Accessing 7‐Azaaurones of Controllable E and Z Configurations from 8‐Azaflavones via a Rearrangement‐Acylation‐Photoisomerization Sequence

Abstract

The amine‐promoted rearrangement of 3‐halogenated and 3‐tosylated flavones into amino‐substituted aurones is a reliable but little‐explored method in aurone synthesis. We extend it to 8‐azaflavones, readily prepared from 3‐cyano‐2‐pyridones by the Baker‐Venkataraman methodology. They rearrange into 7‐azaaurones under mild conditions in the presence of a broad range of aliphatic primary and secondary amines, including bulky amines for which steric hindrance issues are overcome by Lewis base organocatalysis. Primary amines selectively give the E configuration through an intramolecular stabilising hydrogen bond between the amino substituent and the carbonyl oxygen. Suppressing such hydrogen bonds by N‐acylation allows accessing the Z configuration by simple photoisomerization. Thus, we propose a methodology that allows access to the 7‐azaaurone scaffold and allows controlling the E/Z configuration by switching from an amino to an amido substituent at the double bond. Finally, the rearrangement‐acylation‐photoisomerization sequence is successfully extended to 2‐ethylidenefuropyridin‐3‐ones.