Utilization of 1-Aryl-2,2-dibromocyclopropanes in Synthetic Approaches to Phenanthroquinolizidine and Phenanthroindolizidine Alkaloids

The 1-aryl-2,2-dibromocyclopropane 8 was treated with silver acetate in acetic acid to give the allylic acetate 19. Exposure of the derived chloride 26 to racemic 2-piperidinemethanol (7) then afforded the allylic amine 6, which engaged in a Pd(0)-catalyzed cross-coupling reaction with arylboronate 29 to provide the cis-stilbene 25. The chloride 4 (X = Cl) derived from compound 25 failed to cyclize in the presence of base to give the desired phenanthroquinolizidine alkaloid julandine 1. This outcome resulted in a re-examination of the closing stages of a previously reported synthesis of the phenanthroindolizidine alkaloid ent-septicine (ent-3). Towards this end, chloride 26 was reacted with (S)-2-pyrrolidinemethanol (32) to give the allylic amine 33, which was cross-coupled with boronate ester 34 to afford cis-stilbene 35. Contrary to literature reports, compound 35 was converted into the corresponding chloride 37, rather than the expected mesylate, upon reaction with methanesulfonyl chloride in the presence of pyridine. Moreover, chloride 37 was not converted into ent-septicine (ent-3) on exposure to sodium hydride, thus calling into question a previously reported synthesis of this natural product.