Nonplanar Aromatic Compounds. 6. [2]Paracyclo[2](2,7)pyrenophane. A Novel Strained Cyclophane and a First Step on the Road to a "Voegtle" Belt

Article abstract of DOI:10.1021/ol016053i

(formula presented) A benzene ring nestled into the concave face of a bent pyrene characterizes the title compound in the crystal. The synthesis of this compound was accomplished using the valence isomerization-dehydrogenation (VID) method and marks the official launch of our journey en route to aromatic belts first proposed by Prof. Voegtle.

Full text of DOI:10.1021/ol016053i

ORGANIC
LETTERS
2001
Vol. 3, No. 13
2093-2096
Nonplanar Aromatic Compounds. 6.
[2]Paracyclo[2](2,7)pyrenophane. A
Novel Strained Cyclophane and a First
Step on the Road to a “Vo1gtle” Belt†
Graham J. Bodwell,* David O. Miller, and Rudolf J. Vermeij
Department of Chemistry, Memorial UniVersity of Newfoundland,
St. John’s, NF, Canada A1B 3X7
gbodwell@mun.ca
Received May 2, 2001
ABSTRACT
A benzene ring nestled into the concave face of a bent pyrene characterizes the title compound in the crystal. The synthesis of this compound
was accomplished using the valence isomerization−dehydrogenation (VID) method and marks the official launch of our journey en route to
aromatic belts first proposed by Prof. Vo1gtle.
We have recently developed a general route to the [n](2,7)-
pyrenophanes 31 and several analogues containing oxygen
atoms in the bridge.2-4 The lynchpin of this strategy is the
conversion of a tethered syn-[2.2]metacyclophanediene sys-
tem 1 to the corresponding pyrenophane 3 by a valence
isomerization-dehydrogenation (VID) protocol (Scheme 1).
polycyclic aromatic hydrocarbon (PAH) moieties during the
key step and the availability of gram quantities of the
pyrenophanes using this approach.
With reliable access to bent pyrenes, the application of
the VID methodology to the challenging goal of preparing
aromatic belts consisting of a repeating pyrene motif, i.e., 4
(Figure 1) can now be targeted realistically. The 5-fold
symmetric belt 4a manifests itself in the equators of the
5
fullerenes D5h C70 and D5d C80,6 whereas the 6-fold sym-
Scheme 1
(2) Bodwell, G. J.; Bridson, J. N.; Houghton, T. J.; Kennedy, J. W. J.;
Mannion, M. R. Angew. Chem., Int. Ed. Engl. 1996, 35, 1320-1321.
(3) Bodwell, G. J.; Bridson, J. N.; Houghton, T. J.; Kennedy, J. W. J.;
Mannion, M. R. Chem. Eur. J. 1999, 5, 1823-1827.
(4) Bodwell, G. J.; Fleming, J. J.; Miller, D. O. Tetrahedron 2001, 57,
3577-3585.
(5) (a) Nikolaev, A. V.; Dennis, T. J. S.; Prassides, K.; Soper, A. K.
Chem. Phys. Lett. 1994, 223, 143-148. (b) van Smaalen, S.; Petricek, V.;
de Boer, J. L.; Dusek, M.; Verheijen, M. A.; Meijer, G. Chem. Phys. Lett.
1994, 223, 323-328. (c) Balch, A. L.; Catalano, V. J.; Lee, J. W.; Olmstead,
M. M.; Parkin, S. R. J. Am. Chem. Soc. 1991, 113, 8953-8955. (d) Bu¨rgi,
H. B.; Venugopalan, P.; Schwarzenbach, D.; Diederich, F.; Thilgen, C. HelV.
Chim. Acta 1993, 76, 2155-2159.
Noteworthy features of this strategy are the mild conditions
(reflux in benzene) required to generate the severely distorted
(6) Wang, C.-R.; Sugai, T.; Kai, T.; Tomiyama, T.; Shinohara, H. J.
