Synthesis of [n]- and [n.n]Cyclophanes by using Suzuki-Miyaura coupling

Article abstract of DOI:10.1021/jo025509m

Reaction of the bis-9-BBN adduct of several dienes with 1,3-dibromobenzene via Suzuki coupling leads to a series of [n]metacyclophanes ranging in size from 10 to 17 atom members. In each case, two carbon-carbon bonds are formed in one reaction vessel. However, when the bis-9-BBN adduct of 1,5-hexadiene is coupled with a variety of aryl dihalides, larger [n.n]cyclophanes were formed in preference to the [n]cyclophanes. Four carbon-carbon bonds are formed in this instance. Single-crystal X-ray analyses of these [n.n]cyclophanes reveal interestingly shaped molecules with large cavities.

Full text of DOI:10.1021/jo025509m

Syn th esis of [n ]- a n d [n .n ]Cyclop h a n es by Usin g Su zu k i-Miya u r a
Cou p lin g
Beverly B. Smith,#,† Darron E. Hill,† T. Ashton Cropp,† Rosa D. Walsh,‡ David Cartrette,#,†
Sherry Hipps,† Amy M. Shachter,§ William T. Pennington,‡ and William R. Kwochka*,†
Department of Chemistry and Physics, Western Carolina University, Cullowhee, North Carolina 28723,
Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905,
and Department of Chemistry, Santa Clara University, Santa Clara, California 95053
kwochka@email.wcu.edu
Received J anuary 7, 2002
Reaction of the bis-9-BBN adduct of several dienes with 1,3-dibromobenzene via Suzuki coupling
leads to a series of [n]metacyclophanes ranging in size from 10 to 17 atom members. In each case,
two carbon-carbon bonds are formed in one reaction vessel. However, when the bis-9-BBN adduct
of 1,5-hexadiene is coupled with a variety of aryl dihalides, larger [n.n]cyclophanes were formed in
preference to the [n]cyclophanes. Four carbon-carbon bonds are formed in this instance. Single-
crystal X-ray analyses of these [n.n]cyclophanes reveal interestingly shaped molecules with large
cavities.
In tr od u ction
workers used flash vacuum pyrolysis in the extrusion of
SO2 to form a series of medium-sized [n]metacyclo-
phanes.6 An additional, flexible synthesis for all-carbon
systems was developed by Kumada and co-workers in
which several metacyclophanes and (2,6)pyridinophanes
were prepared via the Ni(II) catalyzed coupling of a bis-
Grignard reagent with aromatic dihalides.7 A great deal
is known about the smaller all-carbon [n.n]cyclophanes,
particularly the [2.2]cyclophanes. Perhaps the most suc-
cessful approach to the synthesis of small [n.n]cyclo-
phanes has been sequential Wurtz couplings of haloge-
nated aromatics and SO2 extrusion of dithiacyclophanes.8
Our interest in cyclophane chemistry stems from our
investigations of silicon-containing cage compounds. In
this work, we demonstrated that three sequential carbon-
carbon bonds form to make a silicon-containing cage
compound using Suzuki-Miyaura coupling9 of an aryl
tribromide with the 9-BBN adduct of methyltriallylsi-
lane.10 At that point, we decided to pursue the study of
all-carbon systems using Suzuki-Miyaura coupling and
found that we could prepare [6.6]metacyclophane (an 18-
membered ring) in 5% yield from 1,5-hexadiene and 1,3-
dibromobenzene.11 This rather surprising result, in which
four carbon-carbon bonds were formed in the reaction,
prompted us to investigate the synthesis of all-carbon
cyclophanes further. Herein we report the synthesis of a
series of all-carbon [n]metacyclophanes as well as the
Cyclophanes are bridged aromatic compounds that
have been investigated since the 1950s for the unique
interactions of the π-electron systems of the benzene
rings and for their potential as molecular hosts.1 The first
directed synthesis of a cyclophane was the preparation
of [2.2]paracyclophane performed by Cram and Stein-
berg.2 Since that time, the field has evolved to include
supramolecular systems capable of molecular recognition
in which cyclophanes serve as host molecules.3 [n]-
Metacyclophanes have been prepared in a variety of ways
primarily, it appears, through rearrangement chemistry.4
For example, [5]metacyclophane, the smallest [n]cyclo-
phane known, was synthesized by Bickelhaupt and co-
workers by base-induced rearrangement of a strained
dichloropropellane.5 In another approach, Vo¨gtle and co-
#
The synthesis of the [n.n]cyclophanes was taken, in part, from the
M.S. theses of Beverly B. Smith (1997) and David Cartrette (1997),
Western Carolina University.
