Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams

• Published in: European journal of organic chemistry 2021-03, Vol.2021 (11), p.1726-1731
• Main Authors: Peshkov, Anatoly A., Bakulina, Olga, Dar'in, Dmitry, Kantin, Grigory, Bannykh, Anton, Peshkov, Vsevolod A., Krasavin, Mikhail
• Format: Article
• Language: English
• Subjects: Acidic oxides; Aldehydes; Ammonium acetate; Aromatization; Carbonyl compounds; Carbonyls; Castagnoli-Cushman reaction; Decarboxylation; Double bond isomerization; Isomerization; Ketones
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202001617

A practical straightforward synthesis of medicinally important NH‐δ‐lactams through the three‐component Castagnoli‐Cushman reaction of 3‐arylglutaconic anhydrides with carbonyl compound and ammonium acetate has been developed. The scope of the protocol has been thoroughly explored paying particular attention to the carbonyl component using wide array of aliphatic and aromatic aldehydes as well as rarely involved cyclic and acyclic ketones. Synthetic potential of prepared compounds was demonstrated by a series of post‐modifications, including unexpected isomerization. Three‐component Castagnoli‐Cushman reaction of 3‐arylglutaconic anhydrides with carbonyl compound and ammonium acetate delivers medicinally important NH‐δ‐lactams. The scope of the protocol has been thoroughly explored paying particular attention to the carbonyl component using wide array of aliphatic and aromatic aldehydes as well as rarely involved cyclic and acyclic ketones.