Sonochemical cycloadditions of o-quinones. The search for a cation radical pathway

Article abstract of DOI:10.1016/S0040-4039(00)00578-5

Diels-Alder cycloadditions of an o-quinone monoketal with different furans, under argon, are considerably accelerated by ultrasonic irradiation. Moreover, these sonochemical reactions are regiospecific and proceed with a high diastereoselectivity. The res

Full text of DOI:10.1016/S0040-4039(00)00578-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 4101–4105
Sonochemical cycloadditions of o-quinones.
The search for a cation radical pathway
Martín Avalos,a Reyes Babiano,a José L. Bravo,a Noemí Cabello,a Pedro Cintas,a,∗
Michael B. Hursthouse,b José L. Jiménez,a Mark E. Light b and Juan C. Palacios a
aDepartamento de Química Orgánica, Facultad de Ciencias, Universidad de Extremadura, E-06071 Badajoz, Spain
bDepartment of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
Received 17 March 2000; accepted 5 April 2000
Abstract
Diels–Alder cycloadditions of an o-quinone monoketal with different furans, under argon, are considerably
accelerated by ultrasonic irradiation. Moreover, these sonochemical reactions are regiospecific and proceed with a
high diastereoselectivity. The results can be ascribed to the chemical role of ultrasounds which may favor a single
electron transfer mechanism with respect to ionic or nonpolar pathways. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: cation radicals; Diels–Alder reactions; furans; o-quinones.
Activation of Diels–Alder reactions, especially by Lewis acids1 or nonconventional irradiation
techniques,2 not only enhances the versatility of this powerful methodology, but also enables milder
and more selective cycloadditions. Assuming that Diels–Alder reactions are sensitive to thermal and
pressure effects, they would be susceptible to ultrasonic activation since the cavitational collapse is
capable of creating extremely high local temperatures (∼4500 K),3 though accompanied by modest
pressures (a few kbars), under almost adiabatic conditions (the duration of the hot spots is less than
100 nanoseconds with cooling rates >1010 K/s).3,4 The conditions provided by cavitation would be
comparable to those of flash thermolysis. Unfortunately, little success has so far been encountered in
ultrasound-assisted cycloadditions. This fact can be interpreted by the hypothesis of true sonochemistry,5
pioneered by Luche, stating that chemical effects of ultrasounds will occur only if an elemental process
is the sonication sensitive step, or when the high energy species released after the collapse participate
as reaction intermediates. Accordingly, ultrasounds may favor a radical process by virtue of their ability
in promoting single electron transfers. However, nonvolatile substrates have no probability to penetrate
into the bubble to undergo these extreme conditions, although they may experience the shock waves in
the bulk medium. On the other hand, the formation of cation or anion radicals does require appropriate
∗
Corresponding author. Tel/fax: (34)-924-271-149; e-mail: pecintas@unex.es (P. Cintas)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00578-5
tetl 16857

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electrochemical potentials or the presence of radical holes, acting as intermediates, such as the aminium
radicals exploited by Bauld et al.6
Suitable candidates for sonochemical cycloadditions are quinones,2a because these substances form
redox pairs with potentials lower than those of most aromatic hydrocarbons,7 and their cation radicals
can easily be generated from catechols and catechol ethers.8 In a series of recent papers, Liao et al. have
reported that o-benzoquinones, generated by oxidation of catechols with a hypervalent iodine reagent
(diacetoxyiodobenzene, DAIB), react with furans which act as dienophiles.9 Such reactions require
heating at 50°C or reflux for several hours. Arjona et al. have also described this cycloaddition with enol
ethers.10 Notably, these authors claim that the resulting cycloadducts have the regiochemistry opposite
to those of furan-based cycloadditions on the basis of a small NOE effect (4%) between two distant
protons. It should also be noted that Waldmann and his associates have reported a chemoenzymatic
domino reaction of catechols with enol ethers to give similar adducts.11 It appeared justified to explore
this useful protocol under ultrasonic conditions and especially in order to elucidate the regiochemical
pattern.
Reaction of methyl vanillate with DAIB in methanol under ultrasonic irradiation (bath, ∼35 kHz),
and under an argon atmosphere, gives rise to the corresponding o-quinone monoketal which is trapped
by a series of furans (Scheme 1, Table 1). Remarkably, the process is largely accelerated: reactions
can now be conducted at room temperature and are essentially complete within 15–50 min. Yields are
moderate to good, since the rapid reaction also causes a partial decomposition of the starting catechol,
1
presumably by oligomerization of phenol radicals. H and 13C NMR analyses of the crude samples
evidenced the formation of a single stereomer, the same as the cycloadduct obtained under thermal
conditions. This is particularly remarkable assuming that two regiochemistries are possible, each with
endo or exo orientations. A careful inspection of NMR data clearly indicates that, in the case of 2-
substituted furans, only the unsubstituted double bond reacts.
Scheme 1.
Liao et al. have attempted a theoretical analysis of the regioselectivity by computing the cyclo-
additions of quinones with methyl acrylate and methyl vinyl ketone both at PM3 and RHF/3-21G*
levels;9b these authors note that in most cases the difference in the energy gaps for the two possi-
ble interactions are around 0.5 eV. We have similarly performed a semiempirical PM3 calculation
of the experimental reaction involving oxidized methyl vanillate and furan itself. The energy gaps
were HOMOfuran−LUMOcatechol=0.29 eV and HOMOcatechol−LUMOfuran=0.40 eV. While the former
interaction accounts for an inverse electronic demand cycloaddition, the further calculation of the
atomic coefficients suggests that the opposite regiochemistry (2), should be favored. Fortunately, crystals
appropriate for X-ray diffraction analysis were obtained for the cycloadduct arising from reaction with

