(2,2′)(2,2′)Biphenylophanetriyne: A Twisted Biphenylophane with a Highly Distorted Diacetylene Bridge

Article abstract of DOI:10.1021/ol5004934

Biphenylophane 1 bridged by acetylene and diacetylene linkages was synthesized. X-ray analysis revealed its highly deformed diacetylene unit with a bond angle of 160°. Enantiomers of 1 resolved by chiral HPLC underwent facile racemization with an activation energy of 90.6 kJ mol^-1. Transannular cyclization of 1 was induced by heating to generate benzyne intermediate 8, which was intercepted by furan to give 9, and by treatment with bromine to give dibromodibenzopicene (10).

Full text of DOI:10.1021/ol5004934

Letter
pubs.acs.org/OrgLett
[4.2](2,2′)(2,2′)Biphenylophanetriyne: A Twisted Biphenylophane
with a Highly Distorted Diacetylene Bridge
Shunpei Nobusue,† Hiroshi Yamane, Hirokazu Miyoshi, and Yoshito Tobe*
Division of Frontier Materials Science, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan
S
* Supporting Information
ABSTRACT: Biphenylophane 1 bridged by acetylene and
diacetylene linkages was synthesized. X-ray analysis revealed its
highly deformed diacetylene unit with a bond angle of 160°.
Enantiomers of 1 resolved by chiral HPLC underwent facile
racemization with an activation energy of 90.6 kJ mol−1.
Transannular cyclization of 1 was induced by heating to generate
benzyne intermediate 8, which was intercepted by furan to give 9,
and by treatment with bromine to give dibromodibenzopicene
(10).
iphenylophanes and analogous binaphthylophanes belong
to a unique class of cyclophanes in which biphenyl or
a Ni-catalyzed [2 + 2 + 2] cyclotrimerization approach from
B
structurally related acyclic precursors was reported by Stara
́
and
binaphthyl units are connected by single, double, or triple
bonds. They have attracted considerable interest with regard to
their strain and optical and electronic properties associated with
their twisted geometry.1 In particular, biphenylophanes bridged
by triple bond linkages serve as good models for the study of
stereochemical issues because of their limited conformational
mobility.1f,g,2 Additionally, facile intramolecular bond formation
between the closely located triple bonds leads to structurally
novel polycyclic aromatic compounds which are otherwise
difficult to obtain.3 Although a number of acetylene-bridged
biphenylophanes are known,1f,g,2,3 those with diacetylene
linkages have been scarcely reported.4 Here we report (i) the
synthesis of biphenylophane 1 (Figure 1), in which two
Stary very recently.5
Synthesis of 1 was carried out as outlined in Scheme 1.
Cross-coupling of diboronic acid 3,6 prepared by double
Scheme 1. Synthesis of 1
Figure 1. Chemical structures of biphenylophanes 1 and 2.
biphenyl units are bridged at the 2,2′-position by acetylene and
diacetylene linkages, (ii) its molecular structure with a highly
distorted diacetylene bridge, (iii) optical resolution and kinetics
of racemization that occurs via ring inversion, and (iv)
intramolecular bond formation induced by heating or treatment
with bromine leading to dibenzopicene derivatives. We
envisioned that introduction of a diacetylene bridge into the
biphenylophane framework would not only affect the barrier for
ring inversion compared to the known biphenylophane 2 with
two acetylene linkages2 but also enhance the reactivity toward
intramolecular bond formation due to the enhanced reactivity
of the highly distorted diacetylene bridge. With regard to the
intramolecular cycloaddition of 1, it should be pointed out that
lithiation of diphenylethyne,7 with o-bromobenzaldehyde gave
4, which was converted to triyne 6 via 5 by the Corey−Fuchs
method.8 The same triyne 6 was prepared via a different
synthetic route.5 Copper(II)-mediated oxidative coupling of 6
furnished 19 in 51% yield as a light yellow solid which was
stable in the air for months. Substantial deformation of the
triple bonds of the diacetylene unit of 1 manifests itself in the
chemical shift of the 13C NMR signal of the sp carbon atom
adjacent to the benzene ring, which appears at 96.6 (or 93.3)
Received: February 16, 2014
Published: March 14, 2014
© 2014 American Chemical Society
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Letter
ppm. Downfield shifts due to polarization of triple bonds
enforced to adopt bent geometries have been well docu-
mented.10−12 Compound 1 exhibits an absorption maxima in
CH2Cl2 at ca. 305 (sh, ε ca. 4800) and 273 nm (ε 13 000) with
an absorption tail ending at ca. 400 nm (Figure S1). However,
compound 1 does not fluoresce.
