Synthesis and Structure of a New [6.6]Metacyclophane with Enediyne Bridges

Article abstract of DOI:10.1021/ol006570l

Formula presented Synthesis and structure of a novel [6.6]metacyclophane with enediyne bridges is reported. ? Dedicated to Professor Dr. Henning Hopf on the occasion of his 60th birthday.

Full text of DOI:10.1021/ol006570l

ORGANIC
LETTERS
2000
Vol. 2, No. 24
3849-3851
Synthesis and Structure of a New
[6.6]Metacyclophane with Enediyne
Bridges†
,‡
Manivannan Srinivasan,‡ Sethuraman Sankararaman,* Ina Dix,§ and
Peter G. Jones|
Department of Chemistry, Indian Institute of Technology, Madras-600 036, India,
Institute of Organic Chemistry, UniVersity of Braunschweig, D-38106, Germany, and
Institute of Analytical and Inorganic Chemistry, UniVersity of Braunschweig,
D-38106, Germany
sanka@acer.iitm.ernet.in
Received September 10, 2000
ABSTRACT
Synthesis and structure of a novel [6.6]metacyclophane with enediyne bridges is reported.
The chemistry of enediynes gained prominence among
synthetic and theoretical chemists and also biologists after
the discovery of enediyne antibiotics during the late 1980s.1
Several synthetic model systems have been prepared incor-
porating the basic enediyne skeleton, namely, the hexa-3-
ene-1,5-diyne unit, in order to study the mechanism of
thermally induced cycloaromatization, commonly known as
the Bergman cyclization.2 Synthesis of extended cyclophanes
is another area3 that is actively pursued by synthetic chemists,
and in recent years several cyclophanes bearing extended
acetylenic units as bridges have been constructed.4 Some of
these cyclophanes serve as precursors for the synthesis of
fullerenes, their subunits, graphyne subunits, and nanotubes.5
Cyclophanes bearing enediyne units as the bridges (ene-
diynephanes) offer enormous potential to study both of these
areas in a single system. For example, the strain and the
distance between the termini of the enediyne unit, which is
(3) Hopf, H. Classics in Hydrocarbon Chemistry. Synthesis, Concepts,
PerspectiVes; Wiley-VCH: Weinheim, 2000; Chapter 15, pp 457-472.
Young, J. K.; Moore, J. S. In Modern Acetylenic Chemistry; Stang, P. J.,
Diederich, F., Eds.; VCH: Weinheim, 1995; Chapter 12, pp 426-432.
Zhang, J.; Pesak, D. J.; Ludwick, J. L.; Moore, J. S. J. Am. Chem. Soc.
1994, 116, 4227-4239.
(4) Haley, M. Synlett 1998, 557-565. Kehoe, J. M.; Kiley, J. H.; English,
J. J.; Johnson, C. A.; Petersen, R. C.; Haley, M. M. Org. Lett. 2000, 2,
969-972. Bodwell, G. J.; Houghton, T. J.; Miller, D. Tetrahedron Lett.
1998, 39, 2231-2234. Ensley, H. E.; Mahadevan, S.; Mague, J. Tetrahedron
Lett. 1996, 37, 6255-6258. Hopf, H.; Jones, P. G.; Bubenitschek, P.;
Werner, C. Angew. Chem., Int. Ed. Engl. 1995, 34, 2367-2370. Collins,
S. K.; Yap, G. P. A.; Fallis, A. G. Angew. Chem., Int. Ed. 2000, 29, 385-
388. Kawase, T.; Ueda, N.; Oda, M. Tetrahedron Lett. 1997, 38, 6681-
6684. Yamaguchi, Y.; Kobayashi, S.; Wakamiya, T.; Matsubara, Y.;
Yoshida, Z. J. Am. Chem. Soc. 2000, 122, 7404-7405.
† Dedicated to Professor Dr. Henning Hopf on the occasion of his 60th
birthday.
‡ Indian Institute of Technology.
§ Institute of Organic Chemistry, University of Braunschweig.
| Institute of Analytical and Inorganic Chemistry, University of Braun-
schweig.
(1) For reviews, see: Nicolaou, K. C.; Smith, A. L. In Modern Acetylenic
Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim, 1995; Chapter
7, pp 203-283. Maier, M. E. Synlett 1995, 13-26. Nicolaou, K. C.; Smith,
A. L. Acc. Chem. Res. 1992, 25, 497-503. Nicolaou, K. C.; Dai, W.-M.
Angew. Chem., Int. Ed. Engl. 1991, 30, 1387-1416.
(2) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25-31. Jones, R. R.;
Bergman, R. G. J. Am. Chem. Soc. 1972, 94, 660-661.
(5) Rubin, Y.; Parker, T. C.; Khan, S. I.; Holliman, C. L.; McElvany, S.
W. J. Am. Chem. Soc. 1996, 118, 5308-5309. Jux, N.; Holczer, K.; Rubin,
Y. Angew. Chem., Int. Ed. Engl. 1996, 35, 1986-1990. Anthony, J. E.;
Khan, S. I.; Rubin, Y. Tetrahedron Lett. 1997, 38, 3499-3502. Dosa, P.
I.; Erben, C.; Iyer, V. S.; Vollhardt, K. P. C.; Wasser, I. M. J. Am. Chem.
Soc. 1999, 121, 10430-10431. Boese, R.; Matzger, A. J.; Vollhardt, K. P.
C. J. Am. Chem. Soc. 1997, 119, 2052-2053.
10.1021/ol006570l CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/02/2000

