Mesityl oxide reduction

Before discussing what is known concerning the stereochemistry of hydrodimerization, it will be useful to discuss probable mechansims of hydrodimerization. It appears that a different mechanism is followed in acid than in neutral or alkaline media. In acid the first step is a one-electron reduction of the pro-tonated starting material to form a neutral radical, which then dimerizes. Thus for mesityl oxide (128) ... 

Steric factors are also important in hydrodimerizations carried out in acidic media. Excessive steric hindrance about the 0-carbon in an a, 0-unsaturated carbonyl compound can retard tail-to-tail coupling, e.g., 2 130 - 131, and lead to products of head-to-head (and occasionally head-to-tail) coupling. Thus in the reduction of mesityl oxide at pH lg.4 there is also formed a small amount of ketone 140, apparently formed via head-to-head coupling of 130 and subsequent pinacol rearrangement of 139 134) ... 

The 1,2-hydrosilylation of a,/3-unsaturated ketones is possible and provides a convenient route to allyl alcohols. The standard conditions of Et3SiH/TFA lead to overreduction to the saturated alcohol with mesityl oxide 434,439 The combination of EtsSiH/AlCE/HCl with mesityl oxide gives a mixture of the 1,2-reduction product 4-methylbut-3-ene-2-ol and the fully reduced product, 2-methylpent-2-ene.136 The Ph2SiH2/RhH(PPh3)4 reduction of cyclohexenone gives reaction at... 

Mesityl oxide at a mercury cathode in acetate buffer affords a mixture of tail-to-tail and head-to-tail hydrodimers. The initally formed reduction products undergo further reactions so that 32 and 33 are isolated [106, 107, 108]. A low yield of the head-to-head glycol has been isolated from some reactions [109, 110, 111]. The structures of these products were confirmed in 1955 [112], Methyl vinyl ketone yields a mixture of tail-to-tail and head-to-head hydrodimers [113],... 

Condensation. Although aluminum alkoxides are effective in bringing about the mesityl oxide type condensation of ketones, as, for example, in the formation of dypnoue (XXVII) from acetophenone (XXVI),26 aluminum isopropoxide rarely induces this reaction to any significant degree in the reduction of ketones. 

The reduction of a,p-unsaturated ketones is equally fast and remarkably selective for 1,2-addition of the silane. A variety of both cyclic and acyclic a,p-unsaturated ketones were reduced with diphenylsilane under the standard conditions with yields ranging from 66-99% for 1,2-addition. Cyclic enones were reduced with a higher degree of regioselectivity than the acyclic enone, mesityl oxide. 

Selective hydrogenation of a,/3-olefinic ketones to saturated ketones can be accomplished through careful control of the temperature, duration of reaction, and use of a catalyst active enough to permit low-temperature hydrogenation. Thus, mesityl oxide, benzalacetone, and benzalaceto-phenone have been reduced in S>0-100% yields to the corresponding saturated ketones. Preparations of nickel catalysts used in these reductions are described. ... 

The full paper describing Mori s synthesis of lineatin (296) (Vol. 4, p. 489, Ref. 263) has been published. After converting the lactone 329 to ( )-lineatin using a [2 + 2] cycloaddition, Slessor et al. followed another route from the same lactone 329, which is readily available by the Lewis acid-catalyzed addition of ketene to mesityl oxide. The route is shown in Scheme 25. In this scheme, the mixture arising from the carbene addition is not separated because, at the stage of the epoxide formation, only the major (desired) isomer 330 was isolated, the other being thermally unstable. The exo alcohols obtained in small amounts after the borohydride reduction (step h) were not isolated. To obtain the natural isomer of lineatin [( + )-(l/ ,4S,5/ ,7R)-296] the alcohol 331 was resolved with (—)-(r)-l-(l-nephthyl)ethyl isocyanate/triethylamine. The first stereospecific chiral synthesis of (+)-lineatin (296) started from D-ribonolactone (332), and is illustrated (in somewhat abbreviated form) in Scheme 26 it proceeded in 2.7% overall yield. °... 

Reduced osmium on carbon is an excellent catalyst for selective hydrogenation of aj3-unsaturated aldehydes to unsaturated alcohols.1 Cinnamaldehyde — cinnamyl alcohol (95% yield). Reduced rates are observed with alumina as the support. This selective reduction is not applicable to a,/3-unsaturated ketones thus hydrogenation of mesityl oxide afforded methyl isobutyl ketone. 

Only activated monoenes are hydrogenated . These include carvene, mesityl oxide, 2-cyclohexenone, and benzalacetone . Some styrenes are hydrogenated a-functionalized styrenes react, but )S-functionalized styrenes do not - " . Similarly, only activated ketones such as benzil, diacetyl and p-benzoquinone are hydrogenated to alcohols " . Often catalytic reduction of a ketone is observed only in the presence of added OH . The base is believed to react with an intermediate to give [Co(CN)j(OH)] and the reduced substrate . Aryl ketones such as acetophenone and benzophenone are not reduced . Several examples of nitro and nitroso compound reductions have been reported - . ... 

