Nucleophilic addition Gabriel synthesis

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

The first step of the Gabriel synthesis, the alkylation of potassium phthalimide with alkyl halides, proceeds via an Sn2 reaction. The second step, the hydrazinolysis of the A/-alkylphthalimide, proceeds by a nucleophilic addition of hydrazine across one of the carbonyl groups of the phthalimide. Subsequently, the following steps occur ringopening then proton-transfer followed by an intramolecular SnAc reaction, another proton-transfer and finally, the breakdown of the tetrahedral intermediate to give the desired primary amine and the side product phthalyl hydrazide. 

The Gabriel-malonic ester synthesis begins with (V-phthalimidomalonic ester. Think of (V-phthalimidomalonic ester as a molecule of glycine (aminoacetic acid) with the amino group protected as an amide (a phthalimide in this case) to keep it from acting as a nucleophile. The acid is protected as an ethyl ester, and the a position is further activated by the additional (temporary) ester group of diethyl malonate. 

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