Intramolecular Cyclizations Involving Anion Radicals

DCA-sensitized irradiation of oxime ethers 39e and 40c afforded the corresponding cyclopropanes 41e and 42c in low yield. However, for unknown reasons, irradiation of compound 39f under these conditions gave a complex mixture of products in which the corresponding 1-ADPM product was not present. Irradiation of oxime ether 40c also afforded the [4-1-4]-cycloadduct 60." The mechanism shown in Scheme 15 could justify the formation of 60. This involves the generation of a radical-cation/radical-anion pair 61. Intramolecular cyclization of the radical-cation within the solvent cage generates the intermediate 62, which undergoes intermolecular cycHzation, to yield the observed product (Scheme 15). 

This intennediate is then involved in the cyclization step [132]. However, it has been shown in another series of experiments that enecarboxylate radical-anions dimerize rapidly before protonation when only traces of water are present [43]. On the basis of these findings, it seems more likely that, as originally proposed, intramolecular cyclization occurs at the level of the radical-anion, and that this process is faster than the alternative bimolecular dimerization. 

This kind of reaction is effective with acrylate esters and even with 4-vinylpyridine. Somewhat surprisingly, it works well even with some terminally disubstituted acrylate esters. Intramolecular versions involving cyclization to five-membered rings are especially effective. Mechanistically, these reactions could involve the coupling of two anion radicals or the addition of an anion radical to a corresponding neutral, followed by reduction of the distonic anion radical to the dianion, which is then protonated twice, yielding the hydrodimer. Apparently, the distinction between these two plausible mechanistic types has not yet been decisively made in most cases (however, please see the discussion on intramolecular cyclizations immediately... 

These cyclizations both involve the reductive intramolecular addition of an electron deficient alkene function to an aldehyde carbonyl function, and both are effected in ca 90 % yields. The mechanism of this latter type of electrochemically induced cyclizations of carbon-carbon double bonds to carbonyl double bonds have been studied rather extensively, with especial attention to the fundamental mechanistic question of whether the cyclization step involves an anion radical, radical, or anionic mechanism [122]. The latter two mechanisms would involve the protonation of the initially formed anion radical intermediate to form a radical, which could then cyclize or, alternatively, be further reduced to an anion, which could then cyclize. Extensive and elegant electrochemical and chemical studies have led to the formulation of these reactions as involving anionic cyclization (Scheme 74). 

There are many examples of such reactivity and some of these have been reviewed by Roth and coworkers, a research group that is extremely active in this area. An example that is typical of the processes encountered involves the cyclization of the diene geraniol (1). In this case the sensitizer is 9,10-dicyanoanthracene (DCA) and the reactions are carried out in methylene chloride. The authors state that a contact radical-ion parr is involved, i.e. the radical cation of the diene is in close proximity to the radical anion of the DCA. Reaction within this yields the cyclopentane derivatives 2 and 3 in the yields shown. The ring formation is the result of a five centre CC cyclization within the radical cation of 1. When a more powerful oxidant such as p-dicyanobenzene is used as the sensitizer in acetonitrile as solvent, separated radical-ion pairs are involved. This leads to intramolecular trapping and the formation of the bicyclic ethers 4 and 5 . The bicyclic ether incorporates an aryl group by reaction of the radical cation of the diene with the radical anion of the sensitizer (DCB). This type of reactivity is referred to later. Other naturally occurring compounds such as (/fj-f-bj-a-terpineol (6) and (R)-(- -)-limonene (7)... 

The large number of synthetically useful intermolecular hydrodimerizations and intramolecular cyclizations of activated olefins to complex carbon skeletons involves in most cases radical anions as key intermediates [152]. 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Formation of 4- or 5-membered rings follows reduction of dialkyl bromoalkylidenemalo-nates by cyclization onto the 6-carbon of the diactivated double bond [Eq. (48)] [225]. A plausible mechanism may involve C-Br cleavage through inter- or intramolecular electron transfer from the initially formed radical anion to the a orbital. The radical so fonned may add intramolecularly to the activated alkene function. An alternative, 8 2 reaction between the alkene radical anion and the bromide would be expected to occur from the a-carbon of the activated alkene, which bears the higher charge density. 

Although it is not always possible to rule out radical-anion promoted processes definitively, there are many intramolecular addition/elimination sequences involving arenes that are beyond any doubt polar in nature. The spontaneous cyclization of... 

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