Ketyl radicals, dimerization

In this mechanism the excitation of the sensitizer by the absorption of light produces the exclted singlet state from which the photochemlcally reactive n-ir triplet state Is formed by Intersystem crossing. This triplet state abstracts a hydrogen atom from the thiol molecule and forms a ketyl radical and a thlyl radical. The ketyl radicals dimerize to plnacols and the thlyl radicals add to the polymer by a chain mechanism. The ketyl radicals may also Initiate and terminate chains either by direct reaction and/or by hydrogen transfer. The preferred ene compounds are those having the allyllc structure because of their Inherent chemical stability (38). 

Two classes of charged radicals derived from ketones have been well studied. Ketyls are radical anions formed by one-electron reduction of carbonyl compounds. The formation of the benzophenone radical anion by reduction with sodium metal is an example. This radical anion is deep blue in color and is veiy reactive toward both oxygen and protons. Many detailed studies on the structure and spectral properties of this and related radical anions have been carried out. A common chemical reaction of the ketyl radicals is coupling to form a diamagnetic dianion. This occurs reversibly for simple aromatic ketyls. The dimerization is promoted by protonation of one or both of the ketyls because the electrostatic repulsion is then removed. The coupling process leads to reductive dimerization of carbonyl compounds, a reaction that will be discussed in detail in Section 5.5.3 of Part B. 

The initial step of the coupling reaction is the binding of the carbonyl substrate to the titanium surface, and the transfer of an electron to the carbonyl group. The carbonyl group is reduced to a radical species 3, and the titanium is oxidized. Two such ketyl radicals can dimerize to form a pinacolate-like intermediate 4, that is coordinated to titanium. Cleavage of the C—O bonds leads to formation of an alkene 2 and a titanium oxide 5 ... 

Another mechanism, involving addition of the ketyl to another molecule of ester (rather than a dimerization of two ketyl radicals), in which a diketone is not an intermediate, has been proposed Bloomfield, J.J. Owsley, D.C. Ainsworth, C. Robertson, R.E. J. Org. Chem., 1975, 40, 393. 

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

The product distribution observed in the dimerization of polyene-substituted ketyl radicals is also remarkable in that only products involving dimerization at the carbonyl carbon atom are observed (equation 23)82,83. This finding is quite independent of the reducing agent, since ketyl radicals formed by reduction with low-valent transition metal complexes behave analogously84-86. 

Attention has turned recently to the mechanistic details underlying these processes. Probably the most significant development in this area in recent years is the discovery that the ketyl radical produced by electrochemical reduction of benzaldehyde in buffered neutral ethanol is harder to reduce than benzaldehyde itself46. All previous discussions had assumed that the ketyl radical would be reduced as quickly as it is formed, but fast scan cyclic voltammetry demonstrated the existence of a short-lived intermediate, apparently the ketyl radical. Computer simulation of the voltammograms showed that the radical dimerizes at a rate ca 106 1VD1 s 1. 

Another fundamental reaction of >C=0 involves its reactivity as a base. In the Brpnsted sense, >C=0 - may react with a proton donor to produce a neutral ketyl radical (>C(.)OH, Figure 2, reaction 2). This is an important process when the reduction of a carbonyl compound is carried out under acidic conditions or in a protic media (e.g. elec-trochemically, with less reactive reducing reagents such as Mg or Zn, or when >C=0"-is produced via PIET and R3N"+ has available a-protons). The follow-up chemistry of >C(.)OH is that of a neutral free radical (dimerization to form pinacols, addition to unsaturated compounds, fragmentations/ring-openings, etc.), and thus beyond the scope of this chapter. 

The reduction of carbonyl compounds to form pinacol dimers can be accomplished photochemically, electrochemically or with chemical reducing agents. When conducted under acidic conditions or in protic solvents, pinacols are likely produced by coupling of two neutral ketyl radicals (vs radical anions). The electrochemical reduction is especially complicated in terms of the role of the electrode surface, counterion and solvent, and an excellent review has appeared on the subject32. 

Flatta FI, Zhou L, Mori M,Teshima S, Nishimoto S (2001) N(1)-C(5 )-linked dimer hydrates of 5-substi-tuted uracils produced by anodic oxidation in aqueous solution. J Org Chem 66 2232-2239 Flayon E (1969) Optical-absorption spectra of ketyl radicals and radical anions of some pyrimidines. J Chem Phys 51 4881-4892... 

Becker, H.-D. Sanchez, D. Hydrogen transfer by ketyl radicals the reductive dimerization of quinone methides. Tetrahedron Lett. 1975, 3745-3748. 

A new type of photo-dimerization reaction for coumarin derivatives has also been described (Equation 16) <2002TL5161>. Irradiation of coumarin-3-carboxylic acid 180 in ethanol provided three different types of products the 4,4 -dimer of chroman-2-one 181, 3-(l -hydroxyethyl)-coumarin 182, and coumarin 183. The authors postulated that for the formation of 181, a ketyl radical is first formed, and the equilibrium between the 2-position and 4-position radical favors the latter. Dimerization of the 4-position radicals, followed by tautomerization and decarboxylation, provides dimer 181. 

The reduction mechanism of carbonyl compounds and its dependence on pH has been outlined in section 8.2. Pinacol formation occurs either by dimerization of the hydroxymethyl radical 101 (Eq. (185) ) or by mixed coupling of 101 with the ketyl 102. Dimerization of 102 seems less probable due to electrostatic repulsion of the two negative charges. Besides coupling, 101 or 102 may be further reduced to the alcohol 103. With active cathodes (e.g., Hg, Sn) 101 forms organo-... 

Studies on the reduction of carbonyl compounds using low-valent metallic reagents, including Sml2, have led to an understanding of the mechanism involved. Single electron transfer to the aldehyde or ketone generates a metal ketyl radical anion 3 that can form dimeric or polymeric ion pairs 4 (Scheme 4.4).10... 

You ve seen examples of pinacol and McMurry reactions of ketones and aldehydes. What about esters You would expect the ketyl radical anion to form from an ester in the same way, and then to undergo radical dimerization, and this is indeed what happens. 

Addition of small amounts of dipolar non-HBD solvents to solutions of the sodium 9-fluorenone ketyl radical in toluene, in which diamagnetic dimers or higher aggregates are present, gives rise to well-resolved HFS patterns. The splitting first decreases with an increase in the mole fraction of the dipolar non-HBD solvent. A limiting value is reached at mole fraction x = 0.2...0.3, due to dissociation into... 

In general, reductive generation furnishes a ketyl radical anion which undergoes radical-radical coupling to form the dimer dianion [251]. This dimerization was found to be faster than the reaction of the radical anion with the parent molecule (e.g. for of p-cyanobenzaldehyde 28.6 m" s" compared with 1.45 M" s" ) [252]. 

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