Tandem Parham cyclisation––α-amidoalkylation reaction in the synthesis of the isoindolo[1,2-a]isoquinoline skeleton of nuevamine-type alkaloids

C-12b substituted isoindolo[1,2-a]isoquinolones 4 are prepared efficiently via a tandem Parham cyclisation––α-amidoalkylation reaction. Thus, Parham cyclisation on imide 1 generates a 12b-hydroxy isoindolo[1,2-a]isoquinolone, which is an immediate precursor of an N-acyliminium ion. Intermolecular alkylation with different π-nucleophiles (allyl silanes or enol ethers) is accomplished upon treatment with Lewis acids (BF3·OEt2, TiCl4) to obtain nuevamine-type derivatives in high yields (69–95%) under mild conditions.