Ketone reaction with NaBH

Thus, (-)-frontalin 19 (Scheme 4), pheromone of Dentroctonus Frontalis bark beetle, was obtained from the methyl ketone 12 through the intermediacy of the adduct 20, that was obtained as the sole transformation product by reaction with 4-methyl-pent-4-enylmagnesium bromide in THF. The latter material, once O-benzy-lated, with acid hydrolysis yielded 22, and was then converted into 23 by periodate oxidation, followed by NaBH reduction. 

Alcohols are among the most versatile of all organic compounds. They occ. widely in nature, are important industrially, and have an unusually he chemistry. The most important methods of alcohol synthesis start with carbonyl compounds. Aldehydes, ketones, esters, and carboxylic acids are reduced by reaction with either NaBH,i or LiAIH4. Aldehydes, esters, and carboxylic acids yield primary alcohols (RCHgOH) on reduction ketones yield secondaiy alcohols (R CHOH). 

Treatment of a monosaccharide with NaBH, reduces it to a polyalcohol called an alditol. The redxiction occurs by interception of the open-chain form present in the aldehyde/ketone-hemiacctal equilibrium. Although only a small amount of the open-chain form is present at any given time, that small amount is reduced then more is produced by opening of the pyranose form and that additional amount is reduced and so on, until the entire sample has undergone reaction. 

Reformatsky-type reactions and reductions. Enolates generated from a-bromoketones by reaction with BiClj-Al in an aqueous medium condense with various aldehydes to give J-hydroxy ketones." A modification of reaction conditions (BiClj-NaBH ) and in the absence of aldehydes leads to hydrodehalogenation of the haloketones. ... 

NaBHj/NiC or Raney nickel, the menthyloxy group is removed with NaBH /KOH to give 3,4-disubstituted butyrolactones with a high diastereo- and enantioselectivity (Figure 7.69). Corey and Houpis [1458] have described asymmetric Michael reactions of ketone enolates with a 2-thiophenyl crotonate of 8-phenmenthol. Chirality has also been introduced on the amino group of 2-ami-nomethyiacrylates to perform the asymmetric addition of the anion of the tert-Bu ester of cyclopentanecarboxylate [1459], More important developments have been reported with chiral a,p-unsaturated sulfoxides and nitro compounds as Michael acceptors (see below). 

Section 8-6 presents two u.seful reduction processes. Carbonyl compounds such as ketones and aldehydes arc useful precursors (starting materials) for the synthesis of alcohols. Either metal-catalyzed Ht addition or reaction with the hydride reagents NaBH and LiAIH converts aldehydes to primary alcohols. The same processes convert ketones to secondary alcohols. The.se hydride reductions are the lirst of many examples that you will. see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important clas.ses of reactions in organic chemistry. 

Oxymercuration occurs with an alkyne as with an alkene, but differences in reactivity lead to a modification in the procedure. For reasons that will not be discussed, a mixture of mercuric sulfate (HgS04) and mercuric acetate [Hg(OAc)2] is used. When 1-heptyne is treated with this mixture in aqueous solvent, the initially formed enol (107) tautomerizes to 2-heptanone (108), which is isolated in 80% yield. Note that the ketone product mentioned in connection with vinyl chloride 92 in Section 10.4.5 results from formation of an enol. There is an important difference in the oxymercuration of alkynes and alkenes that is notable in this transformation. The mercury reacts with the alkyne, but the mercury is lost when the enol is formed and there is no need to add NaBH in a second step. This observation is general for oxymercuration of alkynes under these conditions. The more stable secondary vinyl carbocation is an intermediate, but the vinyl-mercury compound formed by reaction with the carbocation is unstable in the presence of water, so the enol is the product. 

Sodium borohydride has been extensively used as a reducing agent. The solid state reduction with NaBH requires longer time and use of solvents slow down the reaction. A microwave irradiation reaction has been developed for the reduction of aldehydes and ketones using alumina supported NaBH (Scheme 23). 

Aqueous suspensions of ferrocenyl ketone p-CD inclusion complexes are reduced with NaBH, [77], The presence of salting-out agents (LiCl, NaCl, KCl) increases the enantioselectivity of the reaction (Table 6.10). 

Ketones undergo a reduction when treated with sodium borohydride, NaBH What is the structure of the compound produced by reaction of 2-butanone with NaBH4 if it has an IR absorption at 3400 cm-1 and M+ = 74 in the mass spectrum ... 

Formation of an Alcohol The simplest reaction of a tetrahedral alkoxide intermediate is protonation to yield an alcohol. We ve already seen two examples of thi.s kind of process during reduction cif ketones and uldchydcs with hydride reagents such as NaBH, and LiAIH (Section 17.5), and during Qrignard reactions (Section 17.6). In the case of reduction, the nucleophile that adds to the carbonyl group is a hydride ion, H while in the case of Grignard reaction, the nucleophile is a carbanion, R ,C . ... 

Treatment of a ketone or aldehyde with LiAlH or NaBH4 reduces the carbonyl group and yields an alcohol (Section 17.5). Although the exact details of carbonyl-group reduction are complex, LLAIH4 and NaBH act as if they were donors of hydride ion, H , and the key step is a nucleophilic addition reaction (Figure 19.7). Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

The mechanism of the mercurydD-catalyzed alkyne hydration reactioi is analogous to the oxymercuration reaction of alkenes (Section 7.4). Elec trophilic addition of mercury(II) ion to the alkyne gives a vinylic cation which reacts with water and loses a proton to yield a mercury-containii eiio) intermediate. In contrast to alkene oxymercuration, no treatment witll NaBH is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8,3), A mixture of both possible ketones results when an unsymmetrically substituted internal alkyne (RCsCR ) is hydrated. The reaction is therefor ... 

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. ... 

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