Cycloaddition cation radical Diels-Alder

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]. 

The cation radical Diels-Alder cycloadditions of cis- and franx-prop-1-enyl aryl ethers to cyclopenta-1,3-diene catalysed by tris(4-bromophenyl)aminium hexachloroantimonate are stepwise processes involving an intermediate distonic cation radical in which the carbocationic site is stabilized by the electron-donating functionality (Scheme 9). " ... 

Harirchian, B. and Bauld, N.L. (1989) Cation radical Diels-Alder cycloadditions in organic synthesis a formal total synthesis of (—)-(S-selrnene. Journal American Chemical Society, 111, 1826-1828. 

Cation Radical Diels-Alder Cycloadditions Historical... 

The uncatalyzed Diels-Alder reaction is well known to be highly stereospecific, preferentially occurring via syn addition to both the diene and dienophilic components. Stereochemical studies of the cation radical Diels-Alder reaction have confirmed an analogous stereospecificity in two distinctly different systems. The initial study was carried out using the cycloaddition of the three geometric isomers of 2,4-hexadiene as dienophilic components and 1,3-cyclohexadiene as the diene component [39]. Each of the three isomers of the acyclic diene was found to add stereo-specifically to cyclohexadiene. In a more recent study, the cis and trans isomers of 1,2-diaryloxyethenes were found to add stereospecifically to 1,3-cyclopentadiene (Scheme 17) and also to 2,3-dimethyl-l,3-butadiene [46]. 

With respect to the matter of steric sensitivity, the reaction of 2,5-dimethyl-2,4-hexadiene with 1,3-cyclohexadiene is instructive [39]. Apparently, no Diels-Alder additions of this sterically hindered acyclic diene, either as the dienophilic or dienic component, have ever been reported. However, the cation radical Diels-Alder cycloaddition referred to above (Scheme 20) occurs smoothly, the readily ionizable acyclic diene serving as the dienophilic component. 

Although neutral Diels-Alder reactions of stilbene as a dienophile are unknown, the cation radical Diels-Alder reaction cited above occurs smoothly [51]. Trans stilbenes yields only trans adducts, while cw-stilbenes yield primarily, but not exclusively, cis adducts. The stereospecificity of the cycloaddition step in the latter reaction system was, however, not readily evaluated because of the occurrence of competing cis to trans isomerization of the starting material. It was established, however, that at low conversions, the reaction tends toward stereospecificity. Since cw-stilbene is much less readily ionizable than tran -stilbene, the Diels-Alder cycloadditions in the cw-stilbene system were studied using the p,p -6. vciQ hy derivative. 

It should also be born in mind that electron rich alkenes are also especially reactive neutral components of cation radical cycloaddition reactions, since they are also highly nucleophilic. Consequently, in appropriate instances, either role sense of the cation radical Diels-Alder reaction may be operative, i.e. either the diene or the electron rich alkene could be reacting as the cation radical. 

In view of the demonstrated stereospecificity of at least some cation radical Diels-Alder reactions, it is at least possible that these reactions, like the neutral Diels-Alder, are true pericyclic reactions, i.e., they may occur via a concerted cycloaddition. The results of a variety of calculations, however, make clear that the cydoadditions must at least be highly non-synchronous, so that the extent of the formation of the second bond, which completes the cyclic transition state, is no more than slight [55, 56]. If the cation radical Diels-Alder reaction is nevertheless interpreted as pericyclic and the concept of orbital correlation diagrams is applied to them, it emerges that the cycloaddition is symmetry allowed if the ionized (cation radical) component is the dienophile, but forbidden if it is the diene [39, 55], The former mode of reaction has been referred to as the [4-1-1] mode, and the latter as the [3 -t- 2] mode. Interestingly, the great majority of cation radical Diels-Alder reactions thus far observed seem to represent the formally allowed [4-1-1] mode. An interesting case in point is the reaction of l,l -dicyclohexenyl with 2,3-dimethylbutadiene (Scheme 24) [57]. 

