Nucleophilic Addition of 1-Acetylindole Enolates to Pyridinium Salts. Stereoselective Formal Synthesis of (±)-Geissoschizine and (±)-Akagerine via 1,4-Dihydropyridines
journal contributionposted on 03.12.1999, 00:00 by M.-Lluïsa Bennasar, Juan-Miguel Jiménez, Bernat Vidal, Bilal A. Sufi, Joan Bosch
Addition of the enolate derived from 1-acetylindole (3) to pyridinium salt 4b followed by acid-induced cyclization of the resulting 1,4-dihydropyridine 5b in the presence of lithium iodide gives tetracyclic 3,7-methano[1,4]diazonino[1,2-a]indole 6b, which has subsequently been elaborated into the (E)-ethylidene derivative 7b. From this compound is reported a stereocontrolled route to (±)-geissoschizine, involving closure of C ring by Pummerer reaction, methanolysis of the resulting pentacyclic lactam 12, and desulfurization. A similar synthetic sequence starting from the enolate of 3 and 2-fluoropyridinium salt 15b gives access to the pentacyclic dilactam 2, which had previously been converted to (±)-akagerine through opening of the piperidone (D) ring.
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enolateGeissoschizinedesulfurizationcompoundclosuremethanoPyridinium SaltssequenceAkagerinedihydropyridineacetylindoleakagerineaccesspentacyclic lactam 12openingC ringgeissoschizine7 bStereoselective Formal Synthesispresenceethylidenelithium iodidemethanolysiNucleophilic AdditionPummerer reactionpentacyclic dilactam 2pyridinium salt 4 bfluoropyridiniumDihydropyridinepiperidoneindole 6 bcyclizationstereocontrolled routetetracyclicAcetylindoleEnolate