Application Of [4+1] Cyclization Based On Dehydrohalogenation Strategy In The Synthesis Of Five-Membered Heterocycles

Heterocycles are omnipresent in biologically active natural products,medicinally important compounds and synthetic agrochemicals as well as functional materials.The most prominent role is in medicine,more than 70% of the drugs currently on the market contain a heterocyclic unit.For this porpurse,the development of various synthetically feasible protocols for the construction of these important and attractive scaffolds,including new reagents,new reactions and new techniques,is one of the high-value goals of organic synthetic chemists.In this thesis,based on the strategy of dehydrohalogenation to form highly reactive intermediates,[4+1] cycloaddition reaction occurred,and three different heterocyclic compounds were constructed.The details are as follows:1、We have developed a tandem phospha Michael addition/N-acylation/intramolecular Wittig reaction of aza-o-QMs from N-(ortho chloromethyl)aryl amides under mild conditions.This protocol,featured by broad substrate scope,mild and simple reaction procedures,providing a practical access to valuable indole derivatives in moderate and good yields,and this method has a certain potential application in pharmaceutical chemistry.37 examples of2,3-disubstituted indole derivatives were synthesized in up to 91% yield.2、We have reported a facile [4+1] annulation reaction between in situ formed nitrosoalkene intermediates and sulfur ylides via a Michael/intramolecular O alkylation sequence.The protocol provides a direct and efficient pathway to construc valuable2-isoxazoline derivatives in good to excellent yields.The reaction takes place under relatively mild and simple experimental conditions.21 examples of isoxazoline derivatives were synthesized in up to 99% yield.3、A formal [4+1] cyclization reaction between Baylis-Hillman(BH)bromides and sulfur ylides were developed to construct α-methylene-γ-butyrolactone derivatives in a simple and efficient way.25 examples of α-methylene-γ-butyrolactone derivatives were synthesized in up to 93% yield.