Intermolecular Diels–Alder Cycloaddition for the Construction of Bicyclo2.2.2diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide

摘要

A stereoselective intermolecular Diels–Alder cycloaddition of an intermediate pyrazinone with both achiral and chiral acrylate-derived dienophiles provides rapid access to the bicyclo[2.2.2]diazaoctane core shared among several prenylated indole alkaloids. The product derived from cycloaddition with 2-nitroacrylate required an additional five to six synthetic operations to intercept established precursors to premalbrancheamide and brevianamide B. The chemistry detailed in this manuscript constitutes a formal total synthesis (12 steps each) of these [2.2.2]diazabicyclic natural products from proline methyl ester.