Study On The Regio-and Stereochemical Access Via 1,2-Difunctionalization Of Alkynes With Metal-Free Condition

In this thesis,various regio-and stereochemically multi-substituted alkenes and pyrimidines were synthesized by 1,2-difunctionalization of alkynes under metal-free conditions.The main contents are as follows:1.Stereoselective access to highly multisubstituted vinyl ethers with BXTA method for the regio-and stereoselective synthesis of highly multisubstituted iodanyl vinyl ether via 1,2-difunctionalization of alkynes with benziodoxole triflate（BXT）and alcohols is developed（Scheme 1）.When using the unactivated alkyne as the reaction substrate,the iodonium intermediate can be obtained by activating the alkyne in the presence of 2 equivalents of benziodoxole triflate（BXT）,and then 1,2-difunctionalized by nucleophilic addition with alcohols,resulting in a series of regio-and stereochemically multisubstituted iodanyl vinyl ether under argon atmosphere.Kinetic experiments proved that the reaction revealed first-order dependence,and DFT theoretical calculations explained the reason for the occurrence of regiostereoselectivity in the reaction.The reaction tolerates a variety of internal and terminal alkynes as well as various alcohols,affording iodanyl vinyl ethers in good yields with high regio-and stereoselectivities.The benziodoxole moiety of the products can be used as a versatile linchpin for the synthesis of structurally diverse multisubstituted vinyl ethers via different cross coupling reaction,such as Suzuki,Sonogashira,Stille cross coupling reaction,which are difficult to access by other means.The hydrodehalogenation of iodanyl vinyl ethers also proceed smoothly,and the product also can take part in an ytterbium triflate catalyzed Mannich reaction,cyclopropanation reaction and inverse electron-demand hetero-Diels-Alder reaction（Scheme 2）.2.Stereoselective access to highly multisubstituted vinyl ethers with FBX-BF₃A method for the regio-and stereoselective synthesis of highly multisubstituted iodanyl vinyl ether via 1,2-difunctionalization of alkynes with Fluorobenziodoxole（FBX）in ethereal solvent is developed（Scheme 3）.When using the unactivated alkyne as the reaction substrate,the iodonium intermediate can be obtained by activating the alkyne under the combination of 1.2 equivalents of FBX and 1.5 equivalents of BF₃·Et₂O,and then 1,2-difunctionalized by nucleophilic addition with CPME,resulting in a series of regio-and stereochemically multi-substituted iodanyl vinyl ether under air atmosphere.The NMR trapping experiments confirmed the existence of key intermediates BF₄^-and BX⁺,and DFT theoretical calculations also showed that BF₃ was more inclined to interact with the I-F bond of FBX rather than the oxygen atom of the BX ring,providing theoretical support for the proposed mechanism.The reaction tolerates a variety of internal and terminal alkynes,affording iodanyl vinyl ethers in good yields with high regio-and stereoselectivities.3.Stereoselective access to highly multisubstituted enamides with BXTA method for the regio-and stereoselective synthesis of highly multisubstituted iodanyl enamides via 1,2-difunctionalization of alkynes with BXT and nitriles is developed（Scheme 4）.When using the unactivated alkyne as the reaction substrate,the iodonium intermediate can be obtained by activating the alkyne in the present of 2equivalents of BXT,and then 1,2-difunctionalized by nucleophilic addition with nitriles,resulting in a series of regio-and stereochemically multi-substituted iodanyl enamides under argon atmosphere.Labeling experiments proved that the oxygen atom in the amide group came from water,and DFT theoretical calculations explained the reason for the occurrence of regiostereoselectivity in the reaction.The reaction tolerates a variety of internal alkynes as well as nitrile,affording iodanyl enamides in good yields with high regio-and stereoselectivities.The benziodoxole moiety of the products can be used as a versatile linchpin for the synthesis of structurally diverse multisubstituted enamides via different cross coupling reaction,such as Sonogashira,Stille cross coupling reaction,which are difficult to access by other means.The hydrodehalogenation of iodanyl enamides also proceed smoothly,and the product also can explore the application to the pyridine/pyrimidine synthesis（Scheme 5）.4.Metal free access to multisubstituted pyrimidines with Tf₂OA method for the synthesis of highly multisubstituted pyrimidines via[2+2+2]cycloaddition with Tf₂O is developed（Scheme 6）.When using the unactivated alkyne as the reaction substrate,the aza-allene species can be obtained by activating the aliphatic nitrile in the presence of 3 equivalents of Tf₂O,and then resulting in a series of multisubstituted pyrimidines via[2+2+2]cycloaddition under argon atmosphere.Deuterated experiments suggest that the reaction may undergo a process through the aza-allene intermediate.The reaction tolerates a variety of internal and terminal alkynes as well as various aliphatic nitrile,affording multisubstituted pyrimidines in good yields.Furthermore,based on this efficient and concise method for the synthesis of pyrimidines,a Pincer-type pyrimidine ligand can be synthesized in one step by designing 1,3-disubstituted internal alkyne as substrates,which can coordinate with transition metals.It has applications in the field of luminescent materials.For example,through the coordination with platinum salt and then emits at a wavelength of 470 nm blue light with a full width at half maximum of 90 nm.Therefore,this type of product probably can be used as a promising blue light-emitting material to fabricate OLED devices.