Nucleophilic addition of 1-acetylindole enolates to pyridinium salts. Stereoselective formal synthesis of (+/-)-geissoschizine and (+/-)-akagerine via 1,4-dihydropyridines

Addition of the enolate derived from 1-acetylindole (3) to pyridinium salt 4b followed by acid-induced cyclization of the resulting 1,4-dihydropyridin e 5b in the presence of lithium iodide gives tetracyclic 3,7-methano[1,4]di azonino[1,2-alpha]indole 6b, which has subsequently been elaborated into th e (E)-ethylidene derivative 7b. From this compound is reported a stereocont rolled route to (+/-)-geissoschizine, involving closure of C ring by Pummer er reaction, methanolysis of the resulting pentacyclic lactam 12, and desul furization. A similar synthetic sequence starting from the enolate of 3 and 2-fluoropyridinium salt 15b gives access to the pentacyclic dilactam 2, wh ich had previously been converted to (+/-)-akagerine through opening of the piperidone (D) ring.