Sodium borohydride unsaturated ketones

Palladium catalysts resemble closely the platinum catalysts. Palladium oxide (PdO) is prepared from palladium chloride and sodium nitrate by fusion at 575-600° [29,30]. Elemental palladium is obtained by reduction of palladium chloride with sodium borohydride [27, 31], Supported palladium catalysts are prepared with the contents of 5% or 10% of palladium on charcoal, calcium carbonate and barium sulfate [32], Sometimes a special support can increase the selectivity of palladium. Palladium on strontium carbonate (2%) was successfully used for reduction of just y, (5-double bond in a system of oc, / , y, (5-unsaturated ketone [ii]. 

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). 

Reduction of a, -unsaturated ketones to unsaturated hydrocarbon is rather rare, and is almost always accompanied by a shift of the double bond. Such reductions are accomplished in good to high yields by treatment of the p-toluenesulfonylhydrazones of the unsaturated ketones with sodium borohydride [785], borane [786] or catecholborane [559], or by Wolff-Kizhner reduction or its modifications [590]. However, complete reduction to saturated hydrocarbons may also occur during Wolff-Kizhner reduction [597] as well as during Clemmensen reduction [750]. 

Thiophenecarbaldehydes add smoothly to a,f3-unsaturated ketones and nitriles under cyanide ion catalysis to form y-diketones (366) and y-ketonitriles (367) respectively (76CB534). The 2,5-dicarbaldehyde gives the bis-adduct (368). The aldehydes undergo normal reduction to the hydroxymethylthiophenes by sodium borohydride. However, electrochemical reduction of the 2,5-dialdehyde on a mercury electrode at pH 1-3 gives the bimolecular reduction product (369) as a mixture of meso- and ( )-forms in the ratio 7 3. Reduction with zinc and acetic acid gives only the meso -form of (369) (75CR(C)(280)165>. 

Varma reported a facile and rapid method for the reduction of aldehydes and ketones to the respective alcohols, using alumina-supported sodium borohydride and microwave irradiation under solvent-free conditions. Aldehydes tend to react at room temperature, while for the reduction of ketones, short microwave irradiation of 30-180 s was applied to produce the corresponding alcohols in 62-92% yield. With unsaturated carbonyl compounds, reduction at the conjugated C=C bond might occur as a side reaction under these conditions (Scheme 4.9)26. 

The structure of the methyl ester m.p. 174° C. (XL) was proven (5) mainly by the fact that the corresponding dibasic acid (XLI R = H) and its dimethyl ester (XLI R = Me) are oxidized with periodate and that the dimethyl ester is oxidized by manganese dioxide to a trisubstituted a,/ -unsaturated ketone (XLII) which regenerates (XLII R = Me) with sodium borohydride. 

An alternative procedure is to convert the carbonyl compound into the toluene-p-sulphonylhydrazone,12 followed by reduction with either sodium borohydride in acetic acid,13 or with catecholborane, followed by decomposition of the intermediate with sodium acetate or tetrabutylammonium acetate.14 The former method is illustrated by the conversion of undecan-6-one into undecane (Expt 5.6), and the latter by the conversion of acetophenone into ethylbenzene (Expt 6.4, Method B). A feature of these methods is that with a, / -unsaturated ketones, migration of the carbon-carbon multiple bond occurs thus the tosylhydrazone of isophorone gives 3,3,5-trimethylcyclohex-l-ene, and the tosylhydrazone of oct-3-yn-2-one gives octa-2,3-diene. 

Abbreviations Amberlite IRA 400 borohydride resin, commercially available resin for selective reduction of a,/3-unsaturated aldehydes and ketones DBU, 1,8-diazabicyclo [5.4.0]undec-7-en DCM, dichloromethane DMF, dimethylformamide EtOAc, ethyl acetate Et2NH, diethylamine Et3N, triethylamine HBr, hydrobromic acid HC1, hydrochloric acid MS, mass spectrometry MeOH, methyl alcohol NH4OH, ammonium hydroxide NaBHj, sodium borohydride NaOH, sodium hydroxide NaOMe, sodium methanolate PAMAM, polyaminoamide resin (commercially available) RT, room temperature THF, tetrahydrofuran. 

