Synthesis, structure, and transannular π-π interaction of multilayered [3.3]metacyclophanes

Article abstract of DOI:10.1021/jo062220m

(Figure Presented) The synthesis of a series of three- to six-layered [3.3]metacyclophanes ([3.3]MCPs) 3-6 has been successfully accomplished by the (p-tolylsulfonyl)methyl isocyanide (TosMIC) method as a critical coupling reaction. Their important synthetic intermediates are the two- and three-layered bis(bromomethyl) compounds 11, 17, 21, and tetrakis(bromomethyl) compounds 25 and 28. The structures of the three- to six-layered [3.3]MCPs (3-6) as well as three- to six-layered [3.3]MCP-di- (22-24) and tetraones (26, 27, and 29) as the synthetic intermediates have been elucidated based on the ¹H NMR data and X-ray structural analysis. These multilayered cyclophanes are constructed with two different geometries, syn[3.3]MCP and anti-[3.3]MCP-2,11- dione. In principle, their geometries are maintained in the multilayered [3.3]MCPs, but deformation of the dihedral angle of the two benzene rings of the syn-[3.3]MCP moiety is generally observed. In the four-layered MCP 4, the central [3.3]MCP moiety takes an anti geometry. These data indicate the structural flexibility of the [3.3]MCP moiety. In the electronic spectra, rather simple and structureless absorption curves are observed, and the most significant spectral change is observed for the two to three layers and becomes less effective even if it is more layered. In the charge-transfer (CT) bands of the multilayered [3.3]MCPs with tetracyanoethylene (TCNE), the λ_maxmax gradually shifts to the longer wavelength region, but the extent of the shift is much smaller as the number of layers increases. In the multilayered [3.3]MCP-di- and tetraones, the anti-[3.3]MCP-dione moiety works as an insulator. Therefore, the CT interaction of the four- and five-layered [3.3]MCPs with one anti-[3.3]MCP-dione moiety (23 and 24) shows the almost comparable magnitude of the interaction with the two- and three-layered [3.3]MCPs (2 and 3), respectively. The tetraones of the three and four-layered MCPs (29 and 26) do not show CT interactions except for the six-layered MCP 27.

Full text of DOI:10.1021/jo062220m

Synthesis, Structure, and Transannular π-π Interaction of
Multilayered [3.3]Metacyclophanes1
Masahiko Shibahara,*,† Motonori Watanabe,† Tetsuo Iwanaga,‡,§ Keiko Ideta,‡ and
Teruo Shinmyozu*,‡
Department of Chemistry, Faculty of Education and Welfare Science, Oita UniVersity, Dan-noharu 700,
Oita 870-1192, Japan, and Institute for Materials Chemistry and Engineering (ICME) and Department of
Molecular Chemistry, Graduate School of Sciences, Kyushu UniVersity, Hakozaki 6-10-1, Fukuoka
812-8581, Japan
mshiba@cc.oita-u.ac.jp; shinmyo@ms.ifoc.kyushu-u.ac.jp
ReceiVed October 26, 2006
The synthesis of a series of three- to six-layered [3.3]metacyclophanes ([3.3]MCPs) 3-6 has been
successfully accomplished by the (p-tolylsulfonyl)methyl isocyanide (TosMIC) method as a critical
coupling reaction. Their important synthetic intermediates are the two- and three-layered bis(bromomethyl)
compounds 11, 17, 21, and tetrakis(bromomethyl) compounds 25 and 28. The structures of the three- to
six-layered [3.3]MCPs (3-6) as well as three- to six-layered [3.3]MCP-di- (22-24) and tetraones (26,
1
27, and 29) as the synthetic intermediates have been elucidated based on the H NMR data and X-ray
structural analysis. These multilayered cyclophanes are constructed with two different geometries, syn-
[3.3]MCP and anti-[3.3]MCP-2,11-dione. In principle, their geometries are maintained in the multilayered
[3.3]MCPs, but deformation of the dihedral angle of the two benzene rings of the syn-[3.3]MCP moiety
is generally observed. In the four-layered MCP 4, the central [3.3]MCP moiety takes an anti geometry.
These data indicate the structural flexibility of the [3.3]MCP moiety. In the electronic spectra, rather
simple and structureless absorption curves are observed, and the most significant spectral change is observed
for the two to three layers and becomes less effective even if it is more layered. In the charge-transfer
(CT) bands of the multilayered [3.3]MCPs with tetracyanoethylene (TCNE), the λmax gradually shifts to
the longer wavelength region, but the extent of the shift is much smaller as the number of layers increases.
In the multilayered [3.3]MCP-di- and tetraones, the anti-[3.3]MCP-dione moiety works as an insulator.
Therefore, the CT interaction of the four- and five-layered [3.3]MCPs with one anti-[3.3]MCP-dione
moiety (23 and 24) shows the almost comparable magnitude of the interaction with the two- and three-
layered [3.3]MCPs (2 and 3), respectively. The tetraones of the three and four-layered MCPs (29 and
26) do not show CT interactions except for the six-layered MCP 27.
Introduction
various types of new multistory compounds with various types
of structural units by choosing the appropriate cyclophane
building blocks. This structural versatility makes multilayered
cyclophanes suitable model compounds for the study of their
characteristic structural properties and transannular π-π inter-
actions between not only faced aryl rings but remote aryl rings.
These novel properties may lead to applications as new
Multistory compounds constructed with cyclophane building
blocks are called multilayered cyclophanes. We can construct
* To whom correspondence should be addressed. (M.S.) Tel.: +81-97-554-
7553; fax: +81-97-554-7553. (T.S.) Tel.: +81 92 642 2716; fax: +81 92 642
2735.
† Oita University.
‡ ICME, Kyushu University.
§ Department of Molecular Chemistry, Kyushu University.
(1) Multilayered [3.3]cyclophanes, part 1.
10.1021/jo062220m CCC: $37.00 © 2007 American Chemical Society
Published on Web 03/14/2007
J. Org. Chem. 2007, 72, 2865-2877
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Shibahara et al.
nanoscale materials. Among the possible multilayered cyclo-
phanes, the synthesis and interesting chemical and physical
properties of a series of multilayered [2.2]para- (PCP),2 meta-
para- (MPCP),3 and metacyclophanes (MCP)4 were extensively
studied by Misumi and Otsubo.5a-c The synthesis of optically
active multilayered [2.2]PCPs (up to six layers) was ac-
complished by Yamamoto and Nakazaki starting from the (R)-
(-)-4-methyl[2.2]PCP, and their interesting chiroptical prop-
erties were reported.6 The properties of the multilayered [3.3]CPs
have not been as extensively studied as those of the multilayered
[2.2]CPs, probably because of their difficulty in synthesis. In a
series of all carbon multilayered CPs described previously, only
the three-layered [3.3]PCP,7 [3.3]MCP 3 (Figure 1),8 and three-
and four-layered [3.3]orthocyclophanes (OCPs)9 have been
reported to date. Recently, Vo¨gtle et al. reported the synthesis
and structures of a series of multilayered diaza[3.3]MCPs with
N-tosyl groups and named the series of compounds molecular
ribbons.10 They successfully synthesized up to a nine-layered
[3.3]MCP10f with zigzag folded all-syn conformations and
attained π stacks of nanometer dimensions.
