Selective alkylation/oxidation of N -substituted isoindolinone derivatives: synthesis of N -phthaloylated natural and unnatural α-amino acid analogues.

The interchangeability of the isoindolinone group as a nitrogen protecting group for amino acid intermediates is demonstrated by the preparation of several natural and unnatural α-amino acid derivatives using a two-carbon N -isoindolinone (phthalimidine) scaffold. Using a selective benzylic oxidation, the N -isoindolinone group is then converted to the N -phthaloyl group for convenient removal (65-98%). For preparation of the isoindolinone products which were to be the substrates for benzylic oxidation, a range of side chains were installed on the isoindolinone-protected glycine equivalent on deprotonation to demonstrate the utility of the N -protected isoindolinone synthon (51-93%). While the ensuing benzylic oxidation is employed successfully for converting the N -isoindolinone group to the N -phthaloyl group in simple substrates, substrates bearing unsaturated or electron-rich side chains respond poorly to the oxidation.