Chem. Soc., Chem. Commun. 2000, 557-558.
(7) (a) Negri, F.; Orlandi, G.; Zerbetto, F. J. Am. Chem. Soc. 1991, 113,
6037-6040. (b) Manolopoulos, D. E.; Fowler, P. W. J. Chem. Phys. 1992,
96, 7603-7614. (c) Avent, A. G.; Dubois, D.; Pe´nicaud, A.; Taylor, R. J.
Chem. Soc., Perkin Trans. 2 1997, 1907-1910. (d) Cioslowski, J.; Rao,
N.; Moncrieff, D. J. Am. Chem. Soc. 2000, 122, 8265-8270.
† Part 5 in this series: Bodwell, G. J.; Bridson, J. N; Chen, S.-L.; Poirier,
R. A. J. Am. Chem. Soc. 2001, 123, 4704-4708.
(1) Bodwell, G. J.; Fleming, J. J.; Mannion, M. R.; Miller, D. O. J. Org.
Chem. 2000, 65, 5360-5370.
10.1021/ol016053i CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/25/2001

Scheme 2a
Figure 1.
metric homologue 4b can be excised from the equator of
D6h C84.7 Higher homologues (n > 1) are not fullerene
fragments but constitute, as do 4a and 4b, small sections of
nanotubes. With remarkable foresight, Vo¨gtle8 first proposed
these belts as “interesting targets” prior to the discovery of
the fullerenes and nanotubes. We suggest the name “Vo¨gtle
belts” to denote the architectural motif of 4.
To progress from the current state of affairs toward a
successful synthesis of a Vo¨gtle belt, the obvious task at hand
is to replace the aliphatic bridge of 3 with appropriate
aromatic units. Doing so in one fell swoop would be ideal,
but this approach brings with it a number of knotty synthetic
complications. Although we are actively pursuing this avenue
of investigation, a stepwise approach to the problem is also
being pursued. This approach involves the partial replacement
of the aliphatic bridge of 3 with aromatic units to afford pared
down versions of 4 as stepping stones en route to the full
belts.
The first step in this direction is the incorporation of a
single p-phenylene unit, and [2]paracyclo[2](2,7)pyrenophane
5 was consequently identified as the first target. This
compound is also interesting in that it can be viewed as a
hybrid between [2.2]paracyclophane 69 and [2.2](2,7)-
pyrenophane 7.10 A strong indication that 5 was a viable
synthetic target came from the AM1 calculated bend angle
(θ) of its pyrene moiety (100.4°),3 which is well below those
of the more distorted [n](2,7)pyrenophanes that have already
been prepared.1-3
The early stages of the synthesis (Scheme 2) involved the
construction of diyne 11, which contains all of the carbon
atoms required for the construction of 5. This was assembled
from triflate 8,1 1,4-diiodobenzene 12, and trimethylsilyl-
acetylene using Sonogashira chemistry11 by two comple-
mentary routes. In the first of these, 8 was coupled with
trimethylsilylacetylene to provide diester 9 (71%), which was
protodesilylated to give 10 (91%). Coupling of 10 and 12
led to the formation of 11 in 91% yield. In the second route,
a (a) TMS-CtCH, Pd(PPh3)2Cl2, CuI, DBU, benzene, rt; (b)
K2CO3, MeOH, rt; (c) 12, Pd(PPh3)2Cl2, CuI, DBU, benzene, rt;
(d) 8, Pd(PPh3)2Cl2, CuI, DBU, benzene, rt.
coupling of 12 and trimethylsilylacetylene afforded 13 (95%),
and protodesilylation then gave diyne 14 (77%). (WARN-
ING! Purification of this compound by sublimation led in
one instance to explosive decomposition.) The coupling of
8 and 14 then furnished 11 (57%). Although the second route
worked very well, the explosion hazard associated with 14
led us to discontinue its use.
