of 6,14-dimethoxy-1,2-dimethyl[2.4]MCP-1-
ene 3c. Thermal ellipsoids are drawn at the 50% probability level. For
clarity all hydrogen atoms are omitted.
In conclusion, a new synthesis of [2.n]MCP-1-enes and
[2.n]MCP-1,2-diols by
a McMurry cyclization has been
developed. Protic acid- or Lewis acid-induced pinacol
rearrangements of [2.n]MCP-1,2-diols can be applied to the
synthesis of [n.1]MCPs. Further studies on the present novel
ring contraction of [2.n]cyclophanes with glycol units at the
ethylene bridge to afford [n.1]cyclophanes are now in progress.
Fig. 3 X-Ray structure of 11-acetyl-6,15-dimethoxy-11-methyl[4.1]-
MCP 5c. Thermal ellipsoids are drawn at the 50% probability level. For
clarity all hydrogen atoms are omitted.
Experimental
C7–C9 and C9–C10 in the ethylenic chains have suitable values,
1.530(4), 1.507(4), 1.503(4), and 1.509(5) Å, respectively, and
the length of the double bond is 1.359(4) Å. The bond angles
defined by C8–C7–C9 and C7–C9–C9Ј are 124.1(3) and
123.0(3)Њ, showing that 3c displays a slightly distorted conform-
ation. The two benzene rings of 3c distort into a slight boat
shape and slightly deviate from planarity; the dihedral angles of
the plane defined by C3–C4–C6–C7 between the planes defined
by C3–C8–C7 and C4–C5–C6 are 3.67(3)Њ and 1.58(3)Њ, respect-
ively. The tetramethylene bridge chains do not display a fully
extended anti conformation, probably to minimize the strain.
Both methoxy groups on the benzene rings of 3c point towards
the out side, away from the tetramethylene bridge chain. This
might contribute to avoiding steric crowding with hydrogens
and carbons of the bridge chains.
Mps (Yanagimoto MP-S1) and bps are uncorrected. NMR
spectra were determined at 270 MHz with a Nippon Denshi
JEOL FT-270 NMR spectrometer with SiMe4 as an internal
reference: J-values are given in Hz. IR spectra were measured
for samples as KBr pellets or a liquid film on NaCl plates in a
Nippon Denshi JIR-AQ2OM spectrophotometer. UV spectra
were measured by a Shimadzu 240 spectrophotometer. Mass
spectra were obtained on a Nippon Denshi JMS-01SA-2 spec-
trometer at 75 eV using a direct-inlet system through GLC.
Materials
The preparations of 1,n-bis(5-tert-butyl-2-methoxyphenyl)-
alkanes 111 and 1,n-bis(5-acetyl-2-methoxyphenyl)alkanes 2a–
2c13 have been previously described. 1,1-Bis(4-methoxyphenyl)-
ethane 11 was prepared according to the literature procedure.10b
Again, in 5c both methoxy groups on the benzene rings, as in
3c, point towards the outside, away from the tetramethylene
bridge chain. In 5c the two benzene rings also distort into a
slight boat shape. The bond angle of the bridged methylene
moiety, C13–C17–C4 is 106.6 (3)Њ, and the torsional twists of
the two benzene rings (C1–C2–C3–C4–C5–C6 and C11–C12–
Acetylation of 1,n-bis(5-tert-butyl-2-methoxyphenyl)alkanes 1
with acetyl chloride in the presence of AlCl3–MeNO2
Typical procedure. To a solution of 1,5-bis(5-tert-butyl-2-
methoxyphenyl)pentane 1d (3.96 g, 10 mmol) and acetyl chlor-
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097
2093

View Article Online
ide (2.1 cm3, 30 mmol) in CH2Cl2 (80 cm3) was added a solu-
tion of aluminium chloride (5.94 g, 44.5 mmol) in nitromethane
(10 cm3) at 0 ЊC. After the reaction mixture had been stirred
at room temperature for 2 h, it was poured into ice–water
(100 cm3). The organic layer was extracted with CH2Cl2 (50
cm3 × 2). The extract was washed with water (50 cm3 × 2), dried
(Na2SO4), and concentrated. The residue was chromatographed
over silica gel (Wako C-300, 300 g) with CHCl3 as eluent to give
crude 2d as a colorless solid. Recrystallization from hexane–
benzene (1 : 1) gave 1,5-bis(5-acetyl-2-methoxyphenyl)pentane
2d (3.35 g, 80%) as prisms, mp 91–92 ЊC; νmax(KBr)/cmϪ1 1672
4.96 (1 H, d, J 2.4), 5.49 (1 H, d, J 2.4), 6.74 (1 H, d, J 8.8), 6.79
(1 H, d, J 8.8), 7.15 (1 H, dd, J 8.8 and 2.4) and 7.36 (1 H, dd,
J 8.8 and 2.4); m/z 342 (Mϩ) (Found: C, 74.64; H, 7.75.
