Study On The Domino Reactions Of Tert-Amine Substituted Conjugated Yne-Enone Compounds Catalyzed By Lewis Acid

As one of the representative five-membered heterocycles, furans have been founded in many naturally occurring products. What's more, polysubstituted furans can be also found to be the key structural unit in lots of pharmaceuticals. In this dissertation, a series of tert-amino aryl substituted conjugated yne-enones were designed and synthesized, from which, polysubstituted furans and tetrahydroquinolines were obtained in the presence of different Lewis acid. And then the enantioselective synthesis of furan fused polyheterocycles was also reached.Firstly, we developed a novel heterocyclization/1,5-hydride shift/ring-closure domino reaction catalyzed by gold(I) with tert-amino aryl substituted conjugated yne-enones as the starting materials. As for the substrates, the substituent group on the alkynes has great effect on the yield of the reaction. Generally, a higher yield can be obtained with the aryl as the substituent of the alkynes compared to alkyl group. The substituents on the phenyl of the substrates also have great effect on the reaction. As for the tert-amino group, the substrate with the middle-sized cyclic or acycle amino can also proceed smoothly to afford the desired polysubstituted furans with excellent yields. Besides, the mechanism of the heterocyclization/1,5-hydride shift/ring-closure domino reaction catalyzed by gold(I) was discussed.Secondly,1,5-hydride shift/ring-closure domino reaction catalyzed by Lewis acid was developed. After numerous attempts, Sc(OTf)3 was found to be the best catalyst to promote the 1,5-hydride shift/ring-closure domino reaction from the tert-amino aryl substituted conjugated yne-enones and tetrahydroquinolines were obtained with good yields and diastereoselectivities. On the basis of the experiment data, the mechanism of the Sc(OTf)3 catalyzed 1,5-hydride shift/ring-closure domino reaction was also discussed.In the end, based on the work that the intramolecular heterocyclization/1, 5-hydride shift/ring-closure domino reaction catalyzed by gold(I), the enantioselective variant of this transformation was next explored. Polysubstituted furan derivatives were obtained in good to excellent yields and enantioselectivities with (R)-DTBM-MeOBIPHEP as the ligand after the reaction was proceeded under a mild condition.