† Department of Chemistry and Physics, Western Carolina Univer-
sity.
§ Department of Chemistry, Santa Clara University.
‡ Department of Chemistry, Clemson University.
(1) (a). Weber, E. Cyclophanes. In Topics in Current Chemistry;
Springer-Verlag: Berlin, Germany, 1994; Vol. 172. (b) Vo¨gtle, F.
Cyclophane Chemistry: Synthesis, Structures, and Reactions; J ohn
Wiley and Sons: Chichester, UK, 1993. (c) Diederich, F. Cyclophanes;
Royal Society of Chemistry: Cambridge, UK, 1991. (d) Keehn, P. M.;
Rosenfeld, S. M. Cyclophanes; Academic Press: New York, 1983; Vols.
1 and 2. (e) Boekelheide, V. Synthesis and Properties of [2n]Cyclo-
phanes. In Topics in Current Chemistry; Springer-Verlag: New York,
1983; Vol. 113. (f) Smith, B. H. Bridged Aromatic Compounds;
Academic Press: New York, 1964.
(2) Cram, D. J .; Steinberg, H. J . Am. Chem. Soc. 1951, 73, 5691-
5698.
(3) See, for example: Prautzsch, V.; Ibach, S.; Vo¨gtle, F. J . Inclusion
Phenom. Macrocyclic Chem. 1999, 33, 427-457.
(4) Kane, V. V.; De Wolf, W. H.; Bickelhaupt, F. Tetrahedron 1994,
50, 4575-4622. Also, see refs 1b and 1c for a comprehensive overview
of cyclophane syntheses.
(6) Vo¨gtle, F.; Koo, P. K. T. M. Angew. Chem., Int. Ed. Engl. 1978,
17, 60-62.
(7) Tamao, K.; Kodama, S.-I.; Nakatsuka, T.; Kiso, Y.; Kumada, M.
J . Am. Chem. Soc. 1975, 97, 4405-4406.
(8) Vo¨gtle, F.; Neumann, P. Synthesis 1973, 85-103.
(9) For a recent review of the Suzuki-Miyaura coupling reaction
see: Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
(10) Kwochka, W. R.; Damrauer, R.; Schmidt, M. W.; Gordon, M. S.
Organometallics 1994, 13, 3728-3732.
(11) The first large cyclophane we reported was [6.6]metacyclophane:
Smith, B. B.; Kwochka, W. R.; Damrauer, R.; Swope, R. J .; Smyth, J .
R. J . Org. Chem. 1997, 62, 8589-8590.
(5) Turkenburg, L. A. M.; Blok, P. M. L.; de Wolf, W. H.; Bickelhaupt,
F. Tetrahedron Lett. 1981, 22, 3317-3320.
10.1021/jo025509m CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/26/2002
J . Org. Chem. 2002, 67, 5333-5337
5333

Smith et al.
SCHEME 2. Syn th esis of [6.6]Cyclop h a n esa
SCHEME 1. Syn th esis of [n ]Meta cyclop h a n esa
a
Key: (i) 2.5 M 9-BBN in THF, room temperature, 3 h; (ii)
Pd(PPh3)4, NaOH, 1,3-dibromobenzene, THF, reflux overnight.
synthesis and X-ray crystal structures of several [n.n]-
cyclophanes.
a
Resu lts a n d Discu ssion
Key: (i) 2.1 equiv of 9-BBN in THF, room temperature, 3 h;
(ii) Pd(PPh3)4, NaOH, dibromoarene, THF, reflux overnight.
Syn th esis of [n ]Meta cyclop h a n es. Our strategy for
preparing these large- ring systems relies on making
multiple carbon-carbon bonds in a single reaction vessel
with homogeneous catalysis. We chose to use Suzuki-
Miyaura coupling, the palladium-catalyzed coupling of
an alkyl borane with an aryl halide, to make sequential
carbon-carbon bonds for two reasons. The conditions of
the reaction are mild, when the appropriate base is used,
so a wide variety of functional groups can be tolerated
and the starting reagents, dienes and aryl halides, are
readily available. A homologous series of these cyclo-
phanes ranging from [7]metacyclophane (3a ) to [14]-
metacyclophane (3e) has been prepared in fair yields
(Scheme 1). For instance, treatment of 1,5-heptadiene
(1a ) with 2.1 equiv of 9-BBN in THF provides the bis-9-
BBN adduct of heptadiene (2a ). Subsequent reaction of
2a with 1,3-dibromobenzene, NaOH, and 0.3 mol % Pd-
(PPh3)4 in refluxing THF overnight resulted in a 17%
yield of [7]metacyclophane (3a ). As with all the cyclo-
phanes prepared in this study, there are undoubtedly
polymeric side products that have formed, but these were
not characterized.
condensation the crystal structure was not determined.