C21H26O4 requires C, 74.63; H, 7.51%).
Similarly, compounds 6a, 3c–3e, 4a, 4c, 4d and 5d, 5e were
prepared in the same manner as described above. The yields are
listed in Table 1.
1,2-Dihydroxy-6,12-dimethoxy-1,2-dimethyl[2.2]metacyclo-
phane 4a. This compound was obtained as prisms [from
hexane–benzene (1 : 2)], mp 202 ЊC (decomp.); νmax(KBr)/cmϪ1
3505, 3381 (OH), 2960, 2923, 1598, 1502, 1252, 1136, 1081,
1023, 818, 618; δH(CDCl3) 1.30 (3 H, s), 1.54–1.72 (2 H, m), 1.83
(3 H, s), 2.08 (1 H, s, replaced by D2O), 2.94 (1 H, s, replaced by
D2O), 3.47–3.58 (2 H, m), 3.88 (6 H, s), 4.36 (1 H, d, J 2.4), 4.83
(1 H, d, J 2.4), 6.81 (1 H, d, J 8.5), 6.88 (1 H, d, J 8.5), 7.13 (1 H,
dd, J 8.5, 2.4) and 7.40 (1 H, dd, J 8.5 and 2.4); m/z 328 (Mϩ)
(Found: C, 73.34; H, 7.29. C20H24O4 requires C, 73.15; H,
7.37%).
(C᎐O); δ (CDCl ) 1.40–1.46 (2 H, m), 1.60–1.66 (4 H, m), 2.56
᎐
H
3
(6 H, s), 2.63 (4 H, t, J 7.8), 3.89 (6 H, s), 6.86 (2 H, d, J 8.8),
7.77 (2 H, d, J 2.4) and 7.82 (2 H, dd, J 8.8 and 2.4); m/z 368
(Mϩ) (Found: C, 75.20; H, 7.75. C23H28O4 requires C, 74.97; H,
7.66%).
Similarly, compound 2e was prepared in 64% yield in the
same manner as described above.
1,6-Bis(5-acetyl-2-methoxyphenyl)hexane 2e. This com-
pound was obtained as prisms [from hexane–benzene (1 : 1)],
6,12,22,28-Tetramethoxy-1,2,17,18-tetramethyl-[2.2.2.2]-
metacyclophane-1,17-diene 6a. This compound was obtained
as prisms [from hexane–benzene (1 : 3)], mp 262–264 ЊC;
νmax(KBr)/cmϪ1 2926, 2833, 1603, 1500, 1458, 1244, 1032 and
810; δH(CDCl3) 2.17 (12 H, s), 2.51 (8 H, s), 3.72 (12 H, s), 6.57
(4 H, d, J 8.8), 6.79 (4 H, dd, J 8.8 and 2.4) and 6.91 (4 H, d,
J 2.4); m/z 588 (Mϩ) (Found: C, 81.35; H, 7.55. C40H44O4
requires C, 81.60; H, 7.53%).
mp 118–120 ЊC; νmax(KBr)/cmϪ1 1667 (C᎐O); δ (CDCl ) 1.35–
᎐
H
3
1.42 (4 H, m), 1.51–1.64 (4 H, m), 2.55 (6 H, s), 2.62 (4 H, t,
J 7.6), 3.88 (6 H, s), 6.87 (2 H, d, J 8.8), 7.77 (2 H, d, J 2.0) and
7.83 (2 H, dd, J 8.8 and 2.0); m/z 382 (Mϩ) (Found: C, 75.52; H,
7.90. C24H30O4 requires C, 75.36; H, 7.91%).
6,14-Dimethoxy-1,2-dimethyl[2.4]metacyclophan-1-ene 3c.
