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

摘要

C-12b substituted isoindolo[1,2-a]isoquinoline 4 are prepared efficiently via a tandem Parham cyclisation-alpha-amidoalkylation reaction.Thus,Parham cyclisatio on imide 1 generates a isoindolo[1,2-a]isoquinoline,which is an immediate precursor of an N-acyliminium ion.Intermolecular alkylation with different pi-nucleophiles (allyl silanes or enol ethers)is accomplished upon treatment with Lewis acids (BF_3(centre dot)OEt_2,TiCl_4)to obtain nuevamine-type derivatives in high yields (69-95%)under mild conditions.