In fact, refinement for the data set of 5 proved to be very
difficult. Close inspection of the ORTEP of 5 in Figure 1
reveals that the thermal ellipsoids representing the
carbons in the methylene chain are quite large, indicating
a significant amount of vibration in the molecule.
When 3,5-dibromotoluene was coupled with 4, the [6.6]-
(3,5)toluenophane (6) was isolated in 5% yield. The
toluene ring planes of 6 are parallel (angle between best-
fit planes ) 0°) (Figure 1). The center-to-center distance
of the rings is 7.907 Å and the width of the cavity is 6.736
Å. Neither 2,6-dibromotoluene nor 2,6-dibromomesity-
lene, when subjected to the same reaction conditions,
provided any of the corresponding [6.6]metacyclophanes.
This result is not surprising considering the steric
obstacles to overcome during the coupling.
Incorporation of a heteroatoms into a cyclophane
system was accomplished by Suzuki-Miyaura coupling
of 4 with 2,6-dibromopyridine to provide [6.6](2,6)pyri-
dinophane (7) in 6% yield. As with cyclophanes 5 and 6,
the aromatic rings of 7 are parallel (Figure 2), but in this
instance, the system has the unusual arrangement of four
unique molecules per unit cell (P1h space group). The N-N
distances between the undistorted pyridine rings are
6.244, 6.265, 6.549, and 6.557 Å (cavity length) and the
corresponding cavity widths are 7.326, 7.258, 4.879, and
4.864 Å. Predictably, the longer N-N distances cor-
respond to shorter cavity widths. The ORTEP represen-
tation of 7 clearly shows the preferred anti conformation
of the cyclophane. Likewise, the [2.2](2,6)pyridinophane
adopts an anti conformation. In contrast, the [3.3](2,6)-
1
An interesting feature of the H NMR spectrum of 3a
is the strong shielding effect exhibited by the π cloud of
the benzene ring on the methylene chain. This effect is
particularly apparent with the hydrogens of the fourth
carbon on the seven carbon bridge, which appears as a
broad singlet at δ ) -0.15 ppm. Each of the homologues
in the series shows this upfield shift, which predictably
diminishes as the bridge length increases.
Syn th esis a n d Cr ysta l Str u ctu r es of [6.6]Cyclo-
p h a n es. We are limited in constructing the [n]metacy-
clophanes using Suzuki coupling to dienes containing
seven carbon atoms or more; when the bis-9-BBN adduct
of 1,5-hexadiene was combined with 1,3-dibromobenzene
only the [6.6]metacyclophane was isolated and none of
the [6]metacyclophane could be detected.10 Thus, in an
analogous series of reactions, treatment of 1,5-hexadiene
(4) with 2.1 equiv of 9-BBN in THF affords the bis-9-
BBN adduct of hexadiene. Reaction of this bis-adduct
with 1,4-dibromobenzene, NaOH, and 0.3 mol % Pd-
(PPh3)4 in refluxing THF overnight provided the desired
[6.6]paracyclophane (5) in 6% yield (Scheme 2).
1
pyridinophane, as inferred from H NMR studies, exhibits
syn geometry.12
In an analogous reaction, this time with 3,5-dibro-
mopyridine as the coupling partner, we anticipated
formation of [6.6](3,5)pyridinophane; however, none of
this isomeric cyclophane was detected. This outcome is
not terribly surprising since, aside from entropic factors,
nucleophilic substitution is electronically unfavorable at
the bromine-bearing carbons. It was Malenfant and
Fre´chet’s elegant work in the solid-phase synthesis of
oligothiophenes13 that prompted us to investigate incor-
Crystal structure determination of [6.6]paracyclophane
(5) indicates that the benzene rings are parallel to each
other (Figure 1). The center-to-center distance of the
rings is 6.257 Å and the width of the cavity is 6.682 Å.
Interestingly, when Cram and co-workers first reported
the synthesis of [6.6]paracyclophane via the acyloin
(12) (a) For [3.3](2,6)pyridinophane see: Shinmyozu, T.; Hirai, Y.;
Inazu, T. J . Org. Chem. 1986, 51, 1551-1555. (b) For [2.2](2,6)-
pyridinophane see: Pahor, N. B.; Calligaris, M.; Randaccio, L. J . Chem.
