Iron-Catalyzed Aerobic C-H Functionalization Of Pyrrolones

Pyrrolone systems and related derivatives is a kind of important compounds containing N atom. They have special pharmacological properties, especially in the area of anti-cancer, anti-tumour therapy and they have potential drug research prospects. What's more, they can easily be transformed into highly reactive N-acyliminium ions, which can be quenched with various nucleophilic reagents to generate some important lead compounds, thus attracted the attention of many research groups. According to literatures, we find that until now most of the strategies focus on the combination of transition metal catalysts and peroxide which has some extent of dangerous as well as the reaction temperature is high, so developing a green, safe and efficient methodology for the functionalization of pyrrolones is necessary.Herein, we disclosed an efficient and practical method for the functionalization of pyrrolones by using O2 as the oxidant and Fe(OTf)3 as the catalyst. Features of this reaction include: 1) realizing the oxidation of amide which is more difficult to be oxidized generally; 2) using green and atom-efficient O2 as the oxidant which make the methodology safer and greener; 3) synthesizing a series of pyrrolone derivatives; 4) generating new C-C bond and C-O bond.We choose a variety of substituted pyrrolones as substrates, Iron(III) trifluomethanesulfonate as the catalyst, oxygen as the oxidant, and 20 pyrrolone derivatives with potential pharmacological activities have been synthesized in acetonitrile under heating. All the compounds have been well characterized by 1H NMR, 13 C NMR, IR, LR-MS and HR-MS.A plausible mechanism of the reaction process has been proposed. The discovery of eliminate products 141 o and 141 p as well as some experimental facts prove the rationality of the mechanism. In addition, we also explored the application of this method and through oxidative dehydrogenative coupling, deprotection of the protecting groups, we synthesized 155, the precursor of natural product Jatropham.