Efficient syntheses of substituted (±)-3-oxoisoindoline-1-carbonitriles and carboxamides using OSU-6

Abstract

An efficient synthesis of 3-oxoisoindolines is described from 2-carboxybenzaldehyde, TMSCN and benzylic or aliphatic amines using a Strecker approach with OSU-6 as the catalyst. The reaction can be tuned to generate two different products: a substituted (±)-3-oxoisoindoline-1-carbonitrile at 23 °C or the corresponding C1 primary amide at 78 °C. Aromatic amines divert from this reactivity to give isobenzofuranone derivatives. The formation of primary amides in these Strecker cyclizations has not been previously reported. The OSU-6 catalyst is a newly developed MCM-41 type hexagonal mesoporous silica with high Lewis acid strength and robust character, which facilitates recycling.