one among the factors responsible for its reactivity, and the
structure and conformation of the extended cyclophanes can
be easily manipulated by the phane connectivity and sub-
stituents present in the aromatic and the bridging units.
Besides, synthesis of isomeric [6.6] enediynephanes and
multibridged [6n] enediynephanes offers challenge to the
synthetic chemists. Although several enediynephanes are
known, the enediyne units in these cyclophanes are invariably
connected to the aromatic units through a heteroatom, either
oxygen, nitrogen, or sulfur.6 Cyclophanes in which the
enediyne bridges are directly connected to the aromatic unit
through C-C bonds are rare, although they have been
postulated as intermediates in Bergman cyclization. In their
classical work on cycloaromatization of polyeneyne systems
Sondheimer7 and Masamune8 have proposed aromatic ene-
diynes as intermediates during the Bergman cyclization.
These intermediates could well be regarded as ortho ene-
diynephanes, and as a result of the strain associated with
these cyclic enediynes they undergo cyclization spontane-
ously at ambient conditions. Herein we report the synthesis
and structure of a novel [6.6]metaenediynephane, namely,
[6.6]metacyclophan-3,15-diene-1,5,13,17-tetrayne.
Scheme 2
The Pd(0)-mediated coupling of (Z)-1,2-dichloroethene (1)
with 1,3-diethynylbenzene (2) under high dilution condition
yielded the desired metaenediynephane (3) albeit in very low
yield of 2% (Scheme 1).
Therefore, aldehyde 4 was protected using ethylene gylcol
to the acetal 5 (93%), which underwent coupling reaction
with 1 smoothly to furnish the bisacetal 6 (67%). Hydrolysis
of the bisacetal 6 using hydrated ferric chloride yielded the
dialdehyde 7, although in a moderate yield of 32%. The
bisacetal 6 was resistant to hydrolysis with aqueous oxalic
acid and 3 N HCl. The dialdehdye 7 in which one of the
enediyne bridge is already in place in the cis configuration
is ideally suited for the construction of the second bridge
through McMurry coupling, which offers a convenient
methodology for the construction of medium- and large-ring
alkenes in good yields.9 The McMurry coupling of 7 using
TiCl3 and Zn-Cu couple in DME at -78 °C yielded the
target metaenediynephane 3 as the sole product in 69% yield.
Enediynephane 3 is a pale yellow solid and is highly
fluorescent, as would be expected for a fully conjugated rigid
planar system. In the electronic absorption spectrum of 3
well resolved absorption bands at 224, 244, 300, 316 (sh),
328 (sh), 338, 350, and 363 nm are observed in cyclohexane.
Excitation of 3 at any one of the absorption bands above
300 nm gives identical fluorescence spectra showing emis-
sion maxima at 384 (sh), 398, 408, 434, and 446 (sh) nm,
Scheme 1
Therefore, an alternative five-step route was executed in
which the enediyne bridges were constructed in a stepwise
manner (Scheme 2). 1,3-Diethynylbenzene (2) was converted
into the monoaldehyde 4 using ethylmagnesium bromide and
DMF in 52% yield along with the corresponding bisaldehyde
(16%). Attempted McMurry coupling of the bisaldehyde to
3 lead to intractable material. Also, attempted Pd(0)-mediated
coupling of the monoaldehdye 4 with 1 resulted in uniden-
tifiable mixture of products, and none of the desired
dialdehyde 7 was obtained.
1
and the fluorescence quantum yield (Φf) is 0.42. In the H
NMR spectrum of 3 the intra-annular protons appear as a
singlet at δ 7.82, more deshielded than the rest of the
aromatic protons, which appear between δ 7.15 and 7.4, and
the olefinic protons appear as a singlet at δ 6.05. In the mass
spectrum of 3 the molecular ion peak at m/z 300 appears as
(6) Ko¨nig, B.; Pitsch, W.; Thondorf, I. J. Org. Chem. 1996, 61, 4258-
4261. Ko¨nig, B.; Hollnagel, H.; Ahrens, B.; Jones, P. G. Angew. Chem.
1995, 107, 2763-2765. For a review, see: Ko¨nig, B. Eur. J. Org. Chem.
2000, 381-385.
(7) Wong, H. N. C.; Sondheimer, F. Tetrahedron Lett. 1980, 21, 217-
220.
(8) Darby, N.; Kim, C. U.; Salauen, J. A.; Shelton, K. W.; Takada, S.;
Masamune, S. J. Chem. Soc., Chem. Comm. 1971, 1516-1517. Also see
Sander, W. Acc. Chem. Res. 1999, 32, 669-676 for the generation of highly
strained cyclic enediynes and diendiynes.
(9) McMurry, J. E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. J. Org.
Chem. 1978, 43, 3255-3266. Baumstark, A. L.; McClosky, C. J.; Witt, K.
E. J. Org. Chem. 1978, 43, 3609-3611.
3850
Org. Lett., Vol. 2, No. 24, 2000

