Conjugate reduction chemoselective

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. 

DIBAL was used for the conjugate reduction to produce aluminum enolates in the presence of MeCu catalyst [39]. Unlike strong bases fhat readily deprotonate the a-hydrogen of carbonyl compounds, fhis mefhod tolerates a ketone carbonyl and its a hydrogen, and was fhus chemoselective as well as quantitatively reducing fhe a,/ -unsaturated ester (Scheme 6.19). 

Conjugate Reduction. The carbon-carbon double bonds of various a, 8-unsaturated ketones and related compounds can be selectively reduced with a heterogeneous palladium catalyst. When nonpolar solvents such as toluene were employed, 1,4-reduction products of a,/8-unsaturated ketones, esters, amides, and nitriles were obtained in high yields (87-100%) with high chemoselectivities in the presence of a catalytic amount of Pd/C(2.5-5 mol %) and acetic acid. Highly-polar solvents enhanced 1,2-reduction to afford alcohols as a result of overreduction. 

Moreover, the reactivity differences between the tin and silicon hydrides can be exploited for functional-group differentiation. For example, in the presence of Pd(0), tri-butyltin hydride reduces a,/3-unsaturated aldehydes and ketones rapidly but silicon hydrides are unable to do so. Thus, the treatment of a mixture of an allylic acetate and an unsaturated ketone with tin hydride and Pd(0) catalyst results in total conjugate reduction of the latter and unreacted allylic acetate. In contrast, employment of silicon hydride provides complementary chemoselectivity allylic reduction was completed before any reduction of the Michael acceptor could be detected (Scheme 15). 

The second strategy involves addition of a group 14 metal hydride to palladium. For example, a combination of either tributyltin hydride or various silicon hydrides and palladium catalyst are efficient systems that affect the conjugate reduction of enones with high chemoselectivity and regioselectivity. 

Other Reactions. The 1 1 silylcuprate, prepared from the iodide rather than the cyanide, added to diisobutylaluminum hydride, makes a more chemoselective reagent for conjugate reduction of the Hajos-Parish diketone than did the earlier t-butylcopper additive (eq 18). ... 

Electrocatalytic hydrogenation has the advantage of milder reaction conditions compared to catalytic hydrogenation. The development of various electrode materials (e.g., massive electrodes, powder cathodes, polymer film electrodes) and the optimization of reaction conditions have led to highly selective electrocatalytic hydrogenations. These are very suitable for the conversion of aliphatic and aromatic nitro compounds to amines and a, fi-unsaturated ketones to saturated ketones. The field is reviewed with 173 references in [158]. While the reduction of conjugated enones does not always proceed chemoselectively at a Hg cathode, the use of a carbon felt electrode coated with polyviologen/Pd particles provided saturated ketones exclusively (Fig. 34) [159]. 

Chemoselectivity is often a major issue in the reduction of multifunctional organic substrates such as substituted conjugated enones. The corresponding unsaturated alcohols have found use as building blocks for pharmaceutically active molecules for example (i-amino-a-phenylethanol is used for the synthesis of (5-blockers which are the active molecules for controlling hypertension and other cardiac disorders. 

Chemoselective reduction of conjugated enones to allylic alcohols via hydrogen transfer from propan-2-ol over metal oxides is investigated in vapour phase conditions. The unique ability of Mgo to reduce exclusively carbonyl group is observed. However, because of the high basicity of MgO side reactions are present. It is shown that by doping the Mgo catalyst with HC1 a significant decrease of its basicity occurs and consequently side reactions are minimized. 

Chemoselective reduction of the conjugated double bond of a, /f-unsaturated aldehydes such as citral (556) to give citronellal (577) is possible by Pd-catalysed hydrostannation in the presence of AcOH [213],... 

The Cp2TiCl/H20 combination can also be used for the chemoselective reduction of aromatic ketones. The reaction discriminates between ketones and alkenes, between ketones and esters and, remarkably, between conjugated and non-conjugated ketones [80]. There is strong evidence that this reduction proceeds via ketyl-type radicals, which are finally reduced by H-atom transfer from 42 [81]. Under dry conditions, titanium-promoted ketyl radicals from aromatic ketones can be used for intermolecular and intramolecular cross-coupling of ketones [82], Thus, depending on whether water is added or not, complementary and versatile synthetic procedure protocols are available. 

Treatment of particular fully conjugated heterocyclic enaminediones with NaBH4 resulted in a chemoselective reduction of the keto carbonyl group, followed by a stereoselective reduction of the carbon-carbon double bond135 (Scheme 100). Catalytic hydrogenation allowed a complete reduction of the second carbonyl group. 

---