Journal of Organic Chemistry
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 cydoaddition 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.
Robins, J. G., Kim, K. J., Chinn, A. J., Woo, J. S., & Scheerer, J. R. (2016). Intermolecular Diels–Alder Cycloaddition for the Construction of Bicyclo [2.2. 2] diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide. The Journal of organic chemistry, 81(6), 2293-2301.