Palladium-Catalyzed Double Carbopalladation/syn-Insertion Cascade toward a Pragmatic Synthesis of Aminated Polyheterocyclic 1,2-Benzothiazepine 1-Oxides

Abstract

A Pd-catalyzed tandem cyclization reaction was developed, which offered the first pragmatic synthesis of aminated tetracyclic 1,2-benzothiazepine 1-oxides bearing a highly fused medium-sized cyclic unit. The acetyl (Ac) group was found to be an optimal protecting group in sulfoximine to reduce the nucleophilic ability of N atom, thus efficiently suppressing the formation of intramolecular 5-exo-dig cyclization side-product. The transformation proceeds through double syn-carbopalladation/annulation sequences to construct the rigid tetracyclic carbo-heterocyclic framework with excellent chemoselectivity and regioselectivity.