A TRIPLE CASCADE SEQUENCE AS A STRATEGY FOR THE CONSTRUCTION OF THE ERYTHRINANE SKELETON

alpha-Thiocarbocations generated from Pummerer reactions of several o- imido sulfoxides were intercepted by adjacent carbonyl groups to produ ce alpha-amido-substituted isobenzofurans as transient intermediates. When an olefinic tether was present, intramolecular Diels-Alder cycloa ddition 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 b oth a Mocking substituent, such as a carbomethoxy group, as a ell as a n activated aromatic pi-tether, the N-acyliminium ion intermediate und erwent stereoselective spirocyclization to afford cis-3,4-benzoerythri nane or homoerythrinane derivatives in good yield. The overall triple cascade sequence represents an efficient one-pot approach toward the e rythrina skeleton in which the spirocyclic ABC skeleton is assembled i n a single operation. The scope and limitations of the triple cascade were explored by varying both the olefinic and nucleophilic tethers. T he required sulfoxide precursors for these Pummerer-induced transforma tions were easily synthesized starting from 2-[(ethylthio)methyl]benzo ic acid. The tandem Pummerer/Diels-Alder/N-acyliminium ion cyclization was used for the synthesis of indoloisoquinoline 38. Since compound 3 8 was converted to 47 which, in turn, was transformed into erysotramid ine (2), its preparation represents an extraordinarily facile, formal synthesis of this member of the Erythrina alkaloid family.