Fulvenes from Enediynes: Regioselective Electrophilic Domino and Tandem Cyclizations of Enynes and Oligoynes

Article abstract of DOI:10.1002/anie.200351195

Complementary products: the electrophilic cyclizations of ortho-benzooligoynes upon bromination give benzopentafulvenes with orthogonal, peripheral phenyl groups. In contrast, the thermal cyclizations of the same starting materials give naphthalene deriva

Full text of DOI:10.1002/anie.200351195

Angewandte
Chemie
Polycyclic Aromatic Hydrocarbons
Surprisingly, the reported spectroscopic data for the
isomeric dibromostilbenes 7 are incomplete. One source
provides a 1H NMR spectrum for (E)-7, and the assigned
configuration is corroborated by an X-ray crystal structure.[13]
Another source reports the 13C NMR signals for (E)-7,[14]
which, however, match ours for (Z)-7. NMR coupling
constants are equally inconclusive. To resolve this issue by
Fulvenes from Enediynes: Regioselective
Electrophilic Domino and Tandem Cyclizations of
Enynes and Oligoynes**
Peter R. Schreiner,* Matthias Prall, and Volker Lutz
The anellation of fulvenoid five- and aro-
matic six-membered rings in fullerenes is
responsible for the curvature in these and
many nonplanar polyaromatic hydrocar-
bons (PAHs).[1] Hence, the rational design
of closed nanotubes or fullerenes[2] must
include strategies for building five-mem-
bered rings, ideally from easily accessible
starting materials that would also allow (by
means of different reaction conditions) the
formation of six-membered rings.
We recently became aware of such a
possibility in our studies on alternatives to
1
6
Scheme 1. The thermal reaction of 1 proceeds by Bergman cyclization to form a six-membered
ring, whereas the bromination yields the benzopentafulvene derivative 4.
À
the C C cyclization of enediyne deriva-
tives such as o-bis(phenylethynyl)benzene
(1, Bergman reaction[3] to short-lived bi-
radical 2) that can, in principle, also lead to
1
5
benzopentafulvenes (C
cyclization to biradical 3;
means of an analogy we brominated 8[15] under identical
conditions to those that gave 7 (0.4m Br2 in CHCl3). The
resulting mixture of (E)-9 and (Z)-9 (60:40) had the same
proportions as the mixture of (E)-7 and (Z)-7 formed in the
bromination of 6. Fractional crystallization gave crystals of
(E)-9 (Scheme 2); its 13C NMR signals at d = 118.48 and
À
C
Scheme 1).[4] While the thermal cyclization yielding 3 is
unlikely because of the high barrier for cyclization (ca.
40 kcalmolÀ1 at UBS-B3LYP6-31G*), pentafulvenes do form
when starting materials such as 1 react with electrophiles
(e.g., bromine, to give 4 but not 5),[5–7] carbanions,[6] and
radicals.[8] Hence, the thermal and reagent-controlled reac-
tions of 1 and its derivatives are nicely complementary and
lend themselves to the production of novel carbon-rich
architectures by means of well-established acetylene chemis-
try.[9]
The incorporation of halogens in compounds such as 4
may be useful in the context of rational fullerene synthe-
ses.[2,10] Although the mechanisms of these reactions appear to
be straightforward, it is startling that not even the electro-
philic addition of bromine to diphenylacetylene (6, Scheme 2)
is entirely understood.[11] The present communication sheds
light on these as well as related reactions, which provide
benzopentafulvenes by regioselective, electrophilic cycliza-
tions.[6,7,12]
[*] Prof. Dr. P. R. Schreiner, Dr. M. Prall, V. Lutz
Institut für Organische Chemie
Justus-Liebig-Universität
Heinrich-Buff-Ring 58, 35392 Giessen (Germany)
Fax: (+49)641-99-34309
E-mail: prs@org.chemie.uni-giessen.de
[**] This work was supported by the Deutsche Forschungsgemeinschaft,
the Fonds der Chemischen Industrie, and the National Science
Foundation (CHE-0209857). We thank Prof. M. Schmittel for
valuable comments.
Scheme 2. Addition of bromine to phenylalkynes 6 and 8 gives E/Z
mixtures of products 7 and 9, respectively. The X-ray crystal structure
of (E)-9 is also shown.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2003, 42, 5757 –5760
DOI: 10.1002/anie.200351195
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5757

