REDUCTION OF KETONES BY USE

REDUCTION OF ALKYL HALIDES AND TOSYLATES WITH SODIUM CYANOBOROHYDRIDE IN HEXAMETHYL-PHOSPHORAMIDE (HMPA) A. 1-IODODECANE TO n—DECANE B. 1-DODECYL TOSYLATE TO n-DODECANE, 53, 107 REDUCTION OF KETONES BY USE OF TOSYLHYDRAZONE DERIVATIVES ANDROSTAN-17 0—OL, 52, 122 REDUCTIVE AMINATION WITH SO-... 

The first report of a polymer-supported oxazaborolidine appeared in 1985 [37]. The polymer-supported chiral ligand amino alcohol (27) was prepared by reaction of chlor-omethylated polystyrene resin and enantiopure amino alcohol 26 with a phenolic hydroxyl group (Eq. 10). Borane reduction of ketones by use of polymer-supported oxazaborolidines proceeded very smoothly to give the corresponding chiral alcohol in quantitative yield. For example, the reduction of butyl phenyl ketone afforded 1-phe-nylpentan-l-ol in 97 % ee (27, Eq. 11). This is somewhat higher than that obtained by... 

The Meerwein-Ponndorf-Verley reduction is so named because of the simultaneous and independent contributions from the labs of Meerwein, Ponndorf and Verley. The first report to appear in the literature was from Meerwein and Schmidt in 1925 who showed that an aldehyde could be reduced to a primary alcohol by Al(OEt)3 in an ethanolic medium.4 Independently, Verley demonstrated that butyraldehyde could be reduced by geraniol and Al(OEt)3.5 The following year, Ponndorf extended this reaction to include the reduction of ketones by using an easily oxidized secondary alcohol, such as i-PrOH, as the hydride source and Al(Oi-Pr)3 as the metal catalyst.6... 

Indeed, recent research on the use of a cyanobacterium as a biocatalyst has opened up this area asymmetric reduction of ketones by a cyanobacteria, Syne-chococcus elongates PCC 7942, with the aid of light energy proceeded smoothly... 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

The asymmetric reduction of ketones by borane catalyzed by oxazaborolidines has been widely studied since the beginning of the 1980s. Despite the use of borane complexes, which are hazardous chemicals, this reaction is an excellent tool to introduce the chirality in a synthesis and has demonstrated its usefulness in industrial preparation of chiral pharmaceutical intermediates. As a result of its performance, versatility, predictability, and scale up features, this method is particularly suitable for the rapid preparation of quantities of complex chiral molecules for clinical trials. 

Enantioselective reduction of ketones by boranes and an enantiomeric catalyst oxazaboro-lidine (the CBS catalyst) is known as the Corey, Bakshi and Shibata method . Both enantiomers of 2-methyl-CBS-oxazaborolidine (6.52 and 6.53) are used for the reduction of prochiral ketones, imines and oximes to produce chiral alcohols, amines and amino alcohols in excellent yields and enantiomeric excesses. 

Application as a Component of an Asymmetric Catalyst. Amino alcohol (1) has proven to be a highly versatile ligand for use in asymmetric catalysts for a series of reactions. One of the most comprehensively studied uses is as an ox-azaborolidine derivative such as 8 for the asymmetric control of the reduction of ketones by borane. Although its use was first described with stoichiometric levels of 1 being employed for the reduction of both ketones and oximes, development of the system has delivered a catalytic method requiring only 5-10 mol % catalyst. Enantiomeric excesses of over 85% and as high as 96% have been achieved for a range... 

Although reductions of ketones by active metals in alcohols have been largely supplanted by other procedures in modem synthetic chemistry, these methods still find occasional use. A modification employing K in r-butyl or r-pentyl alcohol has been used for the stereoselective reduction of 7-keto steroids in high yield,and the Li-ethanol and Na-ethanol reductions of 16-keto steroids have been investigated. Both traditional Na-ethanol °" reductions and a variation using Na-propan-2-ol in toluene - have also been used recently in selected systems. 

Boyer and coworkers [167-170] have investigated the following IPTC reactions using surfactants as the phase transfer catalysts (1) the reduction of ketones by sodium bor-ohydride in the presence of dodecenylsulfonate (monomer and polymer species) [167] and... 

Asymmetric reduction of ketones. This chiral surfactant catalyzes the reduction of ketones by NaBH in H20-l,2-dichloroethane. More interestingly, the reaction is stereoselective ( + )-alcohols are formed in excess, the optical yield depending on the concentration of the catalyst. L-N-Methyl-N-hexadecylephedrinium bromide was also used, but optical yields of alcohols were lower with this reagent. Presumably the alkylephedrinium tetrahydroborate is formed in the aqueous phase and passes into the organic phase, where reduction occurs with stereoselectivity. ... 

Similarly, 7V-sulfonylamino alcohol resins (16) have been used as chiral auxiliaries for the asymmetric reduction of ketones by lithium aluminum hydride. Modest enantioselectivities were achieved (5-43% ee) with resins 16 in the reduction of acetophenone (eq 19). ... 

The nature of the achiral R OH affects chiral selectivity, and by using 3,5-dimethyl-phenol high optical yields of optically active secondary alcohols are obtained from ketones. A similar principle is seen in the alkylative conversion of aldehydes and ketones to alcohols by alkyl transfer from the aluminate (19), and in the reduction of ketones by a-aminoester boranes (20) in the presence of Lewis acids. 

Matsuda, T, Watanabe, K., Kamitanaka, T, Harada, T, and Nakamura, K. (2003) Biocatalytic reduction of ketones by a semi-continuous flow process using supercritical carbon dioxide. Chem, Commun, 1198-1199. 

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