Titanium-Mediated aza-Nazarov Annulation for the Synthesis of N-Fused Tricycles: A General Method to Access Lamellarin Analogues.

Abstract

Fused heterocycles with nitrogen incorporation are of particular bioactive use and high importance in many research fields, especially isoquinoline-based [6/6/5] tricycles. Here, we report a unique strategy to access multifunctional N-fused tricycles from α,β-unsaturated isoquinoline ketone and sulfonamide under mild reaction conditions. The methodology features wide substrate tolerance, and a set of N-fused heteroarenes including quinoline, phthalazine, quinazoline, quinoxaline, and benzothiazole cores are furnished efficiently. Moreover, the protocol is easy to scale up to synthesize lamellarin analogues, and the amide group of the product is also easy to transfer to other functional groups.