In amination of nitrogen heterocycles

Many natural products, drugs, or plant protection agents are amino-nitrogen heterocycles. Thus, methods for their efficient synthesis are of considerable practical and technical interest. This chapter will discuss primarily the advances made in the amination of nitrogen heterocycles since the comprehensive review by Shepherd and Fedrick on Reactivity of Azine, Benzoazine, and Azinoazine Derivatives with Simple Nucleophiles was published in this series in 1%5 (65AHC145). 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

The nitrogen of aliphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, in triphenyl amine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate in high yields by heating the mixtures (24,25). 

Dess and Martin reported that their name reagent reacts with primary amines giving insoluble products, which are difficult to analyze. Nevertheless, there are several reports of oxidation of alcohols, in which primary aromatic amines remain unaffected.47 In these cases, when an aldehyde is obtained, sometimes it is attacked by the amine, resulting in the formation of nitrogen heterocycles.48 There is one report49 in which an alcohol is oxidized to an aldehyde in the presence of a primary aliphatic amine that reacts in situ with the aldehyde. 

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