Carbonyl group selective reduction

For the reduction of carbonyl groups or the oxidation of alcohols in the presence of C-C double and triple bonds, MPVO catalysts seem to be the best choice with respect to selectivity for the carbonyl group, as reductions with com-... 

Selective reduction of carbonyl groups in the presence of an ester group. Selective reduction of various keto esters to hydroxy esters is possible in fair yield with LiAlH4 in the presence of a small amount of silica gel (equation I).1... 

In the metal hydride reduction of two different ketones, the sterically less hindered ketone is generally reduced more easily, and modification of hydride reagents by replacement of the hydrides with sterically bulky substituents or electron-withdrawing groups enhances the chemoselectivity. MAD, however, preferentially forms complexes with sterically less hindered or more basic ketone carbonyls, enabling selective reduction of a more hindered, free ketone. Here, MAD behaves as a protector of carbonyl substrates (Sch. 118) [160]. 

The two carbonyl groups of symmetrical diketones are distinguishable, with the carbonyl group undergoing reduction doing so with enantiotopic specificity. Some acyclic and monocyclic examples are shown in Scheme 9.- 2,44.49.50 Once more, enantiomeric products can be selected by the use of organisms with opposite enantiotopic face specificities, as shown for the reduction of (19) to (/ )- or (S)-(20) (Scheme 10). ... 

In any case, the asymmetric reduction surely takes place in a chiral environment of the protein. A factor determining the stereochemistry of the product must be an asymmetric binding so as to expose one of the enantiofaces of the carbonyl group selectively to the reductant. It is difficult to clarify the details of the interaction between BSA and the substrate and to elucidate the origin of selectivity. The data listed in Table 17 predicts that bulkiness of the substituent in the substrate is not the only factor for the asymmetric induction. 

Carboxylic acids, their esters, and amides are usually resistant to sodium borohydride reduction, whereas carboxylic acid chlorides may be reduced in inert solvents to give alcohols. Where this proves unsatisfactory a new alternative procedure for acid chloride reduction in ether solution involves sodium borohydride adsorbed on alumina. Other recently published borohydride reductions of acid derivatives to primary alcohols include those of the 1-succinimidyl esters (8)" and the N-nitroso-amides (9). 2-Methoxyethoxymethyl (MEM) esters have the possibility of co-ordinating the metal cation of complex hydrides at the MEM group, and hence of activating the carbonyl group towards reduction by intramolecular hydride delivery. The selective reduction of the less hindered ester group in the bis-MEM ester (10) to give (11) illustrates this idea. 

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

Selective reduction of a benzene ring (W. Grimme, 1970) or a C C double bond (J.E. Cole, 1962) in the presence of protected carbonyl groups (acetals or enol ethers) has been achieved by Birch reduction. Selective reduction of the C—C double bond of an a,ft-unsaturated ketone in the presence of a benzene ring is also possible in aprotic solution, because the benzene ring is redueed only very slowly in the absence of a proton donor (D. Caine, 1976). 

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

Hydrogenation of cinnamaldehyde has been studied extensively since selectivity has often been an issue. Under mild conditions the carbonyl group is reduced giving cinnamyl alcohol, whereas at elevated temperatures complete reduction to 3-phenylpropanol [122-97 ] results. It is possible to saturate the double bond without concomitant reduction of the carbonyl group through selective hydrogenation with a ferrous chloride-activated palladium catalyst (30), thereby producing 3-phenylpropanol [104-53-0]. 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

Selective reduction of acetylenes containing carbonyl functions seems to present no difficulties if the groups are not conjugated. 

Reduction of unsaturated aldehydes seems more influenced by the catalyst than is that of unsaturated ketones, probably because of the less hindered nature of the aldehydic function. A variety of special catalysts, such as unsupported (96), or supported (SJ) platinum-iron-zinc, plalinum-nickel-iron (47), platinum-cobalt (90), nickel-cobalt-iron (42-44), osmium (<55), rhenium heptoxide (74), or iridium-on-carbon (49), have been developed for selective hydrogenation of the carbonyl group in unsaturated aldehydes. None of these catalysts appears to reduce an a,/3-unsaturated ketonic carbonyl selectively. 

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