Preparation And Asymmetric Preparation Of Aryl-fused Six-Membered Nitrogen Heterocycles

Aryl-fused and N-containing six-membered heterocycles are an important skeleton structure of the natural products and drug molecules, and two of the typical representative structures are 2- functional substituted 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroquinoxaline. Although the synthesis of those has been reported, the efficient synthesis and asymmetric synthesis are still worthy of study. Our work is focus on palladium-catalyzed oxidative cyclization for olefin and hypervalent iodine-assisted oxidative cyclization for olefin respectively to prepare for 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroquinoxaline derivatives.On the one hand, Pd(II)-catalyzed oxidative cyclization of olefin was developed for the preparation of aryl-fused and N-containing six-membered heterocycles with 2-acetoxy Functionality. Under optimal conditions, the reaction proceeded with high activity and selectivity, with yields of up to 83% being obtained. This procedure provides a facile and efficient route to the aforementioned heterocycles with 2-acetoxy functionality.On the other hand, hypervalent iodine-assisted oxidative cyclization of olefin was developed for the preparation of 2-substituted 1,2,3,4-tetrahydroquinoline derivatives. The reaction can proceed smoothly with diacetate iodine as oxidant. Under optimal conditions, the aforementioned heterocycles can be obtained with high yield. Subsequently, the chiral hypervalent iodine was applied to the synthesis of 2-substituted 1,2,3,4-tetrahydroquinoline. The preliminary exploration suggested that the asymmetric synthesis of 2-substituted-1,2,3,4-tetrahydroquinoline with chiral hypervalent iodine was feasible.