Synthesis of 3‐Substituted 2‐Indol­inones by a Multicomponent Coupling Isocyanide‐Dependent Microwave‐Assisted Intramolecular Transamidation Process

Abstract

AbstractA small‐molecule library synthesis of 3‐substituted 2‐indolinones using methyl isocyanide and a microwave‐assisted intramolecular transamidation process with 10 % TFA in dichloroethane has been achieved in 3 steps. A modified Fe0 Bechamp‐type reduction of a substituted bifunctional substrate, o‐nitrobenzaldehyde, renders 3‐substituted 2‐indolinones in yields ranging from 76–91 % (21 examples). Furthermore, it has been determined that symmetrical 2o N‐alkyl or aryl substituents, as a component of the amine starting material, suppresses 3‐substituted 2‐indolinone rotameric mixtures and allows for facile compound 1H NMR characterization. In the absence of methyl isocyanide, 3,4‐dihydroquinazolines or transamidation products predominate under both Brønsted or Lewis acid conditions in reasonable yields.