The Reactivity of Enantiopure (S)‐6‐Oxopipecolic Acid and Corresponding Pyridoisoquinolines Under Acidic Conditions

• Published in: European journal of organic chemistry Vol. 2018; no. 40; pp. 5499 - 5511
• Main Authors: Šafář, Peter, Marchalín, Štefan, Balónová, Barbora, Šoral, Michal, Moncol, Ján, Ghinet, Alina, Rigo, Benoît, Daïch, Adam
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.11.2018; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Aluminum chloride; Amides; Amino acids; Chemical Sciences; Chemistry; Chemistry, Organic; Cyclization; Nitrogen heterocycles; N‐Acyliminium Species; Physical Sciences; Polycycles; Reagents; Science & Technology; PYROGLUTAMIC ACIDS; MECHANISM; Amino acids; DECARBOXYLATION; PYRROLIDINONES; Polycycles; REARRANGEMENT; POTENT; Cyclization; Nitrogen heterocycles; (S)-(+)-TYLOPHORINE; DEHYDRATION; N-Acyliminium Species; INHIBITORS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201800908

Enantiopure N‐benzyl 6‐oxopipecolic acid, obtained from (S)‐2‐aminoadipic acid, was evaluated under π‐cationic cyclization conditions. If the combination of SOCl2/AlCl3 seems to be superior in terms of the reaction yields, use of PPA, (CF3CO)2O/BF3·Et2O, and Eaton's reagent is also very interesting since in addition to the expected keto‐lactam, reduced‐ and oxidized keto‐lactam, enamides and enamidones containing CF3CO– residue are isolated. Mechanisms leading to these products as well as the ones resulting from their acidic treatment were proposed and discussed with the help, in some cases, of univocal transformations and X‐ray analysis. Enantiopure N‐benzyl 6‐oxopipecolic acid, generated from (S)‐2‐aminoadipic acid, was evaluated under different π‐cationic cyclization conditions. The combination of SOCl2/AlCl3 seems to be superior in terms of the reaction yields. Other activators resulted in a change of the reaction profile and, interestingly, in the diversification of the aza‐heterocyclic systems.