FIGURE 1. Multilayered [3.3]MCPs 2-6 and [3.3]MCP-2,11-dione
1.
because of less strain11 and more flexibility than the [2.2]CP
system, as well as a more suitable transannular distance.12,13
Our recent study on the transannular π-π interaction of a series
of multibridged [3n]CPs (n ) 2-6) showed that their electron-
donating ability increased with the increase in the number of
bridges because of the effective hyperconjugation between the
benzylic hydrogens and the benzene rings. [36]CP shows the
strongest donating ability in the [3n]CPs (λmax of the CT band
with TCNE, 728 nm in CHCl3).14 In contrast, this type of
electronic interaction is hampered in the [2n]CPs by the
significant bending of the methylene groups out of the plane of
the attached benzene ring (20°).15
Another interesting feature of [3.3]CPs stems from their
flexible nature; their conformational behavior in solution has
attracted much attention.16-19 Since our first synthesis of [3.3]-
MCP 2,20 we have studied the conformational behavior of the
[3.3]MCPs21 and related systems.22-25 In [3.3]MCP 2, two
geometries with syn and anti configurations are considered
[3.3]CP is the better system for studying transannular π-π
interactions than the [2.2]CP system and its higher homologues
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2866 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
unique structural units may provide information on the depen-
dence of the transannular π-π interaction on the stacking mode
of the benzene rings (i.e., syn and anti). The purpose of our
present study is (1) to develop general synthetic methods of
multilayered [3.3]MCPs, (2) to elucidate their structural proper-
ties and examine the relationship between the molecular
structure and the electronic π-π interactions as models of the
tilted or partially overlapped π electronic systems, (3) to study
the dynamic conformational behavior in solution, (4) to study
their inclusion phenomena as host molecules with wide π
surfaces for the formation of clathlates with organic molecules,
and (5) to find their practical applications as nanometer scale
materials. We describe here the synthesis, structure, electronic
absorption spectra, and charge-transfer (CT) spectra of the three-
to six-layered [3.3]MCPs 3-6 and 31 as well as the [3.3]MCP-
di- 22-24 and tetraones 26, 27, 29, and 30 as their synthetic
intermediates.
FIGURE 2. Possible conformations of [3.3]MCP 2.
SCHEME 1. Bridge Wobble and Ring Inversion Processes
of [3.3]MCP 2
Results and Discussion
Synthesis. For the synthesis of multilayered [3.3]MCPs, the
(p-tolylsulfonyl)methyl isocyanide (TosMIC) method27 has been
successfully employed in the critical coupling reactions.28 The
key synthetic intermediates are the two- and three-layered bis-
(bromomethyl)[3.3]MCPs 11, 17, and 21 as well as tetrakis-
(bromomethyl) compounds 25 and 28.10g,29 The two-layered
bromides 11 and 17 were synthesized by the coupling reaction
between dimethyl 4,6-bis(bromomethyl)benzene-1,3-dicarboxyl-
ate 7 and the TosMIC adduct 8 or 1428 in the presence of NaOH
and n-Bu4NI in a mixture of CH2Cl2 and water under phase-
transfer conditions, followed by acid treatment to afford the two-
layered ketoesters 9 (37%) and 15 (44%) (Scheme 2).
The Wolff-Kishner reduction of the ketoesters 9 or 15 and
subsequent reduction of the methyl ester of 10 or 16 with LiAlH4
in THF, followed by bromination of the resultant diol with PBr3
in C6H6, gave the desired dibromides 11 (32% from 9) and 17
(34% from 15). The TosMIC adducts 13 and 18 were readily
prepared by the reaction of bromide 11 or 17 and TosMIC 12.
The three-layered bis(bromomethyl) compound 21 was
synthesized in a similar way. Bromide 7 and the two-layered
TosMIC adduct 13 were coupled to give the three-layered
ketoester 19 (42%). Reduction of the carbonyl groups of 19 by
the Wolff-Kishner reduction, followed by esterification, af-
forded the methyl ester 20 (64%). Ester 20 was converted into
the three-layered bis(bromomethyl) compound 21 by LiAlH4
reduction in THF and subsequent bromination with PBr3 in C6H6
(51%).
(Figure 2), and the former is more stable than the latter based
on the experimental data and theoretical calculations.17,21a,b,24
In the three conformations with the syn geometry of 2, the
stability order is syn(chair/chair) > syn(chair/boat) > syn(boat/
boat).17,21a,b,24 In the solid state, 2 adopts the syn(chair/chair)
with the dihedral angle between two benzene rings being 24°,17
and the syn(chair/chair) is the most stable conformation in
solution.17,21a,b In the anti geometry, similar conformations such
as anti(chair/chair), anti(chair/boat), and anti(chair/twist boat)
are also expected.26 In the conformational isomerism of 2, bridge
wobbling (BW) and ring inversion (RI) processes are considered
(Scheme 1). On the basis of the total line shape simulations of
the benzylic methylene region in the temperature-dependent 1H
NMR spectra of 2, we proposed the presence of the RI processes
of the syn(chair/chair) and syn(chair/boat) via anti conforma-
tions.19,26
The two-layered bromide 11 was coupled with the TosMIC
adduct 8 to provide the three-layered dione 22 (22%)
(Scheme 3). The modified Wolff-Kishner reduction of 22
afforded the three-layered CP 3 (82%). A similar coupling
reaction of the dibromide 11 with the two-layered TosMIC
adduct 13 provided the four-layered dione 23 (20%). Reduction
Our multilayered [3.3]MCPs are constructed with two types
of structural units: [3.3]MCP 2 and [3.3]MCP-2,11-dione 1.
In contrast to the stable syn geometry of 2, the dione 1 takes
the anti(chair/boat) in the solid state, and the preferred anti
geometry is expected in solution, as gauged by the strongly
shielded inner aromatic protons (Hi1 δ 5.78 in CDCl3).24
A
systematic study of the multilayered [3.3]MCPs containing these
(27) (a) Hoogenboom, B. E.; Oldenziel, O. H.; van Leusen, A. M.
Organic Syntheses; Wiley: New York, 1988; Vol. 6, pp 987-990. (b)
Possel, O.; van Leusen, A. M. Tetrahedron Lett. 1977, 18, 4229-4232.
(28) (a) Kurosawa, K.; Suenaga, M.; Inazu, T.; Yoshino, T. Tetrahedron
Lett. 1982, 23, 5335-5338. (b) Shinmyozu, T.; Hirai, Y.; Inazu, T. J. Org.
Chem. 1986, 51, 1551-1555. (c) Sasaki, H.; Kitagawa, T. Chem. Pharm.
Bull. 1983, 31, 2868-2878.
(29) (a) Oda, T.; Shinmyozu, T., unpublished results. (b) Shinmyozu,
T.; Kusumoto, S.; Nomura, S.; Kawase, H.; Inazu, T. Chem. Ber. 1993,
126, 1815-1818. (c) van der Made, A. W.; van der Made, R. H. J. Org.
Chem. 1993, 58, 1262-1263.
(22) Anet, F. A. L.; Brown, M. A. J. Am. Chem. Soc. 1969, 91, 2389-
2391.
(23) Sako, K.; Meno, T.; Takemura, H.; Shinmyozu, T.; Inazu, T. Chem.
Ber. 1990, 123, 639-642.
(24) Isaji, H.; Yasutake, M.; Takemura, H.; Sako, K.; Tatemitsu, H.;
Inazu, T.; Shinmyozu, T. Eur. J. Org. Chem. 2001, 2487-2499.
(25) Krois, D.; Lehner, H. Tetrahedron 1982, 38, 3319-3324.
(26) Bialy, S. E.; Shimazaki, T.; Sako, K.; Ideta, K.; Shinmyozu, T., to
be submitted.
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Shibahara et al.
SCHEME 2. Synthetic Route to Two- and Three-Layered Bis(bromomethyl) Compounds 11, 17, and 21
of the carbonyl groups of 23 provided the four-layered CP 4
(77%). The three-layered bromide 21 and two-layered TosMIC
adduct 13 were coupled to give the five-layered dione 24 (32%),
which was converted to the five-layered CP 5 (58%) by the
reduction of the carbonyl groups.