Crystals suitable for X-ray structure analysis were obtained by
recrystallization from benzene−acetonitrile. As shown in Figure
S2, the unit cell contains two pairs of enantiomeric forms of
independent molecules A and B (Z = 8), whose structures are
slightly different. Two side views of the molecular structure of
molecule A are shown in Figure 2. Table 1 lists selected
reproduces the observed parameters. The most notable
structural feature is the small bond angle (159.3(2)°) at C6−
C7−C8 of molecule A, which to our knowledge represents one
of the most distorted diacetylene bonds. The previously known
small bond angles of diacetylene units (<160°) were those
found in an enyne macrocycle11 and an ortho,meta-cyclo-
phane.12 The bond lengths of 1 however are within the normal
range. Compared with molecule A, the triple bonds of molecule
B are slightly less deformed from linearity due the larger
dihedral angle at the biphenyl unit which makes the distance
between the bridged carbons (C5−C10) longer. Another
aspect worth mentioning is the short interatomic distances
between the transannular sp carbons which are below the sum
of van der Waals radii of carbon.
Resolution of the enantiomers of 1 was performed by using a
CHIRALPAK IA column (10 mm ϕ × 250 mm) and hexane/
CH2Cl2 (10/1) as eluent at 15 °C (Figure S3). CD spectra of
the first and second fractions measured in 1,2-dichloroethane at
15 °C exhibit the same profiles with opposite polarity as shown
in Figure 3, indicating that these fractions contain enantiomers.
Figure 2. ORTEP drawing of 1 (Molecule A): (a) a side view with
numbering and (b) another side view. Displacement ellipsoids are
drawn at 50% probability level.
Table 1. Selected Parameters for Experimental and
Theoretical Structures of 1
a
Figure 3. CD spectra of enantiomers of 1 in 1,2-dichloroethane.
b
experimental
However, the peak intensities decreased upon standing the
solution at room temperature (Figure S4), suggesting that the
racemization took place with a relatively low activation energy
similar to the case of biphenylophane 2.2c The decrease of the
CD intensities at 19.8, 25.1, and 30.0 °C was monitored from
which the racemization rates were determined (Table 2). The
c
molecule A
molecule B
theoretical
bond angle/deg
C5−C6−C7
C8−C9−C10
C6−C7−C8
C7−C8−C9
166.7(2)
169.7(2)
159.3(3)
160.8(2)
168.8(2)
170.9(2)
161.5(2)
162.0(2)
169.1
169.1
161.9
161.9
Table 2. Rates of Racemization of 1 in Dichloroethane
interatomic distance/Å
C1−C6
C9−C14
C1−C7
C8−C14
temperature/°C
k/10−3 s−1
3.01
3.03
3.02
3.07
3.07
3.09
3.08
3.10
3.15
3.15
3.17
3.17
19.8
25.1
30.0
2.49 0.23
4.64 0.16
8.73 0.20
dihedral angle/deg
C2−C3−C4-C5
C10−C11−C12-C13
activation energy for the racemization of 1 was calculated to be
90.6 4.2 kJ mol−1, a value which was only slightly smaller
than that for the racemization of 2 (93.2 kJ mol−1),2c despite
the larger flexibility of 1 due to the longer diacetylene bridge.
The transition state for the racemization was elucidated
theoretically by changing the dihedral angle (ϕ1) of one of
the biphenyl units using the same method (the M05-2X/6-
31G(d) level of theory) reported by Toyota (for the detail of
calculations, see Supporting Information).2c As a result, the
transition state was located at the geometry with ϕ1 = −23.0°
(ϕ2 = 59.5°) with an energy 93.3 kJ mol−1 higher than the
global minimum in reasonable agreement with the experimental
value. In the transition state geometry, the most distorted
60.9(3)
56.3(3)
61.5(3)
62.9
62.9
62.8(3)
b
a
Numbering for carbons is shown in Figure 2a. X-ray crystallographic
c
structure analysis. DFT calculations at the B3LYP/6-31G(d) level of
theory.