This compound was obtained as prisms (from methanol), mp
122–124 ЊC; νmax(KBr)/cmϪ1 2955, 2929, 2867, 2834, 1598, 1497,
1457, 1286, 1238, 1137, 1100, 1026 and 811; δH(CDCl3; 27 ЊC)
1.57 (4 H, br s), 2.20 (6 H, s), 2.47 (4 H, br s), 3.77 (6 H, s), 6.62
(2 H, d, J 2.4), 6.79 (2 H, d, J 8.4) and 7.08 (2 H, dd, J 8.4 and
2.4); δH(CDCl3–CS2, 1 : 3; Ϫ70 ЊC) 0.60–0.87 (2 H, m), 1.32–
1.55 (2 H, m), 1.90–2.19 (2 H, m), 2.15 (6 H, s), 2.62–2.84 (2 H,
m), 3.76 (6 H, s), 6.51 (2 H, d, J 2.4), 6.73 (2 H, d, J 8.8) and
7.03 (2 H, dd, J 8.8 and 2.4); m/z 322 (Mϩ) (Found: C, 82.17; H,
8.24. C22H26O2 requires C, 81.95; H, 8.13%).
6,15-Dimethoxy-1,2-dimethyl[2.5]metacyclophan-1-ene 3d.
This compound was obtained as prisms (from methanol), mp
105–107 ЊC; νmax(KBr)/cmϪ1 2926, 1859, 1604, 1504, 1461, 1256,
1238, 1129, 1103, 1033 and 807; δH(CDCl3) 0.73–0.78 (2 H, m),
1.37–1.47 (4 H, m), 2.06 (6 H, s), 2.45–2.49 (4 H, m), 3.65 (6 H,
s), 6.67 (2 H, d, J 8.8), 6.76 (2 H, d, J 2.4) and 6.92 (2 H, dd,
J 8.8 and 2.4); m/z 336 (Mϩ) (Found: C, 81.97; H, 8.46.
C23H28O2 requires C, 82.10; H, 8.39%).
6,16-Dimethoxy-1,2-dimethyl[2.6]metacyclophan-1-ene 3e.
This compound was obtained as prisms (from methanol), mp
114–115 ЊC; νmax(KBr)/cmϪ1 2916, 2855, 1603, 1495, 1463, 1298,
1238, 1132, 1034 and 818; δH(CDCl3) 0.80–0.92 (4 H, m), 1.50–
1.61 (4 H, m), 2.11 (6 H, s), 2.45–2.52 (4 H, m), 3.72 (6 H, s),
6.58 (2 H, d, J 8.8), 6.77 (2 H, d, J 2.4) and 6.80 (2 H, dd, J 8.8
and 2.4); m/z 350 (Mϩ) (Found: C, 82.38; H, 8.68. C24H30O2
requires C, 82.24; H, 8.63%).
11,12-Dihydroxy-6,16-dimethoxy-11,12-dimethyl[4.2]meta-
cyclophane 4c. This compound was obtained as prisms [from
hexane–benzene (2 : 1)], mp 186–189 ЊC (decomp.); νmax(KBr)/
cmϪ1 3488 (OH); δH(CDCl3) 1.06–1.09 (2 H, m), 1.36 (6 H, s),
1.60–1.68 (2 H, m), 2.15–2.32 (2 H, m), 2.52 (2 H, s, replaced by
D2O), 2.81–2.99 (2 H, m), 3.83 (6 H, s), 6.04 (2 H, d, J 2.4), 6.85
(2 H, d, J 8.8) and 7.61 (2 H, dd, J 8.8 and 2.4); m/z 356 (Mϩ)
(Found: C, 73.94; H, 7.86. C22H28O4 requires C, 74.13; H,
7.92%).