1H NMR Spectral Properties.16 As described previously,
the assignment of an anti geometry to 1 is based on the highly
shielded inner aromatic protons [Hi1 δ 5.78 (br s)] from the
outer aryl protons [Ha δ 7.19 (d) and Hb δ 7.32 (t)] due to the
ring current effect of the facing benzene ring (Figure 3).24 Two
kinds of inner aromatic protons of the three-layered tetraone
29 [Hi1 δ 6.09 (br s) and Hi2 δ 5.54 (sharp s) (Figure S35)] are
strongly shielded, while the outer aromatic protons appear in
the normal aromatic region [Ha δ 7.22 (dd) and Hb δ 7.37 (t)],
suggesting the anti-anti geometry. In contrast, the inner
aromatic protons of 2 [Hi1 δ 6.87 (br s)] with a syn geometry
are slightly shielded as compared to the outer aromatic protons
of 1 in CDCl3. Two kinds of highly shielded inner aromatic
protons [Hi3 δ 5.55 (s) and Hi4 δ 5.27 (s) (Figure S29)] as well
as the two kinds of slightly shielded aromatic protons [Hi1 δ
7.00 (br s) and Hi2 δ 6.75 (s)] indicate the anti-syn geometry
for the three-layered dione 22. The fact that the Hi4 proton is
more shielded than the Hi3 proton supports the expected
molecular structure because the [3.3]MCP moiety shows a
stronger diamagnetic ring current effect than the benzene ring.
Similarly, the inner aromatic protons [Hi3 δ 5.06 (s) (Figure
S30)] of the four-layered dione 23 show a more significant
upfield shift than the Hi3 proton of 22, and this indicates the
syn-anti-syn geometry. In the four-layered tetraone 26, only
two kinds of inner aromatic protons [Hi2 δ 5.50 (sharp s) and
Hi1 δ 5.24 (br s) (Figure S33)] are strongly shielded, while other
aromatic protons appear in the normal aromatic region. These
data suggest an anti-syn-anti geometry.
Tetrakis(bromomethyl)[3.3]MCP 25 is a versatile synthetic
intermediate, and this is most conveniently prepared by the one-
step bromomethylation of [3.3]MCP 2 with paraformaldehyde
and 30% HBr in AcOH at 95 °C (62%), which was the modified
reaction conditions originally reported by Vo¨gtle et al.10g First,
we attempted to synthesize the parent six-layered [3.3]MCP and
confirmed its formation by HRMS, but we could not character-
ize it due to its poor solubility in any organic solvents. Therefore,
we introduced tert-butyl groups to the skeleton of the six-
layered [3.3]MCP for improvement of solubility. The tert-butyl
group substituted six-layered [3.3]MCP 6 was synthesized by
the coupling of the tetrakis(bromomethyl) compound 25
with 2 molar equiv of the tert-butyl group substituted two-
layered TosMIC adduct 18, followed by acid hydrolysis (20%)
and reduction of the carbonyl groups of the resultant 27
(8.1%).
For the synthesis of the three-layered [3.3]MCP-tetraone 29,
the one-step coupling between TosMIC adduct 8 and 1,2,4,5-
tetrakis(bromomethyl)benzene 28 in a ratio of 2:1 is the most
convenient method (8.2%). A similar coupling between the tert-
butyl substituted 14 and the tetrabromide 28 gave the tetraone
30 (4.2%). Although the yields were low, the desired three-
layered [3.3]MCPs with the anti-anti geometries 29 and 30
were directly and preferentially formed in this reaction. The
Wolff-Kishner reduction of their carbonyl groups afforded the
three-layered [3.3]MCP 3 (44%) and its tert-butyl derivative
31 (79%).
The one and two inner aromatic protons of 3 [Hi2 δ 5.92 (s)
(Figure S9)] and 4 [Hi2 δ 6.05 (s) and Hi3 δ 6.10 (s)
(Figure S10)] are moderately shielded, whereas the other
aromatic protons appear in the normal aromatic region. These
2868 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
SCHEME 3. Synthetic Route to Three- to Six-Layered [3.3]MCPs 3-6
moderately shielded protons relative to the Hi1 protons of 2 are
attributable to the diamagnetic anisotropy of the stacked benzene
rings in a syn fashion, and this is consistent with syn-syn and
syn-syn-syn geometries for 3 and 4, respectively. The
assignments of the Hi2 and Hi3 proton signals of 4 are made by
the NOESY spectrum (Figure S41). In the five-layered dione
24, the highly shielded inner aromatic protons [Hi5 δ 5.07 (s)
and Hi6 δ 5.00 (s) (Figure S31)] are explained by the anisotropic
ring current effects of the facing two- and three-layered [3.3]-
MCP moieties. These data and the moderately shielded inner
aromatic protons [Hi2 δ 5.88 (s) and Hi3 δ 6.45 (s)] support a
syn-anti-syn-syn geometry for 24. The presence of only two
kinds of highly shielded protons [Hi3 δ 4.96 (s) and Hi4 δ 4.79
(s) (Figure S34)] as well as the appearance of other aromatic
proton signals in the normal region (δ 6.5-7.0) suggest a syn--
anti-syn-anti-syn geometry for the six-layered tetraone 27.
The three kinds of moderately shielded inner aromatic protons
for 5 [Hi2 δ 6.03 (s), Hi3 δ 6.08 (s), and Hi4 δ 6.19 (s)
(Figure S13)] and 6 [Hi2 δ 6.10 (s), Hi3 δ 6.03 (s), Hi4 δ 6.00
(s), and Hi5 δ 6.12 (s) (Figure S15)] are attributable to the
diamagnetic anisotropy of the syn stacked benzene rings, and
these data are consistent with all-syn geometries for 5 and 6.
The assignments of the Hi2, Hi3, and Hi4 protons of 5 are made
based on the NOESY spectrum (Figure S42). Similarly, the
NOESY spectrum of 6 supports the Hi2 to Hi5 proton assign-
ments (Figure S43).
X-ray Structural Analysis. To confirm the crystalline
structure of the multilayered [3.3]MCPs, we carried out single-
J. Org. Chem, Vol. 72, No. 8, 2007 2869

Shibahara et al.
1
FIGURE 3. Selected H NMR data of the aromatic protons of multilayered [3.3]MCPs (δ, CDCl3, 300 MHz).
FIGURE 4. Molecular structures of three-layered [3.3]MCP 3 (-150 °C); top view (A), side skeleton view (B), and dihedral angles at trimethylene
bridges (C).
crystal X-ray structural analyses of some of them. The crystal
data are summarized in Table S1. Figure 4 shows the ORTEP
drawing of three-layered [3.3]MCP 3 (-150 °C) as top (A) and
side views (B). The [3.3]MCP unit takes the syn(chair/chair)
geometry with the tilt of the benzene rings of 34.5°, which is
larger than that of the parent 2 (24°)17 by 10°. Although a twist
in the benzene rings of 2 is ca. 15° about the axis through the
center of each ring,17 the twist of the outer and central benzene
rings of 3 is only ca. 1.3°, and the benzene rings completely
overlap each other (Figure 4A). Corresponding to the increased
tilt of the [3.3]MCP unit of 3, the transannular distance between
C1 and C11 (2.982 Å) is slightly shorter than that of 2
(2.995 Å), while the distance of C1* and C8 (4.507 Å) becomes
longer than the corresponding distance in 2 (4.171 Å)
(Figure 4B).17 The outer benzene ring is slightly deformed into
a boat form, whereas the central benzene ring is deformed into
a chair form; the dihedral angles between the C6-C7-C9-
C10 and C6-C11-C10 planes, the C6-C7-C9-C10 and C7-
C8-C9 planes, as well as the C2-C15-C2*-15* and
C2-C1-C15 planes are 4.70, 1.59, and 2.50°, respectively.
2870 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
FIGURE 5. Molecular structures of four-layered [3.3]MCP-dione 23
(-160 °C); top view (A) and side view (B).
The average bond lengths of the aromatic C-C (1.393 Å),
Carom-Cbenzyl (1.514 Å), and aliphatic C-C (1.540 Å) are
normal. The dihedral angles at the trimethylene bridges are
depicted in Figure 4C, and this indicates that the trimethylene
bridges are in a nearly gauche conformation and that the
deviation from a complete gauche conformation is about 13°.
The gauche conformation of the trimethylene bridge may be
the most important factor for the syn geometry of the multi-
layered [3.3]MCPs.
