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.

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.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Imidazole derivatives R 0190Amino Acid Homologation by the Blaise Reaction: A New Entry into Nitrogen Heterocycles. -Treatment of Cbz-protected amino nitriles of type (IV) derived from α-amino acids with bromoacetate and subsequent base-mediated cyclization provides a new approach to imidazolidinones like (VI). These compounds smoothly undergo stereoselective reduction to give cis-and/or trans-substituted imidazolidinones. Hydrolysis of the latter does not yield the expected β,γ-diamino acids but cyclization products like (IX) and (X). Blaise reaction of the functionalized amino nitrile (XIII) provides the lactam (XIV) instead of the corresponding imidazolidinone. (XIV) undergoes stereoselective reduction giving the trans-substituted lactam (XV). -(HOANG, C. T.; BOUILLERE, F.; JOHANNESEN, S.; ZULAUF, A.; PANEL, C.; POUILHES, A.; GORI, D.; ALEZRA*, V.; KOUKLOVSKY, C.; J.