179945-89-2Relevant academic research and scientific papers
A triple cascade sequence as a strategy for the construction of the erythrinane skeleton
Padwa, Albert,Hennig, Rudiger,Oliver Kappe,Reger, Thomas S.
, p. 1144 - 1155 (2007/10/03)
α-Thiocarbocations generated from Pummerer reactions of several o- imido sulfoxides were intercepted by adjacent carbonyl groups to produce α- amido-substituted isobenzofurans as transient intermediates. When an olefinic tether was present, intramolecular Diels-Alder cycloaddition occurred followed by a ring-opening-elimination sequence that produced an N- acyliminium ion. Deprotonation of the iminium ion led to oxindole derivatives in good yields. When the iminium ion contained both a blocking substituent, such as a carbomethoxy group, as well as an activated aromatic π-tether, the N-acyliminium ion intermediate underwent stereoselective spirocyclization to afford cis-3,4-benzoerythrinane or homerythrinane derivatives in good yield. The overall triple cascade sequence represents an efficient one-pot approach toward the erythrina skeleton in which the spirocyclic ABC skeleton is assembled in a single operation. The scope and limitations of the triple cascade were explored by varying both the olefinic and nucleophilic tethers. The required sulfoxide precursors for these Pummerer-induced transformations were easily synthesized starting from 2-[(ethylthio)methyl]benzoic acid. The tandem Pummerer/Diels-Alder/N-acyliminium ion cyclization was used for the synthesis of indoloisoquinoline 38. Since compound 38 was converted to 47 which, in turn, was transformed into erysotramidine (2), its preparation represents an extraordinarily facile, formal synthesis of this member of the Erythrina alkaloid family.