Figure 5 shows the molecular structures of the four-layered
MCP-dione 23 (-160 °C). The ORTEP drawing shows that the
[3.3]MCP unit takes the syn(chair/chair) conformation with the
tilt of the benzene rings of 26.2°, which is comparable to that
of the parent 2. The twist in the benzene rings of the [3.3]MCP
moiety is only 1.1°. The central [3.3]MCP-dione unit takes the
anti(twist boat/twist boat) conformation, where overlap of the
benzene rings is increased as compared to that of the anti(chair/
chair) conformation of the parent 1 (Figure 5A).24 Similar to
the case of the three-layered MCP 3, the outer benzene rings
are slightly distorted into the boat form [1.60° for C4-C5-
C7-C8 and C5-C6-C7 planes and 4.61° for C4-C5-C7-
C8 and C4-C9-C8 planes], whereas the inner benzene rings
are distorted to the chair form [1.52° for C13-C14-C16-C17
and C13-C18-C17 planes and 2.56° for C13-C14-C16-
C17 and C14-C15-C16 planes, respectively] in 23.
Figures 6 and 7 show the molecular structures of the four-
layered MCP-tetraone 26 (-160 °C) and the short contacts of
the selected crystal-packing diagram, respectively. The ORTEP
drawing shows that the central [3.3]MCP unit takes the syn-
(chair/chair) conformation and that the outer [3.3]MCP-dione
units assume the anti(chair/chair) conformation. Tilting of the
central [3.3]MCP unit is 32.5°, which is slightly greater than
that of 2. Different from the previous examples, the two benzene
rings of the [3.3]MCP-dione unit are not parallel but are
significantly tilted by 28.2° for the C4-C5-C7-C8 and C13-
C14-C16-C17 planes as well as 18.2° for the C22-C23-
C25-C26 and C34-C35-C37-C38 planes. It should be noted
that the twist in the benzene rings of the [3.3]MCP-dione moiety
is quite large [11.6° (C4-C5-C6-C7-C8-C9 and C13-
C14-C15-C16-C17-C18) and 6.6° (C22-C23-C24-C25-
C26-C27 and C34-C35-C36-C37-C38-C39)]. The tran-
sannular distances between the neighboring benzene rings in
26 [2.935 Å (C9-C18), 2.942 Å (C15-C27), and 2.933 Å
(C24-C39)] are much shorter than the corresponding distances
FIGURE 6. Molecular structures of four-layered [3.3]MCP-tetraone
26 (-160 °C); side views (A and B).
of 1 (2.99 Å)24 and 2 (2.995 Å).17 Moreover, the transannular
distance between C18 and C24 in the [3.3]MCP unit (4.363 Å)
is much longer than that of 2 (4.171 Å).17 The outer benzene
rings are slightly distorted to a boat form, whereas the inner
benzene rings deform into the chair form. With regard to the
angle of the C-CO-C bridge, three of the four moieties are
normal values (ca. 120°), but the C10-C11-C12 angle of the
remaining bridge is slightly deformed (116.6°). In the crystal-
packing diagram of 26 (Figure 7A), hydrogen bonds between
the carbonyl oxygen atom and the benzylic proton of the
neighboring molecule are observed [(Figure 7B) O4-H16
(2.571 Å) on the ac-plane and (Figure 7C) O3-H9 (2.595 Å)
overlapped molecules in Figure 7A]. The distance of the former
hydrogen bond is shorter than the sum of the van der Waals
radii30 of a hydrogen atom (1.20 Å) and an oxygen atom (1.40
Å).
Figure 8 shows the molecular structure of the four-layered
MCP 4 (-150 °C). The ORTEP drawing shows that the two
outer [3.3]MCP units are syn(chair/chair) with the tilt of the
two facing benzene rings of 34.6° [C4-C6-C7-C9 and C13-
C15-C16-C18 planes] and 22.3° [C22-C24-C25-C27 and
C34-C36-C37-C39 planes]. The transannular distances of
each unit are 3.009 Å (C5-C14), 4.600 Å (C8-C17), 2.997 Å
(C26-C35), and 3.969 Å (C23-C38). Contrary to our expecta-
tion, the central [3.3]MCP moiety assumes the deformed anti-
(boat-boat) conformation, and the dihedral angle between the
two benzene rings is 42.0° (C13-C15-C16-C18 and C22-
C24-C25-C27 planes). The outer [3.3]MCP units are twisted
0.12° (C4-C5-C6-C7-C8-C9 and C13-C14-C15-C16-
C17-C18) and 0.78° (C22-C23-C24-C25-C26-C27 and
C34-C35-C36-C37-C38-C39), and the inner [3.3]MCP unit
is twisted 1.4°. The second benzene rings are distorted into the
twist chair form by 7.1° [C13-C15-C16-C18 and C13-C14-
C15 planes] and 7.7° [C13-C15-C16-C18 and C16-C17-
C18 planes] as well as 1.3° [C22-C24-C25-C27 and C22-
C23-C24 planes] and 3.0° [C22-C24-C25-C27 and C25-
(30) Pauling, L. The Nature of the Chemical Bond; Cornell University
Press: Ithaca, NY, 1960; p 260.
J. Org. Chem, Vol. 72, No. 8, 2007 2871

Shibahara et al.
FIGURE 7. Short contacts of four-layered [3.3]MCP-tetraone 26. (A) Crystal-packing diagram along the a-axis. (B) Hydrogen bonds between
carbonyl oxygen (O4) and benzylic proton (H16) along the b-axis. (C) Hydrogen bonds between carbonyl oxygen (O3) and benzylic proton (H9).
Hydrogen bonds are represented as dashed lines.
C26-C27 planes]. The dihedral angles of the trimethylene
bridges (C19-C20-C21 and C28-29-C30) of the central anti-
[3.3]MCP unit are depicted in Figure 8B, and the dihedral
anglesare quite different from the corresponding angles of
the three-layered [3.3]MCP 3 with a syn geometry. Almost
eclipsed interactions are observed in C19-C20 and C29-C30
(0.0-3.9°), and this indicates the presence of a repulsive
interaction in the bridges. Thus, the gauche interaction in the
trimethylene bridge is observed in the syn-[3.3]MCP unit,
whereas the eclipsed interaction is present in the anti-[3.3]MCP
unit.
The PM331 calculations predicted that the most stable
geometry of 4 should be all-syn(chair/chair), while the syn-
anti-syn geometry found in the solid state should be less stable
than the all-syn(chair/chair) by 2.1 kcal/mol.32 Formation of the
syn-anti-syn geometry in the solid state may be ascribed to
crystal-packing forces. These results suggest that the structure
of [3.3]MCP and its dione moieties are flexible and can be
(31) Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209-220.
(32) The computations were done with MOPAC2002 programs, graphi-
cally facilitated by CAChe from Fujitsu Limited.
2872 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
FIGURE 8. Molecular structures of four-layered [3.3]MCP 4; side views (A and B).
FIGURE 10. Electronic spectra of multilayered [3.3]MCP-diones 1
and 22-24 in CH2Cl2.
FIGURE 9. Electronic spectra of multilayered [3.3]MCPs 2-6 and
31 in CH2Cl2.
(sh, ꢀ 540), and 321 nm (sh, ꢀ 249) in CH2Cl2] (Figure 10).
The unusual strength of the n-π* transitions has been reported33
and is attributed to the homoconjugation between carbonyl
groups and benzene rings. A similar weak bathochromic shift
and hyperchromic effect of the absorptions are also observed
as an increase of the number of layers in the multilayered [3.3]-
MCP-diones. The spectral change from two to three is more
significant than that from three to four. In the electronic spectra
of a series of multilayered [3.3]MCP-tetraones (Figure 11),
almost no spectral change is observed except the appearance
of the new bands above 350 nm for the tert-butyl substituted
MCPs 27 and 30.
