Reductive of ketones and aldehydes

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

In summary, the reduction of ketones and aldehydes can both be performed with MPV and transition-metal complexes as catalysts. Reductions of alkenes, al-kynes, and imines require transition-metal catalysts MPV reductions with these substrates are not possible. 

The effect of cryptands on the reduction of ketones and aldehydes by metal hydrides has also been studied by Loupy et al. (1976). Their results showed that, whereas cryptating the lithium cation in LiAlH4 completely inhibited the reduction of isobutyraldehyde, it merely reduced the rate of reduction of aromatic aldehydes and ketones. The authors rationalized the difference between the results obtained with aliphatic and aromatic compounds in terms of frontier orbital theory, which gave the following reactivity sequence Li+-co-ordinated aliphatic C=0 x Li+-co-ordinated aromatic C=0 > non-co-ordinated aromatic C=0 > non-co-ordinated aliphatic C=0. By increasing the reaction time, Loupy and Seyden-Penne (1978) showed that cyclohexenone [197] was reduced by LiAlH4 and LiBH4, even in the presence of [2.1.1]-cryptand, albeit much more slowly. In diethyl ether in the absence of... 

The first sub-class of the oxido reductases is 1.1, and it comprises the dehydrogenases which act on primary or secondary alcohols or hemiacetals. They are mostly used for reduction of ketones and aldehydes. Two other categories are oxygenases and oxidases. The latter is not much used in biocatalysis. 

The conversion of a ketone to the halide is usually a two-step process. Akio Baba of Osaka University reports (J. Am. Chem. Soc. 124 13690, 2002), the one-step reduction of ketones and aldehydes to the corresponding chlorides and iodides. It is noteworthy that the reaction proceeds even with aliphatic ketones. 

Ojima and co-workers first reported the RhCl(PPh2)3-catalyzed hydrosilylation of carbonyl-containing compounds to silyl ethers in 1972.164 Since that time, a number of transition metal complexes have been investigated for activity in the system, and transition metal catalysis is now a well-established route for the reduction of ketones and aldehydes.9 Some of the advances in this area include the development of manganese,165 molybdenum,166 and ruthenium167 complex catalysts, and work by the Buchwald and Cutler groups toward extension of the system to hydrosilylations of ester substrates.168... 

Reduction of ketones and aldehydes by hydrogen transfer from alcohols is catalyzed by a variety of oxides [7,10]. For example, alumina catalysts turned out to be active in this reaction both in the gas-solid [11,12] and liquid-solid conditions with the alcohol preadsorbed on the catalyst [13], Also zeolites [14] and hydroxyapatite [15] have been employed in this reaction. However, a,/9 conjugated ketones resulted to be quite resistant to the reduction and poor yields of allylic alcohols or only saturated ketones could be obtained [10-13]. 

The production of alcohols by the reduction of aldehydes and ketones is probably one of the most useful and fundamental steps in the synthetic chemist s arsenal. Although there are many well developed methods for the reduction of ketones and aldehydes to alcohols, there is still much interest in developing new or improved methodologies which are milder and can be brought about under special conditions, especially in the presence of other reducible functional groups. Of particular interest to the modern synthetic organic chemist are the aldehyde and ketone reductions which are accomplished in an enantioselective fashion. Advances in this field up to 1992 have been the subject of a review by Singh198. The present section covers very recent work in this area. 

Scheme 4.1 Reduction of ketones and aldehydes by using the Fe(CO)5 —NEt3 system according to Marko et al.

Figure 28. Dynamic kinetic resolutions by reduction of ketones and aldehydes...

An interesting aspect from the view point of organic chemistry is the reduction of ketones and aldehydes by siloxene345) ... 

Thus, in the fine chemicals industry, reduction of ketones and aldehydes relies mainly on the use of complex metal hydrides that require time-consuming workup of reaction mixtures and produce significant amounts of inorganic and organic wastes. Similarly, the oxidation of alcohols into carbonyls is traditionally performed with stoichiometric inorganic oxidants, notably Cr(VI) reagents or a catalyst in combination with a stoichiometric oxidant [1]. 

For the asymmetric reduction of ketone and aldehyde derivates, two electrochemical reduction systems using ADH as catalyst were examined (Fig. 22) [108]. In system A, the reduced coenzymes are regenerated using either FNR for NADPH or DP for NADH. Methyl viologen serves as electron mediator between the electrode and FNR/DP. System B contains ADH as sole enzyme, which catalyzes both reduction of substrates and regeneration of cofactors. Phenylethanol is oxidized by ADH accompanied by reduction of NADP+ to NADPH and its oxidation product acetophenone is reduced electrochemically at a glassy carbon cathode. 

The reduction of ketones and aldehydes occurs through the reverse reaction of alcohol dehydrogenases (Section 10.3.1) ... 

Numerous methods for the reduction of ketones and aldehydes to the corresponding secondary and primary alcohols, such as the use of several complex metal hydrides, have found wide application in organic synthesis. Lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are the most popular of these achiral reagents. However, since a natural product synthesis has to fulfill demands in terms of both efficiency and stereoselectivity, these methods can seldom be used with prochiral substrates. 

Lithium aluminum hydride, LiAlH, is another reducing agent often used for reduction of ketones and aldehydes. A grayish powder soluble in ether and tetrahydrofuran, LiAlH4 is much more reactive than NaBH4 but also more dangerous. It reacts violently with water and decomposes explosively when heated above 120°C. 

Clemmensen, E. Reduction of ketones and aldehydes to the corresponding hydrocarbons using zinc-amalgam and hydrochloric acid. Chem. Ber. 1913, 46, 1837-1843. 

Okano, T., Matsuoka, M., Konishi, H., Kiji, J. Meerwein-Ponndorf-Verley reduction of ketones and aldehydes catalyzed by lanthanide tri-2-propoxides. Chem. Lett. 1987, 181-184. 

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