The remainder of the synthesis (Scheme 3) involved the
manipulation of the existing carbon skeleton. Catalytic
hydrogenation of 11 afforded tetraester 15 (95%), and this
was reacted with LiAlH4 and then HBr/HOAc to provide
tetrabromide 16 in 85% yield from 15. Treatment of 16 with
12
Na2S/Al2O3 to produce dithiacyclophane 17 proceeded in
a disappointingly low yield of 28%. Bridge contraction of
17 was accomplished by methylation of the sulfur atoms with
(MeO)2CHBF4 (Borch reagent) and then Stevens rearrange-
ment. The resulting mixture of isomers 18 (70%, crude) was
immediately reacted with Borch reagent and then subjected
to the normal Hofmann elimination conditions. From this
was obtained a ca. 1:1 mixture of cyclophanediene 19 and
the desired pyrenophane 513 in ca. 16% combined yield from
17. Treatment of this mixture with 2,3-dichloro-5,6-dicy-
anobenzoquinone (DDQ) in benzene at room temperature
gave 5 in 14% overall yield from 17. The majority of the
(11) (a) Tsuji, J. Palladium Reagents and Catalysts; Wiley: New York,
1995. (b) Modern Cross-Coupling Reactions; Stang, P. J., Diederich, F.,
Eds.; VCH: Weinheim, 1997. (c) Ritter, K. Synthesis 1993, 735-762. (d)
de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379-
2411.
(8) Vo¨gtle, F. Top. Curr. Chem. 1983, 115, 157-159.
(9) (a) Brown, C. J.; Farthing, A. C. Nature 164, 915-916. (b) de
Meijere, A.; Ko¨nig, B. Synlett 1997, 1221-1232.
(10) (a) Umemoto, T.; Satani, S.; Sakata, Y.; Misumi, S. Tetrahedron
Lett. 1975, 3159-3162. (b) Mitchell, R. H.; Carruthers, R. J.; Zwinkels, J.
C. M. Tetrahedron Lett. 1976, 2585-2588. (c) Irngartiner, H.; Kirrstetter,
R. G. H.; Krieger, C.; Rodewald, H.; Staab, H. A. Tetrahedron Lett. 1977,
1425-1428.
(12) Bodwell, G. J.; Houghton, T. J.; Koury, H. E.; Yarlagadda, B. Synlett
1995, 751-752.
1
(13) Data for 5: mp 216-219 °C, H NMR (500 MHz, CDCl3) δ 7.67
(s, 4H), 7.40 (s, 4H), 5.54 (s, 4H), 2.99 (AA′XX′ half spectrum, 4H), 2.32
(AA′XX′ half spectrum, 4H); 13C NMR (125 MHz, CDCl3) δ 135.7, 134.2,
131.3, 129.3, 128.6, 128.0, 126.1, 36.5, 33.8; MS (EI, 70 eV) m/z (%) 332
(11, M+), 228 (100).
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Org. Lett., Vol. 3, No. 13, 2001

A single-crystal X-ray structure determination of 514
(Figure 2) revealed a number of unusual and interesting
Scheme 3a
Figure 2. ORTEP representation of 5 in the crystal. The crystal-
lographic numbering shown differs from the systematic numbering.
Selected bond lengths (Å) and angles (deg): C(1)-C(26) 1.495-
(8), C(26)-C(25) 1.468(9), C(25)-C(22) 1.519, C(15)-C(17)
1.522(7), C(17)-C(18) 1.439(8), C(18)-C(19) 1.509(7); C(1)-
C(26)-C(25) 112.7(5), C(22)-C(25)-C(26) 123.7(5), C(15)-
C(17)-C(18) 111.9(5), C(17)-C(18)-C(19) 124.8(6).
a (a) H2, Pd(OH)/C, benzene, rt; (b) (i) LiAlH4, THF, reflux, (ii)
30% HBr/HOAc, HOAc, reflux; (c) Na2S/Al2O3, 10% EtOH/
CH2Cl2, reflux; (d) (MeO)2CHBF4, CH2Cl2, rt; (e) t-BuOK, THF,
rt; (f) t-BuOK, 1:1 THF/t-BuOH, rt; (g) DDQ, benzene, rt.
