Study On The Synthesis And Application Of Chiral Spiro[4.4]nonane Skeleton

The spirocyclic compounds, belonging to a unique structure incorporating two cycles sharing one quaternary carbon center and having high streic hindrance and strain tension, exists widely in nature. Based on the rigidity of the structure, spiro skeleton has been widely applied in asymmetric catalysis, medicine design and function materials. The spiro skeleton has become a ‘privileged structure’ because of its excellent performance in chiral ligand and catalyst and is extremely popular with chemist. N-heterocyclic carbene, one of the leading role in the field of organic catalysis and metal catalysis, has developed rapidly and become one of the hot spots in the field of catalysis since be isolated in 1990 s. However, the privileged structure of spiro skeleton does not intermarriage with the hot topic of N-heterocyclic carbene—the synthesis and usage of N-heterocyclic carbene with spiro skeleton back bone has rarely been reported. Our group has had a preliminary exploration about the N-heterocyclic carbene fused with spiro[4.4]nonane skeleton. This thesis continues the research direction of our group, the design, synthesis and properties of spiro-fused N-heterocyclic carbenes were further exploered. Meanwhile, considering the preparation of chiral spiro skeleton is a major obstacle that limits the application of spiro skeleton in asymmetric catalysis, further exploration of synthesize chiral spiro[4.4]nonane-1,6-dione and chiral 1-azaspiro[4.4]nonan-6-one has also been researched. This thesis consists of three parts: 1. Research progress of chiral spiro-fused ligand and catalyst; 2. Study on the N-heterocyclic carbene fused with spiro[4.4]nonane skeleton; 3. Br?nsted acid catalytic tandem Nazarov cyclization/semipinacol rearrangement to construct chiral spiro[4.4]nonane-1,6-diones.In chapter 1, we reviewed the preparation and research progress of chiral spiro ligand and catalyst. Accoording to the difference of spiro skeleton, spiro[4.4]nonane skeleton, spirobichroman skeleton and other skeletons were briefly introduced respectively.In chapter 2, we briefly introduced the progress of N-heterocyclic carbene firstly. Then the preparation of N-heterocyclic carbene(the synthesis startd with spiro[4.4]nonane-1,6-dione) and its activity, the corresponding copper(I), gold(I) and rhodium(I) complex were described in detail. Finally, the optimization of the route of synthesis chiral 1-azaspiro[4.4]nonane-6-one and the research of N-heterocyclic carbene which was fused with 1-azaspiro[4.4]nonane scaffold were also introduced in the chapter.In chapter 3, we described the progress in the synthesis of chiral spiro[4.4]nonane-1,6-diones. We developed a tandem Nazarov cyclization/semipinacol rearrangement reaction to get a series of chiral spiro[4.4]nonane-1,6-diones in up to 96% yield, 77% ee and > 99:1 dr using chiral Br?nsted acid as the catalyst. In addition, we have made a preliminary study on the reaction mechanism, substituent effects and stereochemistry.