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

Maddirala, Amarendar Reddy; Andreana, Peter R.

A 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.

INDOLE compounds; METHYL isocyanide; ETHYLENE dichloride; MICROWAVES; ALDEHYDES

European Journal of Organic Chemistry, 2016, Vol 2016, Issue 1, p196

1434-193X

Academic Journal

10.1002/ejoc.201501273