Group 14 atoms nucleophilic substitution, intramolecular

Formation, transamination, and mutual transitions of aminomethyl derivatives of phosphines, representing nucleophilic substitution at the carbon atom in the P—C—O(N) fragment, take place under milder conditions than similar reactions of alcohols and amines. The reason is likely the participation of a phosphino group in intramolecular interactions (86MI1). 

Unfortunately, in many cases the reaction is not so straightforward it becomes complicated because of the nature of the activated component. There is another nucleophile in the vicinity that can react with the electrophile namely, the oxygen atom of the carbonyl adjacent to the substituted amino group. This nucleophile competes with the amine nucleophile for the electrophilic center, and when successful, it generates a cyclic compound — the oxazolone. The intermolecular reaction (path A) produces the desired peptide, and the intramolecular reaction (path B) generates the oxazolone. The course of events that follows is dictated by the nature of the atom adjacent to the carbonyl that is implicated in the side reaction. 

Complexes in which an increase in the coordination number at silicon is achieved by intramolecular ring closure of chelating groups are particularly interesting in relation to the stereochemistry of nucleophilic substitution at silicon. In these compounds the donor atom may play the role of a captive nucleophile , and the nature and behaviour of the intramolecularly coordinated species serve as models for the properties of the intermediates or transition states participating in the substitution processes. 

Intramolecular nucleophilic substitution reactions also are thought to compete with hydrolysis (i.e., 8 2 reaction with H2O) in the hydrolysis of several or-ganophosphorus esters. For example, the C-S cleavage of thiometen (R = H) and disulfoton (R = CH3) can occur by intramolecular nucleophilic substitution by the sulfur atom of the electron-withdrawing group, which results in the formation of the cyclic sulfonium ion which subsequently reacts with water to give 2-(ethylthio)ethanol (Wanner et al., 1989). 

Involving neighboring group participation of the heteroatom X(2) by intramolecular nucleophilic substitution at the R -substituted carbon atom, an identical onium ion G 46 is formed starting from isotwistanes G 44 as well as from twistanes G 45. 

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