Synthetic Application of Sequential Palladium-Catalyzed Allylic Acetate Alkylation and Michael Addition Carbocyclization: Synthesis of (±)-Dihydroerythramine

Abstract

A new synthetic route to aromatic Erythrina alkaloids is reported. (Nitromethyl)arene 3 underwent a palladium-catalyzed annulation reaction with allylic acetate 11 to provide nitro esters 12a and 12b by an (η3-allyl)palladium complex alkylation/Michael addition domino sequence. Reduction of the nitro group of 12a, followed by cyclization of the resulting amino group on the acetate appendage, afforded the bicyclic lactam 29. Two-carbon elongation at the nitrogen atom of 29 by hetero Michael addition of vinyl phenyl sulfoxide, followed by Pummerer-type cyclization, gave cis-11-phenylthioerythrinan-8-one (32a, 32b) along with the rearranged lactam 34. Reductive desulfurization at C-11, and oxidative cleavage of the C-3 exocyclic double bond afforded the 15,16-(methylenedioxy)erythrinan-3,8-dione (42). Reduction of the C-3 carbonyl group and methylation of the resulting alcohol afforded hexahydrocrystamidine (44), which was further reduced by aluminum hydride to give (±)-dihydroerythramine (9).