Synthetic Studies on Pyrrolophenanthridone Skeleton from 1-Benzoyl-7-iododihydroindole Derivatives Using Palladium-assisted Biaryl Coupling Reactions

Abstract

The biaryl coupling reaction of 1-benzoyl-7-iododihydroindole derivatives using Pd reagent was examined.1- [(1,3-Benzodioxol-5-yl)1de]phenanthridin-7-one, which was formed by connection to a more hindered carbon, as a major product.1-(3,4-Dimethoxybenzoyl)-7-iodo-2,3-dihydroindole gave oxoassoanine and 10,11-dimethoxy-4,5-dihydropyrrolo[3,2,1-de]phenanthridin-7-one in an almost equal ratio.Since pyrrolophenanthridine alkaloids (see Scheme 1) have significant biological activities 1 and unique polycyclic structures, 2 attention is still focused on the development of new synthetic methods for these alkaloids. 3Some of these attempts have involved an intramolecular aryl-aryl coupling, in which a hydrogen halide is eliminated from the two aromatic components using a Pd reagent as a key step.3d, 4 Recently, we reported a method of synthesizing several benzo[c]phenanthridine alkaloids using Pdassisted biary coupling reactions of 2-halo-N-naphthylbenzamides via elimination of a hydrogen halide. 5In order to examine the generality of this method, we tried to apply it to the synthesis of pyrrolophenanthridine alkaloids, especially anhydrolycorin-7-one (1) 6 and oxoassoanine (2), 7 which serve as advanced intermediates in the synthesis of other alkaloids. 8To synthesize pyrrolophenanthridine alkaloids, two routes (Routes A and B) are possible, as shown in Scheme 1.The biaryl coupling reactions of 1-(2-iodobenzoyl)-2,3-dihydroindole (3) 9 and 1-benzoyl-7iodo-2,3-dihydroindole (4) were examined as a preliminary study of the synthesis of these alkaloids.The