Soc., Perkins Trans. 2 1978, 38-42.
(13) Malenfant, P. R. L.; Fre´chet, J . M. J . Chem. Commun. 1998,
2657-2658.
5334 J . Org. Chem., Vol. 67, No. 15, 2002

Synthesis of [n]- and [n.n]Cyclophanes
F IGURE 1. X-ray crystal structures of compounds 5 (left) and 6 (right). Thermal ellipsoids are at the 30% probability level.
Hydrogen atoms were omitted for clarity in 6.
F IGURE 2. X-ray crystal structure and packing diagram of compound 7. The asymmetric unit consists of four molecular halves
generating four independent molecules per unit cell. Thermal ellipsoids are at the 30% probability level. Hydrogen atoms were
omitted for clarity.
F IGURE 3. X-ray crystal structure and packing diagram of 8. Thermal ellipsoids are at the 30% probability level. Hydrogen
atoms were omitted for clarity.
porating sulfur atoms into cyclophanes. Thus, we at-
tempted a palladium-catalyzed coupling of 2,5-dibro-
mothiophene with the bis-9-BBN adduct 4 in the hopes
of preparing [6.6]thiophenophane. Once again, however,
none of the desired cyclophane could be isolated, presum-
ably due to the electronic influence of the heteroatom in
the ring. In each case, with both 3,5-dibromopyridine and
2,5-dibromothiophene, all of the aryl dihalide starting
material was consumed in the reaction.
The largest cyclophane system that we prepared also
proved to have the most interesting crystal structure.
Coupling of 2,7-dibromofluorene with the bis-9-BBN
adduct of 4 afforded the cyclophane [6.6](2,7)fluo-
renophane (8) in 1% yield. The crystal structure of 8
clearly depicts a box-shaped molecule with a cavity that
spans 11.20 Å. The fluorene rings of 8 are in an anti,
parallel arrangement and each ring is bent with a 0.11
Å mean deviation from the least-squares plane defined
by C(1)-C(13) (Figure 3). The average distance between
the fluorene rings is 5.09 Å with the closest center-to-
center distance being 4.07 Å. Overall, each fluorene ring
in 8 bends inward by about 0.51 Å. Deformation of this
portion of the smaller [2.2](2,7)fluorenophane is also
obvious, but in this instance, the fluorene moieties bend
outward with separations ranging from 2.79 Å at the side
to 3.82 Å at the center.14 Not only is there significant
intramolecular attraction between the fluorene moieties
in 8, but there is also considerable intermolecular π-π
interaction; the separation between the fluorene moieties
of the [6.6](2,7)fluorenophane molecules is approximately
3.93 Å. In addition, the intramolecular strain in [2.2](2,7)-
fluorenophane, as evidenced by the increased CH2-CH2
bond length (1.56 Å), is greater than that found in 8,
whose relatively strain-free CH2-CH2 bond distances
range from 1.51 to 1.52 Å.
(14) Haenel, M. W.; Irngartinger, H.; Krieger, C. Chem. Ber. 1985,
118, 144-163.
J . Org. Chem, Vol. 67, No. 15, 2002 5335

Smith et al.
1
3a in 17% yield as a colorless oil. H NMR (400 MHz, CDCl3)
δ 7.46 (s, 1H), 7.22 (t, J ) 7.47 Hz, 1H), 6.97 (d, J ) 7.39 Hz,
2H), 2.70 (s, 4H), 1.46 (br s, 8H), -0.15 (br s, 2H); 13C NMR
(100 MHz, CDCl3) δ 142.8, 131.5, 129.4, 125.0, 37.5, 31.3, 29.5.
[8]Meta cyclop h a n e (3b).18 3b was prepared from the bis-
9-BBN adduct of 1,7-octadiene. The organic layer was sepa-
rated, concentrated, and chromatographed on SiO2 (100%
Typically, the aromatic moieties of organic [n.n]cyclo-
phanes bend outward when connected by short bridging
units due to repulsion of these bridging units with the
overlapping aromatic rings.15 However, when the bridg-
ing units of a polycyclic aromatic hydrocarbon consist of
silver ions, the aromatic rings of the metallocyclophane
bend inward.16 The bridging silver ions permit a strain-
free geometry leading to favorable π-π overlap between
the two aromatic systems. In the case of 8, the two six-
carbon bridges are long enough to provide a favorable
environment for intramolecular interaction between the
π-orbitals of the fluorene rings. To the best of our
knowledge, no other organic [n.n]cyclophane has dis-
played this attractive, intramolecular interaction.
