Chemists from Germany have learned to introduce anilines into a cross-coupling reaction with boronic acids. In this case, anilines were intermediately converted into diazonium salts, which oxidatively added to a palladium catalyst. The study was published in Angewandte Chemie International Edition.
In the classic Suzuki cross-coupling, a boronic acid and an aryl halide react to form a carbon-carbon bond in the presence of a palladium catalyst. Anilines can be used in place of aryl halides, but this requires first converting them to unstable and sometimes explosive diazonium salts.
To overcome this problem, chemists led by Tobias Ritter at the Max Planck Institute for Coal Research decided to use a method they had recently developed for generating diazonium salts from anilines using nitrates. They had previously used this method to produce aromatic halogen derivatives from anilines, and it turned out to be safer than classical diazotization because diazonium salts did not accumulate in the reaction mixture.
For the same reason, the chemists decided to apply this method to the Suzuki reaction with anilines. First, they mixed 4-fluoroboronic acid and 4-methylaniline in the presence of various palladium catalysts, tert-butylammonium nitrate, and other additives. As a result, it turned out that the reaction proceeds with a yield of 69 percent if sodium hydrosulfite NaHSO3 is used as a reducing agent. In their previous work, the scientists used sodium thiosulfate Na2S2O3, but, as they assume, it binds too tightly to the palladium catalyst, and the Suzuki reaction practically does not occur in its presence.
The chemists tested the selected reaction conditions on various anilines and boronic acids. It turned out that their conditions allow using not only anilines, but also amino heterocycles. In addition, due to the rapid oxidative addition of diazo compounds, the reaction proceeded selectively even in the presence of aromatic bromine derivatives. The main drawback of this reaction, as the authors of the article note, is the low yields of products when using boronic acids with donor substituents in the aromatic ring.
Thus, the chemists developed a general method for synthesizing biaryl derivatives from anilines and boronic acids. In doing so, they used the safer nitrate method to generate diazo compounds, and most of the products were obtained in yields of 40 percent or more.
We recently reported on how scientists used an iron-based catalyst, rather than palladium, to carry out the Suzuki reaction.
