Palladium-Catalyzed Ullmann Coupling Of Electron-deficient Aryl Iodides In Aqueous Solution

Preparation of biaryls is a kind of useful method widely applied in the synthesis of pharmaceuticals, natural products, agrochemicals, and other chemicals.In the past several decades, many catalytic coupling reactions between aryl halides and aryl-metal complexes to form biaryls were developed successfully, such as Kumada coupling, Stille coupling, Neigishi coupling, Suzuki coupling and Hiyama coupling, etc. However, Ullmann coupling, which especially for the formation of symmetrical biaryls just from aryl halides, is still one of the most simple approaches for generating aryl carbon-carbon bonds in organic synthesis. In the early of last century, Ullmann discovered that biaryls could be prepared from aryl halides through homocoupling reactions in the presence of stoichiometric copper at high temperature (over 200oC). Although transition metal-catalyzed Ullmann reductive couplings have been established since that, additional reductants are necessary in most cases. On the other hand, handling organic reactions in the aqueous phase is always an interesting issue to researchers in the fields of pharmaceutical chemistry and biochemistry, etc.Herein, we describe a Pd(II)-catalyzed Ullamnn coupling reaction of various electron-deficient aryl iodides to afford biaryls in the yields of 55% to 87% without any external reductants in aqueous phase. Furthermore, a reasonable mechanism of this coupling reaction is also proposed, which involves the formation of Pd(IV) intermediate through direct oxidative addition of Pd(II) complex with aryl iodide. After a series of tests, it is also confirmed that aryl iodide itself rather than solvent and base could play the role of reductant to complete the catalytic cycle in this Ullmann reductive coupling.Overall, symmetrical biaryls could be produced easily, economically and conveniently by Pd(II)-catalyzed coupling of electron-deficient aryl iodides in the absence of any additional reductants in aqueous solution. This synthetical method is not only a green one but also a hint to explore more new reactions.