Cyclobutane radical cation

In a reaction quite analogous to cation radical cyclobutanation, cation radicals of some relatively ionizable, but sterically hindered alkenes have been found to add to ground state dioxygen in a very efficient cation radical chain process (Scheme 13) [37]. 

The photochemical dimerization of p-methoxystyrene does not occur in non-polar solvents or in the absence of electron acceptors. This observation has been rationalized in terms of a reaction path in which the first step is photochemically induced electron transfer to give the styrene cation radical. This species reacts with a ground-state partner to give the cyclobutane cation radical which is then neutralized. 

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... 

Hence, cation-radical copolymerization leads to the formation of a polymer having a lower molecular weight and polydispersity index than the polymer got by cation-radical polymerization— homocyclobutanation. Nevertheless, copolymerization occnrs nnder very mild conditions and is regio-and stereospecihc (Bauld et al. 1998a). This reaction appears to occnr by a step-growth mechanism, rather than the more efficient cation-radical chain mechanism proposed for poly(cyclobutanation). As the authors concluded, the apparent suppression of the chain mechanism is viewed as an inherent problem with the copolymerization format of cation-radical Diels-Alder polymerization. ... 

Generally, at least in theory, an important aspect of cation-radical polymerization, from a commercial viewpoint, is that either catalysts or monomer cation-radicals can be generated electrochem-ically. Such an approach deserves a special treatment. The scope of cation-radical polymerization appears to be very substantial. A variety of cation-radical pericyclic reaction types can potentially be applied, including cyclobutanation, Diels-Alder addition, and cyclopropanation. The monomers that are most effectively employed in the cation-radical context are diverse and distinct from those that are used in standard polymerization methods (i.e., vinyl monomers). Consequently, the obtained polymers are structurally distinct from those available by conventional methods although the molecular masses observed so far are still modest. Further development in this area would be promising. 

The cyclodimerization depicted in Scheme 7.19 is one of the many examples concerning cation-radicals in the synthesis and reactions of cyclobutanes. An authoritative review by Bauld (2005) considers the problem in detail. Dimerization is attained through the addition of an olefin cation-radical to an olefin in its neutral form one chain ends by a one-electron reduction of the cyclic dimer cation-radical. Unreacted phenylvinyl ether acts as a one-electron donor and the transformation continues. Up to 500 units fall per one cation-radical. The reaction has an order of 0.5 and 1.5 with respect to the initiator and monomer, respectively (Bauld et al. 1987). Such orders are usual for branched-chain reactions. In this case, cyclodimerization involves the following steps ... 

One of the problems associated with thermal cyclodimerization of alkenes is the elevated temperatures required which often cause the strained cyclobutane derivatives formed to undergo ring opening, resulting in the formation of secondary thermolysis products. This deficiency can be overcome by the use of catalysts (metals Lewis or Bronsted acids) which convert less reactive alkenes to reactive intermediates (metalated alkenes, cations, radical cations) which undergo cycloaddilion more efficiently. Nevertheless, a number of these catalysts can also cause the decomposition of the cyclobutanes formed in the initial reaction. Such catalyzed alkene cycloadditions are limited specifically to allyl cations, strained alkenes such as methylenccyclo-propane and donor-acceptor-substituted alkenes. The milder reaction conditions of the catalyzed process permit the extension of the scope of [2 + 2] cycloadditions to include alkene combinations which would not otherwise react. 

The scope and utility of cation radical induced cyclobutanation1 is greatly enhanced by the option of cross additions, the first of which was the formation of a 3 2 mixture of diastereomeric cyclobutanes in the irradiation of an equimolar mixture of phenyl vinyl ether and 1,1-dimethylindene in the presence of tetraphenylpyrylium tetrafluoroboratc in acetonitrile.2 The scope of PET cyclobutanations was further extended in a synthetic sense by the observation of cross additions of electron-rich alkenes to conjugated dienes.3 4 Examples of such reactions are shown below in the formation of compounds 1, 2, 3 and 4. 

Recently, the distinction between electrophilic and ion radical (electron-transfer) mechanisms of addition reactions to the vinyl double bond of aryl vinyl sulfides and ethers has been achieved by studying substituent effects (Aplin Bauld 1997). Specifically, the effects of meta and para substituents on the rates of electrophilic addition correlate with Hammett cr values, while ionization of the substrates to the corresponding cation radicals correlates with cr+. The significance of the respective correlations was confirmed by statistical tests. The application of this criterion to the reaction of aryl vinyl sulfides and ethers with tetracyanoethylene revealed that formation of cyclobutanes occurs via direct electrophilic addition to the electron-rich alkene and not via an electron-transfer mechanism. 

