Nitrogen Heterocyclic Carbene Catalyzes Tandem Reactions To Synthesize Chiral Polyheterocyclic Compounds

The pyrrolo[3,2-c]quinolone structure is the basic framework widely existed in natural products and drug molecules.There are many steps in the synthesis of such structure by traditional methods.How to synthesize pyrrolo[3,2-c]quinolone structure of a multi-chiral center in one step through a simple and efficient reaction process,it has been the hot and the difficult of organic synthesis.N-Heterocyclic Carbene(NHC)catalysts have become an important branch of organic small molecule catalysts.Its unique catalytic activation mode can not only achieve high yield and high stereoselective control of existing reactions,but also can synthesize novel structural compounds that cannot be synthesized by traditional methods.The cascade reaction based on NHC catalysis not only can control chemical selectivity and regioselectivity,but also can achieve high stereoselective control of complex molecules.The ?,?-unsaturated acylazolium ion intermediate has a unique effect on the construction of different cyclic products.Under the NHC catalysis,?-bromoalkenyl oxidizes itself to form ?,?-unsaturated acylazolium ion and the benzylic carbon atom of the N-Boc-protected o-aminoaromatic aldimine are subjected to a cascade reaction,and a pyrrolo[3,2-c]quinolone structure having four consecutive chiral centers is constructed in one step.(1)The ?,?-unsaturated acylazolium ion intermediate is presented as an electrophile in the NHC catalytic reaction,and it can be obtained through ?,?-unsaturated aldehyde and oxidant,?,?-unsaturated ester,?-bromoalkenyl and so on under the catalystic of NHC.This chapter mainly introduces the literature review of the reaction of ?,?-unsaturated acylazolium ion intermediate in the NHC catalysis in rencent years.(2)This chapter introduces the purpose and significance of this research.Based on the work of reported by our group about 4-nitrobenzylic carbon,we envisioned that the hydrogen on the C-H bond of 4-nitrobenzyls were acidic enough deprotonation under the action of a base to form a carbanion to participate in conjugate additions with ?,?-unsaturated carbonyl compounds.So a model reaction of ?-bromoalkenyl with an imine with a 4-nitrobenzylic carbon as substrates was designed,the synthetic route of the NHC precursors and substrates were introduced.(3)In this chapter,the conditions of the established model reaction are optimized,the conditions are selected from the aspects of catalysts,bases,solvents,temperture and time.Under the relatively good conditions,the universality of the model reaction was explored with excellent yield,enantioselective and diastereoselective to obtain the desired product.The asymmetric synthesis of acetone and isatin was achieved by using the chiral compound 3a as asymmetric catalysis.