HALLER-BAUER Ketone Cleavage

HALLER - BAUER Ketone Cleavage Cleavage ol ketones, lacking a-hydrogen, with sodium amide. 

Stereospecific Haller-Bauer ketone cleavage Replacement of C-acyl by deuterium... 

Haller-Bauer reaction. Cleavage of nonenol-izable ketones with sodium amide, most often applied to ketones ArCOCR, to yield trisubstituted acetic acids. 

Haller-Bauer reaction (cleavage of ketones by sodamide in toluene) ... 

Cleavage of ketones with amide ion (Haller-Bauer)... 

Cleavage of ketones with sodium amide is called the Haller-Bauer reaction.514 As with 2-45, which is exactly analogous, the reaction is usually applied only to nonenolizable ketones, most often to ketones of the form ArCOCR3, where the products R3CCONH2 are not easily attainable by other methods. However, many other ketones have been used, though benzophenone is virtually unaffected. It has been shown that the configuration of optically active R is retained.515 The NH2 loses its proton before the R is cleaved 516... 

Haller-Bauer reaction.1 A study of the base-induced cleavage of the optically active tertiary a-phenyl ketone (l)2 shows that cleavage proceeds with retention with metal amides in benzene and alkoxides in an alcohol or benzene, but with... 

Method A Br-Li exchange, n-BuLi/Et20 followed by CO2 quench. Method B NaNH2 promoted Haller-Bauer cleavage of phenyl ketone. Method C LDA/THF, — 72°C, quench with Mel or MeOD. Method D H-D exchange vs. racemization using NaOMe. Method E LDA/Et20 at 25°C. Method F DNMR. 

It has been shown recently by Paquette and coworkers based on the earlier work of Walborsky and coworkers that under the conditions of a Haller-Bauer cleavage the optically active ketone 306 is transformed into the optically active trimethylsilyl species 307 with complete retention of configuration. 

The Haller-Bauer reaction is applied to nonenolizable ketones which react with fresh sodium amide to form amides (equation 44). Cleavage of aliphatic or alicyclic phenyl ketones to produce tertiary carboxamides is the most useful. With equivalent amounts of l,4-diazabicyclo[2.2.2]octane (DABCO) the reaction proceeds under milder conditions. ... 

Carboxamides. The cleavage of nonenoUzable ketones with sodium amide to form carboxamides (Haller-Bauer reaction ) has been reported to require freshly prepared reagent. Kaiser and Warner, however, report that commercial sodium amide is satisfactory if an equimolar amount of 1,4-diazabicyclo[2.2.2]-octane (DABCO) is added. Benzamide is formed from benzophenone in this way in 73% yield. In the absence of DABCO, the yield is only 18%. 

The base-promoted cleavage of C-C bond of non-enolizable ketones to form a carboxylic acid derivative and a neutral fragment is known as Haller-Bauer (HB) reaction [18, 19]. Sodium amide 2 is always used as the base and the corresponding amide products are produced. The generally mechanism for HB reaction involves nucleophilic addition of the amide to generate a tetrahedral intermediate 3, which could rearrange to form a carboxamide 4 and a carbanion. Then inter-molecular proton transfer leads to a hydrocarbon product (Scheme 3.1). 

All ketones, aldehydes, and esters mentioned so far have had an a-carbon that can lead to an enol, which means that there was a hydrogen on that carbon that could be removed by base. When a ketone does not have such a proton (it is a non-enolizable ketone), treatment with strong base can lead to a C—C bond cleavage reaction. Discovered by Semmeler,52 Haller and Bauer developed the reaction illustrated by reaction of 63 with NaNH2 to give amide 65. Acyl addition of the amide anion to the carbonyl of the ketone led to 64, and loss of the anion Ph" gave the amide product. Workup protonates the anion to give, in this case, benzene. This... 

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