Synthesis And Application Of The Products Of Allylic Alkylation Of Isoquinoline Reissert Compounds

Isoquinoline Reissert compounds are an important class of 1,2-dihydroisoquinolines. The isoquinoline Reissert compounds bearing chiral quaternary carbon were widely used to synthesize a lot of nature products and nitrogen-containing heterocyclic drugs. And, sulfur-containing compounds are widely present in nature and play important roles in biological and medicinal chemistry. Thus, it's of great significance for development of efficient methods to construct isoquinoline Reissert compounds bearing chiral quaternary carbon and transform the products to aza-heterocycles containing sulfur groups. This thesis mainly includes two parts:on the one hand, we develop an asymmetric allylic alkylation of isoquinoline Reissert compounds with Lewis base catalysts; on the other hand, transform the products of allylic alkylation of isoquinoline Reissert compounds to other sulfur-containing aza-heterocycles by cascade and one-pot reaction.First, we developed an asymmetric organocatalytic allylic alkylation of isoquinoline Reissert compounds, which was catalyzed with cinchona alkaloid catalysts. And it has been proved to be a facile way to access chiral 1,1-disubstituted 1,2-dihydroisoquinolines with adjacent quaternary and tertiary stereocenters. After catalysts screening, we discovered that the quinidine was the best catalyst. Hydrogen bond interaction introduced by hydroxyl group at C9 position of quinidine would be the key for this reaction. Under the standard condition, we can get the products in 20%-99% yield with good stereoselectivity (dr 14/1 to>20/l and 79%-94% ee).Next, The products of allylic alkylation of Reissert compounds can be transformed to sulfur-containing N-aromatic rings by stereoselective sulfa-Michael triggered tandem reaction. The carbonyl groups of amide were used as electrophile partner in the tandem reaction. The cascade reaction has a broad substrate scope, the newly constructed N-aromatic heterocyclic compounds could has one or two stereocenters in 60%-95% yield with good to excellent stereoselectivity. The products could be further transformed to other specific structures.Finally, an extension of the allylic alkylation of Reissert compounds in organic synthesis was carried out by an one-pot reaction. we developed a facile way to construct the multifunctional pyrrolo[2,1-a]isoquinolin-3(2H)-ones by combining the sulfa-Michael triggered tandem reaction and acid-promoted intramolecular cyclizaiton into an one-pot reaction. And we successfully introduced sulfur-containing group during the one-pot reaction. The yield of products was 54%-92%.