1
hexanes) to afford 3b in 6% yield as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.26 (s, 1H), 7.22 (t, J ) 7.47 Hz, 1H),
6.94 (dd, J ) 7.48, 1.57 Hz, 2H), 2.61 (t, J ) 6.06 Hz, 4H),
1.53 (m, 4H), 1.29 (m, 4H), 0.67 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 142.4, 130.5, 129.3, 125.6, 36.1, 30.3, 26.9, 23.8.
[9]Meta cyclop h a n e (3c).19 3c was prepared from the bis-
9-BBN adduct of 1,8-nonadiene. The organic layer was sepa-
rated, concentrated, and chromatographed on SiO2 (100%
1
hexanes) to afford 3c in 13% yield as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.23 (s, 1H), 7.21 (t, J ) 7.71 Hz, 1H),
6.98 (dd, J ) 7.52, 1.34 Hz, 2H), 2.71 (t, J ) 6.41 Hz, 4H),
1.68 (m, 4H), 1.15 (m, 6H), 0.86 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 141.5, 130.2, 128.5, 126.2, 35.0, 26.9, 26.2, 25.6, 24.9.
[10]Meta cyclop h a n e (3d ).20 3d was prepared from the bis-
9-BBN adduct of 1,9-decadiene. The organic layer was sepa-
rated, concentrated, and chromatographed on SiO2 (100%
Con clu sion
We have demonstrated that Suzuki-Miyaura coupling
provides a rapid route to novel [n]metacyclophanes and
[n.n]cyclophanes. When the bis-9-BBN adduct of 1,5-
hexadiene is used in the coupling dimerization is pre-
ferred to formation of the [n]cyclophane due simply to
geometric constraints. These [n.n]cyclophanes possess
longer all-carbon bridges than previously reported cyclo-
phanes containing the same aromatic moiety. Due to
competing reactions, such as oligomerization, the yields
of the [n]- and [n.n]cyclophanes are low. Nonetheless,
these large rings were prepared by making two or four
carbon-carbon bonds in a single step from readily
available starting materials under mild conditions. By
incorporating substituents into the cyclophane precur-
sors, the synthesis of even more interesting ring systems,
possibly via self-assembly, exists.
1
hexanes) to afford 3d in 9% yield as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.22 (t, J ) 7.52 Hz, 1H), 7.14 (s, 1H),
7.00 (dd, J ) 7.49, 1.52 Hz, 2H), 2.68 (t, J ) 6.22 Hz, 4H),
1.70 (m, 4H), 1.21 (m, 4H), 1.13 (m, 4H), 0.96 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 142.1, 130.3, 128.6, 125.9, 35.3, 28.3, 26.9,
26.2, 25.6.
[14]Meta cyclop h a n e (3e). 3e was prepared from the bis-
9-BBN adduct of 1,13-tetradecadiene. The organic layer was
separated, concentrated, and chromatographed on SiO2 (100%
1
hexanes) to afford 3e in 7% yield as a colorless oil. H NMR
(300 MHz, CDCl3) δ 7.25 (m, 1H), 7.18 (m, 2H), 6.94 (d, J )
7.16 Hz, 1H), 2.59 (t, J ) 6.33 Hz, 4H), 1.57 (m, 4H), 1.28 (m,
20H); 13C NMR (75 MHz, CDCl3) δ 128.5, 128.3, 125.8, 125.6,
36.1, 35.8, 31.6, 31.4, 29.8, 29.7, 29.6, 29.5, 29.43, 29.42, 28.9.
Anal. Calcd for C20H32: C, 88.16; H, 11.84. Found: C, 88.02;
H, 11.76.
[6.6]P a r a cyclop h a n e (5). 5 was prepared from the bis-9-
BBN adduct of 1,5-hexadiene and 1,4-dibromobenzene. The
organic layer was separated, concentrated, and chromato-
graphed on SiO2 (100% hexanes) to afford 5 in 6% yield as a
colorless solid. Evaporative recrystallization from methanol
provided crystals suitable for X-ray analysis. Mp 90-92 °C;
