Ti-catalyzed Regioselective Ring-opening Alkynylation Of Epoxides With Haloalkynes

Objective:Epoxides are easily available and commonly used intermediates in organic chemistry.They are often used to construct functional organic compounds with diverse structures,such as carbonyl compounds and alcohols.Through literature investigation,it is found that the selective ring opening alkynylation of epoxides is an effective method to prepare propargyl alcohol or homopropargylic alcohol.However,there are few reports on the direct alkynylation of epoxides to produce propargyl alcohol,and the alkynylation reactions of epoxides reported in the existing literature have relatively harsh reaction conditions,relatively narrow substrate range,lack of functional tolerance,excessive dangerous reagents and specifically regioselectivity.Therefore,this paper aims to establish a mild,simple,green and economical epoxide ring opening alkynylation system with good selectivity and applicability,and synthesize a series of different propargylic alcohols or homopropargylic alcohols.Methods:In this paper,α-haloalkynes are used as alkynylation reagent,titanium salt as catalyst and epoxide as electrophilic reagent to construct regioselective propargyl alcohol.Firstly,the corresponding epoxide substrates were selected through literature research,and the reaction conditions were optimized by single variable method to find the better reaction conditions for epoxide ring opening alkynylation.Then,the substrate applicability of the reaction was explored with epoxide substrates containing different functional groups.The structure of the product was characterized by NMR,IR and HRMS,and then the reaction mechanism was explored by radical capture test,single substrate control test and separation of reaction by-products.Results:The results showed that when the equivalent ratio of epoxide to haloalkyne was 1:1.5,dichloromethane was the reaction solvent,Cp₂Ti Cl₂ was the catalyst,triethylamine hydrochloride was the additive,zinc powder was the reducing agent,and the reaction condition was 4 hours under the conditions of argon and room temperature was the optimal reaction condition.Under these optimized conditions,the applicability of epoxide and haloalkyne substrates was explored,and a series of propargylic alcohols were obtained in medium to good yields.Conclusion:We have successfully developed a selective Ti-catalyzed ring-opening alkynylation of epoxides withα-haloalkynes.The reaction system is suitable not only for aromatic or aliphatic terminal epoxides,but also for internal epoxides.The reaction system is mild,simple and has good regional selectivity.It can quickly and efficiently synthesize corresponding propargylic alcohols products,providing some potentially active compounds for clinical drugs and corresponding intermediates for related drug synthesis.