Copper Porphyrin Catalyzed Cross-dehydrogenation Coupling Reaction

Different from the transition metal coupling method,the cross-dehydrogenative coupling（CDC）reaction does not require pre-functionalization of substrates.It is a more straightforward,efficient and highly atom-economical construction of C-X（X=C,O,N）bonds’method.The construction of C-O bond can be used in the synthesis of natural products as well as the synthesis of pharmaceutical molecules and fine chemicals.However,the C-O bond formation via CDC reaction is still of a considerable challenge.Under oxidation conditions,copper porphyrin-catalyzed CDC reaction to build C-O bond has been well developed in the past few years,but there is no exploration of the substituent effect of copper porphyrin catalyst.In order to explore the substituent effect of copper porphyrin catalysts,five copper porphyrins were synthesized to catalyze the CDC reaction of phenol derivatives and 1,4-dioxane.The main research contents are as following:1.In this paper,five porphyrins and the corresponding copper porphyrins Cu TPy P,Cu Tn PP,Cu Tt BP,Cu F₂₀TPP and Cu TPP were synthesized,and they were characterized by UV-Vis spectra,¹H NMR,¹³C NMR and mass spectrometry.The substituents electron-withdrawing ability of Cu TPP,Cu F₂₀TPP and Cu TPy P,and the steric hindrance of Cu Tn PP and Cu Tt BP were analyzed and compared.2.This article explores the substituent effect of the catalyst through the CDC reaction of methyl 4-hydroxybenzoate and 1,4-dioxane for the first time.The results showed that the substituents of copper-porphyrin bearing heteroatom of pyridyl groups,electron withdrawing groups（EWG）,or bulky steric hindrance could improve the catalytic performance.Cu TPy P was the best catalyst among the five copper porphyrins.The optimized reaction conditions are methyl 4-hydroxylbenzoate（0.5 mmol）,DTBP equivalent（6 equiv.）,and Cu TPy P（3 mol%,relative to methyl 4-hydroxylbenzoate）1,4-dioxane（2 ml）as substrate and solvent,were reacted at 120℃for 6 h.3.Under the optimal reaction conditions,31 kinds of substrates were screened,indicating that the conditions are suitable for-COMe,-CN,-CO₂Me,-CF₃,-CONR₂,or polysubstituted phenol derivatives,and the yield was up to 99%.The radical trapping experiment and electron paramagnetic resonance were used to explore the mechanism of copper porphyrin catalyzed by the CDC reaction,and proposed possible reaction paths.