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

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.