Dissolving metals chemoselectivity

A potentially useful chemoselective dissolving metal reagent for the reduction of aromatic ketones in the presence of other functional groups is the combination Zn-DMSO and aqueous potassium hydroxide. In three examples (benzophenone, fluorenone and 4-benzoylpyridine), the yields of secondary alcohols were over 90%. Two other ketones (xanthone and thioxanthone) gave mixtures of alcohol and the hydrocarbon obtained by hydrogenolysis of a carbon-oxygen bond. ... 

In general, the reduction of aromatic carbonyl compounds to the corresponding alcohols by dissolving metals is not a particularly valuable synthetic procedure. Better yields and chemoselectivity are usually obtained using complex metal hydrides. 

In contrast to traditional dissolving metal systems, low-valence metal cations, particularly Sm, show considerable chemoselectivity in carbonyl reductions. In some cases these reagents can effect transformations which are difficult using metal hydrides or other traditional reducing agents. It has been suggested, and is almost certain, that these reductions are mechanistically similar to alkali metal reductions. ... 

Although Smh is more chemoselective than traditional dissolving metal reagents, it does react with sulfoxides, epoxides, the conjugated double bonds of unsaturated ketones, aldehydes and esters, alkyl bromides, iodides and p-toluenesulfonates. It does not, however, reduce carboxylic acids, esters, phosphine oxides or alkyl chlorides. In common with most dissolving metal systems, ketones with an a-hetero substituent suffer loss of the substituent rather than reduction of the carbonyl group. ... 

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. 

Baeyer-Villiger oxidation (p. 853) catalytic hydrogenation (p. 844) chemoselective reaction (p. 848) dissolving-metal reduction (p. 846) enantioselective reaction (p. 857) epoxidation (p. 855) functional group interconversion (p. glycol (p. 858)... 

The hydrosilylation of terminal alkynes disclosed by Trost can be applied to internal alkynes as well. i Remarkably, the (Z)-isomer is generated in this process, resulting from trans addition during hydrosilylation. The protodesilylation of these sily-lated products in the presence of copper(I) iodide and tetrabuty-lammonium fluoride (TBAF) or silver(I) fluoride (eq 15) leads to internal fraws-olefins. This two-step method is a useful synthetic transformation to access ( j-alkenes from internal alkynes. In contrast, the chemoselective reduction of alkynes to the corresponding ( -alkenes is conventionally accomplished readily with Lindlar s catalyst. The complementary process to afford ( )-olefins has proven much more difficult. Methods involving metal hydrides, dissolving metal reductions, low-valent chromium salts provide the desired chemical conversion, albeit with certain limitations. For example, functional substitution at the propargylic position (alcohols, amines, and carbonyl units) is often necessary to achieve selectivity in these transformations. Conversely, the hydrosilylation/protodesilyla-tion protocol is a mild method for the reduction of alkynes to ( )-alkenes. 

Reductions of a,P-unsaturated ketones with solutions of Li, Na, or K in liquid NH3 are chemoselective, resulting in the exclusive reduction of the carbon-carbon double bonds. The reaction involves addition of the substrate dissolved in Et20 or THF to a well-stirred solution of the metal in liquid NH3. Addition of one equivalent of t-BuOH as a proton donor is beneficial for driving the reduction to completion. However, excess alcohol, especially of the more acidic EtOH, causes further reduction of the saturated ketone initially formed to the corresponding alcohol. 

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