Ketones, aliphatic-aromatic reduction

LBADH also catalyzed the asymmetric reduction of a broad variety of differently substituted acetylenic ketones, including aromatic alkynones and a number of aliphatic derivatives [71]. For example, methyl alkynones bearing an aromatic unit attached to the triple bond were reduced to the corresponding (7 )-propargylic alcohols with >99% ee. Similarly, alkylsilyl-substituted... 

As with the aldehyde reductases, ketone reductases are specific for NADPH as reductant. Also, some isoenzymes of ketone reductase have not been purified to homogeneity and therefore not fully characterized. It is clear, however, that the ketone reductases catalyze reduction of aromatic, aliphatic, cyclic, and unsaturated ketones to the corresponding alcohols. The ketone reductases also catalyze reduction of aromatic and aliphatic aldehydes to primary alcohols. The distribution and specificity of ketone reductases has been reviewed (103). 

Accordingly, ATH is a versatile method for the enantioselective reduction of prochiral aromatic ketones. Aliphatic unconjugated ketones, however, are only reduced in poor to moderate enantioselec-tivities up to date (33-36). 

REDUCTION WITH ALUMINUM AMALGAM Reduction of Aliphatic-Aromatic Ketones to Pinacols [144]... 

Ketones, in contrast to aldehydes, occur frequently in plants. A phytochemical reduction of the keto group has been shown in aliphatic, aromatic s and cyclic ketones although it takes longer and is less complete than in the case of aldehydes. (For the theory of this transformation see Neuberg and Gorr. )... 

R) -specific ADH from L. kefir was used for the reduction of various ketones to the corresponding secondary alcohols. Aliphatic, aromatic, and cyclic ketones as well as keto esters were accepted as substrates. The activities achieved with several substrates were compared with the activity obtained with the standard substrate of ADH, acetophenone (Fig. 2.2.4.4). As the figure shows, recombinant LK-ADH has a very broad substrate spectrum, including many types of ketones. 

Contaminants and by-products which arc usually present in 2- and 4-atninophenol made by catalytic reduction can be reduced or even removed completely by a variety of procedures These include treatment with 2-propanol, with aliphatic, cycloaliphatic, or aromatic ketones, with aromatic amines, with loluene or low mass alkyl acetates, or with phosphoric acid, hydroxyacetic acid, hydroxypropionic acid, or citric acid. In addition, purity may be enhanced by extraction with methylene chloride, chloroform, or nitrobenzene. Another method employed is the treatment of aqueous-solutions of aminophenols with activated carbon. 

A major variation is the use of formic acid or one of its derivatives as the reductant (the Leuckart reaction). In the synthesis of 1-phenylethylamine (Expt 5.197), ammonium formate is heated with aceptophenone while the water formed in the reaction is carefully removed by fractional distillation to give the required amine as its N-formyl derivative, (l-phenylethyl)formamide. This is then hydrolysed with acid to yield the primary amine. The procedure has been satisfactorily applied to many aliphatic-aromatic, alicyclic and aliphatic-heterocyclic ketones, some aromatic ketones and aldehydes, and to some aliphatic aldehydes and ketones boiling at about 100 °C or higher. 

The following tables are intended to include all the reductions with aluminum alkoxides which were reported prior to February, 1943, although some examples doubtless have been overlooked. Table I lists the reduction of aldehydes, which have been subdivided into (a) aliphatic aldehydes and (b) alicyclic and aromatic aldehydes. Table II lists the reduction of ketones, which have been classified as (a)-satu-rated and unsaturated aliphatic ketones, (b) aromatic ketones, (c) alicyclic ketones, (d) unsaturated alicyclic and aromatic ketones, (e) a- — halogen substituted ketones, (f) diketones, (g) protected diketones, (h) alcoholic and phenolic ketones (and ethers or esters of these), and (i) keto esters. 

As Table 10 illustrates, using this approach the authors were able to rapidly optimize the reaction conditions, obtaining the target 82 in 91% yield when employing 2 eq. of fenchone (80) and n-BuLi 74. In all cases only a single diastereomer was observed and the authors found that conducting the reaction at 0 °C resulted in a mere 3% reduction in yield. Furthermore, the reaction conditions were found to be suitable for a range of aliphatic/aromatic ketones and brominated compounds. 

In general, catalysis by 84a and 85c resulted in good to excellent enantioselec-tivities in the reduction of lcetimines derived from methyl aryl ketones and aromatic amines (80, R1, R3 = aryl, R2 = Me), where the electronic effects of substituents in both aromatic groups did not show any significant influence [79, 80]. On the other hand, imines obtained from aliphatic amines (80, R3 = alkyl) gave virtually racemic products with 85a [80b]. In the reduction of non-aromatic imines, such as 80c, only catalyst 84a maintained high enantioselectivity (Table... 

A variety of aldehydes—aliphatic, aromatic, and heterocyclic—have been condensed with hydantoin. Sodium acetate in a mixture of acetic acid and acetic anhydride as well as pyridine containing traces of piperidine serves as condensing agent. Reduction of the double bond is accomplished with phosphorus and hydriodic acid, ammonium sulfide, or stannous chloride, In a more recent modification, the hydantoins are synthesized from aldehyde or ketone cyanohydrins and ammonium... 

Stereoselective reduction of a-alkyl-3-keto acid derivatives represents an attractive alternative to stereoselective aldol condensation. Complementary methods for pr uction of either diastereoisomer of a-alkyl-3-hydroxy amides from the corresponding a-alkyl-3-keto amides (53) have been developed. Zinc borohydride in ether at -78 C gave the syn isomer (54) with excellent selectivity ( 7 3) in high yield via a chelated transition state. A Felkin transition state with the amide in the perpendicular position accounted for reduction with potassium triethylborohydride in ether at 0 C to give the stereochemi-cally pure anti diastereoisomer (55). The combination of these methods with asymmetric acylation provided an effective solution to the asymmetric aldol problem (Scheme 6). In contrast, the reduction of a-methyl-3-keto esters with zinc borohydride was highly syn selective when the ketone was aromatic or a,3-unsaturated, but less reliable in aliphatic cases. Hydrosilylation also provided complete dia-stereocontrol (Scheme 7). The fluoride-mediated reaction was anti selective ( 8 2) while reduction in trifluoroacetic acid favored production of the syn isomer (>98 2). No loss of optical purity was observed under these mild conditions. 

Schiff s reagent An aqueous solution of magenta dye decolorized by reduction with sulfur(IV) oxide. It is a test for aldehydes and ketones. Aliphatic aldehydes restore the color quickly aliphatic ketones and aromatic aldehydes slowly aromatic ketones give no reaction. 

Polymethylhydrosiloxane (PMHS) is easy to handle and is finding increasing popularity as a reducing agent. For example, in the presence of catalytic tris(pentafluoroptienyl)borane, B(C6Fs)3, it is effective for the reduction of ketones (both aromatic and aliphatic) to the corresponding methylene compounds at room temperature. ... 

The original synthesis discovered by Leuckart was the reductive alkylation of benzaldehyde to form benzylamine using formamide or ammonium formate as the reducing agent. This was later extended by Wallach and by the Eschweiler-Glarke procedure . The scope of the Leuckart reaction has been reviewed by Moore Apart from the special case of formaldehyde, the reaction is most focile with aromatic aldehydes and water-insoluble ketones. Aliphatic... 

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