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Table 1
Sonochemical cycloadditions of oxidized methyl vanillate with furans
furan, thereby confirming in an unequivocal fashion that the selective approach gives rise to the regiomer
1 (Fig. 1).12
Fig. 1. X-Ray crystallographic view of cycloadduct 1a
The acceleration of the reaction may be consistent with a radical pathway, cavitation providing energy
for homolytic cleavage (Scheme 2). Thus, the possibility that the course of the cycloaddition had now
switched from a concerted to one in which a SET process was now prevalent cannot be discarded.
We have added methyl viologen to the reaction mixture since this redox indicator is a good electron
acceptor13 and the corresponding ion radical is bright red and can be detected by the naked eye. Addition
of this substance under strictly oxygen-free conditions inhibits the formation of o-quinone. This might
be ascribed to the competing formation of the radical cation from methyl viologen, but no discharge
of the red color was observed. Previous formation of o-quinone by catechol oxidation, followed by
addition of methyl viologen and furan, results in a complex reaction mixture and the formation of
an orange color (the background quinone is yellow). It is known that the photolysis of alcohols with
DAIB and iodine proceeds via a radical pathway.14 Recently, sonolysis has emerged as an alternative to
photolysis.15 In our hands, the sonochemical cycloaddition of o-quinone with 2,5-dimethylfuran in the
presence of DAIB/I2 had a higher conversion rate (10 min versus 25 min). In principle, a cation radical
Diels–Alder reaction should be nonstereospecific. However, Bauld and his coworkers have demonstrated

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that these ion radical cycloadditions can be >98% stereospecific, which is consistent with a concerted,
but highly non-synchronous mechanism.16a Nevertheless, this does not exclude the alternative two-step
process involving distonic cation radical intermediates, because such radical cycloadditions are in fact
telomerization reactions in which the dimerization process (which would otherwise produce the observed
DA cycloadduct) has a much higher rate than the subsequent oligomerizations and, likewise, the second
step may be faster than stereorandomizing bond rotations.16b–d There are CIDNP studies providing
evidence for cation radical intermediates,17 and Prokof’ev and his associates have also demonstrated the
formation of radical pairs and electron transfers from hindered phenols in the presence of an ultrasonic
field.18
Scheme 2. Alternative mechanisms for cation radical Diels–Alder reactions
In summary, we have shown that o-benzoquinones can be generated by ultrasonic irradiation and
their [4+2]-cycloadditions with furans are accelerated with respect to thermal reactions. The redox
umpolung provided by electron transfers may account for an alternative cation radical pathway, since
as has been noted by Bauld, stereospecificity is not a rigorous proof of concertedness. The mild nature of
the sonochemical reaction may well prove to be of interest from a synthetic viewpoint. We are currently
evaluating the potential energy hypersurface by ab initio methods in order to locate the competing
concerted and cation radical transition states, which will allow us to gain insights into these unusual
pathways, thereby ascertaining the exact role of sonochemical activation. Such studies are currently under
way in this laboratory.
Acknowledgements
We thank the Spanish Ministry of Education and Culture (DGICYT, grants no. PB98-0997, AMB99-
0591) and the Junta de Extremadura–Fondo Social Europeo (IPR98-A065) for financial support. N.C.
thanks the Junta de Extremadura for a scholarship. Special thanks to Prof. Alexander Prokof’ev for a
valuable exchange of information concerning quinone cation radicals, and Prof. Jean-Louis Luche for
fruitful discussions over the years.
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