Study On The Reaction Of Allenyl Imide And Indol-2-one By Nucleophilic Phosphine

Indolinone derivatives belong to five-membered heterocyclic compounds,which are key structural parts of many natural products,pharmaceutical molecules and organic synthesis intermediates.Therefore,it is of great research significance to develop a simple and efficient synthesis method.Over the past two decades,nucleophilic phosphine catalysis has provided important synthetic strategies for the construction of carbon-carbon and carbon-heteroatom bonds.In particular,tremendous progress has been made in the divergent construction of valuable motifs under phosphine catalysis of allenes.In this thesis,we realized the chemical divergent synthesis of phosphine-catalyzed allenyl imide through simple solvent control.Taking allenyl imide and indol-2-one as the research objects,we solved the synthetic problems of C3 five-membered spirooxindoles compounds and1,3-dihydro-3-alkylidene-2H-indol-2-ones.The details are as follows:（1）The C3 five-membered spirooxindole motif is widely present in biologically active natural products and drug molecules,so its efficient synthesis will be very valuable.However,there are few reports on the direct construction of C3five-membered spirooxindole structures using unsubstituted indol-2-one at 3-position as reaction raw materials.Under the optimal reaction conditions of 20 mol%P-（4-OMe C₆H₄）₃,ethyl acetate,and 30℃,the[4+1]cycloaddition of allenyl imide with indol-2-ones was obtained.The reaction could achieve 13 examples of C3five-membered spirooxindoles compounds with quaternary center in 33-82%yields.We also tried the asymmetric[4+1]cycloaddition reaction of allenyl imide with indol-2-ones.Unfortunately,the synthesis of chiral C3 five-membered spirooxindoles was not achieved.（2）1,3-dihydro-3-alkylidene-2H-indol-2-ones are important cores existing in many natural products and drug molecules.In addition,these compounds are also good Michael acceptors,and it is especially important that spirooxindole compounds can be constructed by cycloaddition reaction.Therefore,research on the synthesis approaches of such compounds has attracted much attention.We designed a novelβ-Michael addition/double bond shift tandem reaction,using allenyl imide and indol-2-one as substrates,by changing the solvent to N,N-dimethylformamide.This strategy could achieve 13 1,3-dihydro-3-alkylidene-2H-indol-2-one derivatives in11-86%yields.Finally,we discussed about the possible reaction mechanism of the tandem reaction.