Reduction of a./?-unsaturated ketones

Full details have been given (2) for the selective 1.2- or 1.4-reduction of a/3-unsaturated ketones. Dihydridosilanes give products of predominant... 

The crystal structure of (232) is reported. Ir complexes bound to the multidentate ligand as in (232) have proved successful in the enantioselective reduction of a,/3-unsaturated ketones to allylic alcohols.404... 

Biochemical reduction of a,/3-unsaturated ketones using microorganisms (best Beauveria sulfurescens) takes place only if there is at least one hydrogen in the /3-position and the substituents on a-carbons are not too bulky. The main product is the saturated ketone, while only a small amount of the saturated alcohol is formed, especially in slightly acidic medium (pH 5-5.5). The carbonyl is attacked from the equatorial side. Results of biochemical reduction of 5-methylcyclohex-2-en-l-one are illustrative of the biochemical reduction by incubation with Beauveria sulfurescens after 24 hours 74% of the enone was reduced to 3-methylcyclohexanone and 26% to 3-methylcy-clohexanol containing 55% of cis and 45% of trans isomer. After 48 hours the respective numbers were 70% and 30%, and 78% and 22%, respectively [878]. 

Selective catalytic hydrogenation with chromium-promoted Raney nickel is reported (e.g. citral and citronellal to citronellol) NaHCr2(CO)io and KHFe(CO)4 reduction of a/3-unsaturated ketones (e.g. citral to citronellal) has been described (cf. Vol. 7, p. 7). The full paper on selective carbonyl reductions on alumina (Vol. 7, p. 7) has been published." Dehydrogenation of monoterpenoid alcohols over liquid-metal catalysts gives aldehydes and ketones in useful yields. ... 

Chemoselective catalytic reduction of a,/3 unsaturated ketones to allylic alcohols is a challenging problem since, but a few exceptions [1-3], this reaction generally proceeds with formation of saturated ketones or saturated alcohols [4]. This reduction indeed is best carried out with stoicheiometric hydrides [4] but even in this case overreduction products are often obtained [5]. Recently, we reported in a preliminary communication [6] the unprecedented observation that a,/3 unsaturated ketones are reduced to the corresponding allylic alcohols by hydrogen transfer from propan-2-ol over MgO as catalyst according to the following scheme ... 

The reduction of a, 3-unsaturated ketones to allylic alcohols can be easily done using lithium aluminium hydride under carefully controlled conditions (Following fig.). With sodium borohydride, some reduction of the alkene also occurs. 

This stereochemistry is similar to that in the reduction of a,/3-unsaturated ketones. Stork found that octalones like 7.88 were reduced exclusively to the frans-decalone 7.90, even in cases when the trans- was less stable than the corresponding c/.v-decalin. In this reaction, an electron is fed into the LUMO... 

The alkene reduction reactions most frequently observed are of a,3-unsaturated aldehydes, ketones, acids and esters. Examples of stereospecific reductions of acyclic substrates are given in Scheme 50.148.157-159 (j, (, e formation of (123), the double bond of (122) is reduced prior to the aldehyde function. The conversion of (124) to (125) involves oxidation of the intermediate alcohol to the carboxylic acid by bubbling air into the fermentation medium. Stereospecific reductions of a, 3-unsaturated ketones may be similarly effected (Scheme 61). The reduction of the chloro ketone (126) gives (127) initially. This epimerizes under the reaction conditions, and each enantiomer is then reduced further to (128) and (129), with the predominance of the (128) stereoisomer increasing with the size of the R-group. Reduction of ( )-(130) leads to (131) and (132). ... 

The reduction of a carbon-carbon multiple bond by the use of a dissolving metal was first accomplished by Campbell and Eby in 1941. The reduction of disubstituted alkynes to c/ s-alkenes by catalytic hydrogenation, for example by the use of Raney nickel, provided an excellent method for the preparation of isomerically pure c -alkenes. At the time, however, there were no practical synthetic methods for the preparation of pure trani-alkenes. All of the previously existing procedures for the formation of an alkene resulted in the formation of mixtures of the cis- and trans-alkenes, which were extremely difficult to separate with the techniques existing at that time (basically fractional distillation) into the pure components. Campbell and Eby discovered that dialkylacetylenes could be reduced to pure frani-alkenes with sodium in liquid ammonia in good yields and in remarkable states of isomeric purity. Since that time several metal/solvent systems have been found useful for the reduction of C=C and C C bonds in alkenes and alkynes, including lithium/alkylamine, ° calcium/alkylamine, so-dium/HMPA in the absence or presence of a proton donor,activated zinc in the presence of a proton donor (an alcohol), and ytterbium in liquid ammonia. Although most of these reductions involve the reduction of an alkyne to an alkene, several very synthetically useful reactions involve the reduction of a,3-unsaturated ketones to saturated ketones. ... 