The final copolymer was obtained in 90% yield it had a molecular weight of 10,800 and a polydispersity index of 2.1. In this case Diels-Alder copolymerization dominates over the cyclobutane homopolymerization of a bi(dienophile). This means that the Diels-Alder addition of the dienophile to the diene is substantially faster than the competing addition of the dienophile cation radical to the neutral dienophile. 

Here a secondary electron transfer between the radical cation and a neutral donor molecule produces a 1,4-cation radical. The acyclic 1,4-cation radical is in equilibrium with a cyclobutane radical cation. Other dimerizations have been described by Farid et al. [73-75], Arnold et al. [76], Pac et al. [77,78], and others [79-81]. 

The enhanced reaction rates and regioselectivities (head-to-head) in the alkene dimerisation (cyclobutane formation e.g. 18-19) via radical cation catalysed reactions have led numerous studies in this direction [5,10, 36-39]. The head-to-head stereochemistry of these dimerisations have been explained in terms of the addition of the radical cation to a neutral molecule giving the stabilised 1,4-radical cation. An interesting application of the cation-radical initiated (2 + 2)-cyclodimerisation strategy was reported by Mizuno et al. [40] for the synthesis of macrocyclic 2-m-dioxabicyclo (m-1,2,0) ring systems (21) from the PET reactions of 20 (Scheme 6). 

Bauld and coworkers have examined the cation radical cycloadditions of 1,3-dienes with electron-rich alkenes and found that, under photosensitized electron-transfer conditions, [2 -i- 2] cycloaddition is in many cases favored over Diels-Alder addition. Thus, as illustrated in equation (30), 1, T-dicyclopentenyl (186) reacts with p-chloroethyl vinyl ether under electron transfer conditions to afford the cyclobutane adduct (187), which was cleaved to the cyclobutanol (188) in 70% yield upon treatment with n-butyl-iithium. Oxyanion-accelerated VCB rearrangement then provided (189) as a mixture of diastereomers in... 

Scope of the cation radical chain cyclobutanation reaction... 

Subsequent to the work of the Ledwith group, cation radical cyclobutanation was extended to a variety of relatively readily ionizable substrates, including styrenes, indenes, and phenyl vinyl ether (Scheme 8) [25, 26]. 

Cation radical cyclobutanation reactions of alkynes, ketenes, and allenes... 

In 1981, this cation radical Diels-Alder cyclodimerization of 1,3-cyclohexadiene was shown to be more cleanly (only 1 % of the cyclobutane dimers is produced), conveniently (in a synthetic organic context), and efficiently (70 % yield) carried out by chemical ionization of the diene, using 3+ (Scheme 15) [39]. 

An intriguing competition arises in the context of cation radical cycloadditions (as in the context of Diels-Alder cycloadditions) which involve at least one conjugated diene component. Since both cyclobutanation and Diels-Alder addition are extremely facile reactions on the cation radical potential energy surface, it would not be surprising to find a mixture of cyclobutane (CB) and Diels-Alder (DA) addition to the diene component in such cases. Even in the cyclodimerization of 1,3-cyclohexadiene, syn and anti cyclobutadimers are observed as 1 % of the total dimeric product. Incidentally, the DA dimers have been shown not to arise indirectly via the CB dimers in this case [58]. The cross addition of tw 5-anethole to 1,3-cyclohexadiene also proceeds directly and essentially exclusively to the Diels-Alder adducts [endo > exo). Similarly, additions to 1,3-cyclopentadiene yield essentially only Diels-Alder adducts. However, additions to acyclic dienes, which typically exist predominantly in the s-trans conformation which is inherently unsuitable for Diels Alder cycloaddition, can yield either exclusively CB adducts, a mixture of CB and DA adducts or essentially exclusively DA adducts (Scheme 26) [59]. 

The reaction of 6 with TCNE yields only the conventional adduct corresponding to the uncyclized probe and none of the product expected from the cation radical cyclization. That the probe cyclization of the cation radical of 6 would have been observed in the context of an ET mechanism, if it had been involved, was demonstrated by generating the contact ion radical pair of 6+7TCNE via excitation of the charge transfer complex of 6 and TCNE. The cyclobutane cyclization product of the probe reaction was easily detected under these conditions. Consequently, an ET mechanism for this reaction can be confidently excluded. In a similar manner, the epoxidation of 5 and 6 by oxidized metalloporphyrins provides strong evidence against a cation radical mechanism for these reactions [76]. 

Although the pericyclic chemistry of anion radicals has been much slower to emerge than that of cation radicals, the number of intriguing examples now available suggests that this could be an attractive area for future development in electron transfer chemistry. Reaction types which have been exemplified include cyclobutanation, retrocyclobutanation, Diels-Alder addition, electrocyclic reactions, and retroelec-trocyclic reactions. 

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