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. 

Under appropriate experimental conditions, hydrogen telluride, phenyl tellurol, and sodium hydrogen telluride perform the selective reduction of double bonds of a,/3-unsaturated carbonyl systems.89 90 This reaction with a,j3-unsaturated ketones complements the cerium trichloride/sodium borohydride method, which reduces the carbonyl group, keeping the carbon-carbon double bond intact92 (Scheme 18). 

The indium hydride compound, generated in situ from sodium borohydride and a catalytic amount of indium(m) chloride, selectively reduces carbon-carbon double bonds in conjugated alkenes such as a,a-dicyano olefins, a,/3-unsaturated nitriles, cyano esters, cyanophosphonates, diesters, and ketones (Scheme 107).372 This combined reagent system in acetonitrile reduces exclusively the a,/3-carbon-carbon double bond in a,/3,7,<5-unsaturated diaryl ketones, dicarboxylic esters, cyano esters, and dicyano compounds (Scheme 108).373... 

Sodium borohydride is a nucleophile that you have seen reducing simple aldehydes and ketones to alcohols, and it usually reacts with a,[3-unsaturated aldehydes in a similar way, giving alcohols by direct addition to the carbonyl group. 

Linear enaminones, protonated by CF3COOH, were successively reduced with sodium borohydride to give the corresponding a,/ -unsaturated ketones, by loss of the amino group134 (Scheme 99). 

Sodium borohydride reduction of dienamines in the presence of a weak acid (acetic acid or methanol) results in kinetically favoured C-/ protonation followed by rapid hydride addition at C-a17. The method therefore provides a convenient method for converting an a,/ -unsaturated ketone into a y,<5-unsaturated amine as in the synthesis of con-nessine17 (Scheme 11). 

Zinc-modified cyanoborohydride, prepared from anhydrous zinc chloride and sodium cyanoborohy-dride in the ratio 1 2 in ether, selectively reduced aldehydes and ketones but not acids, anhydrides, esters and tertiary amides. In methanol the reactivity paralleled the unmodified reagent. Zinc and cadmium borohydrides form solid complexes with DMF, which may prove to be convenient sources of the reducing agents.Aromatic and a,p-unsaturated ketones were reduced much more slowly than saturated ketones, so chemoselective reduction should be possible. 

In order to study the factors determining the regioselectivity of sodium borohydride reduction of a, -unsaturated ketones, reactions with 3-methylcyclohexenone, carvone and cholestenone were carried out in 2-propanol, diglyme, triglyme or pyridine. Mixtures of 1,2- and 1,4-reduction products were obtained in the alcoholic and ether solvents, whereas pure 1,4-reduction was observed in pyridine. Addition of triethylamine to NaBH4 in diglyme led to formation of triethylamine borine, EtsN BHs. Similarly, with pyridine, pyridine borine could be isolated, leading to exclusive 1,4-reductions. 

The transformation of P-ketoester 20 into a,P-unsaturated ester 21 requires the reduction of the ketone chemoselectively in the presence of the ester. Sodium borohydride (NaBH4) is the standard reagent for this type of transformation. Subsequent reaction of the sterically hindered secondary alcohol with benzoyl triflate " provides a good leaving group in P-position to the ester moiety. Elimination under basic conditions provides the a,p-unsaturated ester 21 in 50 % yield over three steps. 

CXLIV to latifoline was achieved by the application of a general method (150, 151) based on conversion of an a,/3-unsaturated ketone to its enol ether and reduction of the enolic double bond in the latter with sodium borohydride. 

The total synthesis of several amaryllidaceae alkaloids including that of narciclasine was accomplished in the laboratory of T. Hudlicky. The C2 stereochemistry was established by a two-step sequence Luche reduction of the a,(3-unsaturated cyclic ketone followed by a Mitsunobu reaction. The ketone was first mixed with over one equivalent of CeCIs in methanol and then the resulting solution was cooled to 0 °C, and the sodium borohydride was added. In 30 minutes the reaction was done, and the excess NaBH4 was quenched with AcOH. The delivery of the hydride occurred from the less hindered face of the ketone and the allylic alcohol was obtained as a single diastereomer. 

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