3,4- and 3,5-Disubstituted 2-Pyridones Using an Intermolecular Cycloaddition / Cycloreversion Strategy: Toward the Synthesis of Aristopyridinone A

Maren K Leibowitz; Ethan S Winter; Jonathan R Scheerer

doi:10.1016/j.tetlet.2015.09.067

3,4- and 3,5-Disubstituted 2-Pyridones Using an Intermolecular Cycloaddition / Cycloreversion Strategy: Toward the Synthesis of Aristopyridinone A

Tetrahedron Lett. 2015 Oct 28;56(44):6069-6072. doi: 10.1016/j.tetlet.2015.09.067.

Authors

Maren K Leibowitz¹, Ethan S Winter¹, Jonathan R Scheerer¹

Affiliation

¹ Department of Chemistry, The College of William & Mary, P. O. Box 8795, Williamsburg, VA 23187, USA.

Abstract

The intermolecular cycloaddition of pyrazinone precursors with alkyne substrates was evaluated. The resulting regioisomeric [2.2.2]-diketopiperazine alkene cycloadducts were diverted into 2-pyridone products through cycloreversion of the [2.2.2]-bicyclic intermediates. New insights into the regioselectivity of pyrazinone azadiene Diels-Alder reactions as well as cycloreversion reactivity were revealed in this study. Synthetic sequences using this [4+2]/r[4+2] strategy were determined that can produce predominantly the 3,5-disubstituted 2-pyridone alkaloid structures; pyridones featuring the 3,4-substitution pattern are observed as the minor regioisomeric products.

Keywords: 2-Pyridone; Aristolochia; Aristopyridinone; Cycloaddition/cycloreversion; alkaloid synthesis.

Grants and funding

R15 GM107702/GM/NIGMS NIH HHS/United States