1H NMR (300 MHz, CDCl3) δ 6.96 (s, 8H), 2.52 (m, 8H), 1.51
(m, 8H), 1.13 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 139.5,
128.4, 34.8, 30.2, 29.3. Anal. Calcd for C24H32: C, 89.94; H,
10.06. Found: C, 89.82; H, 10.08.
[6.6](3,5)Tolu en op h a n e (6). 6 was prepared from the bis-
9-BBN adduct of 1,5-hexadiene and 3,5-dibromotoluene. The
organic layer was separated, concentrated, and chromato-
graphed on SiO2 (100% hexanes) to afford 6 in 5% yield as a
colorless solid. Evaporative recrystallization from pentane
provided crystals suitable for X-ray analysis. Mp 81.5-83 °C;
1H NMR (200 MHz, CDCl3) δ 6.81 (s, 6H), 2.55 (t, J ) 7.2 Hz,
8H), 2.32 (s, 6H), 1.62 (m, 8H), 1.33 (m, 8H); 13C NMR (50
MHz, CDCl3) δ 142.8, 137.7, 127.2, 125.2, 35.0, 30.5, 27.5, 21.4.
Anal. Calcd for C26H36: C, 89.59; H, 10.41. Found: C, 89.63;
H, 10.38.
Exp er im en ta l Section
Gen er a l. All reactions were performed in oven-dried glass-
ware under a nitrogen atmosphere unless otherwise stated.
All reagents were purified before use. The 9-BBN was titrated
by using Brown’s method (see: Brown, H. C. Organic Synthesis
via Boranes; Wiley-Interscience: New York, 1975). 1H and 13C
NMR spectra were obtained on a 400, 300, or 200 MHz NMR
spectrometer. Flash chromatography was performed on silica
gel60, 230-400 mesh ASTM obtained from Baxter Scientific.
Atlantic Microlabs Inc., Norcross, GA, performed elemental
analyses.
Gen er a l P r oced u r e for th e P r ep a r a tion of [n ]- a n d
[n .n ]Cyclop h a n es. [7]Meta cyclop h a n e (3a ).17 To a solution
of 26.0 mL of 0.3 M 9-BBN (7.80 mmol) in THF in a 50-mL,
round-bottom flask was added 1,6-heptadiene (0.50 mL, 3.71
mmol) at room temperature. After the mixture was stirred for
3 h, the bis-9-BBN adduct was cannulated into a second round-
bottom flask that contained Pd(PPh3)4 (0.129 g, 0.11 mmol),
NaOH (0.37 g, 9.28 mmol), 1,3-dibromobenzene (0.45 mL, 3.71
mmol), and 400 mL of dry THF. The reaction mixture was
refluxed overnight, cooled to room temperature, then cooled
in an ice bath upon which time 5 mL of 30% H2O2 was added
and stirring was continued for 30 min. The reaction mixture
was then poured into 100 mL of hexanes and extracted with
1 M HCl (50 mL), saturated aqueous NaHCO3 (50 mL), and
brine (50 mL). The organic layer was separated, concentrated,
and chromatographed on SiO2 (0.5% Et2O/hexanes) to afford
[6.6](2,6)P yr id in op h a n e (7). To a solution of 44.3 mL of
0.4 M 9-BBN (17.73 mmol) in THF was added 1,5-hexadiene
(1.00 mL, 8.44 mmol) at room temperature. After the mixture
(18) For [8]MCP see: Tamao, K.; Kodama, S.-I.; Nakatsuka, T.; Kiso,
Y.; Kumada, M. J . Am. Chem. Soc. 1975, 97, 4405-4406.
(19) For [9]MCP see: (a) Marchesini, A.; Bradamante, S.; Fusco,
R.; Pagani, G. Tetrahedron Lett. 1971, 12, 671-674. (b) Tamao, K.;
Kodama, S.-I.; Nakatsuka, T.; Kiso, Y.; Kumada, M. J . Am. Chem. Soc.
1975, 97, 4405-4406.
(20) For [10]MCP see: (a) Fujita, S.; Hirano, S.; Nozaki, H.
Tetrahedron Lett. 1972, 13, 403-406. (b) Tamao, K.; Kodama, S.-I.;
Nakatsuka, T.; Kiso, Y.; Kumada, M. J . Am. Chem. Soc. 1975, 97,
4405-4406.
(15) See ref 1b for a more detailed discussion.
(16) Munakata, M.; Ning, G. L.; Suenaga, Y.; Kuroda-Sowa, T.;
Maekawa, M.; Ohta, T. Angew. Chem., Int. Ed. 2000, 39, 4555-4557.
(17) For [7]MCP see: (a) Fujita, S.; Hirano, S.; Nozaki, H. Tetra-
hedron Lett. 1972, 13, 403-406. (b) Hirano, S.; Hara, H.; Hiyama, T.;
Fujita, S.; Nozaki, H. Tetrahedron 1975, 31, 2219-2227.
