Amidoalkylation reagents

Especially the a-methoxylation or acetoxylation of amides like A-acyl and N-alkoxycarbonyl derivatives of amines, amino acids, and peptides leads to the synthetically very useful N,0-acetals, which are powerful amidoalkylation reagents [26] ... 

In the case of A-acylated amino acid derivatives, the oxidation has to take place via an indirect electrochemical process using chloride ions as redox catalysts. In methanol as solvent, methylhypochlorite is formed as oxidant, which yields, via -chlorination, HC1 elimination, and methanol addition, the a-methoxylated amino acids as amidoalkylation reagents [27] ... 

In the so-called non-Kolbe electrolysis, the carboxylate group is substituted by a nucleophile like methanol. This is especially effective if heteroatoms like nitrogen or oxygen are situated in the a-position. A number of amino acid derivatives have thus been transformed into the already mentioned N, (9-acetals as effective amidoalkylation reagents [28] ... 

B. S. Drach, V. S. Brovaretz and O. B. Smolij, Synthesis of Nitrogen-containing Heterocyclic Compounds using an amidoalkylation reagent, Naukova Dumka, Kiev, 1992 (in Russian), pp. 62-76. 

The A -acylenamines and their precursors bis-amides 9 are used as amidoalkylation reagents . The main purpose of the latter is to produce the A-acyliminium ions 2 which act as highly reactive electrophilic reagents . Consequently, the application of N-acyliminium ions 2 considerably extends the preparative possibilities for functionalization of aromatic, heterocyclic and unsaturated compounds. 

When the a cation is formed in methanol or acetic acid, for instance, a methoxy or acethoxy group is introduced to the a position, and the product is a useful reagent for the amidoalkylation as shown below in a general scheme. 

This reactivity of iV-acylenamines 1 has opened up new possibilities for the use of enamides.in photochemical rearrangements as weU as in acid-catalyzed cyclizations , which lead to a variety of complex nitrogen-containing heterocycles from readily available simple precursors. These reactions have also been used to form a wide variety of natural products and polyfunctional compounds. Enamides can be also used as electrophilic reagents for amidoalkylation -, which can occur under certain conditions as a [4 -I- 2] cycloaddition to form 1,3-oxazinium heterocycles... 

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