Basicity ambident nucleophiles

Hydroxylamines and alkylhydroxylamines possess high nucleophilicity and can react with a variety of primary and secondary alkylating agents. The reactivity of hydroxylamines in the majority of these reactions resembles that of primary and secondary amines. While hydroxylamine and Af-alkylhydroxylamines 1 are ambident nucleophiles, under neutral or weakly basic reaction conditions alkylation proceeds exclusively on nitrogen atom to give products of type 2 (equation 1). Deprotonation of the OH group of hydroxylamines results in O-alkylation products. 

Hydroxylamines, as potentially ambident nucleophiles, can utilize either the basic N atom or the O atom in nucleophilic reaction with a variety of electrophilic centers . This is illustrated in Scheme 2 through the box on the left hand side of the diagram. Also shown in Scheme 2 are the dissociation equilibria K,, K a, and K 2- The equilibrium denoted as... 

As already discussed in Section 4.19.2.2.1 hydroxyl derivatives of thiazole are tautomeric, according to Scheme 127, the oxo forms usually being the most stable. The interconversion of the hydroxyl and carbonyl forms proceeds under acid or base catalysis. This protomeric behavior of the thiazolinones corresponds to an ambident nucleophilic reactivity which is most marked for the conjugate anion arising in basic medium. 

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

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