Amino acid homologation by the Blaise reaction: a new entry into nitrogen heterocycles.

A general strategy for the amino acid homologation via Blaise reaction and subsequent reduction is presented. This strategy involves the preparation of protected alpha-amino nitriles from the corresponding amino acids, followed by the zinc-mediated condensation of tert-butyl bromoacetate, to give the imidazolidones after iminozincate cyclization. Reduction gave the saturated imidazolidinones with cis or trans stereochemistry, depending on the reduction conditions. This strategy was applied to nonfunctionalized amino acids and to functionalized amino acids such as serine and aspartic acid. Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described.

Sulfonyl vs. carbonyl group: which is the more electron-withdrawing?

Unexpectedly high reactivity of nitrogenated aromatics protected as amides or carbamates, when compared to sulfonamides, can be explained by a decrease of the aromaticity due to a greater ability of the carbon-centered groups to achieve delocalisation of the nitrogen lone pair, resulting in stronger global withdrawing effects.