Charge-Transfer Bands. The electron-donating ability of a
cyclophane is most conveniently evaluated in a qualitative
manner by the λmax of the CT band with TCNE as an acceptor
in solution.12,34 Previously, we reported that the CT bands of
the multibridged [3n]CPs (n ) 2-6) with TCNE show signifi-
changed to some extent in responding to the external environ-
ment even in the solid state. However, the stable structure of 4
1
is expected to be syn-syn-syn in solution based on the H
NMR data as described previously. Flexibility of multilayered
[3.3]MCPs is in sharp contrast to the rigid structures of
multilayered [2.2]MCPs.7 We have not succeeded in the
preparation of single crystals of 5 and 6 for the X-ray structural
analysis yet, and the result will be reported elsewhere.
Electronic Spectra. Figure 9 denotes the electronic absorp-
tion spectra of the multilayered [3.3]MCPs 2-6 and 31 in CH2-
Cl2. [3.3]MCP 2 with a syn geometry displays two absorption
bands at 230 (ꢀ 5680) and 276 (sh, ꢀ 164) in CH2Cl2. Strong
bathochromic shifts and hyperchromic effects are observed as
the layer is varied from two to three, whereas the magnitude
decreases with an increase in the number of layers. The
absorption curve becomes almost a straight line as the number
of layers increases. It is noteworthy that tert-butyl substituted
MCPs 31 and 6 show new bands at 301 and 341 nm as
shoulders, respectively, probably due to the electron-donating
ability of the tert-butyl groups. The [3.3]MCP-2,11-dione 1 with
an anti geometry shows π-π* bands and abnormally intense
n-π* bands [ 230 (ꢀ 13200), 282 (ꢀ 646), 301 (ꢀ 654), 309
(33) (a) Cookson, R. C.; Wariyar, N. S. J. Chem. Soc. 1956, 2302-
2311. (b) Mislow, K.; Glass, M. A.; O’Brien, R. E. W; Rutkin, P.; Steinberg,
D. H.; Weiss, J.; Djerassi, C. J. Am. Chem. Soc. 1962, 84, 1455-1478. (c)
Labhart, H.; Wagniere, G. HelV. Chim. Acta. 1959, 42, 2219-2227.
(34) Merrifield, R. E.; Phillips, W. D. J. Am. Chem. Soc. 1958, 80, 2778-
2782.
J. Org. Chem, Vol. 72, No. 8, 2007 2873

Shibahara et al.
SCHEME 4. Expected Correlated Inversion Process of the
Benzene Rings in Three-Layered [3.3]MCPs 3, 31, and 22
suggests that the effective overlapping of the facing benzene
rings is one of the most important factors for the strong CT
interaction.
In a series of multilayered [3.3]MCPs 2-6, the λmax of the
CT band gradually shifts to the longer wavelength region as
the number of layers increases (2, 509; 3, 550; 4, 556; 5, 575;
and 6, 588 nm). The effect of an increase in the layers becomes
less significant, and the changes in the λmax values from two to
three, three to four, and four to five are 41, 6, and 9 nm,
respectively. The corresponding change from five to six may
be less than 13 nm because the tert-butyl group substituted MCP
6 may show a stronger donating ability than the parent six-
layered MCP. An appreciable effect may no longer be expected
for more than six. It is worth noting that the tert-butyl group
substituted three-layered [3.3]MCP 31 showed the CT band at
a significantly longer wavelength region (581 nm) as compared
to that of the parent 3 (550 nm), and this is ascribed to the
electron-donating ability of the tert-butyl groups.
In the multilayered [3.3]MCP-keones, the three-layered dione
22 with a syn-anti geometry shows a CT band at 506 nm, and
this value is comparable to that of [3.3]MCP 2 with a syn
geometry (509 nm). Similarly, the four-layered dione 23
(518 nm) and five-layered dione 24 (543 nm) show a similar
magnitude of CT interaction comparable to the two-layered
MCP 2 (509 nm) and three-layered MCP 3 (550 nm), respec-
tively. These data suggest that the anti geometry with -CH2-
COCH2-- bridges behaves as an electron insulator. In fact, the
multilayered [3.3]MCP-tetraones 26, 29, and 30 hardly inter-
acted with TCNE, but the tert-butyl group substituted 27 shows
the transannular interaction comparable to that of 3.
FIGURE 11. Electronic spectra of multilayered [3.3]MCP-tetraones
26, 27, 29, and 30 in CH2Cl2.
cant bathochromic shifts with an increase of the number of
bridges, and [36](1,2,3,4,5,6)CP shows the strongest CT interac-
tion (λmax 728 nm, CHCl3) among the [m.n]CPs and multibridged
CPs.14b The very strong donating ability of [36]CP was further
supported by the first half-wave oxidation potential (E1/2 +0.39
V vs Fc/Fc+ in ClCH2CH2Cl).35 In a similar manner, we
evaluated the electron-donating ability of the multilayered [3.3]-
MCPs. When colorless CHCl3 solutions of the multilayered [3.3]-
MCPs 2-6 (0.86-2.37 × 10-3 mol/L) and TCNE (1.25 × 10-2
mol/L) were mixed, a purplish-red to purple solution appeared.
The CT absorption spectra of the multilayered [3.3]MCPs 2-6
and multilayered [3.3]MCP-di- and tetraones 22-24, 26, 27,
and 29 are shown in Figures S5 and S6, respectively, and the
λmax values of the CT bands are summarized in Table 1.
Although the intensity of the λmax values of the CT band
increased as an increase of the ratio of multilayered MCP/TCNE
(from 1:1 to 1:10), no shift of the λmax of the CT band was
observed in the MCPs 3 and 4, suggesting the 1:1 complex
formation in the solution (Figures S7 and S8).
In the two layered CPs, [3.3]PCP (the λmax of the CT band
606 nm) shows a much stronger CT interaction than [3.3]MCP
2 (λmax 509 nm) and the [3.3]MPCP (λmax 460 nm), and this
type of dependence of the CT interaction on the molecular
geometry was already observed in the intramolecular CT CPs,
such as the [3.3]cyclophanequinones13a and quinhydrones.13b It
should be noted that the anti-[3.3]MCP-dione 1 (λmax 443 nm)
exhibits much weaker CT interaction than the syn-2, and this
Thus, the electron-donating ability of the multilayered [3.3]-
MCPs 2-6 gradually increases with an increase in the layers,
but the magnitude becomes less significant as the number of
layers increases. The anti geometry with the -CH2COCH2--
TABLE 1. Charge-Transfer Bands of Multilayered [3.3]CPs-TCNE in CHCl3
multilayered [3.3]CPs
[3.3]PCP
TCNE complex λmax (nm)
multilayered [3.3]CPs
TCNE complex λmax (nm)
489
606
460
510
509
550
581
556
five-layered [3.3]MCP 5
575
588
443
506
518
543
548
728
t-Bu six-layered [3.3]MCP 6
two-layered [3.3]MCP dione 1
three-layered [3.3]MCP dione 22
four-layered [3.3]MCP dione 23
five-layered [3.3]MCP dione 24
t-Bu six-layered [3.3]MCP tetraone 27
[36](1,2,3,4,5,6)CP14b
[3.3]MPCP
[3.3]MCP 2
three-layered [3.3]MCP 3
t-Bu three-layered [3.3]MCP 31
four-layered [3.3]MCP 4
2874 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
bridges included in the multilayered [3.3]MCPs serves as an
electron insulator. The moderate electron-donating ability of the
multilayered [3.3]MCPs as compared to that of the [3n]CPs may
be ascribed to the tilted overlap of the benzene rings.
the synthesis of multilayered [3.3]PCPs is in progress, and these
results will be reported elsewhere.
