Ketones with borohydride

A diphenylprolinol derivative, having hydrophobic perfluoroalkyl phase tags, has been synthesized and used as a pre-catalyst to generate in situ a fluorous oxaz-aborolidine catalyst for the reduction of prochiral ketones with borohydride. The system afforded high enantioselectivities and the pre-catalyst is easily separated and recycled.272 Reduction of enantiopure A-p-toluenesulfinyl ketimines derived from 2-pyridyl ketones with sodium borohydride affords A-p-toluenesulfinylamines with good yields and diastereoselectivities.273... 

Trialkyl borates, generated in situ from sodium borohydride and an alcohol, catalyse reduction of ketones with borohydride. With (-)-menthol as the initiating alcohol, the... 

Both 0- and C-labeled analogs of BZ have been synthesized (Calvin et ak, 1949). The source of the carbon label was labeled carbon dioxide (Prenant et ak, 1989). The oxygen label was introduced as a result of reacting enriched water with quinuclidinone and then reducing the labeled ketone with borohydride (Sniegoski et al., 1989). The synthesis of a number of tritium labeled neurochemicals, including BZ, has been reported (Bloxsidge et al., 1981). 

Our mechanism for reduction of the ketone with borohydride is of course not yet complete there is another step to follow—the protonation of the alkoxide by the ethanol solvent. We can add this step to our energy profile diagram. 

It has been claimed that the previously proposed four-centre mechanism plays no part in the reduction of ketones with borohydride whether this mechanism is involved in the photochemically accelerated borohydride reduction of ketones has yet to be clarified. ... 

The double bond migration which normally occurs on forming ethylene ketals from A -3-ketones has frequently been utilized to form derivatives of the A -system. The related transformation of A -3-ketones into A -3-alcohols is usually accomplished by treatment of the enol acetate (171) (X = OAc) with borohydride. This sequence apparently depends on reduction of the intermediate (172) taking place faster than conjugation ... 

A novel reaction of perchloryl fluoride with aromatic substrates was discovered by Neeman and Osawa, the oxofluorination reaction. These authors found that reaction of indene with perchloryl fluoride in dioxane-water yields five products, the major product being, 2-fluoroindanone. When applied to 6-dehydroestradiol diacetate (24) there is obtained as the major product the 7a-fluoro-6-ketone (25). Borohydride reduction of the... 

The Schiff reaction between chitosan and aldehydes or ketones yields the corresponding aldimines and ketimines, which are converted to N-alkyl derivatives upon hydrogenation with borohydride. Chitosan acetate salt can be converted into chitin upon heating [130]. The following are important examples of modified chitosans that currently have niche markets or prominent places in advanced research. 

In the presence of strong alkali, the rhodium analog of 62, or RhCl(C8H,2)PPh3, hydrogenates aliphatic ketones at 1 atm and 20°C, and after treatment with borohydride the systems similarly reduce aromatic ketones to the alcohols (526). Deuterium exchange data for acetone reduction were interpreted in terms of hydrogen transfer within a mononuclear hydroxy complex containing substrate bound in the enol form (63). 

Asymmetric reduction of dialkyl ketones. The borohydride 1 reduces dialkyl ketones with low enantioselectivity. However, treatment of the lithium dihydri-doborate 2 with methanesulfonic acid provides Reagent I, which consists of 1 equiv. of R,R-1 and 0.2 equiv. of 2,5-dimethylborolanyl mesylate, which serves as a... 

The authors then go on to measure the kinetics in the presence of two oxazabor-ole catalysts, (92a) and (92b).The rate-determining step is the reaction of the ketone with an oxazaborole-borane complex, with the direct reduction competing with the catalytic cycle (as mentioned above). The oxazaborole reaction, like the direct reduction, is significantly accelerated by the presence of sodium borohydride. 

By reduction of aldehydes and ketones Aldehydes and ketones are reduced to the corresponding alcohols by addition of hydrogen in the presence of catalysts (catalytic hydrogenation). The usual catalyst is a finely divided metal such as platinum, palladium or nickel. It is also prepared by treating aldehydes and ketones with sodium borohydride (NaBH4) or lithium aluminium hydride (LLAIH4). Aldehydes yield primary alcohols whereas ketones give secondary alcohols. 

Synthesis ofLysergic Acid, By reacting N-benzoyl-3-(B-carboxyethyl)-dihydroindole (see JCS, 3158 (1931) for the preparation of this compound) with thionyl chloride, followed by aluminum chloride gives l-benzoyl-5-keto-l,2,2a,3,4,5-hexahydrobenzindole. This is then brominated to give the 4-bromo-derivative, which is converted to the ketol-ketone by reacting with methylamine acetone ethylene ketol. This is then hydrolized by acid to yield the diketone and treated with sodium methoxide to convert it to the tetracyclic ketone. Acetylate and reduce this ketone with sodium borohydride to get the alcohol, which is converted to the hydrochloride form, as usual. 

Reduction of a, -unsaturated ketones to unsaturated hydrocarbon is rather rare, and is almost always accompanied by a shift of the double bond. Such reductions are accomplished in good to high yields by treatment of the p-toluenesulfonylhydrazones of the unsaturated ketones with sodium borohydride [785], borane [786] or catecholborane [559], or by Wolff-Kizhner reduction or its modifications [590]. However, complete reduction to saturated hydrocarbons may also occur during Wolff-Kizhner reduction [597] as well as during Clemmensen reduction [750]. 

Treatment of aldehydes or ketones with ammonia, primary or secondary amines in reducing media is called reductive alkylation (of ammonia or amines) or reductive amination (of aldehydes or ketones). Reducing agents are most frequently hydrogen in the presence of catalysts such as platinum, nickel or Raney nickel [955], complex borohydrides [705, 954, 955], formaldehyde or formic acid [522]. 

Consequently, by choosing proper conditions, especially the ratios of the carbonyl compound to the amino compound, very good yields of the desired amines can be obtained [322, 953]. In catalytic hydrogenations alkylation of amines was also achieved by alcohols under the conditions when they may be dehydrogenated to the carbonyl compounds [803]. The reaction of aldehydes and ketones with ammonia and amines in the presence of hydrogen is carried out on catalysts platinum oxide [957], nickel [803, 958] or Raney nickel [956, 959,960]. Yields range from low (23-35%) to very high (93%). An alternative route is the use of complex borohydrides sodium borohydride [954], lithium cyanoborohydride [955] and sodium cyanoborohydride [103] in aqueous-alcoholic solutions of pH 5-8. 

Reduction of the azepinone ring in 63 can be accomplished selectively. Thus, hydrogenation results in selective 1,4-reduction of the enone moiety and furnishes the corresponding saturated ketone 65. Selective enone 1,2-reduction can be performed with n-BuLi-BHs to produce allylic alcohol 64. Reduction with borohydride is non-selective and gives saturated hydroxyl compound 66 (Scheme 13, Section 2.1.1.5 (2000T9351)). 

The original racemic patents described the use of resolution to give a chiral oxirane, such as 25, as an intermediate or the use of a chiral auxiliary (20) to produce the salmeterol enantiomers. Alkylation of chiral amine 20 with 2-benzyloxy-5-(2-bromo-acetyl)-benzoic acid methyl ester, followed by diastereoselective reduction of the ketone with lithium borohydride furnished intermediate 21 after chromatographic separation of the diasteromers. Removal of the benzyl group and the chiral auxiliary was... 

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