Formation of 4,5,6,7-tetrahydroisoindoles by palladium-catalyzed hydride reduction.
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.
Hou
Duen-Ren
DR
Department of Chemistry, National Central University, Jhong-Li City, Taoyuan, Taiwan. drhou@cc.ncu.edu.tw
Wang
Ming-Shiang
MS
Chung
Ming-Wen
MW
Hsieh
Yih-Dar
YD
Tsai
Hui-Hsu Gavin
HH
D002384:Catalysis; D005561:Formates / Q000737:chemistry; D006865:Hydrogenation; D054833:Isoindoles / Q000138:chemical synthesis*; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
D005561:Formates; D054833:Isoindoles; C032391:palladium hydride; D010165:Palladium