Divergent Synthesis of 6- or 7-Aza-Indazoles via Intramolecular Diels-Alder Cascade of Pyrazines

Org Lett. 2023 Nov 3;25(43):7847-7851. doi: 10.1021/acs.orglett.3c03052. Epub 2023 Oct 25.

Abstract

Pyrazines are reactive 4π partners in intermolecular Diels-Alder cycloaddition with exceptionally activated dienophiles or in an intermolecular version at elevated temperatures. Herein, it is shown that an intramolecular cascade could occur even at room temperature, delivering a collection of 6- or 7-aza-indazoles. An interesting substituent effect of the cycloaddition precursor on the product distribution was uncovered, and in situ NMR studies were conducted to gain insights into this unexpected selectivity.