Work

Intermolecular Diels–Alder Cycloaddition for the Construction of Bicyclo[2.2.2]diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide

Year: 2016

Type: article

Abstract: 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.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.5b02744

Authors: Jacob G. Robins, Kyu J. Kim, Alex J. Chinn, John S. Woo, Jonathan R. Scheerer

Institution: William & Mary

Language: English

Topic: Advanced Synthetic Organic Chemistry

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green