5336 J . Org. Chem., Vol. 67, No. 15, 2002

Synthesis of [n]- and [n.n]Cyclophanes
was stirred for 3 h, the bis-9-BBN adduct was cannulated into
a second round-bottom flask that contained Pd(PPh3)4 (0.488
g, 0.422 mmol), NaOH (2.617 g, 65.43 mmol), 2,6-dibromopy-
ridine (2.00 g, 8.44 mmol), and 400 mL of dry THF. The
reaction mixture was refluxed overnight, cooled to room
temperature, and then cooled in an ice bath. Five milliliters
of 30% hydrogen peroxide was then slowly added to consume
any unreacted 9-BBN. The reaction mixture was warmed to
room temperature, diluted with 500 mL of ethyl ether, and
extracted with 1 N HCl (3 × 100 mL). The organic layer was
discarded. The acid wash was made basic with 1 N NaOH and
extracted with ethyl ether (3 × 50 mL). The ether wash was
dried with MgS04 for approximately 15 min, filtered, and
finally concentrated on a rotary evaporator. The residue was
chromatographed on SiO2 (67% diethyl ether/33% hexanes) to
afford 7 in 6% yield as a colorless solid. Evaporative recrys-
tallization from pentane provided crystals suitable for X-ray
analysis. Rf ) 0.64 (67% diethyl ether/33% hexanes); mp 90-
colorless blocks of C26H36; monoclinic, space group P21/n, with
a ) 11.9063(11), b ) 5.5631 (5), c ) 16.833(2) Å, R ) 90°, â )
100.646(7)°, γ ) 90°, V ) 1095.8(2) Å3, z ) 2, µ ) 0.059 mm-1
,
F
calc ) 1.056 g/cm3, M ) 348.55. 2390 reflections were collected;
1678 independent reflections with R(int) ) 0.0173 and 1634
with I > 2σ(I). The numbers of parameters was 119. The final
wR(F2) ) 0.1424, while the conventional R(F) ) 0.0475 for
1634 reflections. For all data, wR(F2) ) 0.1635 and R(F) )
0.0529. The goodness of fit was 1.094. Crystal data for 7:
colorless blocks of C22H30N2; triclinic, space group P1h, with a
) 8.7420(7) Å, b ) 12.9751(11) Å, c ) 17.3626(14) Å, R )
90.138(6)°, â ) 90.773(6)°, γ ) 91.771(7)°, V ) 1968.3(3) Å3, z
) 4, µ ) 0.063 mm-1, Fcalc ) 1.088 g/cm3, M ) 322.48. 8366
reflections were collected; 6896 independent reflections with
R(int) ) 0.0145 and 6465 with I > 2σ(I). The number of
parameters was 471. Four crystallographically independent
molecules were in each unit cell. A small amount of disorder
was modeled for the alkane chains in one molecule. The final
Rw(F2) ) 0.1703, while the conventional R(F) ) 0.0562 for
6465 reflections. For all data, wR(F2) ) 0.1982 and R(F) )
0.0690. The goodness of fit was 1.029. Crystal data for 8:
colorless plates of C38H40; monoclinic, space group P21/n, with
a ) 14.537(2) Å, b ) 5.5063(9) Å, c ) 19.003(3) Å, R ) 90°, â
) 111.711(13)°, γ ) 90°, V ) 1413.2(4) Å3, z ) 2, µ ) 0.065
mm-1, Fcalc )1.167 g/cm3, M ) 496.7. 2953 reflections were
collected; 2067 independent reflections with R(int) ) 0.0187
and 1965 with I > 2σ(I). The numbers of parameters was 173.
The final Rw(F2) ) 0.1170, while the conventional R(F) )
0.0428 for 1965 reflections. For all data, wR(F2) ) 0.1296 and
R(F) ) 0.0524. The goodness of fit was 1.057. For 6, 7, and 8
data were collected on a Seimens P4 diffractometer at 294 K.
Structures were solved by direct methods and refined by full-
matrix least-squares on F2 with Siemens SHELXTL version
5.03.
1
91 °C; H NMR (200 MHz, CDCl3) δ 7.41 (t, J ) 7.7 Hz, 2H),
6.85 (d, J ) 7.7 Hz, 4H), 2.69 (t, J ) 6.9 Hz, 8H), 1.72 (m,
8H), 1.19 (m, 8H); 13C NMR (50 MHz, CDCl3) δ 161.9, 136.3,
120.5, 38.1, 29.4, 28.9. Anal. Calcd for C22H30N2: C, 81.94; H,
9.38, N, 8.69. Found: C, 81.92; H, 9.36, N, 8.66.
