Dissolving metals enones

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. 

Dissolving metal reduction of enones gives enolates regiospecifically... 

Na, or Li in liquid ammonia, for example) to reduce aromatic rings and alkynes. The dissolving metal reduction of enones by lithium metal in liquid ammonia is similar to these reactions—the C=C bond of the enone is reduced, with the C=0 bond remaining untouched. An alcohol is required as a proton source and, in total, two electrons and two protons are added in a stepwise manner giving net addition of a molecule of hydrogen to the double bond. 

Methods for reduction of enones may be divided conveniently into four historically based classes. The earliest procedures employed dissolving metals more recent developments, such as reduction with low-valent transition metal compounds and electrochemical processes, may also be included in this category as they all proceed via sequential addition of electrons and protons to the substrate molecule. These methods are discussed in Section 3.5.2. 

Because of the intermediacy of radical anions and/or hydroxyallyl free radicals in dissolving metal reductions of enones, dimerization may compete with simple reduction. Scheme 7 shows the three types of dimers that may be produced. 

Many other examples of chemoselective enone reduction in the presence of other reducible functionalities have been reported. For instance, the C—S bonds of many sulfides and thioketals are readily cleaved by dissolving metals. " Yet, there are examples of conjugate reduction of enones in the presence of a thioalkyl ether group." " Selective enone reduction in the presence of a reducible nitrile group was illustrated with another steroidal enone. While carboxylic acids, because of salt formation, are not reduced by dissolving metals, esters" and amides are easily reduced to saturated alcohols and aldehydes or alcohols, respectively. However, metal-ammonia reduction of enones is faster than that of either esters or amides. This allows selective enone reduction in the presence of esters"" and amides - -" using short reaction times and limited amounts of lithium in ammonia. 

Catalytic hydrogenation of an enone would not be chemoselective if an isolated double bond were also present in the molecule. However, isolated double bonds are inert to dissolving metal reduction. On the other hand, a variety of functional groups are reduced with alkali metals in liquid ammonia. These include alkynes, conjugated dienes, allylic, or benzylic halides and ethers. 

Extension of the dissolving metal reduction of enones to a,[3-unsaturated carboxylic acid esters converts the ester moiety to an amide. However, a, 3-unsaturat-ed esters undergo double bond reduction on treatment with magnesium in methanol. ... 

In addition to being more selective, dissolved calcium metal functions in a similar way to lithium and sodium metals towards organic functional groups [45]. Tab. 4.2 lists reductions giving the same products by the three dissolved metals. Among these, calcium affords the highest yields for some substrates (entries 1-3). The compounds in Tab. 4.2 include an aldehyde, indole [46], aryl ketone, enone, naphthalene [47], pyridine N-oxide [48], benzyl alcohol, styrene, and buckminster-fullerene. 

Stable conformation of an excited enone which has a substantially pyramidalized P-carbon. For example, addition of allene to octalone (19) produces (20) which results from addition of allene oiqmsite the angular substituent (equation 30). Similar results are obtained in the dissolving metal reductions of... 

The following enone is subjected to dissolving metal reduction in the presence of an appropriate protonating species such tot-butanol. Please write the structures of all the possible products and calculate their relative energies. Which product will you predict to predominate if allowed to consider the product s thermodynamic stability as the control factor ... 

Two mechanistic pathways will be discussed for the dissolving metal reduction of enones30. In both cases the first step is the reversible transfer of an electron from the metal to a vacant orbital of the substrate, yielding a radical anion. This can be protonated to the neutral radical which can dimerize or accept another electron and a proton, Alternatively, a second electron can be transferred reversibly to the radical anion, giving the dianion capable of accepting two protons. The sequence and timing of these steps depends on the substrate, the reduction potential of the reaction medium and the nature of the proton source, as well as on various other factors. In general, the thermodynamically more stable product is formed predominantly, as illustrated in the reduction of cxocyclic enone 134. The rrmw-substituted cyclohexane, with both substituents in an equatorial position, is formed preferentially if the reaction is carried out in the presence of /erf-butyl alcohol as proton source. 

Because enones are much more reactive towards dissolving metal reductions than nonactivated double bonds it is possible to selectively reduce the former in the presence of the latter type of double bond (Table 5, entries 1, 5 and 6). Furthermore, inverse addition of the lithium in ammonia solution to the substrate dissolved in diethyl ether allows selective reduction in the presence of other highly sensitive functional groups such as vinyl chlorides (entry 5). Under normal reaction conditions the chlorine is removed yielding the corresponding olefin49. 

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