Phosphine-Promoted Reactions Of 1,2-Dicarbonyl Compounds With Electrophiles

The development of new methodologies for chemo-and stereoselective bond formation is a fundamental task in organic synthesis,which has a profound impact on drug synthesis and natural product total synthesis.In recent years,the phosphine-promoted reactions have attracted much attention due to their ready availability of the starting material,enabling chemo-and stereoselective construction of complex molecular skeletons via cascade transformations under mild conditions.In these reactions,the phosphine functions as either a reagent to participate in the reaction or a catalyst to facilitate the reaction.This dissertation has explored the new reactivity patterns of 1,2-dicarbonyl compounds with electrophiles under the influence of phosphine,and three types of new methodologies including both stoichiometric phosphine participation and phosphine catalysis have been developed.The main achievements in this dissertation are listed as follows:1.On the basis of the 1,1-dipolar structural characteristic of the Kukhtin-Ramirez adduct generated from 1,2-dicarbonyl compounds and organophosphorus,a P?NMe₂?₃-mediated C-X insertion of isatins into allylic and benzylic halogens has been realized.Under the optimized conditions,the reaction exhibits a broad substrate scope,which provides a step-economical access to 3-halo 3,3'-disubstituted oxindoles.Mechanistically,the reaction proceeds via a cascade S_N2-S_N2 process,and highlights the unique dual nucleophilic-electrophilic reactivity pattern of the Kukhtin-Ramirez adduct.Upon treatment with trifluoroacetic acid,biologically important spirooxindole-?-butyrolactones have been facilely prepared from the corresponding insertion products.It represents a novel metal-free C–Heteroatom bond insertion,which provides a new strategy for convergent C–C and C–Heteroatom bond formations.2.The reactivity patterns of the Kukhtin-Ramirez adduct with biphiles bearing both nucleophilic and electrophilic units has been explored,which leads to a P?NMe₂?₃-mediated[1+4]annulation of ethyl aroylformates with tosylamino-substituted enones.The reaction exhibits a good substrate scope,high stereo-and chemoselectivity,and represents a unique preparation of pyrrolidines via[1+4]annulation mode.Mechanistically,the annulation reaction proceeds via a cascade Michael addition-proton transfer-intramolecular S_N2 sequence.It represents an unprecedented reactivity mode of the Kukhtin-Ramirez adduct via[1+4]annulation with biphiles,and also provides an efficient synthesis of pyrrolidines.3.A chemoselective phosphine-catalyzed cyanoacylation of?-dicarbonyl compounds has been developed,leading to the synthesis of cyanohydrin esters bearing one quaternary stereocenter.The cyanoacylation reaction works well with a wide range of substrates.?-Dicarbonyl compounds such as isatins,aroylformates,and?-diketones are all viable substrates,which could be smoothly cyanoacylated by acyl cyanides bearing different substituents,affording a broad array of cyanohydrin esters bearing one quaternary stereocenter in moderate to excellent yields.The preferential interaction of the phosphine with acyl cyanide instead of?-dicarbonyl compound to form the Kukhtin-Ramirez adduct governs the chemoselectivity and leads to a highly efficient phosphine-catalyzed cyanoacylation reaction.It represents a novel phosphine-catalyzed cyanoacylation of?-dicarbonyl compounds,which provides a general and efficient synthesis of cyanohydrin esters bearing one quaternary stereocenter.Features of this reaction include mild conditions,readily available starting material,broad substrate scope,and complete atom economy.