the base peak, and the salient feature of the spectrum is that
the intensity of the fragment ions are very weak. The
structure of 3 was confirmed by single-crystal X-ray dif-
fraction data,10 and Figure 1 shows the structure of 3 in the
crystal.
between the layers is 547.7 pm. Along the Z-axis an ABAB
arrangement of two layers is observed, and the angle between
the two layers is 71.18°. The calculated energy minimized
structure based on semiempirical AM1 calculations is nearly
identical to the X-ray structure.
Currently we are investigating the synthesis of the corre-
sponding ortho and para isomers of 3 and the effect of intra-
annular substituents (C-9, Figure 1) on the structure and
conformation of the phane and the reactivity of the enediyne
bridge.
Acknowledgment. This work is supported by the Volks-
wagen Stiftung, Germany. The authors thank the Indian
Institute of Technology, Madras (M.S.) and the Alexander
von Humboldt Stiftung (S.S.) for research fellowships. The
altruistic support and encouragement of Prof. Dr. Henning
Hopf is gratefully acknowledged.
Supporting Information Available: Experimental pro-
cedure for the synthesis of 3, excitation and emission spectra
of 3, and complete spectroscopic characterization data for
compounds 3-7. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL006570L
(10) Crystallographic data for 3. Data collection was performed on a
Siemens P4 diffractometer with the ω-scan method using a graphite
monochromator for Mo KR radiation (λ ) 0.71073 Å). The structure was
solved by direct method and refined anisotropically on F2 using all
reflections.11 C24H12, MW ) 300.34, monoclinic, space group P21/n, a )
1002.0 (3), b ) 545.72 (16), c ) 1501.3 (4) pm, R ) γ ) 90°, â )
102.934(6)°, V ) 0.8001 (4) nm3, Z ) 2, Fcalc ) 1.247 Mg m-3, µ ) 0.071
mm-1, reflections measured 4836, unique reflections 1631, 2θmax ) 52°, T
) 143 K, Rint ) 0.0397, R ) 0.0613 and Rw ) 0.0889. Further details of
the crystal structure investigation may be obtained from the Director of the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, U.K. on quoting the full journal citation.11 Sheldrick, G. M. SHELXL-
97 A Program for Crystal Structure Refinements, University of Gottingen,
1997.
Figure 1. Structure of 3 in the crystal.
The structure is nearly planar, and it belongs to D2h point
group symmetry. The distance between the intra-annular
hydrogens is 251.7 pm. The distance between the acetylenic
termini of the bridge is 427.6 pm. In the crystal lattice there
are layers in the packing, and along the Y-axis the molecules
are stacked exactly on one another. The mean distance
Org. Lett., Vol. 2, No. 24, 2000
3851