Selectivity in Radical Cation Cycloadditions

As a result, the transition state of the radical cation cycloaddition is much more reactant-like and the activation energy will be much smaller than in case of the cycloadditions between two neutral reactants. Finally, the thermodynamic driving force for this radical cation/neutral addition is equal to the large difference in ionization potentials between the bonded and the nonbonded orbitals. 

The Bauld analysis highlights the fact that radical cations are highly reactive species. Surprisingly, they have at the same time been empirically found to be highly selective. In direct comparisons with neutral reactions, the ETC cycloaddition reaction was found to be more selective in both [4 + and [2 + 2] reactions, which is in 

Several factors that are less important in the case of neutral cycloadditions have to be considered because they can potentially be exploited for greater selectivity. As a result of the charged nature of the radical cations, solvents and the solvation state of the ions as contact ion pairs, solvent separated ions pairs, or free ion pairs involved in the reaction now play a much greater role than for the cycloadditions of a neutral substrate, which for the most part show only a weak solvent dependence. The 

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TABLE 4.9 Dimerization of 8a SELECTIVITY IN RADICAL CATION CYCLOADDITIONS Ratio 9a/10a in CH3CN Sensitized by 6 ... 

As shown in Table 4.1, formation of the mixed adduct is favored over homodimerization of 8a with the simple styrene 13a, but this selectivity is inverted for the case of the more bulky dienophile tra 5-[3-methylstyrene 13b, presumably due to steric effects. Although the overall reaction is highly exothermic on the radical cation surface, the reaction is not insensitive to steric effects. Chemoselectivity in the radical cation cycloaddition is largely a consequence of a substrate s ability to stabilize the radical cation of the oxidized species through the formation of a weakly bound ion-molecule complex. Such complexes have been known for a long time in gas-phase... 

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... 

Alongside homopolymerization, copolymerization has been studied in the framework of the initiation by tris(4-bromophenyl)ammoniumyl hexachloroantimonate (Bauld, Aplin, et al. 1998). In general, cation radical cycloaddition occurs more efficiently when the reactive cation radical is the ionized dienophile (Bauld 1989, 1992). In the cited work on copolymerization, the bi(diene) was chosen to be resistant to ionization by the initiator used. As to dienophile functionality, propenyl rather than vinyl moieties were selected because terminal methyl groups greatly enhance the ionizability of the alkene functions. The polymerization shown in Scheme 6-14 was performed in dichloromethane at 0°C. 

Electron transfer catalyzed cycloadditions via radical cations show remarkable selectivity that could be exploited for expanded synthetic methodology. As a complement to the neutral Diels-Alder reaction, ET catalysis hlls the void of the electron-rich diene/electron-rich dienophile cyclizations. In attempt to understand the intricate details of the reaction, experimentalists and theorists have uncovered a range of novel factors to control and manipulate these high-energy reactive intermediates. As exemplihed by the cases discussed in this contribution, the charged character of the intermediates and the presence of back electron transfer leading to the biradical reaction manifold opens new pathways to control the chemo-, peri-, and stereochemical patterns in these dynamic species. 

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... 

Tris(4-bromophenyl)ammoniumyl hexachloro antimonate is commercially available (e.g., Fluka product, 5g cost 70). It is commonly used as an oxidizing reagent by means of electron transfer and is elegantly applied to induce cycloadditions and cyclodimerization ([2 -I- 2] reactions) by Bauld [115]. However, aromatic amine radical cations as the oxidizing reagent can be easily obtained anodically [116] and their redox potentials (between -1-1 V and -1-2 V vs. NHE) modulated as a function of different substituents for utilization if indirect oxidation reactions are to be conducted. Therefore, such a redox catalysis process appears to be a cheap and elegant method to selectively achieved in situ oxidation, provided that polar solvents, electrolytes, and room temperatures are acceptable experimental conditions to perform a given reaction. 

The concerted mechanism, in which the two new bonds form synchronously (Fig. 7), is probably less common than generally assumed. A concerted non-synchronous mechanism can involve diradicals or zwitterions, which means more or less dissymmetry, geometrical and/or electronic, in the bond formation, which can be increased by the presence of catalysts, such as Lewis acids, especially lithium salts,26 or solvent effects.27 Ionization of one of the reactants (Fig. 8), frequently the dienophile, is efficient in promoting cycloadditions with unreactive reagents, e.g., the [4+2] dimerization of dienes, by a selective transformation to the reactive radical cations ("hole" catalysis). ... 

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