Carbonylative coupling processes form ketones

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. 

Catalytic processes based on the use of electrogenerated nickel(O) bipyridine complexes have been a prominent theme in the laboratories of Nedelec, Perichon, and Troupel some of the more recent work has involved the following (1) cross-coupling of aryl halides with ethyl chloroacetate [143], with activated olefins [144], and with activated alkyl halides [145], (2) coupling of organic halides with carbon monoxide to form ketones [146], (3) coupling of a-chloroketones with aryl halides to give O -arylated ketones [147], and (4) formation of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal carbonyl [148]. 

As already indicated, carbonyl compounds such as ketones, aldehydes, enones, and quinones possess the property to act as effective electron acceptors in the excited state for generating radical anions in the presence of electron-donating partners such as alkenes, aromatics, ruthenium complexes, amines, and alcohols. We will not consider the reactivity of enones and quinones, but we will focus our attention on the behavior of the radical anions formed from ketones and aldehydes. Four different processes can occur from these radical anions including coupling of two radical anions and/or coupling of the radical anion with the radical cation formed from the donor, abstraction of hydrogen from the reaction media to produce alcohols, cyclization, in the case of ce-unsaturated radical anions, and fragmentation when a C -X bond (X=0, C) is present (Scheme 18). 

Palladium-catalyzed carbonylation of organic halides to form esters, amides, ketones, and aldehydes (Equation 17.58) has been studied and reviewed extensively. " These reactions are closely related to the palladium-catalyzed cross-coupling processes presented in Chapter 19. However, the addition of CO to ttiese processes generates organic carbonyl compounds, rather than products from direct cross coupling. 

Termination is principally via radical coupling forming hexabutylditin, or to a lesser degree via the coupling of ketyl radicals. In the case of the mr ketones a different mechanism is proposed. The rate of abstraction of H from the tributyltinhydride by benzylic radicals is slower than the corresponding abstraction by alkyl radicals. Since the rate at which the tributyltin radical will add to aromatic carbonyls is similar to the addition rate to aliphatic carbonyls, the dominant radical species for the tttt systems is the ketyl radical. The primary termination process involves the coupling of the predominant radical species resulting in pinacol formation. 

Intermolecular coupling of ketones and alkenes, promoted by SmH, occurs with excellent stereochemical control. In one such reaction, samarium(II) iodide has been used to prepare cyclobutanones and cyclobutanols from chiral, 6-oxohex-2-enoates (equation 137)520. The reaction is performed in THF in the presence of HMPT and occurs in good yield with excellent stereocontrol. If appropriately located carbonyl and alkene moieties are present in a molecule, then Sml2-HMPT can be used to form cyclooctanols by a radical cyclization process in some cases there is a reasonable degree of diastereoselectivity (equation 138)521,522. 

There is an inherent competition between simple reduction of the ketone and the reductive cyclization process with unsaturated carbonyl substrates. Cyclization processes that are slower than that of the ketyl-alkene cyclization forming a five-membered ring, suffer frtxn lower yields owing to this competition. For example, ketyl-alkyne coupling can also be achieved when mediated by Smb, but yields are lower than those achieved with analogous keto-alkenes (equation 68). This might have been expected on the basis that radical additions to alkynes are slower than corresponding additions to alkenes. Similarly, the rate... 

Although reduction of ketones with alkali metals, for example, sodium (Na°) in ethanol (CH3CH2OH), to the corresponding alcohol, as already noted, has been replaced with complex hydrides, a minor product in the original reaction, the result of coupling two ketones at their respective carbonyl carbons, was occasionally found on workup of the reaction mixture. The diol (a pinacol) thus formed could be made the major product if the reaction was carried out with magnesium (Mg°) or amalgamated aluminum (Al-Hg) instead of sodium (Na°). The process, which doubtlessly involves a series of one-electron transfer reactions, is shown in Equation 9.21. 

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