General procedure for the McMurry coupling reaction of 2
Typical procedure. The McMurry reagent was prepared from
TiCl4 [23.8 g (13.8 cm3), 125 mmol] and 18 g (275 mmol) of Zn
powder in 500 cm3 of dry THF, under nitrogen. A solution
of 1,3-bis(5-acetyl-2-methoxyphenyl)propane 2b (2.14 g, 6.3
mmol) and pyridine (22.8 cm3, 200 mmol) in dry THF (250 cm3)
was added within 60 h to the black mixture of the McMurry
reagent by using a high-dilution technique with continuous
refluxing and stirring. The reaction mixture was refluxed for an
additional 8 h, cooled to room temperature, and hydrolyzed
with 10% aq. K2CO3 (200 cm3) at 0 ЊC. The reaction mixture
was extracted with CH2Cl2 (200 cm3 × 3). The combined
extracts were washed with water, dried with Na2SO4, and con-
centrated. The residue was chromatographed over silica gel
(Wako C-300, 300 g) with hexane–benzene (1 : 1)benzene and
CHCl3 as eluents to give 3b (1.55 g, 80%), 6b (10 mg, 0.5%) and
4b (151 mg, 7%) each as a colorless solid. Recrystallization of
crude 3b from methanol gave 6,13-dimethoxy-1,2-dimethyl-
[2.3]metacyclophan-1-ene 3b as prisms, mp 122–125 ЊC;
νmax(KBr)/cmϪ1 2911, 2836, 1598, 1498, 1458, 1252, 1237, 1142,
1029 and 803; δH(CDCl3; 27 ЊC) 1.69 (2 H, br m), 1.95 (2 H, br
m), 2.19 (6 H, s), 2.92 (2 H, br m), 3.83 (6 H, s), 5.69 (2 H, br s),
6.72 (2 H, br d) and 7.03 (2 H, br dd); δH(CDCl3–CS2, 1 : 3;
Ϫ40 ЊC) 1.59–1.77 (2 H, m), 1.90–2.05 (2 H, m), 2.20 (6 H, s),
2.86–2.98 (2 H, m), 3.85 (6 H, s), 5.68 (2 H, d, J 2.4), 6.73 (2 H,
d, J 8.3) and 7.08 (2 H, dd, J 2.4 and 8.3); m/z 308 (Mϩ) (Found:
C, 81.88; H, 7.74. C21H24O2 requires C, 81.78; H, 7.84%).
6,13,23,30-Tetramethoxy-1,2,18,19-tetramethyl[2.3.2.3]-
metacyclophane-1,18-diene 6b. This compound was obtained
as prisms [from hexane–benzene (1 : 1)], mp 234–236 ЊC;
νmax(KBr)/cmϪ1 2949, 2832, 1606, 1500, 1463, 1244, 1033
and 890; δH(CDCl3) 1.34–1.47 (4 H, m), 2.14 (12 H, s),
2.22 (8 H, t, J 7.8), 3.72 (12 H, s), 6.63 (4 H, d, J 8.3), 6.65 (4
H, d, J 2.4) and 6.87 (4 H, dd, J 8.3 and 2.4); m/z 616 (Mϩ)
(Found: C, 81.84; H, 7.85. C42H48O4 requires C, 81.78; H,
7.84%).
12,13-Dihydroxy-6,17-dimethoxy-12,13-dimethyl[5.2]meta-
cyclophane 4d. This compound was obtained as prisms [from
hexane–benzene (2 : 1)], mp 154–156 ЊC; νmax(KBr)/cmϪ1 3495
(OH); δH(CDCl3) 1.11–1.16 (2 H, m), 1.34–1.43 (4 H, m), 1.54
(6 H, s), 2.06–2.10 (2 H, m), 2.40 (2 H, s, replaced by D2O),
2.73–2.78 (2 H, m), 3.83 (6 H, s), 6.13 (2 H, d, J 8.8), 6.84 (2 H,
d, J 2.4) and 7.57 (2 H, dd, J 8.8 and 2.4); m/z 370 (Mϩ) (Found:
C, 74.54; H, 8.19. C23H30O4 requires C, 74.56; H, 8.16%).