Experimental Section
5,7-Bis(bromomethyl)[3.3]metacyclophane 11. A mixture of
n-Bu4NI (3.3 g), CH2Cl2 (1.0 L), and NaOH (30 g) dissolved in
water (80 mL) was heated to reflux with stirring. To the mixture
was added dropwise a mixture of bromide 7 (6.68 g, 17.6 mmol)
and TosMIC adduct 8 (8.68 g, 17.6 mmol) in CH2Cl2 (700 mL)
over a period of 8 h, and the mixture was refluxed for an additional
3 h. The cooled mixture was washed with water and concentrated
to a volume of ca. 300 mL. To the concentrate was added concd
HCl (50 mL), and the mixture was stirred for 2 h at room
temperature. The mixture was washed with brine and concentrated
to dryness to afford dark brown oil. To the oil was added MeOH
(50 mL), and the mixture was sonicated and triturated. The
precipitate was collected by filtration, washed with MeOH, and
air-dried. Similar reactions were repeated 5 times on similar scales
(total 88.0 mmol of 7 was used). Purification of the crude product
by silica gel column chromatography with CH2Cl2 afforded
ketoester 9 (12.3 g, 37%). -9: Colorless needles (EtOH/benzene),
mp 196.5-197.5 °C; IR (KBr) ν 1716 (ester CdO), 1708 (ketone
CdO) cm-1; 1H NMR (300 MHz) δ3.51 (s, 4H, CH2COCH2), 3.75
(s, 4H, CH2COCH2), 3.97 (s, 6H, OCH3), 5.69 (s, 1H, Hi1), 6.08
(s, 1H, Hi2), 7.11 (dd, J ) 7.6, 1.5 Hz, 2H, Ha), 7.30 (t, J )
7.5 Hz, 1H, Hb), 8.69 (s, 1H, Hc); MS (EI) m/z 380 [M+]. Anal.
Calcd for C22H20O6: C, 69.46; H, 5.30. Found: C, 69.31; H, 5.33.
Conclusion
We have successfully synthesized up to six-layered [3.3]-
MCPs using a TosMIC method as a critical coupling reaction
via repetitive processes. Structures in solution of all the MCPs
1
could be assigned on the basis of the H NMR data using the
significantly shielded inner aromatic proton of the anti-[3.3]-
MCP-dione 1 and moderately shielded inner aromatic proton
of the syn-[3.3]MCP 2 as a diagnostic tool. The all-syn
conformations are expected for multilayered [3.3]MCPs 2-6
in CDCl3 solution, but the X-ray structural analysis revealed
that the central [3.3]MCP unit of the four-layered MCP 4 takes
anti geometry with the dihedral angle of the two benzene rings
being 42.0°. The dihedral angle of the two benzene rings in the
incorporated [3.3]MCP unit becomes larger (3, 34.5°) than that
of the parent 2 (24°). These data indicate that [3.3]MCP unit is
flexible to some extent and can change its conformation so as
to be adapted to the environment such as crystal-packing forces.
In the electronic spectra, rather simple and structureless absorp-
tion curves are observed, and the most significant spectral
change is observed from two to three layers but becomes less
effective even if more layered. In the CT bands of the
multilayered [3.3]MCPs, the λmax gradually shifts to the longer
wavelength region, but the extent of the shift is much smaller
as the number of layers increases. In the multilayered [3.3]MCP-
ketones, the trans-[3.3]MCP-dione unit serves as an electric
insulator. In fact, the CT interaction of the four- and five-layered
[3.3]MCPs with one trans-[3.3]MCP-dione unit (23 and 24)
shows almost a comparable magnitude of the interaction to the
two- and three-layered MCPs (2 and 3). The tetraones of the
four- and six-layered MCPs (26 and 27) do not form CT
complexes. The CT data suggest the moderate electron-donating
ability of the multilayered [3.3]MCPs with all-syn geometries
as compared to that of multibridged [3n]CPs (n ) 2-6).35
A mixture of the ketoester 9 (11.9 g), KOH (23 g), 100% NH2-
NH2‚H2O (40 mL), and diethylene glycol (200 mL) was heated at
130 °C for 2 h and then 200 °C for 3 h. After cooling, the mixture
was acidified by the addition of concd HCl. The precipitate was
collected by filtration, washed with water, and dried at 120 °C for
4 h to give crude dicarboxylic acid as a brown powder (8.59 g),
which was treated with MeOH (500 mL), concd H2SO4 (15 mL),
and benzene (100 mL) at reflux for 1 day with gradual removal of
the benzene-water azeotrope. The mixture was concentrated to a
volume of ca. 100 mL, and the concentrate was diluted with water
and extracted with CH2Cl2. The combined CH2Cl2 extracts were
washed with brine, dried with MgSO4, and filtered. Removal of
the solvent followed by purification of the residue by silica gel
column chromatography with CH2Cl2 gave dimethyl [3.3]metacy-
clophane-5,7-dicarboxylate 10 (4.63 g, 42% overall). -10: Color-
less needles (MeOH/CH2Cl2): mp 113-114 °C; IR (KBr) ν 1721
1
The H NMR study of the multilayered [3.3]MCPs showed
that they were mobile in solution because of the sharp singlet
of the benzylic protons of the [3.3]MCP-2,11-dione moiety as
well as the averaged signals of the trimethylene bridges of the
[3.3]MCP moiety. In connection with the conformational
behavior of the parent [3.3]MCP 2, much more complex
dynamic conformational behavior would be expected for the
multilayered [3.3]MCPs. For example, the simultaneous RI
processes of the two outer benzene rings are required for the
conformational isomerism of the three-layered MCPs 3 and 31
(Scheme 4). Similar correlated RI processes may be observed
in the three-layered MCP-dione 22. For the elucidation of the
dynamic conformational behavior, the temperature-dependent
NMR study of 31 and 22 is in progress.
We will continue the synthesis of more layered [3.3]MCPs
as model compounds for the development of new electron-
transfer systems through π electrons of the benzene rings. In
the multilayered [3.3]MCPs with electron-donor and -acceptor
moieties at each end of the layers, electron transfer from a donor
to an acceptor may be observed. Furthermore, our efforts toward
1
(CdO) cm-1; H NMR (300 MHz) δ2.0-2.2 (m, 4H, CH2CH2-
CH2), 2.6-2.8 (m, 4H, CH2CH2CH2), 3.0-3.2 (m, 4H, CH2-
CH2CH2), 3.86 (s, 6H, OMe), 6.65 (dd, J ) 7.6, 1.5 Hz, 2H, Ha),
6.82 (t, J ) 7.3 Hz, 1H, Hb), 6.84 (s, 1H, Hi2), 6.94 (br s, 1H,
Hi1), 8.13 (s, 1H, Hc); MS (EI) m/z 352 [M+]. Anal. Calcd for
C22H24O4: C, 74.98; H, 6.86. Found: C, 74.60; H, 6.85.
A mixture of the ester 10 (2.06 g, 5.85 mmol), LiAlH4 (1.00 g,
26.4 mmol), and THF (80 mL) was refluxed for 4 h with stirring.
After cooling, AcOEt, H2O, and diluted HCl were added succes-
sively to the mixture. The mixture was extracted with Et2O, and
the combined extracts were washed with brine, dried with MgSO4,
and filtered. Removal of the solvent and drying of the residue in
vacuo at room temperature gave alcohol, which was used without
further purification.
A mixture of the diol, PBr3 (8.0 mL, 85 mmol), and benzene
(70 mL) was stirred for 6 h at room temperature. The reaction
mixture was washed with brine, dried with MgSO4, and passed
through a short silica gel column with benzene. Concentration of
the eluate provided two-layered bromide 11 (1.85 g, 75% in two
steps). -11: Colorless needles (hexane/CH2Cl2), mp 106-107 °C;
1H NMR (300 MHz) δ2.0-2.3 (m, 4H, CH2CH2CH2), 2.6-2.9 (m,
8H, CH2CH2CH2), 4.38 (s, 4H, CH2Br), 6.64 (s, 1H, Hi2), 6.70
(dd, J ) 7.4, 1.3 Hz, 2H, Ha), 6.79 (t, J ) 7.4 Hz, 1H, Hb), 6.95
(s, 1H, Hc), 6.99 (s, 1H, Hi1); MS (EI) m/z 420 (M+, 7%),
(35) Yasutake, M.; Koga, T.; Sakamoto, Y.; Komatsu, S.; Zhou, M.;
Sako, K.; Tatemitsu, H.; Onaka, S.; Aso, Y.; Inoue, S.; Shinmyozu, T. J.
Am. Chem. Soc. 2002, 124, 10136-10145.
