Ketyl anions

More generally, double bonds between two carbons or one carbon and a heteroatom, possibly conjugated with other unsaturated moieties in the molecule, are eligible for two-electron/two-proton reactions according to Scheme 2.20. Carbonyl compounds are typical examples of such two-electron/two-proton hydrogenation reactions. In the case of quinones, the reaction that converts the quinone into the corresponding hydroquinone is reversible. With other carbonyl compounds, the protonation of the initial ketyl anion radical compete with its dimerization, as discussed later. 

The first (reversible) electron transfer generates the ketyl anion-radical. The ketyl moiety then attacks the aryl group in the ortho position. The resulting cyclohexadienyl radical is reduced to a cyclohexadienyl anion by a second electron transfer, and the anion is finally protonated. HMPA as... 

The three-membered ring in metal-ketyl anion-radicals can be readily opened. In steroid synthesis, this reaction is a classic procedure for introducing angular methyl groups (Dauben and Deviny 1966 Scheme 7.45). 

Reactions with Radicai ions of Like Charge. In the final section, we briefly mention reactions between radical ions of like charge. One of the longstanding problems of radical ion chemistry involves the actual stmcture of ketyls. Following extensive conductivity and magnetic susceptibility studies in the 1930s detailed ESR and optical studies have demonstrated the existence and interconversion of at least four distinct species a free ketyl anion a monomer ion pair a... 

Ketyl radicals have been observed in the reactions of Grignard reagents with aromatic ketones (103). Similarly, reactions of Grignard reagents with the chelate, nickel(II) 3,5-diisopropylsalicylate, give rise to ketyl anion radicals (126). 

Radical anions generated from ketones (or aldehydes) are referred to as ketyl anions. Common methods for generation of >C=0 are summarized in Figure 1. 

The simplest method for generation of a ketyl anion is via direct reduction (chemically of electrochemically) of an aldehyde or ketone (Figure 1, reaction 1). Historically, it was via direct reduction of a ketone with an alkali metal that ketyl anions were first discovered. 

Ketyl anions can also be formed via the abstraction of a proton from a neutral ketyl radical (Figure 1, reaction 2). This process is best depicted as an equilibrium (vide infra)5. 

Although less common, ketyl anions can also be generated by removal of an a-hydrogen from an alkoxide (Figure 1, reaction 3). An interesting example where a ketyl anion is formed as an intermediate in this manner is provided by the electrochemically-initiated reduction of an aryl halide by an alkoxide anion via the free radical chain process illustrated in Scheme l6. 

Finally, radical anions of carbonyl-containing compounds are often produced unexpectedly in reactions involving nucleophiles or easily oxidized free radicals. In a seminal 1964 report, Russell, Janzen and Strom noted that ketyl anions could be detected by ESR... 

With regard to Figure 2, reactions 1-3 Because the recent work dealing with these reactions is only tangentially related to ketyl anions, these reactions will not be considered further in this chapter. The remaining reactions (4-6) depicted in Figure 2 represent the bulk of the mechanistic and synthetic work which was reported in the 1985-1995 period, and will be the primary focus of the remainder of this section. 

There has been considerable interest in ring opening of cyclopropyl-containing ketyl anions from both a mechanistic and synthetic viewpoint. Cyclopropyl substituents are often... 

Cyclopropyl groups have been used to probe for ketyl anion intermediacy in reactions of Sml2 with ketones. In 1991, Molander reported that treatment of cyclopropyl ketone 15 with Sml2 yields ring-opened product 16 in 81% overall yield (equation 10)56 Timberlake and Chen reported that several cyclopropyl-ring-opened products result from treatment of 17 with Sml2 (Scheme 17)57. 

A number of intramolecular ketyl anion/olefin coupling reactions promoted by Sml2 have been reported since 1985. In general, Sml2 reactions give extremely high yields and exhibit high diasteroselectivity. 

Several examples of intramolecular ketyl anion/unactivated olefin coupling reactions were reported by the Molander group, one of which is illustrated in equation 2884. An interesting facet of this reaction is that it is possible to further react the cyclized samarium(III) intermediate (47) with a variety of electrophiles, thereby enhancing the... 

A similar cyclization of a ketyl anion (produced via reaction with SmE) onto an allene was reported by Gillmann in 1993 (equation 29)85 The regiochemistry and high diasterose-lectivity associated with this process was explained on the basis of a chelation-controlled cyclization (e.g. TS 48). The same reduction carried out with n-Bu3SnH resulted in only a 37% yield and a 5 1 ratio of diastereomers. 

Analogous intramolecular chelation-controlled ketone/olefin couplings with Sml2, in which Sm+3 was complexed in a cyclic manner to the ketyl anion and a /1-carbonyl of an ester or amide functionalilty, were reported as early as 1987 (Scheme 31)86. The cyclized samarium intermediate 49 could be further reacted with added electrophiles such... 

Cyclization of ketyl anions onto allyl sulfides or sulfones were reported to yield 2-vinylcyclopentananols according to equation 3088. 

The effect of the counterion on the outcome of this reaction was attributed to ion-pairing effects (Scheme 32). It was suggested that the ketyl anion 52 is more easily reduced when Li+ is the counterion, and that this second reduction occurs faster than cyclization90. 

Intramolecular cyclizations of ketyl anions (generated electrochemically at a Sn cathode in isopropanol) onto a remote C=N were reported in 199291. a-Hydroxyketones are produced in yields ranging from 60-80%, depending on the structure of the substrate (Scheme 33). 

Imine radical anions appear to be substantially more basic than their ketyl anion counterparts. In 1991, Zhan and Hawley reported that Ph2C=NH (generated via the electrochemical reduction of benzophenone imine) was a sufficiently strong base to depro-tonate weak carbon acids whose pK values were as high as 33185. 

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