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

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 ( plus or minus )-3-oxoisoindoline-1-carbonitrile at 23 degree C or the corresponding C1 primary amide at 78 degree 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.