Ketone Reduction to alcohol

Ketone reduction to alcohols, BOROHYDRIDE REDUCTION KETONIZATION... 

Arene oxides show the characteristic reactions of epoxides (isomerization to ketones, reductions to alcohols, nucleophilic additions, deoxygenations) and olefins or conjugated dienes (catalytic hydrogenation, photochemical isomerization, cycloaddition, epoxidation, metal complexation). Where a spontaneous, rapid equilibration between the arene oxide and oxepin forms exists, reactivity typical of a conjugated triene is also found. 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

A-ring conjugated ketones do not normally interfere with the epoxidation reaction, but hydride reduction will reduce any ketone groups to alcohols. These can be reoxidized by conventional means. 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

Later, Araki et al. found that the allylation of aldehydes and ketones can be carried out by using catalytic amounts of indium(III) chloride in combination with aluminum or zinc metal.109 This reaction was typically performed in a THF-water (5 2) mixture at room temperature, although the conversion was much slower compared to the same reaction mediated by use of a stoichiometric amount of indium and it required days to complete. When the reaction was carried out in anhydrous THF alone, the yield dropped considerably and side-reactions such as reduction to alcohol increased. The combinations of Al-InCL or Zn-InCl3 gave comparable results. 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

The reaction tolerates ketone, chloride, internal C=C bonds, esters, nitriles, and ether functional groups. Given that the DIBAL-H reduction of acid derivatives often suffers from over-reduction to alcohols, these catalytic procedures are of synthetic value for laboratory-scale syntheses. However, it is likely that the requirement for excess (tBuCO)20 will prevent this reaction from ever being used in commercial production. 

Hydrogen and a catalyst.2 0 The most common catalysts are platinum and ruthenium, but homogeneous catalysts have also been used.281 Before the discovery of the metal hydrides this was one of the most common ways of effecting this reduction, but it suffers from the fact that C=C, CssC, C=N and C=N bonds are more susceptible to attack than C=0 bonds.282 For aromatic aldehydes and ketones, reduction to the hydrocarbon (9-37) is a side reaction, stemming from hydrogenolysis of the alcohol initially produced (0-78). 

Reactive aldehydes and ketones can be detoxified by reduction to alcohols by aldehyde dehydrogenase. 

Stereoselectivity in the reaction of acyclic ketone 270 is different from that of the cyclic ketone 256. The acetate in 271, prepared by reduction of the ketone 270 to alcohol with LiAlH and acetylation, was displaced with Me A1 from the exo side to give 272 with retention of the stereochemistry. No racemization of benzyl cation was observed. However, reaction of 270 with MeLi gave 274. The OH group of 274 was removed with hydride from the less hindered side as shown by 275 to give 276 with... 

Reduction of aromatic ketones. It has been generally assumed that metal ammonia reduction of aromatic ketones leads to alcohols, mainly because benzo-phenone (1) is reduced to diphenylmcthanol (2, benzhydrol) by sodium in liquid ammonia. However, Hall and co-workers report that aromatic ketones are reduced,... 

They are both chrysanthemic acid esters of (5-benzylfuran-3-yl)methanol (Elliott alcohol, 1) [15]. Patented methods [16] for the industrial preparation of Elliotf s alcohol are demanding or such as to be hardly exploited in industrial-scale plants. For instance, in one of these methods [17] (5-benzyl-3-furyl)methanol is obtained by a sequence of Claisen condensation of benzyl cyanide and a dialkyl succinate, hydrolysis, esterification, protection of the ketone group, formylation, cyclization to 5-benzyl-3-furfuryl ester and reduction to alcohol with lithium aluminium hydride. 

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