Ketones cleavage with amide bases

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... 

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... 

Gallc er and co-workers devised a formal enantioselective synthesis of ( — )-3 in wduch the stereogenic center at C-6 was derived fiom Cbz-protected (S)-2-amino-4-pentenoic acid (36) (44). Acylation of 3,3-dimethoxy-pyrrolidine (37) with this acid yielded amide 38, which was converted into aldehyde 39 by cleavage of the terminal alkene vnth osmium tetroxide and sodium periodate (Scheme 5). The indolizidine nucleus was constructed from 39 by a problematic intramolecular aldol condensation, which was eventually optimized by using 2,2,6,6-tetramethylpiperidine as base followed by adsorption onto, and elution from, silica gel (45). Diastereoselective reduction of the ketone group of the aldol product 40 was accomplished in better than 95% enantiomeric excess (ee) with the Corey... 

Methoxyamine solid supports 7x can be used to anchor carboxylic acids in the presence of BOP/DIEA as Weinreb amides [338,339]. The resultant anchor is compatible with peptide assembly using Boc or Fmoc strategies, and treatment of the final sequence with LiAlH4 in THF led to release of peptide aldehydes. A related support with RAM as the base resin has also been used to prepare resin-bound Weinreb amides, which afforded ketones on cleavage induced by reaction with Grignard reagents [340]. 

Insertion of carbon monoxide followed by reductive coupling is an old reaction that continues to be studied and developed. Examples of this reaction are the carbonylation of nickel dialkyl complexes to give ketones, " alkyl-alkoxides to yield esters, and alkyl-amides to give organic amides (Equation (79)). The carbonylation of the binuclear complex 145 leads to the formation of an isoquinolone ring with the elimination of one of the two Ni atoms, but no GO insertion occurs at the second metal moiety. Hydrolytic cleavage of the remaining Ni-G bond provides the free heterocyclic base (Scheme 45). ... 

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