Communications
117.34 ppm are closer to those for (E)-7 than for
(Z)-7. Hence, the 13C NMR signal assignment in
ref. [14]is likely to be incorrect. The lack of
selectivity of the bromine addition supports the
notion of an open cationic intermediate.[14]
The electrophilic cyclization of 1 to give 4
(Scheme 3) can be rationalized by the formation
of the stabilized cation 10.[6] The cyclization to
give an aromatic six-membered ring would yield a
highly unfavorable naphthyl cation. The isomers
of 4 can be separated by recrystallization, and
Scheme 4. Electrophilic domino cyclization of 11 to give (E)-12 and 13
((E)-12/13=4:1, NMR).
second and third phenyl group (3.1 Š) is
significantly shorter than that between the
first and the second, and is comparable to
that in [3.3]paracyclophanes (3.2 Š).[18]
This synthesis of 12 allows convenient
access to cyclopent[cd]indenes, which can
be exploited as redox-active PAHs.[19]
This strategy can be extended for the
electrophilic domino cyclization of more
highly substituted phenylethynylbenzene
derivatives to produce carbon-rich fulve-
noid materials. Indeed, the cyclization of
14 gives the half-bowl compound 15
(based on the NMR spectrum of the
product mixture; Scheme 5). At least one
other compound is present, which is likely
the next higher analogue of 13. Owing to
their similarity and insolubility, the prod-
ucts cannot be separated. We are currently
preparing p-alkyl-substituted phenyle-
thynyl derivatives, which should display
less self-association and better solubility.
Scheme 3. Electrophilic domino cyclization of 1 to give (E)-4 and (Z)-4 (5:1). The X-ray crystal structure
of (E)-4 is also shown. The LUMO of the bromovinyl unit and the HOMO of the phenylethynyl unit are
shown to demonstrate the orbital-controlled preference of the fulvene cyclization.
the crystal structure of the major product (E)-4 (> 80%)
supports the structural assignment. The peripheral phenyl
groups are oriented coplanar with a separation of about 3.8 Š
and are perpendicular to the fully conjugated benzopentaful-
vene moiety. These results and the calculations for (E)-4 in
the gas phase (B3LYP6-31G*)[16] concur.
The approach of the LUMO of the bromovinyl moiety
and the HOMO of the phenylethynyl moiety shows that the
endergonic cyclization is initially orbital-controlled. This is
evident from the reduced distance between the orbital lobes
When these problems typical for PAHs are solved, the
electrophilic “zipper” cyclization should be an interesting
alternative for the synthesis of anellated benzopentafulvenes.
As a test of the pronounced regioselectivity of the
cyclization, we brominated the tetrayne 16 (Scheme 6). The
selective formation of the previously unknown bisfulvene 17
can be explained only by the attack of “Br+” at the more
electron-rich diyne unit (arrows in Scheme 6). The cycliza-
tions to give the two pentafulvene units occur in a tandem
À
responsible for the C C bond formation. In contrast to earlier
work, we note that the bromovinyl cation is a true minimum
(at B3LYP6-31G*) with a classic, nonbridging structure.[14]
As one of the resonance structures of 10 is a vinyl
cation,[17] we envisaged that an adjacent third phenylethynyl
moiety (as in 11, Scheme 4) could be attacked in a domino
reaction[5] to give a product with a second fulvene ring. The
reaction of 11 with bromine yields not only the major product
(E)-12 but also the acenaphthalene derivative 13 (Scheme 4;
(E)-12/13 = 4:1, NMR). The separation of these two products
is not easy. The major product (E)-12 readily isomerizes to
(Z)-12 during column chromatography and even in CDCl3
(due to traces of HCl). In the computed structure of (E)-12
the phenyl groups are also coplanar; the distance between the
Scheme 5. Electrophilic domino cyclization of 14 leads to the half-bowl
compound 15.
5758
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Angewandte
Chemie
cation 20. The subsequent loss of a
proton with formation of an extended
conjugated system is preferred over
bromide capture. However, maximiz-
ing conjugation alone does not explain
the formation of product 21, which
displays significant twisting around the
exocyclic double bond (dihedral angle:
228, computed: 238). The computed
structure also indicates that the phenyl
groups are not aligned for perfect
conjugation; in other words, this is
not a packing effect.
The electrophilic cyclizations of
aromatic systems having adjacent
alkyne moieties to give benzopentaful-
vene derivatives complement their
thermal reactions, which give aromatic
six-membered rings. This strategy can
be used to introduce curved structure
elements into carbon-rich compounds
that are synthesized by, for example, by
the vaporization of graphite. After
electrophilic aromatic halogenation
and alkynylation, the resulting ortho-
Scheme 6. Electrophilic tandem cyclization of tetrayne 16 upon bromination to give bisfulvene
17. The X-ray crystal structures of 16 and 17 are depicted.
fashion, and the domino cyclization to give naphthyl deriv-
atives does not compete. Note that in the crystal structure of
17 the two benzopentafulvene moieties are not in conjugation
(twist angle at the central butadiene moiety = 888).
Finally, the question of differences in the reactivity of
double and triple bonds in electrophilic reactions[11,20] was
also addressed through the bromination of the novel eneyne
18 (Scheme 7). Remarkably, the addition of the Br+ ion is
followed by the expected regioselective fulvene cyclization
and then by formal loss of a proton. Hence, this reaction is an
example for a rare electrophilic vinylic substitution.[21] The
oligoynes can then be cyclized to give anellated benzopenta-
fulvenes. This approach is not limited to bromine (or other
halogens) as the electrophile; acid-catalyzed cyclizations of
enediynes are also known, which after air oxidation give five-
membered derivatives.[22] As all of the fulvene cyclization
products contain bromine as a heteroatom, further function-
alization is straightforward and should make this approach
broadly applicable to the rational synthesis of a large variety
of PAHs.
alternative mechanism—an addition/elimination—is unlikely Experimental Section
because the BrÀ ion is a weak base. The observed mode of the
reaction is explained by the occurrence of the stabilized
Details of the preparation and characterization of 4, 9, 12, 16–18, and
21 can be found in the Supporting Information.
Received: February 17, 2003
Revised: August 20, 2003 [Z51195]
Keywords: alkynes · bromine · cyclization ·
.
polycycles · tandem reactions
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