The reduction of a,3-unsaturated ketones with alkali metals in HMPA in the absence of a proton donor has been proposed to proceed via the mechanism shown in equation (22), in which a dianion is formed. Protonation during work-up results in the formation of the final reduced product (63). 

As an alternative route to the reduction of a, 3-unsaturated ketones accompanied by introduction of a silyl group at the 3-position, a silylcuprate reagent is applicable (equation 57). ... 

Dissolving metal reduction of a,(3-unsaturated ketones regiospecifically produces enolates that, on removal of ammonia, may be reacted with electrophiles. 

Breitner et al. of Engelhard Industries report comparisons of the activities of commercial preparations of Rh-C, Ru-C, Pt-C, and Pd-C (all on Norit). Rhodium-C and ruthenium-C appear to be the catalysts of choice for the hydrogenation of ketones in a neutral or basic medium. These catalysts can be used for the reduction of a,/3-unsaturated ketones, via the saturated ketones, to the saturated alcohols. 

Selective reduction of Ike carbonyl group of tf-cyclopentenones The reduction of a,/3-unsaturated ketones to the corresponding curbinols by complex hydrides is accompanied with concomitant saturation of the double bond. This undesired reaction is particularly noted in the case of A2-cyclopentenones. However, use of aluminum hydride (inverse addition) produces the unsaturated carbinols in satisfactory yields. 

Reduction of a,fi-unsaturated ketonesThis highly hindered borane accepts an electron from sodium metal to give a blue solution of the radical anion which can serve as a conductor of electrons for reduction of a,/3-unsaturated ketones. Thus A1,9-octalone-2 (1) is reduced by TMB, sodium, and a proton source (t-butanol) in anhydrous 1,2-dimethoxyethane (nitrogen) in high yield (85-95%) to a mixture of / j-2-decalone (70%) and cw-2-decalone (30%), the equilibration point for this reduction. Overreduction to the alcohol is negligible. If the reduction... 

The Luche reduction is an excellent method for the 1,2-reduction of a, 3-unsaturated ketones. In addition, ketones are reduced selectively in the presence of aldehydes. 

Allylic alcohols are the almost exclusive products of the rapid reduction of a,)3-unsaturated ketones [e.g. (4i )-(-)-(18), pulegone (21), piperitone] using... 

The enolate that is required for the aldol reaction can be generated in other ways, too. For example, trimethylsilyl enol ethers react with TBAF (tetrabutyl-ammonium fluoride, Bu4N" F ) to give the corresponding enolates. Enolates may also be prepared by the dissolving metal reduction of a,)3-unsaturated ketones (see Chapter 5). 

The first step in the reduction of a,(3-unsaturated ketones is the formation of the radical anion 60, which subsequently abstracts a proton from the ammonia or from added alcohol to give 61 (7.43). After addition of another electron, the enolate anion 63 is formed. In the absence of a stronger acid, this enolate remains unprotonated and resists addition of another electron, which would correspond to further reduction. Acidification with ammonium chloride then leads to the saturated ketone product. The reaction of ammonium ions with solvated electrons apparently destroys the reducing system before further reduction of the ketone to the alcohol can take place. 

Reduction Reactions. A modification of the Wolff-Kishner reduction, which is particularly useful for the reduction of a, /3-unsaturated ketones, involves the reaction of carbonyl hydra-zones and semicarbazones with f-BuOK in PhMe at reflux. The reduction of ( )-3-oxo-a-cadinol to ( )-a-cadinol and its isomer (eq 46) provides an exan5)le of this method. ... 

Kawai, Y, Saitou, K., Hida, K., and Ohno, A. (1995) Asymmetric reduction of a, 3-unsaturated ketones with bakers yeast. Tetrahedron Asymmetry, 6, 2143-2144. 

Zagozda, M. and Plenkiewicz, J. (2006) Enantioselective reduction of a, 3-unsaturated ketones by Geotrichum candidum, Mortierdla isahellina and Rhodotorula rubra yeast. Tetrahedron Asymmetry, 17, 1958-1962. 

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