Study On The Construction Of Novel Cycloheptanone Skeletons Via Intramolecular [3+2] Cycloaddition Reactions

The development of chemical substances especially medium-sized ring structures has always been welcomed and encouraged by pharmaceutical and agrochemical fields.Among these,seven-membered carbocycles have more potential application value because of their structural profusion in natural products,drugs,and biologically active compounds.As yet,many strategies have been developed for the synthesis of medium-sized carbocyclic scaffolds.However,these efforts have largely been limited due to non-desired entropic reasons along with steric effects.In the field of asymmetric catalysis,the development of privileged seven-membered carbocycles has benefited considerably from different cycloaddition synthetic approaches but synthesis via the[3+2]cycloaddition approach has less extensively explored.Because of the structural novelty and potential biological activity of seven-membered carbocyclic compounds,it is of great value to research new synthetic methodology for these structures.Cycloheptanone featuring compounds can be constructed efficiently via the intramolecular[3+2]cycloaddition reaction in which diethylaminomalonate hydrochloride coupling partner with in-situ formed dipolarophile.The reaction conditions are mild,the atom economy is high,and it is in line with the characteristics of green organic synthesis.In this thesis,a cycloaddition approach is employed using diethylamino malonate hydrochloride and in-situ derived dipolarophile from 1,3 dipolar cycloaddition reaction,and an intramolecular[3+2]cycloaddition reaction occurs to realize the construction of cycloheptanone skeleton.Through the screening of reaction conditions such as catalyst,solvent,base,and molecular sieve,the final reaction conditions were determined as follows:dichloromethane as solvent(0.1 mol/L),and 10 mol%dimethyl amino pyridine(DMAP)as a catalyst,using sodium carbonate(Na₂CO₃)as a base,adding 3(?)molecular sieves,and reacting at room temperature under an air atmosphere to obtain a cycloaddition product in 9 h with 96%yield and>20/1 dr.The reaction substrate has a wide scope from which a series of seven-membered carbocyclic adducts has been constructed.This strategy provides a novel synthetic idea for the construction of seven-membered carbocycles along with five-membered pyrrole featuring three stereogenic centers.