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

Abstract

Electrochemically induced multicomponent transformation of salicylaldehydes and two different C À 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 À 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.

Electrochemically Induced Michael Addition Reaction: An Overview

“…Significant MCR to the synthesis of substituted medicinally privileged 2‐amino‐4 H ‐chromene moiety 27 via the electrocatalysis of an alcoholic solution of salicylaldehyde and two different carbon‐hydrogen acids has been reported by Elinson and co‐workers in 2008 . Based on the optimized reaction conditions (current density 10 mA/cm 2 , 0.1 F/mol passed, ethanol as solvent), the electrolysis of salicylaldehydes 25 , carbon‐hydrogen acids 26 and essential cyano‐substituted carbon‐hydrogen acids 11a – c in an undivided cell at room temperature produced functionalized 2‐amino‐4 H ‐chromene derivatives 27 in yields of 69–86 %.…”

Grindstone Chemistry: An Efficient and Green Synthesis of 2-Amino-4H-benzo[b]pyrans

“…Furthermore, these compounds exhibit unique pharmacological activities including treatment of human inflammatory TNF-mediated diseases, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Parkinson's disease [11,12]. Moreover, functionally substituted 4H-pyrans have played increasing role in synthetic approaches to promising compounds in the field of medicinal chemistry [13,14]. For example, 2-amino-4H-pyran derivatives bearing nitrile functionality exhibit potential applications in the treatment of psoriatic arthritis and rheumatoid, and also in cancer therapy [15][16][17][18].…”

Synthesis of 2‐Amino‐3‐cyano‐4H‐chromene‐4‐carboxamide Derivatives by an Isocyanide‐Based Domino Conjugate Addition/O‐Trapping Rearrangement Sequence

“…[16][17][18][19][20][21] Reactions with Ncontaining nucleophiles gave access to 2-N-substituted products, [16] whereas with other nucleophiles, for example, C-, S-, or P-containing compounds, attack at C-4 by conjugate addition was preferred. [17][18][19][20][21] Figure 1. Three-centered imino-chromene-carboxamide framework.…”