Haller-Bauer reaction

Base-induced cleavage of non-enolizable ketones leading to cait)Oxylic amide or acid derivative and a neutral fragment in which the carbonyl group is replaced by a hydrogen. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 126, Springer International Publishing Switzerland 2014 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 118, Springer-Verlag Berlin Heidelberg 2009 

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Acid derivatives that can be converted to amides include thiol acids (RCOSH), thiol esters (RCOSR), ° acyloxyboranes [RCOB(OR )2]. silicic esters [(RCOO)4Si], 1,1,1-trihalo ketones (RCOCXa), a-keto nitriles, acyl azides, and non-enolizable ketones (see the Haller-Bauer reaction 12-31). A polymer-bound acyl derivative was converted to an amide using tributylvinyl tin, trifluoroacetic acid, AsPh3, and a palladium catalyst. The source of amine in this reaction was the polymer itself, which was an amide resin. 

Haller-Bauer reaction, 9, 1 Halocarbenes, synthesis and reactions of, 13, 2... 

Acid derivatives that can be converted to amides include thiol acids RCOSH, thiol esters RCOSR,911 acyloxyboranes RCOB(OR )2,912 silicic esters (RCOO)4Si, 1,1,1-trihalo ketones RCOCX3,913 a-keto nitriles, acyl azides, and nonenolizable ketones (see the Haller-Bauer reaction 2-33). 

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... 

This reaction, called the Haller-Bauer reaction, has utility for the preparation of amides of the types ArCONH2 and P /T-RCONH2, and, through hydrolysis, the corresponding carboxylic acids. 

Exercise 17-14 The Haller-Bauer cleavage of 2,2-dimethyl-1-phenyl-1-propanone with sodium amide forms benzenecarboxamide and 2-methylpropane. Write a mechanism for the Haller-Bauer reaction analogous to the haloform cleavage reaction. 

Review Org Prep Free Int 22 167 (1990) (Haller Bauer reaction)... 

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... 

A nice complement to the Haller-Bauer reaction (Section II.B) is the decarbonylation of aldehydes with (Ph3P)3RhCl (Wilkinson s catalyst) A recent example comes from the work of Baldwin and Barden and is shown in Figure 5. Interestingly, partial optical resolution was achieved in this synthesis by use of an optically active copper catalyst for the preparation of the labeled phenylcyclopropane carboxylic acid. The resolution to optical purity was then accomplished by recrystallization of the quinine salt of the acid. 

Most alkyl carbanions undergo facile pyramidal inversion. Cyclopropyl anions are an exception, presumably because the transition state, with a planar trigonal carbon, is more strained than the ground state. The configurational stability of cyclopropyl anions is of value in the synthesis of deuterated cyclopropanes by the Haller-Bauer reaction (see Section II.B). An interesting dilemma arises when a cyclopropyl anion is stabilized by a n-electron acceptor substituent such as a nitrile or an ester. Will the anion then retain its pyramidal equilibrium geometry for the strain reasons alluded to above, or will it become planar in order to maximize overlap of the filled orbital on carbon with the n orbital of the substituent Walborsky and coworkers addressed this question in a series of experiments in which rates of H/D exchange and racemization were compared for an optically active cyclopropane exposed to a base in a deuterated hydroxylic solvent. The outcome can be illustrated with the particular example of 1,1-diphenylcyclopropane-2-... 

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. ... 

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

Fig. 20. Haller-Bauer reaction with cyclopropyl phenyl ketones.

Originally the Haller-Bauer reaction was designed to serve as a method for amides synthesis (ref. 108). More recently the process has been extended to the preparation of hydrocarbons by replacement of a benzoyl group by a hydrogen atom (ref. 111). Applied to optically active ketones (Fig. 21), the Haller-Bauer rearrangement leads to the optically active hydrocarbons with about 45 % of retention (ref. 112) with NaNH2 (best results are obtained with the use of potassium t-butoxide). The selectivity can be enhanced with the use of refluxing n-butylamine as the solvent (ref. 113). 

Owing to the interest of optically active C-centered organosilanes, Paquette and co-workers (refs. 116-118) have applied the Haller-Bauer reaction to optically active non-enolizable a-silyl phenyl ketones. An optically active silane (Fig. 23) was obtained with retention of configuration (96 to 98 %). These results are interpreted on the basis of an initial a-silyl carbanion formation within a solvent shell that also encases benzamide. 

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