Transamidation carboxylic acid amides from

Carboxylic acid amides from carboxylic acids by transamidation... 

NH3 or RNH2 or R2NH Amide formation from carboxylic acid derivatives (mild) or from carboxylic acids (A technical synthesis of nylon-6,6) transamidation [capro-lactame —> nylon-6 (perlon)] Peptide synthesis (Section 6.4.3)... 

In a later development by Bedenbaugh et methylamine was used as solvent and lithium as electron donor. No proton donor was required, suggesting that the lithium salt (28) of hemiaminal (27) is stable under the reaction conditions (both aldehydes and aldimines are reduced by the reagent cf. the analogous reduction of carboxylic acids, Section 1.12.2 and Scheme 2). Yields of aldehydes produced by this method are shown in Table 8. It is notable that only tertiary amides are reduced satisfactorily. A major limitation of the reaction is the substantial formation of side products resulting from transamid-ation by the methylamine solvent (/. e. RCONHMe from RCONR 2). 

Aside from the outstanding and reliable diastereoselectivity, two more advantageous features helped the method to success the easy, one-step preparation of various N-acylated derivatives from the parent oxazolidinones and the cleavage of the auxiliary by hydrolysis, transamidation to the Weinreb amide, esterification, and reduction, as outlined in Section 4.1. A typical Evans aldol procedure with phenylalanine-derived oxazolidinone (S)-47, including the preparation of propionic imide 73 and cleavage of the auxiliary, is shown in Scheme 4.47. Typically, the boron aldolate resulting from the addition to the aldehyde has to be cleaved by an oxidative work-up. The hydrolysis of the aldol adduct 211 occurs without detectable epimerization that liberates diastereomerically and enantiomerically pure carboxylic acid 212 besides the auxiliary (S)-47 [110]. 

Altering the iV-substitution of an amide by the introduction of an amine is termed transamidation it offers an interesting approach to the construction of functionalised amide bonds. It can allow alternative disconnection pathways that may suffer from decarboxylation if carboxylic acids are... 

The amide transfer reactions can be distinguished from the transamidation reactions studied by Fruton et al. as follows. The enzyme is not a peptidase or protease. The amide (or hydroxylamine) transfer is restricted to the /3-carboxyl of aspartic acid or the y-carboxyl of glutamic acid the transfer is not associated with hydrolysis of the amide it does depend on ATP or ADP, arsenate or phosphate, and Mn++, but this dependence notwithstanding, it shares with the peptidase-protease type of transamidation its independence of energy or phosphate transfer. 

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