structural parameters, i.e. the bond angles of the diacetylene
unit, the nonbonded interatomic distances between the sp
carbons, and the inner dihedral angles of the biphenyl unit. For
comparison, the parameters for the theoretical structure of 1
optimized by DFT calculations at the B3LYP/6-31G(d) level of
theory are also included. The calculated structure reasonably
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Letter
acetylenic bond is that of the acetylene linkage (C2−C1−C14)
with a bond angle of 159.1°, contrary to the ground state
structure (Figure S6). On the other hand, the bond angles at
the center of the diacetylene bridge are 162.3° (C6−C7−C8)
and 161.6° (C7−C8−C9), which are similar to those of the
ground state structure.
dibenzopicene framework due to the higher degree of
unsaturation in the staring material.
In summary, we synthesized biphenylophane 1, in which two
biphenyl units were bridged at the 2,2′-position by acetylene
and diacetylene linkages, and revealed that it has the most
highly deformed diacetylene unit with a bond angle of 160°.
Enantiomers of 1 were successfully resolved, while they
underwent facile racemization with an activation energy of
90.6 kJ mol−1. Heating a solution of 1 at 70 °C brought about
intramolecular cycloaddition to generate benzyne intermediate
8, which was intercepted by furan to give [4 + 2] adduct 9.
Transannular cyclization was also induced by an electrophile
giving dibromodibenzopicene (10).
Finally, transannular bond formation reactions of 1 were
examined. Heating a degassed 1,2-dichloroethane solution of 1
at 70 °C resulted in the formation of a complex mixture of
products including small amounts of dibenzopicene (7a, 6%)13
and its chloro derivative 7b (5%), suggesting the presence of
benzyne intermediate 8 which abstracted hydrogen and/or
chlorine atoms from the solvent. Whereas the formation of
benzyne intermediates by intramolecular cycloaddition between
two diacetylene units, in which one acted as a formal 2π
component, has been well documented,14 such reactions
between an electronically nonactivated acetylene and a
diacetylene are rare.15 Indeed, it has been estimated
theoretically that the barrier for the acetylene−diacetylene [4
+ 2] addition, which proceeds by either a concerted or stepwise
mechanism, is considerably high (153 or 155 kJ mol−1,
respectively).16 Experimentally, a high activation energy was
required to bring about this reaction even in an intramolecular
fashion.15 The relatively low temperature required for the
thermal reaction of 1 is therefore ascribed to the large strain
imposed on the diacetylene unit and the close proximity of the
reaction centers. To intercept 8, the reaction was carried out in
furan at 70 °C to give [4 + 2] adduct 917 in 54% yield (Scheme
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details for the synthesis of new compounds,
resolution of enantiomers, and racemization kinetics of 1,
details and the CIF file for the X-ray crystallographic analysis of
1, computational details for racemization process of 1, and
NMR spectra of 1, 4−6, 7b, 9, and 10. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: tobe@chem.es.osaka-u.ac.jp.
Present Address
1
2). In the H NMR spectrum of 9, two sets of signals for
†Department of Chemistry, Graduate School of Science,
Nagoya University, Furo, Chikusa, Nagoya, Aichi 464-8602,
Japan.
Scheme 2. Transannular Cyclizations of 1
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by The Grant-in-Aid for Scientific
Research on Innovative Areas “Organic Synthesis based on
Reaction Integration” (No. 2105).
REFERENCES
■
(1) (a) Reiss, J. A. In Cyclophanes; Keehn, P. M., Rosenfeld, S. M.,
Eds.; Academic Press: New York, 1983; Vol. II, pp 443−484.
