Reduction of saturated ketone

There are ample precedents for reductions of double bonds in conjugated enones with lithium in deuterioammonia (see section V-C). Examples of the reduction of saturated ketones in deuterated media appear only as side reactions (over reductions) during the above mentioned conversions. For experimental details, therefore, one should consult the literature for the analogous reductions in protic medium (see also chapter 1). The use of deuterioammonia is essential for labeling purposes since by using liquid ammonia and methanol-OD the resulting alcohol contains no deuterium. For the preparation of deuterioammonia see section IX-D. 

General procedure for reduction of saturated ketones using [(Ph3P)CuH]6 and Me2PPh... 

Reduction of saturated ketones to alcohols is very easy by many means but is distinctly slower than that of comparable aldehydes. It is frequently possible to carry out selective reductions of the two types (p. 97). 

This mixture can be used for the stereoselective reduction of saturated ketones... 

Reduction of saturated ketones (+)-Dihydrocarvone (101a ), (-)-isodihydrocarvone... 

Optimum conditions for the reduction of saturated ketones by the complex reducing agent formed from sodium hydride, sodium t-amylate, and Ni" acetate (NiCRA) have been delineated.Reoxidation of the secondary alcohol products is dramatically postponed by the addition of alkali- or alkaline-earth-metal salts, and catalytic ketone reductions are achieved with NiCRA-MgBr2 mixtures. Full details of the reducing properties of various complex metal hydrides (12) of copper, formed by reaction of UAIH4 with appropriate lithium methylcuprates [equation (1)], have been published for example enones are reduced pre-... 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Reductions of unsaturated ketones and a-acetoxy ketones usually are effected with an excess of reducing agent. For optimum yields of saturated ketones, the intermediate enolate salt obviously must not become protonated while... 

Reduction of the ketone carbonyl of cis-1, 2,3,4,4a,9b-hexahydro-8-hydroxydi-benzofuran-3-one with trifluoroacetic acid and triethylsilane at 0° produces a mixture of the a- and /3-isomers of the C3 alcohol with an u / ratio of 1 4 (Eq. 211).394 This result can be compared with the isomer ratio of 100 1 that results when sodium borohydride is used as the reducing agent.394 The same cis pair of alcohol isomers is formed in 77% combined yield, but in a reversed ratio of a /3 = 4 1, when the less saturated tetrahydrodibenzofuran analog is used as the substrate (Eq. 212).394... 

One or both carbonyls in /3-diketones can be reduced, as well as the carbonyl function in acyl cyanides (210). Similar treatment of a,/3-unsat-urated ketones and aldehydes can lead to the saturated carbonyl products via selective reduction of the olefinic bond (207, 208, 210) see Eq. (51) in Section III,A,4. Some terpenes (a- and /3-ionone, pulegone) were reduced in this way (208). Platinum(II) phosphine complexes have been used for the hydrosilylation of saturated ketones and could be used for the reduction (211). 

A difference in the reactivities and selectivities between tetra-n-butylammonium borohydride and sodium borohydride in the reduction of conjugated ketones is well illustrated with A1-9 2-octalone (Scheme 11.3) [17], Reduction with the sodium salt in tetrahydrofuran is relatively slow and produces the allylic alcohol (1) and the saturated alcohol (2) in a 1.2 1 ratio whereas, in contrast, tetra-n-butylammonium borohydride produces the non-conjugated alcohol (3) (50%) and the saturated alcohol (2) (47%), with minor amounts of the ketone (4), and the allylic alcohol (1) [16]. It has been proposed that (3) results from an initial unprecedented formation of a dienolate anion and its subsequent reduction. 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

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 ketone to an alkene is feasible not only for unsaturated ketones (Figures 17.68 and 17.71) but for saturated ketones as well. To this end, the latter can be converted into enol phosphonoamidates or enol dialkylphosphonates via suitable lithium eno-lates. One substrate of each type is shown in Figure 17.73 (A and B). Lithium dissolved in EtNH2/iert-BuOH mixtures is a suitable reducing agent for both these compounds. Their Cvp2—O bond is cleaved by a sequence of three elementary steps with which you are famil-... 

Mylroie et al. studied the optimal conditions for reductive alkylation of A-(4-ni-trophenyl)acetamide with ketones using Pt-C and sulfided Pt-C.49 In general, the sulfided catalyst was superior in the yield of the alkylated amines. There was no indication of either reduction of the ketone or saturation of the ring. With a higher loading of ketone (6 equiv) at 100°C and 6.9 MPa H2 in ethanol, excellent yields (98.5-99%) of the alkylated amines were obtained from the reaction of acetone (eq. 6.24), cyclohexanone, 2-pentanone, and 3-pentanone with A-(4-ni-trophenyl)acetamide. 

The Clemmensen reduction of saturated steroid ketones (zinc amalgam and hydrochloric acid) has not been examined in detail, although it was frequently used in early steroid chemistry to reduce a C==0 group to CH2 [37J. The mechanism inferred from studies on other ketones involves ratedetermining addition of zinc to the carbonyl group, and subsequent transformations of the type indicated (Fig. 28) [38]. 

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