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Organocritical Suzuki

Organocritical Suzuki
20 March 2021 - Counter reports

Remember when in the beginning of the year Hai-Zhu Yu and Hua-Jian Xu (call them team A) reported an organocatalytic Suzuki (aromatic amine plus potassium carbonate) reaction? (blog) The claim was met with skepticism because surely there must have been some trace palladium (the staple metal in a Suzuki) in the vicinity, for example accumulated through the synthesis of the amine catalyst in a palladium catalyzed Buchwald-Hartwig amination? We already have one counter-report from catalysis detectives Gonda, Tolnai and Novak (team B). (blog) The key piece of evidence they presented to the jury was the palladium-free synthesis of the same catalyst which subsequently was found to be catalytically inactive. They also re-did catalyst synthesis and did find trace amounts of palladium where team A did not find any.

Robin Bedford is one of the authors in 24 (!) person team (team C) of a second counter-report that is now available on ChemRxiv (DOI). The Bedford group is totally dedicated to catalysis and the result of their investigation is also negative.

The first thing team C did was to repeat the catalyst synthesis and Suzuki reaction according to the original procedure. They were able reproduce the results but also noted that the Suzuki reaction actually improved in the presence of water. Now the reaction mechanism proposed by team A is featuring an organopotassium intermediate which can impossibly co-exist with water. For this reason alone team C discredits the proposed reaction mechanism.

Detecting trace metal can be tricky! Team A relied on IPC-MS and to the best of their efforts they did not find any (< 1 ppb). In the new report team C arrives at 7,5 million ppb which corresponds to half the palladium used in the synthesis. The new report also describes a combination of reductive electrolysis and energy-dispersive X-ray spectroscopy by which palladium again was found. Electrolysis was also used to "clean" the catalyst from any metal. Post-treatment, the catalyst was again not active. Where team A spent a lot of effort to remove metals by dedicated scavengers it was also possible to remove all metal by a simple recrystallization step. This again rendered it inactive. Like team B in their report, the authors note that a clean catalyst sample is colorless and not colored as in the team A samples.

Team C also performed a palladium-free catalyst synthesis, this time based on a Chan-Lam coupling (SI not yet available). The catalyst made in this way was also found to be catalytically inactive.

In the meanwhile the journal Nature Catalysis, home of the original paper has issued a warning that "the conclusions of this paper are subject to criticisms that are being considered by the editors".