Borohydride reduced Pd is also a versatile hydrogenation catalyst that effects the partial reduction of multifunctional unsaturated compounds selectively. It can reduce the w-bond of C=C, N=N, N=0, but not the w-bond of C=N, C=0, nor the --bond of C— N, C—O. Allylic alcohols, allylic amines, allylic ethers, a-methylstyrene, acrylamide, 3-butene nitro, and also mesityl oxide, crotonaldehyde, and maleic anhydride are among the selectively reduced substrates. ... 

Similarly Ni catalysts are useful substitutes to Pd for the selective olefin reduction in an a,/8-unsaturated ketone. Finely divided Ni (and partially deactivated by washing it with a 0.1% MeOH solution of acetic acid) in a mixture 5% HCCl3/EtOH is efficient at RT and atm P. Neutral catalysts, U—Ni—N, obtained by refluxing precipitated Ni with isopropanol, also shows selectivity, mesityl oxide being reduced to methyl-1 pentanone-2 . 4-Cyclopentene-l,3-dione, 5, can be converted into 1,3-cyclo-pentanedione, 6, by hydrogenation over partially deactivated neutral Ni catalyst ... 

Unsaturated aldehydes and ketones can be selectively hydrogenated to the corresponding saturated carbonyl however, it is difficult to reduce the ethylenic group without also attacking the carbonyl group, although such a reduction may be achieved for certain compounds such as mesityl oxide (2-methyl-pentene-2-one-4) using a platinum catalyst at room temperature. 

Diacetone alcohol is obtained by the Aldol condensation of two moles of acetone in the presence of barium hydroxide. On dehydration diacetone alcohol yields mesityl oxide, which upon amination gives diacetoneamine. This on treatment with diethyl acetal imdergoes cyclization with the elimination of two moles of ethanol to give vinyl diacetoneamine. The cyclized product on reduction followed by benzoylation and treatment with hydrogen chloride yields benzamine hydrochloride. 

Functional groups tend to deactivate the catalysts but reduction can be achieved by working at 100 atm H2 and 20°C under these conditions, diolefins (e.g., vinylcyclohexene, 1,5-hexadiene) are reduced to paraffins (ethylcyclohexane, hexane), and unsaturated ketones or esters (mesityl oxide, vinyl acetate) are reduced (to methyl (isobutyl) ketone or ethyl acetate). 

Interesting synthetic approaches for the construction of the tricyclo[5.2.2.0k5]undecane skeleton of the eremanes have been developed, but only two have been successful. The synthesis of ( )-eremolactone relied on an acid-catalysed double Michael addition on the silyloxydiene (Scheme 45) (127). This on treatment with mesityl oxide in the presence of titanium (IV) chloride gave, inter alia, an inseparable 1 2 mixture of diastereisomers (189) in 64% yield. Reduction with NaBH4 gave the separable hydroxy ketones (190 and 191, 1 2), the relative stereochemistry of which was secured from an X-ray study of 190. Following the introduction of the double bond, the side chain was elaborated on each of the two diastereoisomers as shown in Scheme 45. This synthesis has a number of problems. A complex mixture of isomers is generated in the first step, the cyclohexene... 

In a model synthesis <81CC524>, a nitro-Michael addition of the readily available nitroalkyl pyrrole 36 to mesityl oxide was used to introduce a geminally dimethylated structural element into an AD component rac-39 for the desired chlorin. Reduction of the nitro function in rac-37 leads to the desired AD dimer rac-38 which is combined in the presence hydrobromic acid with the well known a-bromo-a -bromomethyl dipyrromethene 40 after acid induced ester clevage and decarboxylation to yield the tetrapyrrolic biline rac-41. In the final step the linear tetrapyrrole rac-41 undergoes oxidation and cyclization in the presence of copper(II) acetate to give the copper chlorin. The cyclization occurs via the enamine tautomer of rac-41 by nucleophilic attack of the enamine structure on the bromo imine part of the linear tetrapyrrole. 

A number of metal complexes catalyze the hydrosilylation of various carbonyl compounds by triethylsilane. Stereoselectivity is observed in the hydrosilylation of ketones as in the reactions of 4-t-butylcyclohexanone and triethylsilane catalyzed by ruthenium, chromium, and rhodium metal complexes (eq 4). Triethylsilane and Chlorotris(triphenylphosphine)rho-dium(I) catalyst effect the regioselective 1,4-hydrosilylation of Q ,/3-unsaturated ketones and aldehydes. Reduction of mesityl oxide in this manner results in a 95% yield of product that consists of 1,4- and 1,2-hydrosilylation isomers in a 99 1 ratio (eq 5). This is an exact complement to the use of phenylsilane, where the ratio of respective isomers is reversed to 1 99. ... 

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