Synthesis Of Functionalized Olefins From Alkynes Via C-C/C-N Bond Cleavage Reactions

Alkynes,as a kind of common unsaturated hydrocarbon,are important synthons for the construction of olefin derivatives due to their various functional group transformations.In many alkyne conversion reactions,the synthesis of functionalized olefin compounds by alkyne addition is considered to be a direct and atom-economically synthetic strategy.C-C/C-N bonds exist widely in organic molecules and biomacromolecules.It is usually difficult to cut C-C/C-N bond because of its inherent chemothermodynamic stability and kinetic inertia.In recent decades,the selective insertion of alkynes into the C-C/C-N bond to achieve C-C/C-N cleavage reaction has been developed.The type of reaction mainly includes C-C/C-N bond cleavage catalyzed by transition metal,C-C/C-N bond cleavage involving actived arynes,and C-C/C-N bond cleavage reactions facilitated directly or by base.Selective insertion of alkynes into C-C/C-N bonds usually requires a transition metal catalyst,which is expensive and potentially harmful to the environment.Functional groups such as sulfonyl and trifluoromethyl exist widely in drug candidates,which can effectively improve the physical and chemical properties and enhance biological activities of compounds.In this paper,the base-promoted selective insertion of alkynes into C-C/C-N bonds without any transition metal catalyst has been used to introduce special functional groups,such as sulfonyl and trifluoromethyl into alkenes.Several highly functional olefins have been synthesized with atom-economy and efficiency.Part Ⅰ:Simple and readily available alkynones were used as substrates to react with cyclicβ-ketone sulfones.In the presence of sodium carbonate and DMSO,alkynes can be selectively inserted into the C-Cσbond ofβ-keto sulfones in one pot to achieve ring expansion reaction.Twenty-eight seven-,eight-and nine-membered ring sulfonyl compounds were synthesized with the successful introduction of sulfonyl substituents into medium-size-ring compounds with the yield of43%-98%.Part Ⅱ:We have designed and synthesized trifluoroacetamide compounds reacting with alkynones to achieve Cs₂CO₃-promoted intermolecular insertion of alkynes into C-N bonds of trifluoroacetamides.Twenty-six trifluoromethyl-containing Z-tetrasubstituted olefins have been synthesized with 58%-99%yields.Alkyl-substituted trifluoroacetamides can also be directly involved in the reaction and the reaction has good substrate tolerance.This scheme provides a simple and atom-economical method for the efficient synthesis of trifluoromethyl-containing tetra-substituted olefin derivatives.Part Ⅲ:We synthesized a series ofα,α-dithione compounds reacting with aryne precursors.Under the combined action of Cs F and t-Bu OK,the in-situ-generated arynes are selectively inserted into the C-Cσbond ofα,α-dithiones,successfully achieving the 1,2-bifunctional aromatics.In addition,1,3-dithithiane can be successfully removed from the C-Cσbond cleavage product under the catalysis of 0.2 equivalent NBS to achieve the goal of carbonaldehydeylation of aromatic with the yield of 90%.This reaction provides a new idea for the 1,2-dicarbonylation of aromatics.