Selective alkylation/oxidation of N-substituted isoindolinone derivatives: Synthesis of N-phthaloylated natural and unnatural α-amino acid analogues. Issue 38 (20th September 2017)

• Record Type: Journal Article
• Authors: Patil, Pravin C.; Luzzio, Frederick A.; Ronnebaum, Jarrid M.
• Is Part Of: Tetrahedron letters. Volume 58:Issue 38(2017)
• Page Start: 3730
• Page End: 3733
• Publication Date: 2017-09-20
• Subjects: Amino acids -- Isoindolinones -- Oxidation -- Protecting groups -- Non-proteinogenic; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.08.032
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: A range of α-amino acid derivatives may be prepared depending on the alkyl halide. The N -isoindolinone protecting group is removed by a mild two-step sequence. Oxidation of the isoindolinone gives the easily-removable N -phthaloyl group. A de novo synthesis of an N -, carboxyl-protected arginine derivative was done. The oxidation method may be useful for 4, 5-diphenyloxazole cleavage. Abstract: 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.