Ketones with alcohols

Figure 8.2 Reduction of ketone with alcohol dehydrogenase from Thermoanaerobacter brockii using glucose-6-sulfate as a hydrogen source [3],...

Asymmetric electroreduction of ketones to the corresponding chiral alcohols has recently been reported. Typical examples are the reduction of ketones bearing chiral auxiliaries [68, 69], and the indirect reduction of ketones with alcohol dehydrogenase (ADH), as a mediator (Scheme 32) [70]. 

Scheme 32 Electroenzymatic reduction of ketones with alcohol dehydrogenase Rh aryl, R alkyl, CHO, CO2H, yields 92-100%, 0 - 100% ee.

The a-alkylation of enolates derived from ketones with alkyl halides is a very important and frequently used method for forming new carbon-carbon bonds in organic synthesis [40]. Yet, if the a-alkylation of enolates derived from ketones with alkyl halides can be replaced by the direct reaction of ketones with alcohols, this method would provide a very useful waste-free, green route to a-alkylation, producing no side products other than water. 

IrCl(cod)]2, in the presence of PPh3 and KOH, catalyzed the a-alkylation of ketones with alcohols [41]. As an example, the reaction of 2-octanone 87 with 1-butanol 88 was catalyzed by the iridium complex to give 6-dodecanone 89 in 80% yield (Equa-hon 10.19). The alkylation proceeded with complete regioselectivity at the less-hindered side of 2-octanone, and the reaction was promoted by a catalytic quantity of KOH (10mol%) in the absence of both a hydrogen acceptor and a solvent. 

E Keinan, EK Hafeli, KK Seth, RR Lamed. Thermostable enzymes in organic synthesis. 2. Asymmetric reduction of ketones with alcohol dehydrogenase from Ther-moanaerobium brockii. J Am Chem Soc 108 162-168, 1986. 

The reaction is carried out by allowing the aldehyde to stand with an excess of the anhydrous alcohol and a little anhydrous acid, usually hydrogen chloride. In the preparation of ethyl acetals the water is often removed as it is formed by means of the azeotrope of water, benzene, and ethyl alcohol (b.p. 64.9 Sec. 15.6). (Simple ketals are usually difficult to prepare by reaction of ketones with alcohols, and are made in other ways.)... 

The acetalization of aldehydes and ketones with alcohols is catalyzed by SbCb in the presence of Fe or Al (Scheme 14.5) [21]. The selective acetahzation of aldehydes can also be performed by combined use of Sb(OR)3 (R=Et, iPr) and allyl bromide [26]. Sb(OEt)3 promotes intermolecular amidation between amines and esters or carboxylic acids [27]. When tetraamino esters are used as substrates, the antimony(Ill)-templated macrolactamization occurs to yield macrocychc spermine alkaloids (Scheme 14.6). 

Alkylation. Viologen-supported nanoparticles of palladium prepared from PdCl2 show an activity of promoting alkylation of methyl ketones with alcohols in the air at 100°. A 1,3-cycloaIkanedione undergoes alkylation but the ring is opened. The reaction also requires a base such as Ba(OH)2 H2O or Sr(OH)2 8H20. ... 

X = Cl. Br. T Treatment of polystyryl diphenylphosphine with CL, Br, or I, in CH,CL.24 Halohydrins from epoxides yields and selectivities compare well with those obtained with monomeric triphenyl phosphine-halogen complexes.2 11 Open and cyclic acetals and thioacetals by treatment of aldehydes and ketones with alcohols or thiols in the presence of polystyryl diphenylphosphine iodine complex.249... 

Oxidoreductases Interconvert ketones with alcohols, double bonds with single bonds, etc. yeast/horse liver alcohol dehydrogenase oxygenases... 

After discovering the catalytic activity of aldehydes, Xu and co-workers later extended the method to TM-free aldehyde-catalyzed C-alkylation of secondary alcohols with primary alcohols [199] and catalyst-free C-alkylation reactions of methyl ketones with alcohols [200]. In 2013, Wu and co-workers also reported a closely related TM-free ketone-initiated C-alkylation of indole and pyrrole with secondary alcohols [201]. Similarly, Shi and co-workers employed conjugated ketones to catalyze the TM-free A/-alkylation reaction of amines with alcohols in 2015 (Scheme 42) [202], which is mainly suitable for benzylic and heterobenzylic alcohols, and anilines and heteroarylamines. Different ketones showed variant activities in the reaction (the catalysts were added in the same amount of 50 mg regardless of their molecular weights). In mechanistic studies such as the control reactions of the ketone catalyst and the substrate alcohol, up to 92 % ratio of the corresponding alcohol derived from reduction of the ketone catalyst can be detected in addition to formation of aldehdye intermediates derived from substrate alcohol. 

Liao S, Yu K, Xu Q et al (2012) Copper-catalyzed C-afkylation of secondary alcohols and methyl ketones with alcohols employing the aerobic relay race methodology. Org Biomol Chem 10(15) 2973-2978... 

Xu Q, Chen J, Tian H et al (2014) Catalyst-free dehydrative a-alkylation of ketones with alcohols green and selective autocatalyzed synthesis of alcohols and ketones. Angew Chem Int Ed 53(l) 225-229... 

Many steps are nearly the same in acid-catalyzed reactions of aldehydes and ketones with alcohols and amines. Compare the mechanisms vertically to see the similarities and differences. Note differences in completion of the mechanism for each type of product. 

Table 2.16 Hetero Michael addition of a,P-unsaturated ketone with alcohols...

In subsequent studies, Esteruelas et at disclosed the synthesis of another cationic complex, [(IPr)Os(OH)(p-cymene)][OTf] 52, which was an efficient pre-catalyst for transfer hydrogenation of aldehydes with isopropanol, for hydration of nitriles into amides, and for a-alkylation of arylacetonitriles and methyl ketones with alcohols (Scheme 7.10). All these transformations were assumed to involve cationic hydrido intermediates formed by hydrogen transfer from one of the substrates to the osmium active species. 

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