Pd-catalyzed Ortho-Olefination Of Aromatic Acetyl Esters

Objective:This project investigats the optimum conditions for the palladium-catalysed ortho carbon-hydrogen bond alkenylation of phenylacetates.On the basis of the optimized conditions,we have expanded the range of aromatic acetates and the range of different olefin reactants,and discussed the reaction mechanism of this reaction.The ortho-alkylated product of phenylacetate is an important intermediate for the synthesis of 2-tetralone derivatives.The study of this reaction will provide some experience in the synthesis of 2-tetralone derivatives.Methods:Firstly,the conditions of ligand,oxidant,solvent,reaction time and so on were optimized by single factor rotation method.The chemical structures of the ortho-ortho-alkenylated products were characterized by ¹H NMR,¹³C NMR and High Resolution Mass Spectrometry?HRMS?.Finally,the reaction mechanism was discussed by kinetic isotope effect.Results:In this project,we selected ibuprofen methyl ester?1a?and methyl acrylate?2a?as the substrate of the experiment to select the optimal conditions for the ortho-carbon-hydrogen bond alkenylation of phenylacetate under palladium catalysis:best catalyst N-acetyl-L-alanine?Ac-Ala-OH?;optimum oxidant silver nitrate?Ag NO₃?;best solvent1,1,1,3,3,3-hexafluoro-2-propanol?HFIP?and the optimum reaction time for 6 hours.A series of ortho alkenylation products had been designed and synthesized in this project,and altogether 18 new compounds that had not been reported in literature were obtained.It was found that this reaction can perfectly overcome the changes in the order of magnitude by the expansion reaction in the gram-level,suggesting this reaction has potential industrial applicability.The mechanism of the study shows that the reaction is palladium-mediated hydrogen bond breakage and transition metal palladium participation in this reaction is indispensable.