structural features. The bend angle (θ)3 in the pyrene moiety
is 89.7°, which is an anomalously large 10.7° below the AM1
calculated angle of 100.4°. Up to now, the AM1 calculations
have consistently exceeded the measured bend angles by just
4-7°.1,3 On the other hand, the â angles,15 at 16.1° {C(26)-
C(1)-Du(1)16} and 16.3° {C(17)-C(15)-Du(2)16}, are
considerably higher than those previously observed (<9.0°)1-3
and those in the AM1 calculated structure (11.0°).
losses during the conversion of 17 into 5 were suffered during
the transformation of 18 into 19. In line with previous
experience,1-4 this step continues to be problematic.
The formation of some 5 during the Hofmann elimination
and the ease of the conversion of cyclophanediene 19 to 5
were somewhat surprising. Earlier studies1,4 have shown that
even pyrenophanes with considerably lower bend angles than
that of 5 (vide infra) do not form as easily as 5. The reactivity
of 19 is likely a consequence of the rigidity of the p-xylyl
unit in the tether, which forces open (and thus strains) the
syn-[2.2]metacyclophanediene system. A result of this is that
the two internal carbon atoms are pushed toward one another.
A noteworthy feature of the synthesis is the manner in
which the ethano bridges were installed. To the best of our
knowledge, this is the first example of the application of
such an approach to the preparation of a [2.2]cyclophane.
The isolated benzene ring is essentially planar (R angles15
< 1°), but the â angles of 4.0° {C(25)-C(22)-Du(3)16} and
4.6° {C(18)-C(19)-Du(4)16} are significant. The direction
of this distortion is such that the p-xylyl unit is bowed toward
the concave face of the pyrene unit. Although this effect is
small, it is opposite to what is normally observed in small
cyclophanes, in which face-to-face situated arenes are bowed
away from one another.17 In fact we are not aware of any
other “spoons-like” arrangement of arenes within the same
molecule.
The bridges are close to being fully eclipsed, the torsion
angles about the central C-C bonds being 1(1)° {C(1)-
C(26)-C(25)-C(22)} and 7(1)° {C(15)-C(17)-C(18)-
C(19)}. As a result, the pyrene and benzene decks are almost
perfectly aligned. The most striking feature of the bridges is
the unusually large bond angles at the carbon atoms benzylic
to the benzene ring.18 These are 123.7(5)° {C(22)-C(25)-
C(26)} and 124.8(6)° {C(17)-C(18)-C(19)}, which is
(14) Crystal data for 5: colorless prism (0.30 × 0.15 × 0.40 mm3) from
heptane, C26H20, Mr ) 332.44, orthorhombic, P212121 (No. 19), a ) 12.451-
(2), b ) 15.773(3), c ) 9.203(2) Å, V ) 1807.4(5) Å3, Z ) 4,•dcalc
)
1.222 g cm-3, F(000) ) 704, µ(Cu KR) ) 5.20 cm-1, T ) 299 K, Rigaku
AFC6S diffractometer, graphite-monochromated Cu KR radiation (λ )
1.54178 Å), ω-2θ scan type with ω scan width ) 0.84 + 0.14 tan θ, ω
scan speed 4.0° min-1 (up to five rescans for weak reflections), 1577
reflections measured, empirical absorption correction (max, min corrections
) 1.00, 0.93), secondary extinction correction (coefficient ) 1.79589 ×
10-5), giving 1556 with I > 0.00σ(I). Solution and refinement by direct
methods using the teXsan package (Molecular Structure Corporation); all
non-hydrogen atoms refined anisotropically; hydrogens included in calcu-
lated positions but not refined; full matrix least squares refinement on F2
with 284 variable parameters led to R1 ) 0.059, wR2 ) 0.085, GOF )
1.84. CCDC-160393.
(16) In determining â angles, the following dummy atoms (Du) were
placed in the structure: Du(1) at the C(2)-C(6) centroid; Du(2) at the
C(14)-C(16) centroid; Du(3) at the C(21)-C(23) centroid; Du(4) at the
C(20)-C(24) centroid.