[6.6](2,7)F lu or en op h a n e (8). To a solution of 49 mL of 0.4
M 9-BBN (19.44 mmol, 2.1 equiv) in THF was added 1,5-
hexadiene (1.10 mL, 9.26 mmol) at room temperature. After
the mixture was stirred for 3 h, the bis-9-BBN adduct was
cannulated into a second round-bottom flask that contained
Pd(PPh3)4 (0.535 g, 0.463 mmol, 0.05 equiv), NaOH (2.870 g,
71.75 mmol, 7.75 equiv), 2,7-dibromofluorine (3.00 g, 9.26
mmol, 1 equiv), and 400 mL of dry THF. The reaction mixture
was refluxed overnight, cooled to room temperature, then
cooled in an ice bath at which time 5 mL of 30% H2O2 was
added and stirring was continued for 30 min. The reaction
mixture was then poured into 100 mL of hexanes and extracted
with 1 M HCl (50 mL), saturated aqueous NaHCO3 (50 mL),
and brine (50 mL). The organic layer was separated, concen-
trated, and chromatographed on SiO2 (10% CH2Cl2/hexanes)
to afford 8 in 1% yield as a colorless solid. Evaporative
recrystallization from methylene chloride provided crystals
suitable for X-ray analysis. Rf ) 0.15 (10% CH2Cl2/hexanes);
Acknowledgment is made to the donors of the Petro-
leum Research Fund, administered by the American
Chemical Society (W.R.K., No. 33037-GB1), and the
Camille and Henry Dreyfus Foundation for support of
this research. A.M.S. acknowledges funding for the
diffractometer which was provided through a NSF-ILI
grant (DUE-9650341) to Santa Clara University. W.R.K.
acknowledges funding for the NMR spectrometer which
was provided through a NSF-ILI grant (DUE-9851659)
to Western Carolina University. W.T.P. acknowledges
the financial support of the National Science Foundation
for purchase of the CCD-based X-ray system (CHE-
9808165) at Clemson University. Dr. Mariusz Krawiec
is gratefully acknowledged for his assistance with the
X-ray analysis of 5. The structure of 8 was also
determined during the course of a workshop in X-ray
crystallography sponsored by the Camille and Henry
Dreyfus Foundation and held in the Department of
Chemistry at Clemson University.
1
mp 238.5-241 °C; H NMR (200 MHz, CDCl3) δ 7.61 (d, J )
7.9 Hz, 4H), 7.12 (d, J ) 7.9 Hz, 4H), 7.01 (s, 4H), 3.30 (s,
4H), 2.65 (m, 8H), 1.56 (m, 8H), 1.25 (m, 8H); 13C NMR (50
MHz, CDCl3) δ 143.6, 140.9, 139.6, 127.5, 125.9, 119.4, 36.5,
34.5, 30.9, 26.3. Anal. Calcd for C38H40: C, 91.88; H, 8.12.
Found: 91.74; H, 8.20.
Solid -Sta te Str u ctu r es of 5-8. Crystallographic analysis
of 5: C24H32, fw ) 320.50, monoclinic crystal system, P21/ n
(No. 14), a ) 10.8250(12) Å, b ) 5.9661(10) Å, c ) 16.481(3)
Å, â ) 100.000(12)°, V ) 1048.2(3) Å3, Z ) 2 (molecule situated
about the inversion center at (0.5, 0.5, 0.5). Dcalc ) 1.015 Mg/
m3, µ ) 0.056 mm-1 (no absorption correction needed). Data
collected on a Rigaku AFC8 diffractometer equipped with
Mercury CCD area detector. Frames of 0.5° in ω were
measured in duplicate for 30 s to a 2θmax value of 46.0°.
Structure solution was by direct methods and refinement was
based on F2 (both from SHELXTL-Plus). Final residuals of R1
) 0.1040 for 1099 observed data (I > 2σ(I)) and wR2 ) 0.2357
on all 1440 unique data were obtained. The crystals used in
this study were waxy in appearance and of very poor quality.
Numerous samples were studied, and the results reported
represent the best sample analyzed. Crystal data for 6:
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for the [n]cyclophanes 3a -e and [6.6]cyclophanes 5-8
and X-ray structure tables for the [6.6]cyclophanes 5-8. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O025509M
J . Org. Chem, Vol. 67, No. 15, 2002 5337