Catalysis of salicylaldehydes and two different C-H acids with electricity: First example of an efficient multicomponent approach to the design of functionalized medicinally privileged 2-amino-4H-chromene scaffold

Electrochemically induced multicomponent transformation of salicylaldehydes and two different C-H acids in alcohols in an undivided cell in the presence of sodium bromide as an electrolyte results in the efficient and selective formation of diversely functionalized, medicinally privileged 2-amino-4H-chromene scaffolds in 65-86% yields. The developed electrocatalytic system affords the distinction between two C-H acids according to their reactivity, and offers an efficient approach to the 2-amino-4H-chromene scaffold with a predefined arrangement of desired substituents. The electrocatalytic multicomponent reaction smoothly proceeds with salicylaldehydes bearing both electron-donating and electron-withdrawing groups. Thus, fifteen previously inaccessible, close structural analogues of the tumor antagonists HA14-1 and MX58151 have been synthesized. The electrocatalytic process was found to be advantageous in terms of selectivity and yields compared to classic chemical base catalysis, and includes a remarkable mechanistic feature that is promising for the further development of 2-amino-4H-chromene chemistry. The application of this convenient electrocatalytic multicomponent method to the formation of medicinally relevant 2-amino-4H-chromenes is also beneficial from the viewpoint of diversity-oriented large-scale processes and represents a novel, facile and environmentally benign synthetic concept for multicomponent reaction strategy.