Studies On Lewis Acid-catalyzed Cyclization Reactions Of Propargylic Alcohols

Cyclic compounds are key structural units in many biologically active molecules and natural products.The cascade reaction of propargylic alcohol compounds to synthesize various cyclic compounds has always been a research focus for organic chemists.Under the catalysis of Lewis acid or Bronsted acid,propargyl alcohol can react with nucleophiles to synthesize 1,3-dicarbonyl compounds,propargyl compounds,allene compounds,or various cyclic compounds.However,most of the current synthesis methods are based on experimental research on simple compounds,and there is little research on the multi-step cascade reaction of propargyl alcohol.In this paper,the reactions of propargyl alcohols with various nucleophiles catalyzed by lewis-acid were studied,the substrate compatibility and mechanisms of these reactions were discussed.including the following six chapters:1.The development of methodologies employing propargylic alcohols as synthons and the reaction types and reaction mechanisms of propargylic alcohols were reviewed.The research progress of rearrangement reactions,nucleophilic substitution reactions,and tandem cyclization was discussed.2.A novel copper catalytic system was described to realize the cascade cyclization of propargylic alcohols with diphenylphosphine oxide.In this reaction,O-hydroxy/amino substituted propargyl alcohols were used to synthesize cyclic organic phosphines and dienyl organic phosphines.The reaction,which has good functional group compatibility,and insensitivity to air humidity,can synthesize organophosphorus compounds in good yield under mild conditions.The mechanism of the reaction has been proved by the X-ray crystal diffraction analysis of the intermediate and isotope analysis experiments.3.A Cu（OTf）₂ catalyzed cascade cyclization of propargyl alcohols with alkenylindoles was studied.The reaction goes through a sequential Meyer-Schuster rearrangement/intermolecular nucleophilic addition/intramolecular cyclization process to generate carbazole derivatives.The reaction conditions are simple and mild,and various substituted propargyl alcohol substrates in good yields.4.2-hydropyridine derivatives are prevalent in many biological and pharmacological active molecules.They are synthetic precursors of many important alkaloids.In this chapter,we developed an Ag OTf catalyzed formal[3+3]annulation of propargyl alcohols with alkenylamides to synthesize 2-hydropyridine derivatives.The reaction conditions and substrate compatibility of tertiary alkynol and secondary alkynol were investigated in this section.It is a highly efficient,simple to operate,and substrate-compatible reaction.5.In this chapter,we reported an Au/Cu-catalyzed tandem annulation of two different alkynols by two steps in one pot,leading to a variety of polycyclic dihydrobenzofuran derivatives.The reaction mechanism was verified by intermediate capture experiments.Most benzofuran products showed the properties of solid fluorescence and mechanochromism,which reveal their potential application value.6.In this chapter,we developed a nucleophilic reaction between tertiary cyclic alcohols and propargylic alcohols under the catalyst of Lewis acid to generate six or seven-membered carbon ring products.Both the control experiment and DFT calculation experiment verified the feasibility of the ring-opening reaction mechanism.This method is simple in operation and avoids the use of excessive oxidants or precious metals.The reaction,which tolerates good substrate practicability,provided an efficient method for the formation of six and seven-membered rings and four-membered carbon ring compounds.