Castagnoli‐Cushman Reaction of 3‐Aryl Glutaric Acids: A Convenient, Diastereoselective Reaction for 6‐Oxo‐2, 4‐diarylpiperidine‐3‐carboxylic Acid Scaffold. Issue 3 (21st January 2022)

• Record Type: Journal Article
• Authors: Paramonova, Polina; Bakulina, Olga; Nabiyev, Alem; Dar'in, Dmitry; Krasavin, Mikhail
• Is Part Of: ChemistrySelect. Volume 7:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-21
• Subjects: lactams -- anhydrides -- Castagnoli-Cushman reaction -- 3-arylglutaric acids -- in situ dehydration -- acetic anhydride -- diastereoselectivity; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202104011
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 3‐Aryl glutaric acid anhydrides have been explored as substrates for the Castagnoli‐Cushman reaction with imines. A series of 3‐aryl glutaric acids was synthesized according to literature protocols and introduced into the reaction with imines in the presence of acetic anhydride. The latter acted as a dehydrating agent leading to in situ generation of a cyclic anhydride from the dicarboxylic acid starting material. Reassuringly, the reaction gave the desired δ‐lactams with three newly created stereocenters as predominantly one diastereomer whose relative configuration was established by single‐crystal X‐ray crystallography. Abstract : The Castagnoli‐Cushman reaction of 3‐aryl glutaric anhydrides (generated in situ from corresponding diacids and acetic anhydride) with imines gave tetrasubstituted δ‐lactams with remarkable diastereoselectivity over three newly formed stereocenters (confirmed by X‐ray analysis). The reaction was found to be insensitive to the nature of aryl moiety of diacid. This general approach opens access to rare trans‐ configured 4, 6‐disubstituted 2‐piperidones.