Radical anions reactions with electrophiles

O. Hammerich, M. F. Nielsen, The Competition Between the Dimerization of Radical Anions and Their Reactions with Electrophiles, Acta Chem. Scand. 1998, 52, 831-857. 

The formation of ring systems by the anionic cyclization of olefinic alkyl, aryl and vinyl-lithiums is an interesting synthetic transformation that provides a regiospecific and highly stereoselective route to five-membered carbocycles and heterocycles99. Most importantly, it is possible to functionalize the initially formed cyclization product by a tandem reaction with electrophiles, a reaction that is not generally possible in the case of radical cyclizations. 

Although aliphatic nitriles take part in alkylation reactions with tri- and tetracyanobenzenes (Sect. 2.1.3), irradiation of DCA and an amine in aqueous acetonitrile takes a different course giving 9-amino-10-cyanoanthracene, a reaction in which the amine serves as the donor, but then the DCA radical anion reacts with acetonitrile functioning as an electrophile leading via an isomerization-elimination process to the final product [32],... 

Radical ions are created in solution by chemically or electrochemically induced electron transfer to or from a conjugated ir-system. Even if these ions are thermodynamically stable they are only of limited persistence since they are susceptible to reactions with electrophiles and nucleophiles or undergo other processes like dimerization or electron-transfer induced bond cleavage [9, 10]. Pairs of radical anions and radical cations can also be formed by electron transfer between neutral donors and acceptors either in the ground state or upon photochemical excitation [11, 12]. 

Metal Complexes.—Minoura and Tsuboi have studied the reactivity of thiobenzophenone towards alkali metals. When dissolved in THF under an atmosphere of nitrogen, the thioketone reacted with one equivalent of alkali metal to form the rather unreactive radical anion (72). With more than two equivalents of alkali metal, however, the very reactive dianion complex (73) was formed according to the equilibrium (72) -I- Na (73). The structure of (73) was established mainly on the basis of the reactions with electrophilic reagents. Thus the reactivity of (73) closely parallels that of the thiobenzaldehyde dianion (12). ... 

The reductive couphng of imines can follow different pathways, depending on the nature of the one-electron reducing agent (cathode, metal, low-valent metal salt), the presence of a protic or electrophihc reagent, and the experimental conditions (Scheme 2). Starting from the imine 7, the one-electron reduction is facihtated by the preliminary formation of the iminiiim ion 8 by protonation or reaction with an electrophile, e.g., trimethylsilyl (TMS) chloride. Alternatively, the radical anion 9 is first formed by direct reduction of the imine 7, followed by protonation or reaction with the electrophile, so giving the same intermediate a-amino radical 10. The 1,2-diamine 11 can be formed from the radical 10 by dimerization (and subsequent removal of the electrophile) or addition to the iminium ion 8, followed by one-electron reduction of the so formed aminyl radical. In certain cases/conditions the radical 9 can be further reduced to the carbanion 12, which then attacks the... 

The wide diversity of the foregoing reactions with electron-poor acceptors (which include cationic and neutral electrophiles as well as strong and weak one-electron oxidants) points to enol silyl ethers as electron donors in general. Indeed, we will show how the electron-transfer paradigm can be applied to the various reactions of enol silyl ethers listed above in which the donor/acceptor pair leads to a variety of reactive intermediates including cation radicals, anion radicals, radicals, etc. that govern the product distribution. Moreover, the modulation of ion-pair (cation radical and anion radical) dynamics by solvent and added salt allows control of the competing pathways to achieve the desired selectivity (see below). 

The attachment of an electron to an organic acceptor generates an umpolung anion radical that undergoes a variety of rapid unimolecular decompositions such as fragmentation, cyclization, rearrangement, etc., as well as bimolecular reactions with acids, electrophiles, electron acceptors, radicals, etc., as demonstrated by the following examples.135"137... 

Compared with the anodic oxidation of a 1,3-diene, the cathodic reduction of a 1,3-diene may be less interesting since the resulting simple transformation to monoolefin and alkane is more conveniently achieved by a chemical method than by the electrochemical method. So far, only few reactions which are synthetically interesting have been studied15. The typical pattern of the reaction is the formation of an anion radical from 1,3-diene followed by its reaction with two molecules of electrophile as exemplified by the formation of the dicarboxylic acid from butadiene (equation 22)16. 

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]. 

Radical anion EGBs derived from aromatic carbonyl compounds are expected to be relatively weak bases but since the radical anions undergo dimerization, the more basic dimer dianions may be active as EGBs for substrates with pK values in the range 20 to 23. Aromatic carbonyl compounds have primarily been used as PBs in catalytic reactions in which the PB also functions as an electrophile (cf. Sect. 14.9.2). 

Nucleophilic reagents can attack the N—H hydrogen to yield an anion (15) which reacts readily with electrophiles at the nitrogen, oxygen and /3-carbon atoms (Scheme 3). Strong nucleophiles may attack directly at the carbonyl groups to afford (16,17) or in conjugate fashion to produce (18,19) these intermediates usually rearomatize to pyridines (see Chapter 2.06). Reactions of free radicals with pyridinones are not very numerous. 

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