From this perspective, it emerges that the kinetic driving force for the cation radical cycloaddition relative to the corresponding neutral one can be expressed as the difference in the ionizabilities of the reactant and the transition state. As a specific example, we may consider a highly non-synchronous TS for cation radical Diels-Alder cycloaddition—which is supported by theoretical calculations (vide infra). This transition state is essentially a distonic cation radical, the radical site of which is easily ionized because the odd electron is in a non-bonding MO. In contrast, the... 

Bauld, N. L., and Yang, J. "Stereospecificity and Mechanism in Cation Radical Diels-Alder and Cyclobutanation Reactions." Org. Lett, X 773-774 (1999). Gao, D., and Bauld, N. L. Mechanistic Implications of the Stereochemistry of the Cation Radical Diels-Alder Cycloaddition of 4-(cis-2-Deuteriovinyl)anisole to 1,3-Cyclopentadiene." /. Org. Chem., 65,6276-6277 (2000). Saettel, N. J., Oxsgaard, J., and Wiesl, O. "Pericyclic Reactions of Radical Cations." Eur. /. Cftem., 1429-1439 (2001). 

The cation-radical Diels-Alder reactions of cis- and fran5 -l,2-(diaryloxy)ethenes with butadienes are stereospecific, in agreement with a concerted cycloaddition mechanism. " Tris(4-bromophenyl)aminium hexachloroantimonate catalyses the two-step, non-stereospecific cation-radical Diels-Alder reaction of cis- and traui-prop-l-enyl aryl ethers with cyclopenta-1,3-diene in CH2CI2 solution. 

A number of electrocyclic reactions under PET conditions have been reported. In this way, A-benzyl-2.3-diphcnylaziridinc (40) underwent a 3 + 2-cycloaddition with alkene and alkyne dipolarophiles to afford substituted pyrrole cycloadducts (41) via the radical cation intermediate (42) see Scheme 7.80 Elsewhere, novel arylallenes have been used as dienophiles in a radical cation-catalysed Diels-Alder cycloaddition reaction with 1,2,3,4,5-pentafluromethylcyclopentadiene, which often occurred with peri-, chemo-, facial- and stereo-selectivity.81... 

Bauld and coworkers, especially, developed the analogous Diels-Alder (4 + 2) cycloaddition reactions. These reactions are conveniently catalyzed by tris(4-bromophenyl)aminium hexachloroantimonate (78) or by photosensitization with aromatic nitriles. The radical cation-catalyzed Diels-Alder reaction is far faster than the uncatalyzed one, and leads to some selectivity for attack at the least substituted double bond for the monoene component (Scheme 18, 79 —> 80), but only modest endo selectivity (e- and x-80) [105]. Cross reactions with two dienes proved to be notably less sensitive to inhibition by steric hindrance of alkyl groups substituted on the double bonds than the uncatalyzed reactions, as cyclohexadiene adds detectably even to the trisubstituted double bond of 2-methylhexadiene (82), producing both 83 and 84. Dienes such as 85 react with donor-substituted olefins (86) to principally give the vinylcyclobutene products 87, but they may be thermally rearranged to the cyclohexene product 88 in good yield [105]. Schmittel and coworkers have studied the cation radical catalyzed Diels-Alder addition of both... 

The radical cation-catalyzed cycloadditions of the Diels-Alder type are well known and have been the subject of a number of studies to which reader is referred for details [115-118]. 

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. 

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. 

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. 

A cation radical chain cycloaddition-polymerization catalysed by tris(4-bromophenyl)aminium hexachloroantimonate has been reported to afford polymers with an average molecular weight up to 150000. Both cyclobutanation and Diels-Alder polymers were obtained. " The reactivity of the phospine radical cation towards nucleophiles was studied. Tributylphosphine reacted with l,l-dimethyl-4,4-bipyridinium (methyl viologen, MV) in the presence of an alcohol or thiol (RXH X = O, S), which resulted in the gradual formation of the one-electron reduced form... 

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