J. Org. Chem, Vol. 72, No. 8, 2007 2875

Shibahara et al.
422 [(M + 2)+, 15%], 424 [(M + 4)+, 7%]. Anal. Calcd for C20H22-
Br2: C, 56.90; H, 5.25. Found: C, 57.15; H, 5.20.
acetone/hexane (1:1), and insoluble solid was collected by filtration
to give the tetrabromide 25 (27.5 g, 62%) as a white powder. -25:
1H NMR δ 2.21-2.25 (m, 4H, CH2CH2CH2), 2.92 (br s, 8H, CH2-
CH2CH2), 4.39 (s, 8H, CH2Br), 6.99 (s, 2H, ArH), 7.04 (s, 2H,
ArH).10g,29b
5,7-Bis[2-isocyano-2-(tolylsulfonyl)ethyl][3.3]metacyclo-
phane 13. A mixture of n-Bu4NI (250 mg), NaOH (6.0 g) dissolved
in 15 mL of water, and CH2Cl2 (25 mL) was cooled in an ice bath
with stirring. To the mixture was added in one portion a CH2Cl2
(25 mL) solution of TosMIC 12 (3.61 g, 18.5 mmol). After 30
min, the bromide 11 (2.31 g, 5.47 mmol) dissolved in CH2Cl2 (20
mL) was added in one portion. The mixture was stirred for 1 h in
the ice bath, then at room temperature for 3 h. The reaction mixture
was washed with water and concentrated to a volume of ca. 20
mL. The concentrate was diluted with MeOH (ca. 100 mL) and
stored in a freezer. The precipitate was collected by filtration and
washed with MeOH. Silica gel chromatography of the crude product
with CH2Cl2 afforded pure 5,7-bis[2-isocyano-2-(tolylsulfonyl)ethyl]-
[3.3]metacyclophane 13 (2.51 g, 71%) as white powder. -13:
White powder (MeOH/CH2Cl2). mp 125 °C (dec); IR (KBr) ν 2132
(NC), 1333, 1151 (SO2) cm-1; 1H NMR (300 MHz) δ2.0-2.2 (m,
4H, CH2CH2CH2), 2.49 (s, 6H, CH3), 2.6-2.8 (m, 8H, CH2-
CH2CH2), 2.80 (dd, J ) 14.0, 11.4 Hz, 2H, CH2CH), 3.46 (dd, J
) 14.0, 2.4 Hz, 2H, CH2CH), 4.42 (dd, J ) 11.5, 2.5 Hz, 2H,
CH2CH), 6.58 (s, 1H, Hi2), 6.60 (dd, J ) 7.6, 1.4 Hz, 2H, Ha),
6.74 (s, 1H, Hc), 6.77 (t, J ) 7.5 Hz, 1H, Hb), 7.00 (s, 1H, Hi1),
7.43 (dd, J ) 8.3, 1.8 Hz, 4H, TsH), 7.88 (dd, J ) 8.3, 1.7 Hz,
4H, TsH). Anal. Calcd for C38H38N2O4S2: C, 70.12; H, 5.88; N,
4.30. Found: C, 70.01; H, 5.89; N, 4.26.
Four-Layered [3.3]Metacyclophane 4. Four-Layered Tetra-
one 26. (67%): Colorless crystals (CH2Cl2), mp >300 °C; IR (KBr)
ν 1701 (CdO) cm-1 1H NMR (300 MHz) δ2.0-2.1 (m, 4H,
;
CH2CH2CH2), 2.7-2.9 (m, 8H, CH2CH2CH2), 3.30 (s, 8H, CH2-
COCH2), 3.33 (s, 8H, CH2COCH2), 5.24 (s, 2H, Hi1), 5.50 (s, 2H,
Hi2), 7.01 (dd, J ) 6.9, 1.3 Hz, 4H, Ha), 7.02 (s, 2H, Hi3), 7.19 (t,
J ) 7.3 Hz, 2H, Hb); HRMS (FAB) m/z calcd for C42H40O4
608.2927 [M+], found 608.2903. Anal. Calcd for C42H40O4‚0.05
CH2Cl2: C, 82.39; H, 6.59. Found: C, 82.25; H, 6.67.
Four-Layered [3.3]Metacyclophane 4. (81%): Colorless crys-
1
tals (dioxane), mp 212-214 °C. H NMR (300 MHz) δ1.9-2.0
(m, 12H, CH2CH2CH2), 2.4-2.5 (m, 8H, CH2CH2CH2), 2.5-2.6
(m, 8H, CH2CH2CH2), 2.6-2.7 (m, 8H, CH2CH2CH2), 6.05 (s, 2H,
Hi2), 6.10 (s, 2H, Hi3), 6.70 (d, J ) 7.3 Hz, 4H, Ha), 6.71 (s, 2H,
Hi1), 6.85 (t, J ) 7.6 Hz, 2H, Hb); 13C NMR (75 MHz) δ 26.2,
28.1, 32.3, 32.7, 36.2, 125.5, 127.8, 133.9, 134.2, 134.5, 134.6,
135.2, 140.1; HRMS (FAB) m/z calcd for C42H48 552.3756 [M+],
found 552.3737. Anal. Calcd for C42H48: C, 91.25; H, 8.75.
Found: C, 90.98; H, 8.77.
Five-Layered [3.3]Metacyclophane 5. Five-Layered Dione 24.
(32%): Colorless crystals (dioxane), mp 278-280 °C; IR (KBr) ν
General Synthetic Procedures of Multilayerd [3.3]Meta-
cyclophanes. To a refluxing mixture of n-Bu4NI, NaOH dissolved
in water, and CH2Cl2 was added dropwise a mixture of the TosMIC
adduct and the bromide dissolved in CH2Cl2, and the mixture was
refluxed for an additional hour. After cooling, the mixture was
washed with water and concentrated, and the concentrate was treated
with concd HCl at room temperature. The mixture was washed with
brine and concentrated to dryness. To the residue was added acetone
(tetraone) or MeOH (dione), and the mixture was sonicated. The
resulting precipitate was collected by filtration to give the ketone.
A mixture of the ketone, 100% NH2NH2‚H2O, KOH, and
polyethylene glycol was heated at 130 °C and then at 200 °C with
stirring. After cooling, the mixture was diluted with water, acidified
with concd HCl, and extracted with CH2Cl2. The CH2Cl2 solution
was washed with brine, dried with MgSO4, and filtered. The filtrate
was concentrated to dryness to give the multilayered [3.3]MCP.
Three-Layered [3.3]Metacyclophane 3. Three-Layered Tet-
raone 29. (8.2%): Colorless crystals (CH2Cl2), mp >300 °C; IR
1695 (CdO) cm-1 1H NMR (300 MHz) δ1.8-2.1 (m, 12H,
;
CH2CH2CH2), 2.4-2.6 (m, 4H, CH2CH2CH2), 2.5-2.7 (m, 16H,
CH2CH2CH2), 2.7-2.8 (m, 4H, CH2CH2CH2), 3.16 (br s, 4H, CH2-
COCH2), 3.18 (br s, 4H, CH2COCH2), 5.00 (s, 1H, Hi6), 5.07 (s,
1H, Hi5), 5.88 (s, 1H, Hi2), 6.45 (s, 1H, Hi3), 6.57 (s, 1H, Hi4),
6.61 (s, 1H, Hi7), 6.63 (d, J ) 7.4 Hz, 2H, Hc), 6.66 (dd, J ) 7.5,
1.4 Hz, 2H, Ha), 6.74 (s, 1H, Hi1), 6.75 (t, J ) 7.4 Hz, 1H, Hd),
6.83 (t, J ) 7.5 Hz, 1H, Hb), 6.97 (s, 1H, Hi8); HRMS (FAB) m/z
calcd for C54H58O2 738.4437 [M+], found 738.4484. Anal. Calcd
for C54H58O2: C, 87.76; H, 7.91. Found: C, 87.77; H, 7.88.
