Enolate radical, oxygenation

This oxidative process has been successful with ketones,244 esters,245 and lactones.246 Hydrogen peroxide can also be used as the oxidant, in which case the alcohol is formed directly.247 The mechanisms for the oxidation of enolates by oxygen is a radical chain autoxidation in which the propagation step involves electron transfer from the carbanion to a hydroperoxy radical.248... 

As in the reductive ring-opening, titanocene—oxygen bonds have to be protonated. Here, a titanium enolate, which is generated after reductive trapping of an enol radical, has to be protonated, in addition to a simple titanocene alkoxide. As before, 2,4,6-collidine hydrochloride constitutes a suitable acid to achieve catalytic turnover, but here zinc dust turned out to be the reductant of choice [31c], The features of the stoichiometric reaction are preserved under our conditions. Acrylates and acrylonitriles are excellent radical acceptors in these reactions. Methyl vinyl ketone did not yield the desired addition product. Under the standard reaction conditions, a-substituted acceptors are readily tolerated, but (3-substitution gives the products only in low yields. 

Protonation of the radical-anion occurs on oxygen to give an enol-radical. The latter species is a resonance hybrid. It takes part in a fast irreversible radical-radical dimerization step and since the species has two potential radical sites, three structural isomers of the hydrodimer can be formed. The main product is formed from a transition state with minimum steric hindrence between the radical centres. 

Another example of the application of the spin-center-shift concept is depicted in Scheme 8b. On irradiation of /3-ketoamides 43, hydrogen abstraction occurs from the d-position, followed by smooth elimination of methanesulfonic acid. In contrast with the applications of spin-center-shift mentioned above, the enolate radical moiety of biradicals 44 reacts solely as oxygen radicals 44b to give the oxa-zinones 45 [20],... 

The pathway in Scheme 3 relates mainly to alkenes activated by keto or aldehyde groups, for reduction in hydroxylic solvents. Under these conditions, radical anions derived from carbonyl compounds are protonated at oxygen, and the resulting enolic radical, HI, is more difficult to reduce than the starting compound. Consequently, fast dimerization of the enol radicals may compete with further reduction. For other substrate types, especially in aprotic solvents containing added acids, proton transfer is to carbon... 

Enones may react either as ketones (cf. Chapter 10) or as activated alkenes thus giving pinacols, y6,y6 -coupling, or mixed coupling products. Another feature of enone reduction is that the radical anions, A, in the presence of proton donors are protonated at oxygen in a fast process, and the resulting enol radical, B , is more difficult to reduce than the neutral substrate (Sec. II.A. 1). Radical anions derived from other activated double bonds tend to protonate at carbon in the presence of proton donors, and the resulting radical is more easily reduced than the neutral substrate (Schemes 1 and 3). 

The cyclizations of 5-hexenyl radicals sulfonylated at C-l show an unexpected stereoselectivity8. The sulfone cyclizations, for example, to an alkene or an enol ether, give cyclopcntane derivatives in good yields and with high trails selectivity. The stereoselectivity in this case is attributed to steric interactions and electronic repulsion between the oxygen at the sulfur and the enol ether oxygen. 

The synthesis of vinylcyclohexanones through fragmentation of oxygen-substituted vinyl cyclopropanes has also been reported (Scheme 5) [7]. After addition of the thiophenyl radical to the olefin, benzophenone is extruded to yield an unsaturated enol radical. The reaction sequence is completed as described above for the [3+2] annulation. 

In a study on the synthesis of the antibiotic SF 2315B, the core structure of the natural product was assembled in stereocontrolled fashion by TBAF-induced autoxidation of a quinone (cf. 8 —> 9, Seheme 16), thereby forming three stereocenters and three C O bonds in a single operation [38]. A reaction cascade involving sequential oxygenation of an enol radical, cyclization and cleavage of the resultant endoperoxide accounts for this transformation [38]. 

Carbon radicals generated by the addition of enol radicals derived from 1,3-dicarbonyl compounds to alkenes are efficiently trapped by oxygen in a chain reaction leading to hemiperacetals [51], The process is illustrated by the electrochemical or AIBN-initiated reaction of 2-methyl-1,3-cyclopentanedione with styrene and oxygen in acetonitrile, which provides the thermodynamically favored all-c bicyclic peroxide in good yield (Scheme 23) [51],... 

The radicals that are formed from the enolate in this process are rapidly destroyed so that only the stable semidione species remains detectable for EPR study. Semidiones can also be generated oxidatively from ketones by reaction with oxygen in the presence of base. The diketone is presumably generated oxidatively and then reduced to the semidione via reduction by the enolate derived from the original ketone. 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

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