Total Syntheses of (+/-)-Deethylibophyllidine Using a Crisscross Annulation: Ring Cleavage of Octahydroindolo[2,3-a]quinolizines Followed by Tandem Cyclizations of Octahydroazecino[5,4-b]indoles.

The total synthesis of (+/-)-deethylibophyllidine (1) is described. Three different sequences provide this pentacyclic alkaloid using a common strategy involving a crisscross annulation. Key steps include (i) C/D ring cleavage of a 2-formyloctahydroindolo[2,3-a]quinolizine to obtain octahydroazecino[5,4-b]indoles, via either a chloroformate induced process or a quaternary ammonium salt formation followed by treatment with lithium, and (ii) a tandem process consisting of an intramolecular Pictet-Spengler double cyclization upon a beta-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center of the pentacyclic skeleton of ibophyllidine alkaloids. Attempts to extend the procedure to the construction of the pentacyclic framework of (+/-)-ibophyllidine result in very low yield.