Radical anions intramolecular reaction

The previous chapter covered radical cation cyclization reactions that were a consequence of single-electron oxidation. In the following section, radical anion cyclization reactions arising from single-electron reduction will be discussed. In contrast to the well documented cyclization reactions via carbon-centered free radicals [3, 4], the use of radical anions has received limited attention. There are only a few examples in the literature of intramolecular reductive cyclization reactions via radical anions other than ketyl. Photochemi-cally, electrochemically or chemically generated ketyl radical anions tethered to a multiple bond at a suitable distance, have been recognized as a promising entry for the formation of carbon-carbon bonds. 

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). 

Therefore, the sequence of reactions illustrated in Fig. 1 catalytically (the anthraquinone is regenerated) injects a radical cation into a DNA oligonucleotide that does not simultaneously contain a radical anion. As a result, the lifetime of this radical cation is determined by its relatively slow bimolecular reaction with H20 (or some other diffusible reagent such as 02- ) and not by a rapid intramolecular charge annihilation reaction. This provides sufficient time for the long distance migration of the radical cation in DNA to occur. 

After formation of an O-coordinated ketyl radical anion and a cis coordinated tyrosin via hydrogen abstraction, a rapid intramolecular one-electron redox reaction occurs with release of the product aldehyde and formation of the fully reduced active site containing a Cu(I) ion, which then reacts with 02 to give H202 and the active enzyme. The above sequence represents Nature s mechanistic blueprint for coordination chemists. 

Disproportionation mechanisms have been proposed for protonahon reachons and intramolecular rearrangements (see Sects. 4.3.2 and 4.3.3) [54]. The prominent feature is that follow-up processes at the level of the dianion can already take place at potentials corresponding to radical anion formation. In order to evaluate data for disproportionation reactions it is necessary to know the value of the disproporhonahon equilibrium constant. 

Scheme 6 Intramolecular reaction of a radical anion with an electrophile.

Radical anions resulting from cathodic reductions of molecules react with electrophilic centers. As an example (Scheme 8), the reduction of compounds in which a double bond is not conjugated with a carbonyl group, involves an intramolecular coupling reaction of radical anion with alkene [12]. 

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... 

The photolysis of donor-acceptor systems shows a reaction pattern of unique synthetic value. Direct irradiation of the donor-acceptor pairs, such as arene-amine, leads by intramolecular electron transfer, to amine radical cations and arene radical anions. The generated radical cation and radical anion intermediates undergo cyclization reactions providing efficient synthetic routes to N-heterocycles with a variety of ring sizes. 

Chloroadamantanes (149) and (150) reacted with CH2COPh to afford the monosubstitution products (151) and (152) as intermediates, the intramolecular electron-transfer reaction of the radical anion intermediate being a slow process. Product (151) with chlorine in the 1-position reacted further to give (153), whereas (152) with chlorine in the 2-position is unreactive, showing that the 1-position is the more reactive. 1,2-Diiodoadamantane (154) reacted with CH2NO2 to give the monosubstitution products (155) and (156). This implies that the intramolecular electron-transfer reaction of the radical anion is a slow process. The fact that (155) was formed as major product and (156) was the minor product shows that, when (154) accepts an electron, fragmentation occurs faster at the 1-position than the 2-position. 

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. 

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. 

The intramolecular reaction of activated alkenes of the type 8 leads to the formation of 5- or 6-membered rings [26] and has been carried out only at a mercury cathode in a divided cell. In these processes, the activated alkene radical-anion is formed at a less negative potential than that required for cleavage of the carbon-bromine bond. Cyclization then occurs by nucleophilic substitution. 

The radical-anions from from alkenes with electron withdrawing substituents will add to carbon dioxide [28]. This process involves the alkene radical-anion, which transfers an electron to carbon dioxide for which E° = -2.21 V vs. see [29]. Further reaction then occurs by combination of carbon dioxide and alkene radcal-anions [30]. The carbanion centre formed in this union may either be protonated or react with another molecule of carbon dioxide. If there is a suitable Michael acceptor group present, this carbanion undergoes an intramolecular addition reaction... 

The radical-anions from enecarboxylates show nucleophilic reactivity on the p-carbon atom. Intramolecular carbon-carbon bond formation occurs when a suitably placed alkyl bromide, see p. 58 [26], or carbonyl [128] function is available. Related reactions are shown by the radical-anions from enenitriles [128]. The... 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

A. J. Moye (California State College, Los Angeles, Calif.) An alternative mechanism to the intramolecular hydrogen transfer could be the transfer of a single electron to give a radical-anion intermediate in place of the radical-peroxide of Reaction 4. Have you considered this possibility ... 

Interesting variations of these reactions are observed when the a-silylamine donor funtion is tethered to an enone. For example, the intramolecular ET reaction of 143 results in two divergent cyclizations. Methanol assists the cleavage of the C—Si bond the resulting biradical anion 146 couples protonation and tautomer-ization then leads to 147. In acetonitrile, on the other hand, transfer of an a proton to the enone radical anion function forms biradical 144 coupling and tautomer-ization then generates 145. " ... 

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