Model Studies Examining the Application of Allyliminium Salt Photospirocyclization Methodologies in Synthetic Approaches to the Harringtonine Alkaloids

Article abstract of DOI:10.1021/jo00176a003

Exploratory studies have been conducted to test features of two strategies established for synthesis of members of the harringtonine alkaloid family.In order to assess the feasibility of synthetic approaches in which the spirocyclic CD-ring portions of these substances are fabricated by allyliminium salt photocyclizations, we prepared the tricyclic and B-ring-incomplete <<(trimethylsilyl)methyl>allyl>iminium perchlorates 8-10 and subjected them to photochemical investigations.While irradiation of the tricyclic salts 8 and 9 fails to induce cyclization reactions, photolysis of the B-ring-incomplete iminium perchlorate 10 leads to efficient formation of the spirocyclic amine 30.Detailed mechanistic studies have shown that the source of these differences in excited-state reactivity is the ring constraints in 8 and 9, but missing in 10, which enforce conjugation of the electron-rich aryl ring and vinyliminium cation groupings.This causes reductions in both the singlet energies and reduction potentials of the iminium cation chromophores in 8 and 9 and results in inefficient, intramolecular electron transfer which serves as the obligatory step in photospirocyclization.