Metal-free Synthesis Of Ortho-CHO Diaryl Ethers By A Three-component Sequential Coupling Of Arynes, N,N-dimethylformamide, And Diaryliodonium Salts

The metal catalysis represents a classical method for the efficient synthesis of the unique Diaryl Ethers units. Nevertheless, such transition-metal catalyses always rely on the use of noncommercially available or expensive ligands and generally suffer from the use of excess amount of reagents, limited substrate tolerance, high temperature, and long reaction time, which severely restrict its application in organic and pharmaceutical synthesis.Herein, a practical, metal-free, mild reaction conditions and highly chemo-selective approach was developed for the synthesis of ortho-CHO diaryl ethers by a three-component sequential coupling of arynes, N,N-dimethylformamide(DMF), and diaryliodonium salts. A C-C bond and two new C-O bonds simultaneously formed in the three-component coupling reaction, in which highly reactive intermediates benzoxetene and its isomer ortho-quinone methide would form by [2+2] cyclization of aryne with DMF. We speculate that an extra electrophile could trap intermediates at the oxygen position to format a new O-E(E+ = Ar+, herein) bond and an ortho-imine group that leads to an ortho-CHO group formation at the aryl ring after simple work-up. Mechanistically, isotopic labelled experiments reveal that the diaryliodonium salt serves as an electrophile to trap the transient intermediates generated from the [2+2] cyclization of aryne and DMF.Under the optimized reaction conditions, we examined the substrate scope with respect to both aryne procurers and diaryliodonium salts to the novel sequential coupling reaction. Various functional groups including halo-, nitro-, bulkysubstituents, and heteroaromatic rings could be well tolerated. Importantly, the three component coupling process for the synthesis of ortho-CHO diaryl ethers under mild reaction conditions avoids the use of any transition metal catalysts, ligands and stoichiometric of dangerous strong base that is necessary for CHO group introduction in the traditional approach.