p-Benzyne Monochlorination:Total Syntheses of Cyanosporaside and Fijiolide Aglycons

Abstract

Cyanosporasides (1, 2) and Fijiolides (3, 4) were isolated from the culture broth of marine actiomyces. These natural products possess a novel cyclopenta[a]- indene framework, which is considered to be a product of cycloaromatization of bicyclo[7.3.0]dodecenediyne (5). Hydrogen and chlorine should be incorporated during the cycloaromatization.

We succeeded in synthesis of the corresponding bicyclo[7.3.0]dodecenediyne aglycons (17, 32), and demonstrated their cycloaromatization to form the chlorocyclopenta[a]indene structures (21, 22, 35).We found that p-benzyne biradical (19) generated from 9-membered enediyne (17) undergoes a radical monochlorination in Et₂O/CCl₄ to give selectively 21, and in striking contrast, in the presence of LiCl in DMSO to afford 22 selectively via an ionic pathway. These regioselective monochlorinations were utilized for differential syntheses of protected aglycons of cyanosporasides A and B (23, 24). Protected aglycon of fijiolides (35) was also synthesized via the ionic pathway.