Synthesis Of Indolizine And ?-Naphthol Derivatives By Cyclization Reactions Involving Alkynes

Objective: Alkyne is one of the most important starting materials for organic synthesis and are widely used in various organic conversion reactions.In this paper,alkynes are used as starting materials to study the cyclization reactions involving selective formation of C-N bonds and C-C bonds,which provides a convenient method for the efficient synthesis of indolizines and ?-naphthol derivatives.Methods: In this thesis,alkynes are used as starting materials,and the following two aspects of research work are mainly carried out: 1.This paper uses2-(pyri-din-2-yl)acetates as the substrate to react with different alkynes in the presence of iodine.The fine-tuning of the reaction conditions resulted in the regioselective and chemoselective synthesis of polysubstituted indolizines,and2,2'-biindolizines have been prepared for the first time through a two-step reaction.(1): Under iodine-promoted reaction conditions,terminal alkynes could react with2-(pyridin-2-yl)acetates to give substituted indolizines via carbon radical process;(2):When the ligand in the reaction was removed,the amount of iodine was halved,and when the reaction solvent was replaced from DMF to DMA,ethyl phenylpropynoate or phenyl propiolaldehyde could work smoonthly with 2-(pyri-din-2-yl)acetates to afford the multi-substituted indolizine compounds via nitrogen radicals process,which enabled the regioselective synthesis of polysubstituted indolizines;(3): For the reaction of phenyl propiolaldehyde with 2-(pyri-din-2-yl)acetates,on the basis of the reaction conditions of terminal alkyne and 2-(pyri-din-2-yl)acetates,the amount of iodine was increased from 2.0 equiv.to 3.5 equiv.and 2.0 equiv.Cu I was added to the reaction system,the product C3-acylated indolizines with chemoselectivity was obtained via a condensation/intramolecular cyclization pathway.2.Ethyl benzoylacetate was used as a substrate,and a free radical cyclization reaction with terminal alkynes was performed under the action of manganese(III)acetate to efficiently synthesize ?-naphthol derivatives.Results: Under iodine-promoted reaction conditions,terminal alkynes and 3-phenylpropiolate could react with2-(pyridin-2-yl)acetates to give substituted indolizines regioselectively via radical process.Additionally,3-phenylpropiolaldehyde could react with 2-(pyridin-2-yl)acetates to chemoselectively give C3-acylated indolizines via a condensation/intramolecular cyclization pathway,or give C2-carbaldehyde substituted indolizines via a nitrogen radical process pathway.The research method in this thesis successfully yieled 25 examples of 1,3-substituted indolizines and two examples of 2,2'-biindolizines,12 examples of multi-substituted indolizines and 7examples of C3-acylated indolizines.A total of 46 examples of indolizine compounds,including 21 new compounds.At the same time,the plausible mechanism of the reaction was proposed after the investigation of control experiments.2.In the presence of manganese(III)acetate,ethyl benzoylacetate and terminal alkynes undergo radical cyclization reaction to give 22 examples of ?-naphthol derivatives,including 4 new compounds.At the same time,the plausible mechanism of the reaction was proposed after the investigation of control experiments.Conclusions:In this thesis,alkynes are used as starting materials,two regio-and chemo-selective synthetic methods have been developed.They provide convenient and efficient protocols for the rapid construction of indolizines and ?-naphthol derivatives.Furthmore,it also provides a reference for the subsequent study of alkynes in heterocyclic synthesis.