10,11-Dihydroxy-5,15-dimethoxy-10,11-dimethyl[3.2]meta-
cyclophane 4b. This compound was obtained as prisms [from
hexane–benzene (2 : 1)], mp 216–218 ЊC (decomp.); νmax(KBr)/
cmϪ1 3400 (OH), 2941, 1606, 1505, 1250, 1108, 1032, 818;
δH(CDCl3) 1.40 (3 H, s), 1.78 (3 H, s), 1.78–1.99 (2 H, m), 2.04–
2.18 (2 H, m), 2.30 (1 H, s, replaced by D2O), 2.91–3.06 (2 H,
m), 3.02 (1 H, br s, replaced by D2O), 3.86 (3 H, s), 3.87 (3 H, s),
2094
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097

View Article Online
12-Acetyl-7,16-dimethoxy-12-methyl[5.1]metacyclophane 5d.
was added BF3ؒEt2O (8.4 mg, 0.059 mmol) and the mixture was
This compound was obtained as prisms (from hexane), mp
stirred at room temperature for 30 min. The reaction mixture
was quenched by water (5 cm3), and extracted with CH2Cl2
(10 cm3 × 2). The combined extracts were washed successively
with 5% aq. NaHCO3 (10 cm3) and water (10 cm3 × 2), dried
with Na2SO4, and concentrated to leave a residue, which was
chromatographed over silica gel (Wako C-300, 300 g) with ben-
zene as eluent, and recrystallized from hexane–benzene (1 : 1)
to give 5c (11 mg, 33%) as colorless prisms.
161–164 ЊC; νmax(KBr)/cmϪ1 1708 (C᎐O); δ (CDCl ) 1.20–1.26
᎐
H
3
(2 H, m), 1.40–1.50 (4 H, m), 1.84 (3 H, s), 2.19 (3 H, s), 2.48–
2.54 (4 H, m), 3.83 (6 H, s), 6.72 (2 H, d, J 2.4), 6.78 (2 H, d,
J 8.8) and 7.10 (2 H, dd, J 8.8 and 2.4); m/z 352 (Mϩ) (Found: C,
78.07; H, 7.99. C23H28O3 requires C, 78.38; H, 8.01%).
13-Acetyl-8,17-dimethoxy-13-methyl[6.1]metacyclophane 5e.
This compound was obtained as pale yellow prisms (from
hexane), mp 144–146 ЊC; νmax(KBr)/cmϪ1 1711 (C᎐O);
Similarly, compounds 4d and 4e were treated with BF3–
diethyl ether as described above to give 5d and 5e in 62, 96%
yield, respectively.
᎐
δH(CDCl3) 1.12–1.18 (4 H, m), 1.63–1.75 (4 H, m), 1.74 (3 H, s),
2.11 (3 H, s), 2.54–2.62 (4 H, m), 3.83 (6 H, s), 6.80 (2 H, d,
J 8.8), 6.90 (2 H, d, J 2.9) and 7.08 (2 H, dd, J 8.8 and 2.9); m/z
366 (Mϩ) (Found: C, 78.76; H, 8.25. C24H30O3 requires C, 78.65;
H, 8.25%).
Treatment of 4b with trifluoromethanesulfonic acid in
dichloromethane
To a suspension of 4b (34 mg, 0.1 mmol) in CH2Cl2 (4 cm3) was
added trifluoromethanesulfonic acid (0.02 cm3, 0.2 mmol)
and the mixture was stirred at room temperature for 30 min.
The cooled solution was quenched by water (5 cm3), and
extracted with CH2Cl2 (10 cm3 × 2). The combined extracts
were washed successively with 5% aq. NaHCO3 (10 cm3) and
water (10 cm3 × 2), dried with Na2SO4, and concentrated to
leave a residue, which was chromatographed over silica gel
(Wako C-300, 300 g) with benzene as eluent and recrystallized
from hexane–benzene (1 : 1) to give 9b (30 mg, 98%) as pale
brown solid. Recrystallization from methanol to give 3,6-
dimethoxy-9,10-dimethyl-4,5-propanophenanthrene 9b as color-
less prisms, mp 161–163 ЊC; νmax(KBr)/cmϪ1 2927, 1588, 1498,
1264, 1218, 1131, 1032 and 798; δH(CDCl3) 2.45–2.56 (2 H, m),
2.59 (6 H, s), 2.81–2.84 (4 H, m), 3.97 (6 H, s), 7.27 (2 H, d,
J 8.8), 7.88 (2 H, d, J 8.8); m/z 306 (Mϩ) [Calc. for C21H22O2
(306.41): C, 82.32; H, 7.24. Found: C, 82.07; H, 7.20%].
