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Organocatalytic Suzuki

Organocatalytic Suzuki
29 January 2021 - Orgo

metalfreeSuzukiLeiXu2021.PNGA group of Chinese researchers report a new type of Suzuki-Miyaura reaction that does away with the usual metal-containing catalyst and instead relies on an organocatalyst (DOI). Great news of course because the Suzuki reaction is one of the staple reactions in organic chemistry and any metal in the group of palladium, nickel and copper has certain environmental and / or costs issues. On the other hand the Suzuki reaction is a type of Coupling reaction that is almost inconceivable to take place without a metal catalyst present. Reports on metal-free coupling reactions in the past have found themselves in controversial hot waters as randomly snapped in these blogs from 2009 and 2010. The reaction can work with the tiniest amounts of catalyst and there is always a metal around be it as a contaminant.

In the new work the organocatalyst is 1,3-diamino-2-methylbenzene with 2-toluenyl groups stuck to the amine groups. The substrates are a simple bromoaryl and a simple arylboronic acid with potassium carbonate as a base and o-xylene as solvent. Yields can be as high as 93% which is impressive.

But the reaction mechanism! We are so used to a central Palladium atom with two aryl substituents in classical oxidative addition and reductive elimination it his hard to imagine an alternative. But the mechanism as proposed in the article is interesting and should be made into a movie! In it two potassium carbonate molecules conspire with the boronic acid to form a peculiar activated complex which looks like a B-O-K cage with the arene part completed dislocated from the boron part. In fact the only neighbors the naked aryl can see are the potassiums. By then the amine organocatalyst has long since vanished and the boronic acid never knew it was there. The thing the amine does is coaching the two potassium carbonate units to sever the aryl-boron bond via its two aryl hands. The closing credits are already running when finally the bromoaryl enters the stage and conscious coupling with the organopotassium in the finale will come as no surprise.

The mechanism is based on calculations and it has supporting evidence. Adding a radical trap has no effect on the reaction which rules out a SET reaction. Deuterium labelling experiments demonstrate an aryne mechanism is unlikely as well. Potassium is key: using sodium carbonate instead of potassium carbonate ruins everything. Potassium hydroxide will also work.

How about the presence of trace metals in the reaction? The catalyst itself is made in a classic palladium Buchwald–Hartwig amination, trace metals can also lurk on the surface of reactors and glassware. The researchers are confident the amount of trace metal in the reaction is less than 1 ppb (ICP-MS). They also deliberately added up to 10 ppm of palladium, nickel and iron but the reaction kinetics were not affected.

More Suzuki from the archives: Failed Suzuki, Suzuki mystery, Another no-metal Suzuki.

CRD file 1784847



CRD file 1784848