(b) Niederalt, C.; Grimme, S.; Peyerimhoff, S. D.; Sobanski, A.;
diastereotopic protons are observed for aromatic, vinyl, and sp3
methine groups (see Supporting Information) indicating that 9
adopts C1 symmetry. This observation is interpreted by the
slow flipping of the [5]helicene part of the molecule on the
NMR time scale in accordance with the reported barrier of
racemization of [5]helicene (98.2 kJ mol−1).18
Since transannular cyclization of cyclic aryleneethynylens
induced by an electrophile has been known to produce unique
π-conjugated systems,19 the reaction of 1 with bromine was
examined. As expected, treatment of 1 with bromine at room
temperature gave dibromodibenzopicene (10)20 in 55%
isolated yield. As a synthetic method, the overall efficiency of
the thermal and electrophile-induced cyclizations of 1 to
dibenzopicenes 9 and 10 is less effective than the recently
reported [2 + 2 + 2] cyclotrimerization approach from acyclic
precursors such as 6.4 However, the present method may have
an advantage in view of the potential to introduce various
functional groups at the central aromatic ring of the
Vogtle, F.; Lutz, M.; Spek, A. L.; van Eis, M. J.; de Wolf, W. H.;
̈
Bickelhaupt, F. Tetrahedron: Asymmetry 1999, 10, 2153−2164. (c) An,
D. L.; Nakano, T.; Orita, A.; Otera, J. Angew. Chem., Int. Ed. 2002, 41,
171−173. (d) An, D.-L.; Zhang, Y.-J.; Chen, Q.; Zhao, W.-Y.; Yan, H.;
Orita, A.; Otera, J. Chem.Asian J. 2007, 2, 1299−1304. (e) Orita, A.;
An, D. L.; Nakano, T.; Yaruva, J.; Ma, N.; Otera, J. Chem.Eur. J.
2002, 8, 2005−2010. (f) Marsella, M. J.; Kim, I. T.; Tham, F. J. Am.
Chem. Soc. 2000, 122, 974−975. (g) Marsella, M. J.; Piao, G.; Tham, F.
S. Synthesis 2002, 1133−1135.
(2) (a) Staab, H. A.; Wehinger, E. Angew. Chem., Int. Ed. 1968, 7,
225−226. (b) Staab, H. A.; Wehinger, E.; Thorwart, W. Chem. Ber.
1972, 105, 2290−2309. (c) Toyota, S.; Kawai, K.; Iwanaga, T.;
Wakamatsu, K. Eur. J. Org. Chem. 2012, 5679−5684. (d) Utsumi, K.;
Kawase, T.; Oda, M. Chem. Lett. 2003, 32, 412−413.
(3) Fukazawa, A.; Oshima, H.; Shiota, Y.; Takahashi, S.; Yoshizawa,
K.; Yamaguchi, S. J. Am. Chem. Soc. 2013, 135, 1731−1734.
(4) (a) Anderson, S.; Neidlein, U.; Gramlich, V.; Diederich, F. Angew.
Chem., Int. Ed. 1995, 34, 1596−1600. (b) Campbell, K.; Tykwinski, R.
R. In Carbon-Rich Compounds; Haley, M. M., Tykwinski, R. R., Eds.;
Wiley-VCH: Weinheim, 2006; pp 229−294.
1942
dx.doi.org/10.1021/ol5004934 | Org. Lett. 2014, 16, 1940−1943

Organic Letters
Letter
(5) Janca
J.; Pohl, R.; Bednar
̌
rí
̌
k, A.; Rybac
́
e
̌
k, J.; Cocq, K.; Chocholouso
̌
va,
́
J. V.; Vacek,
́
ova, L.; Fielder, P.; Císaro
́
̌
va, I.; Stara,
́
́
I. G.; Stary, I.
́
Angew. Chem., Int. Ed. 2013, 52, 9970−9975.
(6) Letsinger, R. L.; Nazy, J. R. J. Am. Chem. Soc. 1959, 81, 3013−
3017.
(7) Kowalik, J.; Tolbert, L. M. J. Org. Chem. 2001, 66, 3229−3231.
(8) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769−3772.
1
(9) Compound 1: H NMR (400 MHz, CDCl3) δ 7.50−7.45 (m,
2H), 7.42−7.34 (m, 10H), 7.26−7.25 (m, 2H), 7.19 (d, J = 7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 146.1, 141.6, 133.9, 132.2,
131.3, 129.6, 129.1, 128.1, 127.48, 127.47, 123.4, 121.8, 96.6, 93.3,
82.7.
(10) (a) Kawase, T.; Darabi, H. R.; Oda, M. Angew. Chem., Int. Ed.
1996, 35, 2664−2666. (b) Hisaki, I.; Sonoda, M.; Tobe, Y. Eur. J. Org.
Chem. 2006, 833−847.
(11) Eisler, S.; McDonald, R.; Loppnow, G. R.; Tykwinski, R. R. J.
Am. Chem. Soc. 2000, 122, 6917−6928.