Similarly, compound 2a was treated with trifluoromethane-
sulfonic acid as described above for 1 min to give 9a in 98%
yield.
Treatment of 4c with iodine–acetic acid in 1,4-dioxane
To a solution of 1,2-dihydroxy-6,14-dimethoxy-1,2-dimethyl-
[2.4]metacyclophane 4c (356 mg, 1 mmol) in a mixture of 1,4-
dioxane (20 cm3) and acetic acid (40 cm3) was added powdered
iodine (100 mg, 0.39 mmol) at room temperature. After the
reaction mixture had been stirred under reflux for 30 min, it was
poured into ice–water (100 cm3). The organic layer was
extracted with CH2Cl2 (50 cm3 × 2). The extract was washed
successively with 10% aq. sodium thiosulfate (20 cm3 × 2) and
water (50 cm3 × 2), dried (Na2SO4), and concentrated. The resi-
due was chromatographed over silica gel (Wako C-300, 300 g)
with hexane–benzene (1 : 1), benzene, benzene–CHCl3, and
CHCl3 as eluent and recrystallization from methanol or
hexane–benzene (1 : 1) to give 8c (29 mg, 7%), 5c (156 mg,
45%), 7c (20 mg, 5%), and 2c (30 mg, 8%) as colorless prisms,
respectively.
6,16-Dimethoxy-11,12-dimethylene[4.2]metacyclophane 8c.
This compound was obtained as prisms (from methanol), mp
101–102 ЊC; νmax(KBr)/cmϪ1 2929, 1500, 1244, 1119, 1029 and
902; δH(CDCl3) 1.33–1.44 (4 H, m), 2.46–2.58 (4 H, m), 3.76
(6 H, s), 5.04 (2 H, d, J 2.2), 5.46 (2 H, d, J 2.2), 6.42 (2 H, d,
J 2.0), 6.73 (2 H, d, J 8.3) and 6.99 (2 H, d, J 2.0 and 8.3); m/z
320 (Mϩ) (Found: C, 82.04; H, 7.75. C22H24O2 requires C, 82.46;
H, 7.55%).
3,6-Dimethoxy-9,10-dimethyl-4,5-ethanophenanthrene
9a.
This compound was obtained as pale brown prisms (from
MeOH), mp 198–200 ЊC; δH(CDCl3) 2.54 (6 H, s), 3.14 (4 H, s),
3.88 (6 H, s), 7.16 (2 H, d, J 9.3), 7.77 (2 H, d, J 9.3); m/z 292
(Mϩ) [Calc. for C20H20O2 (292.38): C, 82.16; H, 6.89. Found: C,
82.23; H, 6.73%].
11-Hydroxy-6,16-dimethoxy-11-methyl-12-methylene[4.2]-
metacyclophane 7c. This compound was obtained as yellow oil;
νmax(NaCl)/cmϪ1 3488 (OH); δH(CDCl3) 1.07–1.44 (4 H, br m),
1.67 (3 H, br s), 2.18–2.75 (4 H, br m), 2.68 (1 H, s, replaced by
D2O), 3.79 (3 H, s), 3.84 (3 H, s), 4.86 (1 H, d, J 1.7), 5.44 (1 H,
d, J 1.7), 5.57 (1 H, br d), 6.60 (1 H, br d), 6.77 (1 H, d, J 8.3),
6.91 (1 H, d, J 8.3), 6.99 (1 H, dd, J 8.3 and 2.0) and 7.42 (1 H,
br d); m/z 338 (Mϩ) (Found: C, 78.34; H, 7.67. C22H26O3
requires C, 78.07; H, 7.74%).
