An efficient strategy for construction of tricyclic thiazino[3,4-a]isoquinolines has been achieved via 4-dimethyl- amino-pyridine (DMAP) promoted [5＋1] annulation of simple and readily available isoquinoline 1,4-zwitterion with α-bro- moketone. This protocol showed good substrate compatibility as an array of structurally and electronically diverse thiazino[3,4-a]isoquinolines prepared efficiently in moderate to good yields. It is particularly emphasized that although this reaction exhibits moderate stereoselectivity, the two diastereomers can be separated by column chromatography, providing an important molecular diversity foundation for the screening and structural optimization of subsequent drug lead compounds, as well as a simple and efficient method for constructing complex nitrogen-containing and sulfur-containing heterocyclic compounds. It has potential application value in the fields of medicinal chemistry and organic synthesis.

Key words: [5＋1] annulation, isoquinoline derivative, 1,4-thiazine derivative