(12) Collins, S. K.; Yap, G. P. A.; Fallis, A. G. Org. Lett. 2002, 4, 11−
14.
(13) (a) Jenard-De Koninck, A.; Defaym, N.; De Ridder, R. Bull. Soc.
Chim. Belg. 1960, 69, 558−562. (b) Seibel, J.; Allemann, O.; Siegel, J.
S.; Ernst, K.-H. J. Am. Chem. Soc. 2013, 135, 7434−7437.
(14) (a) Miyawaki, K.; Suzuki, R.; Kawano, T.; Ueda, I. Tetrahedron
Lett. 1997, 38, 3943−3946. (b) Miyawaki, K.; Kawano, Y.; Ueda, I.
Tetrahedron Lett. 1998, 39, 6923−6926. (c) Miyawaki, K.; Kawano, T.;
Ueda, I. Tetrahedron Lett. 2000, 41, 1447−1451. (d) Tsui, J. A.;
Sterenberg, B. T. Organometallics 2009, 28, 4906−4908. (e) Hoye, T.
R.; Baire, B.; Niu, D.; Willoughby, P. H.; Woods, B. P. Nature 2012,
490, 208−212. (f) Baire, B.; Niu, D.; Willoughby, P. H.; Woods, B. P.;
Hoye, T. R. Nat. Protoc. 2013, 8, 501−508.
(15) Bradley, A. Z.; Johnson, R. P. J. Am. Chem. Soc. 1997, 119,
9917−9918.
(16) Ajaz, A.; Bradley, A. Z.; Burrell, R. C.; Li, W. H. H.; Daoust, K.
J.; Bovee, L. B.; DiRico, K. J.; Johnson, R. P. J. Org. Chem. 2011, 76,
9320−9328.
(17) Compound 9: 1H NMR (400 MHz, CDCl3) δ 8.68 (dd, J = 6.2,
3.4 Hz, 1H), 8.64−8.61 (m, 1H), 8.54 (dd, J = 6.2, 3.4 Hz, 1H), 8.48
(d, J = 8.0 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H),
8.06 (dd, J = 8.4 Hz, 1H), 8.00−7.98 (m, 1H), 7.75−7.72 (m, 4H),
7.69 (dd, J = 5.6, 1.6 Hz, 1H), 7.60 (dd, J = 5.6, 1.6 Hz, 1H), 7.50−
7.43 (m, 2H), 7.14−7.09 (m, 2H), 6.96 (s, 1H), 6.60 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 146.7, 146.3, 144.1, 144.0, 132.7, 132.6,
131.4,131.3, 130.3, 129.9, 129.6, 129.5, 127.79, 127.76, 127.6, 127.44,
127.39, 127.35, 127.3, 127.1, 126.7, 126.5, 126.32, 126.26, 125.6,
123.9, 123.8, 123.6, 123.5, 84.7, 83.5.
(18) Geodicke, Ch.; Stegemeyer, H. Tetrahedron Lett. 1970, 937−
940.
(19) (a) Zhou, Q.; Carroll, P. J.; Swager, T. M. J. Org. Chem. 1994,
59, 1294−1301. (b) Takeda, T.; Inukai, K.; Tahara, K.; Tobe, Y. J. Org.
Chem. 2011, 76, 9116−9121. (c) Umeda, R.; Hibi, D.; Miki, K.; Tobe,
Y. Org. Lett. 2009, 11, 4104−4106. (d) Xu, F.; Peng, L.; Orita, A.;
Otera, J. Org. Lett. 2012, 14, 3970−3973.
(20) Compound 10: 1H NMR (400 MHz, CDCl3) δ 9.29 (d, J = 8.4
Hz, 2H), 8.56 (d, J = 8.0 Hz, 2H), 8.46 (d, J = 8.0 Hz, 2H), 8.00 (d, J
= 8.4 Hz, 2H), 7.73 (ddd, J = 8.0, 8.0, 0.8 Hz, 2H), 7.62 (ddd, J = 8.0,
8.0, 0.8 Hz, 2H), 7.50 (ddd, J = 8.0, 8.0, 0.8 Hz, 2H), 7.15 (ddd, J =
8.0, 8.0, 0.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 131.5, 131.4,
131.1, 130.7, 130.1, 129.5, 129.2, 128.9, 128.0, 127.8, 126.1, 125.3,
123.7, 123.2, 123.0.
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