Acid-mediated intramolecular cationic cyclization using an oxygen atom as internal nucleophile: synthesis of substituted oxazolo-, oxazino- and oxazepinoisoindolinones

• Published in: Tetrahedron letters Vol. 43; no. 27; pp. 4747 - 4751
• Main Authors: Sikoraiová, Jana, Marchalı́n, Štefan, Daı̈ch, Adam, Decroix, Bernard
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2002; Elsevier
• Subjects: amino-alcohol; bicyclic lactam; Catalysis; cationic cyclization; Chemical Sciences; Chemistry; Chemistry, Organic; isoindolinone; Medicinal Chemistry; N-acyliminium ion; Organic chemistry; oxazepine; oxazine; oxazole; Physical Sciences; Science & Technology; isoindolinone; cationic cyclization; N-acyliminium ion; bicyclic lactam; oxazine; amino-alcohol; oxazepine; oxazole; BICYCLIC LACTAMS; REACTIVITY; RING-SYSTEM; PI-CYCLIZATIONS; CONSTRUCTION; AMIDOALKYLATION; STEREOSELECTIVE-SYNTHESIS; INHIBITORS; FACILE; HIGHLY DIASTEREOSELECTIVE SYNTHESIS
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/S0040-4039(02)00910-3

Efficient assembly of substituted oxazolo-, oxazino-, and oxazepinoisoindolinones ( 5– 7 , 12– 15 and 19 ) is described in three steps according to an acidic α-oxoamidoalkylation reaction from ready available phthalic anhydride by successive imidation, sodium borohydride reduction and intramolecular cationic cyclization involving N-acyliminium species. The relative stereochemistry accompanying these reactions was also discussed. Various substituted bicyclic lactams 5– 7 , 12– 15 and 19 as oxazolo-, oxazino- and oxazepinoisoindolinones were synthesized efficiently in an acidic medium from phthalic anhydride and amino-alcohols 1 , 8 and 17 in three sequential set.