Electrochemically Induced Three-Component Synthesis of Chromenes

Significance

Described is a fast and effective electrochemically induced three-component reaction of salicylaldehyde 1 and different C-H acids 2 and 3, which provides a modestly general synthesis of diversely functionalized 2-amino-4H-chromenes 4. The reaction occurs in an undivided cell in the presence of sodium bromide as an electrolyte and proceeds smoothly with salicylaldehyde bearing both electron-donating and electron-withdrawing groups. Thus, fifteen previously inaccessible, close structural analogues of the tumor antagonists HA14-1 (J. Skommer et al. Leukemia Res. 2006, 30, 322) and MX58151 (W. Kemnitzer et al. J. Med. Chem. 2004, 47, 6299) have been synthesized. A reasonable mechanism for the reaction is proposed. This is the first reported efficient procedure that leads to the 2-amino-4H-chromene scaffolds with a predefined arrangement of desired substituents through a one-pot condensation reaction. This process is advantageous in terms of selectivity and yields compared to previous methods.