Cleavage reaction of ketones 5 with KOH to give 10
Typical procedure. A mixture of 5c (33 mg, 0.1 mmol) and
potassium hydroxide (1.6 g, 40 mmol) was heated at 180 ЊC for
3 h. The cooled melt was dissolved in water (10 cm3) and
extracted with CH2Cl2 (20 cm3 × 3). The combined extracts
were washed with water, dried with Na2SO4, and concentrated.
The residue was chromatographed over silica gel (Wako C-300,
300 g) with hexane–benzene (1 : 1) as eluent to give 10c (28 mg,
91%) as a colorless solid. Recrystallization of crude 10c from
methanol gave 6,15-dimethoxy-11-methyl[4.1]metacyclophane
10c as prisms, mp 148–149 ЊC; νmax(KBr)/cmϪ1 2862, 1498,
1254, 1235, 1110, 1034 and 806; δH(CDCl3) 0.74–0.94 (2 H, m),
1.50–1.69 (2 H, m), 1.63 (3 H, d, J 7.2), 2.22–2.34 (2 H, m),
2.62–2.82 (2 H, m), 3.75 (3 H, s), 3.76 (3 H, s), 4.12 (1 H, q,
J 7.2), 6.00 (1 H, br s), 6.21 (1 H, br s), 6.68 (1 H, d, J 8.3), 6.73
(1 H, d, J 8.3), 7.11 (1 H, dd, J 8.3 and 2.4), 7.17 (1 H, dd, J 8.3
and 2.4); m/z 296 (Mϩ) (Found: C, 81.22; H, 8.03. C20H24O2
requires C, 81.04; H, 8.16%).
11-Acetyl-6,15-dimethoxy-11-methyl[4.1]metacyclophane 5c.
This compound was obtained as prisms [from hexane–benzene
(1 : 1)], mp 126–128 ЊC; νmax(KBr)/cmϪ1 1704 (C᎐O); δ (CDCl )
᎐
H
3
0.84–1.06 (2 H, m), 1.56–1.81 (2 H, m), 1.80 (3 H, s), 2.22 (3 H,
s), 2.27–2.41 (2 H, m), 2.62–2.77 (2 H, m), 3.80 (3 H, s), 3.81
(3 H, s), 6.33 (1 H, br s), 6.56 (1 H, d, br s), 6.66 (1 H, d, J 8.3),
6.72 (1 H, d, J 8.3), 6.91 (1 H, dd, J 8.3 and 2.4) and 7.21 (1 H,
dd, J 8.3 and 2.4); δC(CDCl3) 24.15, 24.22, 24.35, 27.81, 55.04,
61.33, 107.34, 107.39, 123.87, 124.59, 126.78, 127.75, 133.92,
136.88, 137.87, 140.35, 156.62, 156.90 and 208.98; m/z 338 (Mϩ)
(Found: C, 78.28; H, 7.67. C22H26O3 requires C, 78.07; H,
7.74%).
Similarly, compounds 10d and 10e were prepared in 95, 68%
yield in the same manner as described above.
7,16-Dimethoxy-12-methyl[5.1]metacyclophane 10d. This
compound was obtained as prisms (from MeOH), mp 105–
106 ЊC; νmax(KBr)/cmϪ1 2930, 1498, 1239, 1124, 1034 and 810;
δH(CDCl3) 0.94–1.13 (2 H, m), 1.35–1.48 (4 H, m), 1.65 (3 H, d,
J 7.3), 2.42–2.54 (4 H, m), 3.79 (6 H, s), 4.09 (1 H, q, J 7.3), 6.56
(2 H, d, J 2.2), 6.73 (2 H, d, J 8.3) and 7.12 (2 H, dd, J 8.3 and
Similarly, compounds 5d and 5e were prepared in 65, 95%
yields in the same manner as described above.
Treatment of 4c with BF3–diethyl ether in dichloromethane
To a suspension of 4c (35.6 mg, 0.1 mmol) in CH2Cl2 (3 cm3)
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097
2095

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Table
4
Crystallographic data and data-collection details for
6,14-dimethoxy-1,2-dimethyl[2.4]MCP-1-ene 3c and 11-acetyl-6,15-
Crystallographic data and data-collection details for 3c and
5c are given in Table 4.
