Tellurium-Mediated Cycloaromatization of Acyclic Enediynes under Mild Conditions

Article abstract of DOI:10.1021/ja0389467

The cycloaromatization of acyclic enediynes typically requires very high temperatures (>160 °C) and dilute conditions to proceed in a synthetically useful yield. These conditions hinder reaction throughput, inhibiting the use of this reaction for the large-scale production of materials. The reaction of sodium telluride with acyclic arenediynes yields the corresponding tellurepine, which under gentle heating extrudes Te° to yield the cycloaromatization product. We have developed conditions that form sodium telluride from inexpensive tellurium metal in situ, and that also perform the desilylation of silylated arenediynes in the same process. Under our conditions, we are able to perform desilylation and cycloaromatization at temperatures as low as 40 °C and on a scale as large as 5 g in standard laboratory glassware. Copyright

Full text of DOI:10.1021/ja0389467

Published on Web 01/17/2004
Tellurium-Mediated Cycloaromatization of Acyclic Enediynes under Mild
Conditions
Chad A. Landis, Marcia M. Payne, David L. Eaton, and John E. Anthony*
Department of Chemistry, UniVersity of Kentucky, Lexington, Kentucky 40506-0055
Received October 8, 2003; E-mail: anthony@uky.edu
Scheme 1a
The cycloaromatization of easily prepared enediynes1 is becom-
ing a reliable tool for the formation of fused aromatic systems.
Recent explorations of the synthetic aspect of enediyne chemistry
have led to the preparation of aromatic rings fused to saturated
ring systems,2 of linear acenes and peri-condensed naphthalenes,3
as well as of highly substituted poly(paraphenylene)s4 and cross-
linked polymers.5 The discovery of technologically promising
electronic properties in fused aromatic compounds6 underscores the
importance of new synthetic routes to such systems.
A significant drawback to the cycloaromatization reactions of
the synthetically useful acyclic enediynes is the high temperature
required for the reaction (typically in excess of 180 °C) combined
with the expense of the volatile hydrogen atom source required for
the reaction. Both of these factors severely reduce material
throughput, limiting the utility of the reaction. Inducing cycloaro-
matization of enediynes under milder conditions has been an active
area of research for the past decade. Photochemical Bergman
reactions, for example, have been reported to occur at room
temperature, but typically require specific substitution of the alkynes
(i.e., 1, R ) R′ ) alkyl or aryl), and the high dilution conditions
required to avoid intermolecular reactions further limit synthetic
applicability.7 The promotion of cycloaromatization with organo-
metallic species has proved to be a somewhat more versatile
strategy, with the most common approach involving the function-
alization of the ends of the enediyne with ligands or metal chelators.8
Other approaches involve addition of vinylidine carbene to a
monosubstituted enediyne9 and rate acceleration by aryl complex-
ation of Cp*Ru to a cyclic enediyne.10 These systems all undergo
cycloaromatization at lower temperatures in the presence of metal
ions, the drawback being the requirement of specific functional
groups on the alkynes.
In 1991, Tsuchiya and co-workers explored the synthesis of
benzotellurepines by the hydrotelluration of an enediyne.11 While
the expected benzotellurepine was indeed formed in good yield,
the authors noted that the major decomposition product of this
species was naphthalene - in essence, the cycloaromatization
product! In light of the rich chemistry that has since been developed
around the reaction of tellurium and tellurides with alkynes,12 we
decided to investigate hydrotelluration as a milder alternative to
thermal cycloaromatization of acyclic enediynes.
a Reaction conditions: (a) 180 °C, benzene, 1,4-cyclohexadiene, sealed
vessel. (b) Na2Te, hydrazine, benzene/water, PTC, 60-70%.
Scheme 2a
a Reaction conditions: (a) benzene, 10% aqueous NaOH, hydrazine, 1.1
equiv of Te°, 2 equiv of NaBH4, Aliquat 464, 40 °C, ultrasound 8 h, 73%.
(b) benzene, 10% aqueous NaOH, hydrazine, 0.1 equiv of Te°, 2 equiv of
NaBH4, Aliquat 464, 40 °C, ultrasound, 24 h, 69%. (c) benzene, 40%
aqueous NaOH, 1 equiv of Te°, 3 equiv of NaBH4, Aliquat 464, 200 W
tungsten lamp, 60 °C, 6 days, 65%.
layer. Fortuitously, this added base also performs desilylation of
enediynes such as 2, allowing direct conversion of the more stable
silylated enediynes to the cycloaromatized product. Performing this
reaction in an ultrasonic bath leads to efficient mixing of the
aqueous and organic layers and dramatically accelerates the rate
of the reaction (most likely at the Te extrusion step).14
As shown in Scheme 2a, desilylation/cycloaromatization of the
simple silylated arenediyne occurs in >70% yield at 40 °C, using
stoichiometric Te°. This reaction is scalable, with only a slight
decrease in yield (68%) on a 5-g scale of 2. In principle,
regeneration of the telluride during the course of the reaction could
be exploited to make the reaction catalytic in Te°. Indeed, the
reaction proceeds in nearly the same yield when only 10 mol % of
tellurium is used, with the only difference being an increase in
reaction time (Scheme 2b). In practice, the low cost, low toxicity,
and ease with which the tellurium byproducts can be removed make
the faster stoichiometric reaction more synthetically useful.
It has been speculated that the addition of telluride to alkynes
proceeds by a radical-anion-chain mechanism, with the hydrazine
acting as an electron donor.15 Recent reports of carbotelluration of
alkynes under illumination16 led us to suspect that the hydrazine
could be eliminated if the reaction were carried out photochemically.
Thus, the conditions shown in Scheme 2c were used to produce
naphthalene in 65% yield. While the ability to carry out the reaction
in the absence of reactive hydrazine is advantageous, the significant
increase in reaction time again makes the thermal conditions more
generally useful.
The conditions reported for the reaction shown in Scheme 1 (path
b, R ) R′ ) H) involved the addition of sodium telluride to a
biphasic (benzene/water) mixture of the arenediyne, hydrazine, and
phase-transfer catalyst. Our investigations of this reaction had the
goals of finding an alternative to expensive and air-sensitive sodium
telluride,13 optimizing conditions for efficient conversion to the
cycloaromatized product, and exploring the range of functionality
tolerated by the reaction.
Sodium telluride is conveniently generated from tellurium powder
and sodium borohydride in water. To stabilize the aqueous
borohydride solution, sodium hydroxide was added to this aqueous
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J. AM. CHEM. SOC. 2004, 126, 1338-1339
10.1021/ja0389467 CCC: $27.50 © 2004 American Chemical Society

