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. (C) 2015 Elsevier Ltd. All rights reserved.
Leibowitz, M. K., Winter, E. S., & Scheerer, J. R. (2015). 3, 4-and 3, 5-disubstituted 2-pyridones using an intermolecular cycloaddition/cycloreversion strategy: toward the synthesis of aristopyridinone A. Tetrahedron letters, 56(44), 6069-6072.