The Use of Aryl-Substituted Homophthalic Anhydrides in the Castagnoli-Cushman Reaction Provides Access to Novel Tetrahydroisoquinolone Carboxylic Acid Bearing an All-Carbon Quaternary Stereogenic Center

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 23; p. 8462
• Main Authors: Moshnenko, Nazar, Kazantsev, Alexander, Bakulina, Olga, Dar'in, Dmitry, Krasavin, Mikhail
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.12.2022; MDPI
• Subjects: all-carbon quaternary atom; Anhydrides; Anhydrides - chemistry; Aromatic compounds; Carbon; Carboxylic Acids; Castagnoli–Cushman reaction; Chromatography; homophthalic anhydride; Hydrochloric acid; imine; Imines; Imines - chemistry; lactam; Molecular Structure; Schiff bases; Solvents; Stereoselectivity; Substitution reactions; tetrahydroisoquinolone; Russia; tetrahydroisoquinolone; lactam; all-carbon quaternary atom; homophthalic anhydride; Castagnoli–Cushman reaction; imine
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27238462

Novel aryl-substituted homophthalic acids were cyclodehydrated to the respective homophthalic anhydrides for use in the Castagnoli-Cushman reaction. With a range of imines, this reaction proceeded smoothly and delivered hitherto undescribed 4-aryl-substituted tetrahydroisoquinolonic acids with remarkable diastereoselectivity, good yields and no need for chromatographic purification. These findings significantly extend the range of cyclic anhydrides employable in the Castagnoli-Cushman reaction and signify access to a novel substitution pattern around the medicinally relevant tetrahydroisoquinolonic acid scaffold.