A Triple Cascade Sequence as a Strategy for the Construction of the Erythrinane Skeleton

Abstract

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 homoerythrinane 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.