(17) (a) Cyclophanes, Vols. 1 and 2; Keehn, P. M., Rosenfeld, S. M.,
Eds.; Academic Press: New York, 1983. (b) Vo¨gtle, F. Cyclophan-Chemie;
B. G. Teubner: Stuttgart, 1990. (c) Diederich, F. N. Cyclophanes; Royal
Society of Chemistry: London, 1991. (d) Hopf, H. Classics in Hydrocarbon
Chemistry; Wiley-VCH: Weinheim, 2000.
(15) The angles R and â used here are directly analogous to those used
for smaller cyclophanes, such as the [n]paracyclophanes. See ref 17.
Org. Lett., Vol. 3, No. 13, 2001
2095

substantially higher than those in the AM1 calculated
structure (117.7° for both). It would appear as though the
origin of these large bond angles is related to the inward
bowing effect discussed above. Normal tetrahedral angles
about C(18) and C(25) would cause the benzene deck to be
pushed up well into the concave face of the pyrene deck.
Repulsions between the π clouds of the opposing arenes
presumably disfavor the adoption of this arrangement, and
the bond angles at C(18) and C(25) are forced open as the
benzene ring is repelled from the pyrene moiety. A further
unusual feature of the bridge is the unexpectedly short bond
lengths in the central bonds, i.e., 1.468(9) Å for C(25)-
C(26) and 1.439(8) Å for C(17)-C(18).18 The remaining
bond lengths in the bridges are within the normal range
(1.50-1.52 Å). The AM1 calculations on 5 do not predict
any unusual bond lengths in the bridges.
Having established that 5 is an accessible system, we are
now working toward the synthesis of related systems that
will bring us closer to our ultimate goal of the Vo¨gtle belts.
Pyrenophane 20 has the same basic skeleton of 5 and is a
direct precursor (via valence isomerization of the Dewar
benzene moieties to benzene systems) to a 34-carbon
fragment of D5h C70, which is a belt consisting of a (2,7)-
pyrenyl and three p-phenylene units (Figure 3). The synthesis
The 1H NMR spectrum of pyrenophane 5 contains signals
for the pyrene system at δ 7.67 and 7.40, which are
comparable to those of [8](2,7)pyrenophane1 (θ ) 80.8°, δ
7.84 and 7.59), and 1,8-dioxa[8](2,7)pyrenophane (θ ) 87.8°,
δ 7.84 and 7.44).2 However, the signal for the benzene deck
is observed at δ 5.54, roughly 1.5 ppm upfield from the
corresponding signals of p-xylene (δ 7.07). That pyrene is,
as a whole, much broader than benzene accounts for the
observation that the protons of the benzene ring are shielded
by the pyrene moiety, but those of the pyrene moiety appear
to experience little magnetic anisotropy from the benzene
ring.
Figure 3.
of 20 poses a stiff challenge, but cyclophanediene 21 or
related systems, which may be accessible using an approach
similar to that described above, may serve as useful progeni-
tors. We are also pursuing the synthesis of pyrenophanes
such as 22, in which two p-phenylene units have been
inserted into the bridge of 3.
Acknowledgment. Support of this work from the Natural
Sciences and Engineering Research Council (NSERC) of
Canada and PetroCanada is gratefully acknowledged.
(18) The somewhat large thermal ellipsoids at C(25) and (especially)
C(18) mean that the exact values of the measured bond angles and lengths
should not be viewed with a high degree of confidence, but there is little
doubt that the bond angles are indeed unusually large and the bonds
unusually short.
OL016053I
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Org. Lett., Vol. 3, No. 13, 2001