Formation of 4,5,6,7-Tetrahydroisoindoles by Palladium-Catalyzed Hydride Reduction

• Published in: Journal of organic chemistry Vol. 72; no. 24; pp. 9231 - 9239
• Main Authors: Hou, Duen-Ren, Wang, Ming-Shiang, Chung, Ming-Wen, Hsieh, Yih-Dar, Gavin, Hui-Hsu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.11.2007; Amer Chemical Soc
• Subjects: Catalysis; Chemical reactivity; Chemistry; Chemistry, Organic; Exact sciences and technology; Formates - chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydrogenation; Isoindoles - chemical synthesis; Kinetics; Models, Chemical; Organic chemistry; Oxidation-Reduction; Palladium - chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; Stereoisomerism; Thermodynamics; AROMATICITY; CYCLIZATIONS; PYRROLE; INDOLE; CENTER DELOCALIZATION INDEXES; ISOINDOLES; CHEMISTRY; SYSTEMS; INHIBITORS; DERIVATIVES; Catalytic reaction; Aromaticity; Nitrogen heterocycle; Theoretical study; Palladium complex; Air; Diketone; Isoindole derivatives; N-Bromosuccinimide; Chemical reduction; Amine; Dehydrogenation; Halogen compound; Formate; Oxidation; Indole derivatives; Chemical reactivity; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo7016845

Substituted 1,3-dihydro-2H-isoindoles (2, isoindolines) were prepared and subjected to palladium-catalyzed formate reduction. Alkyl isoindolines were reduced to 4,5,6,7-tetrahydro-2H-isoindoles (1). Only partial reduction was observed for 5-methoxyisoindoline, and 4-methoxy-, 5-carbomethoxy-, amino-, and amidoisoindolines were inert to the reaction. Halogen-substituted isoindolines were dehalogenated and reduced to 4,5,6,7-tetrahydro-2H-isoindoles. Isoindole 24 was also reduced to a mixture of an isoindoline and a 4,5,6,7-tetrahydro-2H-isoindole. In contrast, 2,3-dihydro-1H-indoles 21 underwent dehydrogenation to give thermodynamically stable indoles. Theoretical calculations show the significant difference in aromaticity between isoindoles and indoles, corresponding to the observed differences in reactivities. Tetrahydro-2H-isoindoles 1 were oxidized to 4,5,6,7-tetrahydroisoindole-1,3-diones in the presence of NBS and air.