C O MMU N I C A T I O N S
Table 1. Tellurium-Mediated Cycloaromatization Reactions of
Substituted Arenediynes
enediynes further substituted on the alkyne were also not amenable
to cycloaromatization under these conditions.21 Disubstituted
derivatives (1, R ) R′ ) alkyl or aryl) were completely unreactive,
while monosubstituted derivatives (1, R ) H, R′ ) alkyl) underwent
hydrotelluration of the terminal alkyne (in poor yield), but no further
reaction occurred even at elevated (>100 °C) temperature.22
In conclusion, we have demonstrated a rapid, mild, and scalable
tellurium-mediated cycloaromatization reaction. The reaction condi-
tions tolerate the typical functionality required for solubilization
of organic electronic materials based on polycyclic aromatic
compounds and allow the large-scale preparation of technologically
important fused aromatic systems in generally good yield.
Acknowledgment. We are grateful to the NSF (CHE-9875123)
for support of this research. D.L.E. acknowledges the support of a
Kentucky Opportunity Fellowship. We also thank one of the
reviewers of the original version of this manuscript for suggestions
that led to significant improvements in the procedure.
Supporting Information Available: Experimental procedures and
characterization data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
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of dehalogenated material (2-tert-butylnaphthalene) was also formed.
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sodium telluride to be consistently reproducible.
(14) The reaction can be performed without the assistance of ultrasound, but
requires longer reaction times (2 days) and higher temperatures (60 °C).
The extrusion is likely a radical process: Clive, D. L. J.; Anderson, P.
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Arenediynes substituted on the aromatic ring also underwent
tellurium-mediated cycloaromatization under these conditions (Table
1) in generally good yield. Remarkably, even enediynes that
underwent thermal cycloaromatization in very poor yield, such as
diethynyl acenaphthylene 4,17 formed the expected cycloaromati-
zation product in reasonable yield under these conditions. The
extremely reducing conditions required for reaction do limit the
functional groups tolerated. These conditions can be used to an
advantage, as 4-nitroarenediyne 5 underwent desilylation, cycloaro-
matization, and reduction to 2-aminonaphthalene in a single step.
Although an explicit hydrogen atom source is not required for
the tellurium-mediated reaction, the hydrotelluration of alkynes is
still a radical process.18 While intermolecular polymerization
reactions were not observed even in reactions run at relatively high
(>0.4 M) concentrations, intramolecular radical reactions were
observed in the case of the tellurium-catalyzed cycloaromatization
of alkylated 7 (R′ ) hexyl). Just as with the attempted thermal
cycloaromatization of this compound,19 the tellurium-mediated
cycloaromatization led to an inseparable mixture of compounds,
all containing the anthracene chromophore, that appeared to be
products of hydrogen atom abstraction or cyclization with the
adjacent alkyl groups. In contrast, the unsubstituted derivative (7,
R′ ) H) produced anthracene in good yield. The radical nature of
the hydrotelluration intermediate, just as with the diradical inter-
mediate of the Bergman reaction, limits the groups that can be
placed ortho to the alkynes.
(21) Telluride cyclization of 1,2-bis(phenylethynyl)benzene was shown to yield
a mixture of five-membered ring products: Blum, J.; Baidossi, W.;
Badrieh, Y.; Hoffman, R. E. J. Org. Chem. 1995, 60, 4738.
(22) Comasseto, J. V.; Tucci, F. C.; Chieffi, A. J. Org. Chem. 1996, 61, 4975.
Nonaromatic enediynes typically undergo hydrotelluration with
the opposite regiochemistry of the corresponding aryl species20 and
did not undergo cycloaromatization under these conditions, instead
forming intractable mixtures of oligomeric species. Aromatic
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