Five-Layered [3.3]Metacyclophane 5. (58%): Colorless crystals
1
(CH2Cl2), mp 244-245 °C; H NMR (300 MHz) δ1.8-2.1 (m,
16H, CH2CH2CH2), 2.3-2.8 (m, 32H, CH2CH2CH2), 6.03 (s, 2H,
Hi2), 6.08 (s, 2H, Hi3), 6.19 (s, 2H, Hi4), 6.68 (d, J ) 7.4 Hz, 4H,
Ha), 6.69 (s, 2H, Hi1), 6.84 (t, J ) 7.5 Hz, 2H, Hb); 13C NMR
(150 MHz) δ 26.3, 28.1, 32.5, 36.2, 125.5, 127.8, 134.2, 134.5,
134.6, 134.8, 134.9, 135.3, 140.1; HRMS (FAB) m/z calcd for
C54H62 710.4852 [M+], found 710.4873. Anal. Calcd for C54H62‚0.15
CH2Cl2: C, 89.86; H, 8.68. Found: C, 89.89; H, 8.74.
1
(KBr) ν 1694 (CdO) cm-1; H NMR (300 MHz) δ3.53 (s, 8H,
CH2COCH2), 3.62 (s, 8H, CH2COCH2), 5.54 (s, 2H, Hi2), 6.09 (s,
2H, Hi1), 7.22 (dd, J ) 7.3, 1.6 Hz, 4H, Ha), 7.37 (t, J ) 7.6 Hz,
2H, R ) Hb); HRMS (FAB) m/z calcd for C30H26O4 451.1909 [(M
+ H)+], found 451.1850. Anal. Calcd for C30H26O4‚0.45CH2Cl2:
C, 74.83; H, 5.55. Found: C, 74.64; H, 5.47.
tert-Butyl Group Substituted Six-Layered [3.3]Metacyclo-
phane 6. tert-Butyl Group Substituted Six-Layered Tetraone
27. (20%): White powder (CH2Cl2), mp > 300 °C; IR (KBr) ν
1701 (CdO)cm-1; 1H NMR (300 MHz) δ 0.94 (s, 18H, t-Bu), 1.8-
2.1 (m, 12H, CH2CH2CH2), 2.4-2.7 (m, 24H, CH2CH2CH2), 3.06
(br s, 16H, CH2COCH2), 4.79 (s, 2H, Hi4), 4.96 (s, 2H, Hi3), 6.50
(d, J ) 1.2 Hz, 4H, Ha), 6.64 (s, 2H, Hi2), 6.79 (s, 2H, Hi1), 6.93
(s, 2H, Hi5); HRMS (FAB) m/z calcd for C74H84O4 1036.6370 [M+],
found 1036.6364. Anal. Calcd for C74H84O4‚0.2CH2Cl2: C, 84.52;
H, 8.07. Found: C, 84.44; H, 8.07.
tert-Butyl Group Substituted Six-Layered [3.3]Metacyclo-
phane 6. (8.1%): White powder (CHCl3), mp > 300 °C; 1H NMR
(300 MHz) δ 1.08 (s, 18H, t-Bu), 1.8-2.0 (m, 20H, CH2CH2CH2),
2.3-2.7 (m, 40H, CH2CH2CH2), 6.00 (s, 2H, Hi4), 6.03 (s, 2H,
Hi3), 6.10 (s, 2H, Hi2), 6.12 (s, 2H, Hi5), 6.56 (s, 2H, Hi1), 6.58 (s,
4H, Ha); 13C NMR (150 MHz) δ 26.3, 26.5, 28.3, 29.7, 31.1, 32.5,
32.6, 33.2, 34.2, 36.7, 122.2, 130.9, 133.2, 134.3, 134.5, 134.5,
134.7, 135.1, 135.2, 135.5, 140.0, 149.8; HRMS (FAB) m/z calcd
for C74H92 980.7199 [M+], found 980.7137.
Three-Layered [3.3]Metacyclophane 3. (44%): Colorless
1
needles (dioxane), mp 268-270 °C; H NMR (300 MHz) δ1.8-
2.0 (m, 8H, CH2CH2CH2), 2.4-2.7 (m, 16H, CH2CH2CH2), 5.92
(s, 2H, Hi2), 6.69 (d, J ) 7.0, 4H, Ha), 6.70 (s, 2H, Hi1), 6.85 (t,
J ) 7.6 Hz, 2H, Hb); 13C NMR (75 MHz) δ 27.9, 32.6, 36.2, 125.5,
127.8, 133.9, 134.1, 135.1, 140.1; HRMS (FAB) m/z calcd for
C30H34 394.2661 [M+], found 394.2663. Anal. Calcd for C30H34:
C, 91.32; H, 8.68. Found: C, 91.30; H, 8.73.
5,7,14,16-Tetrakis(bromomethyl)[3.3]metacyclophane 25. The
original synthetic procedures reported by Vo¨gtle et al.10g were
modified. A mixture of [3.3]MCP 2 (17.3 g, 73.0 mmol), paraform-
aldehyde (16.2 g), and acetic acid (36 mL) was heated to 95 °C
under N2 with mechanical stirring. To the mixture was added
30 wt % HBr in acetic acid solution (90 mL) in one portion, and
then the mixture was stirred for 27 h. As the reaction proceeded,
precipitate appeared, and the quantity was gradually increased. After
the reaction mixture was allowed to cool to room temperature, the
precipitate was collected by filtration, and the solid was dissolved
in CH2Cl2 and concentrated. The concentrate was diluted with
X-ray Crystallographic Study. All measurements were made
with graphite-monochromated Mo KR (λ ) 0.71069 Å) radiation
and a rotating anode generator. The crystal structures were solved
2876 J. Org. Chem., Vol. 72, No. 8, 2007

Multilayered [3.3]Metacyclophane π-π Interaction
by direct methods [SIR92]36 (23) and [SIR97]37 (3, 4, and 26) and
refined by the full-matrix least-squares method. The non-hydrogen
atoms were refined anisotropically, and hydrogen atoms were
refined isotropically. All the computations were performed using
the teXan package.38 Crystallographic data for the structural analyses
of 3, 4, 23, and 26 have been deposited within the Cambridge
Crystallographic Data Centre (CCDC) as 293730, 293733, 293732,
and 293731, respectively. Copies of this information may be
obtained from The Director, CCDC, 12 Union Road, Cambridge,
CB21EZ,UK(fax: +441223336033ande-mail: deposit@ccdc.cam.ac.uk)
or http://www.ccdc.cam.ac.uk/deposit.
financial support from a Theme Project of Molecular Archi-
tecture of Organic Compounds for Functional Design (Prof.
Tahsin J. Chow), Institute of Chemistry, Academia Sinica,
Taiwan R.O.C. We are also grateful for financial support by a
Grant-in-Aid for Scientific Research (B) (18350025) from the
Ministry of Education, Culture, Sports, Science and Technology,
Japan.
Supporting Information Available: Experimental details;
summary of crystallographic data and refinement details of 3, 4,
23, and 26; molecular stacking forms of 3, 4, 23,and 26; charge-
transfer absorption bands of multilayered [3.3]MCPs-TCNE, mul-
tilayered [3.3]MCP-ketones-TCNE, three-layered [3.3]MCP 3-TC-
NE, and four-layered [3.3]MCP 4-TCNE in CHCl3; 1H NMR
spectra of multilayered [3.3]MCPs and ketones; 13C NMR spectra
of multilayered [3.3]MCPs; and coordinates of the four-layered [3.3]-
MCP 4 by PM3 calculations. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. We are indebted to Prof. Takahiko Inazu
for his helpful suggestions. T.S. gratefully acknowledges the
(36) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.; Giaco-
vazzo, C.; Guagliardi, A.; Polidori, G. J. Appl. Crystallogr. 1994, 27, 435.
(37) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna,
R. J. Appl. Crystallogr. 1999, 32, 115-119.
(38) Crystal Structure Analysis Package; Molecular Structure Corpora-
tion: 1985 and 1999.
JO062220M
J. Org. Chem, Vol. 72, No. 8, 2007 2877