Radical Cation Diels-Alder Reaction

Conjugated cations, anions and radicals can give the Diels-Alder reaction. In such a case, the two cr bonds are formed in two separate steps (stepwise... 

Radical Diels-Alder reactions have been used mainly to synthesize polycyclic molecules. These reactions, like those that involve cations and anions as components, proceed quickly but generally do not give high yields. Thus, the tricyclic enone 14 is the result of an intramolecular Diels-Alder reaction of quenched vinyl radical intermediate 13 obtained by treating the iododienynone 12 with n-tributyltin hydride/2,2 -azobisisobutyronitrile (AIBN) [28] (Equation 1.11). 

The first studies on cation-radical Diels-Alder reactions were undertaken by Bauld in 1981 who showed [33a] the powerful catalytic effect of aminium cation radical salts on certain Diels-Alder cycloadditions. For example, the reaction of 1,3-cyclohexadiene with trans, iraw5-2,4-hexadiene in the presence of Ar3N is complete in 1 h and gives only the endo adduct (Equation 1.14) [33]. 

As a continuation of these studies, Bauld recently reported evidence of a stepwise mechanism in the cation-radical Diels-Alder reaction of phenyl vinyl sulfide with cyclopentadiene [34, 35] (Scheme 1.6). 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Luche and coworkers [34] investigated the mechanistic aspects of Diels-Alder reactions of anthracene with either 1,4-benzoquinone or maleic anhydride. The cycloaddition of anthracene with maleic anhydride in DCM is slow under US irradiation in the presence or absence of 5% tris (p-bromophenyl) aminium hexachloroantimonate (the classical Bauld monoelectronic oxidant, TBPA), whereas the Diels Alder reaction of 1,4-benzoquinone with anthracene in DCM under US irradiation at 80 °C is slow in the absence of 5 % TBPA but proceeds very quickly and with high yield at 25 °C in the presence of TBPA. This last cycloaddition is also strongly accelerated when carried out under stirring solely at 0°C with 1% FeCh. The US-promoted Diels Alder reaction in the presence of TBPA has been justified by hypothesizing a mechanism via radical-cation of diene, which is operative if the electronic affinity of dienophile is not too weak. 

Photo-induced Diels Alder reaction occurs either by direct photo activation of a diene or dienophile or by irradiation of a photosensitizer (Rose Bengal, Methylene Blue, hematoporphyrin, tetraphenylporphyrin) that interacts with diene or dienophile. These processes produce an electronically excited reagent (energy transfer) or a radical cation (electron transfer) or a radical (hydrogen abstraction) that is subsequently trapped by the other reagent. 

Acetylchloride is a trapping agent that allows the reaction to go completion, transforming the product into a less oxidizable compound.The results of other reactions between indole (57) and substituted cyclohexa-1,3-dienes show that the photo-induced Diels-Alder reaction is almost completely regioselective. In the absence of 59 the cycloaddition did not occur the presence of [2+2] adducts was never detected. Experimental data support the mechanism illustrated in Scheme 4.14. The intermediate 57a, originated from bond formation between the indole cation radical and 58, undergoes a back-electron transfer to form the adduct 60 trapped by acetyl chloride. 

The long-lived isomeric xylylene cation radical then undergoes either coupling to the adducts in equation (72) or back electron transfer followed by Diels-Alder reaction of the resulting neutral xylylenes and chloranil. 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

Limonene, one of the most prominent natural monoterpenes (cf Section VII), represents a particular derivative of 4-vinylcyclohexene since it has been studied with respect to the pronounced energy dependence of its fragmentation behaviour (Scheme 7). Counterintuitively, and in contrast to 4-vinylcyclohexene, the radical cations of limonene (27) do not undergo the retro-Diels-Alder reaction if the internal energy of the ions is low. As... 

It is important to note that the reactions are fundamentally different from similar radical cation Diels-Alder reactions initiated with the use of a photochemical electron-transfer reaction [35, 36]. In photochemical reactions, a one-electron oxidation of the substrate leads to a cycloaddition that is then terminated by a back electron transfer . No net change is made in the oxidation state of the substrate. However, the reaction outlined in Scheme 13 involves a net two-electron oxidation of the substrate. Hence, the two pathways are complementary. 

The prototype hole-catalyzed Diels-Alder reaction between the butadiene radical cation and ethylene has also been studied by Bauld [53]. He finds strongly exothermic formation of a l-hexene-3,6-diyl radical cation intermediate without activation energy followed by a weakly activated (activation energy 2.3 kcal mol ) closure of the second C-C bond to form the cyclohexene radical cation, The reaction shows no overall activation energy relative to the... 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

The ion-radical Diels-Alder reactions represent a new development (see, e.g., reviews by Hintz et al. 1996, Berger and Tanko 1997). These reactions initiated with ion-radicals proceed faster by several orders of rate magnitude than the corresponding conventional reactions. This section presents the most important cyclizations developed through cation- and anion-radical schemes and the scheme that includes both cation- and anion-radicals. 

Naturally, the question arises as to whether the diene component really has to be in its i -cis form for the cation-radical Diels-Alder reaction. According to calculations by Hofmann and Schaefer 1999, the i-trani-butadiene is more stable than its s-cis, isomer by 12 kJ moE, and for the cation-radicals, the trans preference is even somewhat pronounced (16 kJ moE )-... 

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