The refined non-hydrogen atomic coordinates, temperature
factors (anisotropic for carbon atoms), scale factor, and sec-
ondary estimation coefficient are available, on request, from the
Cambridge Crystallographic Data Centre.
dimethoxy-11-methyl[4.1]MCP 5c
3c
5c
Formula
FW
C22H26O2
322.45
C22H26O3
338.45
Size/mm
Crystal system
Space group
a/Å
b/Å
c/Å
0.35 × 0.35 × 0.10
Orthorhombic
Pbcn (No. 60)
8.6418 (6)
10.318 (1)
19.776 (1)
0.30 × 0.25 × 0.20
Monoclinic
P21/c (No. 14)
14.8271 (13)
12.8995 (1)
9.5892 (5)
95.9810 (57)
1824.1 (2)
4
1.066
295
Cu-Kα
1.541 84
6.02
4061
3665
2489
0.083
0.121
3.89
References
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β/Њ
V/Å3
1763.4 (2)
4
1.124
295
Cu-Kα
1.541 84
5.19
2101
1813
1039
Z
ρcalc/g cmϪ3
T /K
Radiation
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µ/cmϪ1
No. of reflections
Unique reflections
Observed reflections
R
0.059
0.077
2.51
a
Rw
S
a ω = 4(Fo)2/[(σIo)2 ϩ 0.0016(Fo)4].
2.2); m/z 310 (Mϩ) [Found: C, 81.31; H, 8.54. C21H26O2 (310.44)
requires C, 81.25; H, 8.44%].
8,17-Dimethoxy-13-methyl[6.1]metacyclophane 10e. This
compound was obtained as prisms (from MeOH), mp 115–
116 ЊC; νmax(KBr)/cmϪ1 2933, 1500, 1249, 1112, 1032 and 810;
δH(CDCl3) 0.96–1.05 (4 H, m), 1.52–1.68 (4 H, m), 1.61 (3 H, d,
J 6.8), 2.50–2.54 (4 H, m), 3.82 (6 H, s), 4.10 (1 H, q, J 6.8), 6.57
(2 H, d, J 2.4), 6.79 (2 H, d, J 8.3) and 7.19 (2 H, dd, J 8.3 and
2.4); m/z 324 (Mϩ) [Found: C, 81.53; H, 8.65. C22H28O2 (324.47)
requires C, 81.44; H, 8.7%].
Crystal data and refinement details for 6,14-dimethoxy-1,2-
dimethyl[2.4]metacyclophan-1-ene 3c‡
The X-ray analysis was performed with the MolEN program
package32 and the structure was solved uneventfully by direct
methods (SIR 88).33 Refinement was by full-matrix least
squares and the 110 parameters refined were atomic coordin-
ates, temperature factors (anisotropic for carbon atoms), scale
factor, and secondary extinction coefficient. No corrections
were made for absorption. The 12 independent non-hydrogen
atoms were refined anisotropically. The 13 independent hydro-
gen atoms were located at calculated positions thermally fixed
at Biso = 5.0 Å and were included in refinement, but restrained
to ride on the atoms to which they are bonded.
Crystal data and refinement details for 11-acetyl-6,15-
dimethoxy-11-methyl[4.1]metacyclophane 5c‡
The X-ray analysis was performed with the MolEN program
package32 and the structure was solved uneventfully by direct
methods (SIR 88).33 Refinement was by full-matrix least
squares and the 227 parameters refined were atomic coordin-
ates, temperature factors (anisotropic for carbon atoms), scale
factor, and secondary extinction coefficient. No corrections
were made for absorption. The 25 independent non-hydrogen
atoms were refined anisotropically. The 26 independent hydro-
gen atoms were located at calculated positions thermally fixed
at Biso = 5.0 Å2 and were included in the refinement, but
restrained to ride on the atoms to which they are bonded.
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‡ CCDC reference numbers 155635 and 155636. See http://www.rsc.org/
suppdata/p1/b0/b010075g/ for crystallographic files in .cif or other
electronic format.
2096
J. Chem. Soc., Perkin Trans. 1, 2001, 2089–2097

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