Arndt-Eistert homologation, carbon-chain

The presence of an additional carbon atom between the amino and the carboxy function increases the number of possible constitutional and configurational isomers. Several methods have been developed to prepare N-protected (3-amino acid building blocks for the synthesis of (3-peptide oligomers [95, 96], The Arndt-Eistert homologation and the Evans methodology are two versatile strategies to obtain enantiomerically pure N-protected monomers with the side chains at the C(3) and C(2) carbon atoms, respectively [97, 98],... 

The Arndt-Eistert synthesis allows for the conversion of carboxylic acids 1 into the next higher homolog 4. This reaction sequence is considered to be the best method for the extension of a carbon chain by one carbon atom in cases where a carboxylic acid is available. 

The carbon-chain at the a-position on both adducts 33 and 35 was elongated by Arndt-Eistert sequence to provide the homologated esters 36 and 37. The esters 36 and 37 were transformed into the methyl ketones 40 and 41 via Weinreb s amides 38 and 39. 

A carbon chain may be extended by one unit by using the Arndt-Eistert synthesis. In the first step, an acyl halide is treated with diazomethane to form the a-diazo ketone. This is then treated with water and silver oxide. The resultant product is the free acid. If an alcohol is used instead of water, then the related ester is formed. This is the best way of extending a chain by one unit if the carboxylic acid is available. The process of extension in this manner is called homologation. 

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