Arvela et al (2004)

So we saw Leadbeater’s paper and I’m sure skepticism on whether a palladium free reaction was really observed arose in some of you. Now we are going to be looking a paper that argues that what Leadbeater and the other author observed was not that at all.

If you are wondering about the whole microwave vs conventional heating topic, there is a great paper by Kappe et al. titled “Microwave Effects in Organic Synthesis: Myth or Reality?” That would elucidate everything and if you have time it would be great if you gave it a glance:

DOI:10.1002/anie.201204103

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9 Responses to “Arvela et al (2004)”

  1. Hunter Burgin Says:

    So as it turns out Dr Leadbeater will not be winning his Nobel Prize for the discovery of a non-transition metal catalyzed Suzuki type reaction. However, it is impressive to see a researcher correct his mistakes in the form of this paper. Anyways, on to my question: In the paper Leadbeater discusses his three-step process for purifying the commercial grade boronic acid in order to remove trace amounts of palladium (50ppb). He recognizes the possibility of an impurity within the reagents could have lead to the “false positive” he witnessed in his prior paper, which he mistakenly referred to as a Transition Metal Free Suzuki Type Coupling Reaction. However my question is why did he not analyze the other reagents used in the coupling reaction for impurities. Are the other reagents such as bromobenzene any less likely to be minutely contaminated with trace transition metals?

    • Antony Says:

      They say that their organic reagents are pure and leave it at that but I am convinced that they are cleaner than the sodium carbonate which is mined vs the bromobenzenes are prepared in a lab.

  2. Kevin Greenwood Says:

    I think “oops” may have been uttered by someone after the ICP-MS data came back on the sodium carbonate showing that there was indeed palladium present. If nothing else, this paper showed the extremely low catalyst loading necessary to still get the Suzuki reaction to give products.
    Tony brings up a good point about the microwave though. In table 3, entries 1 – 6, the conventional heating method shows a drop in yield for all substrates, except for the bromotoluene at 250 ppb palladium (entries 2 and 5) which gave better yields than for the microwaved samples. There is a similar pattern in table 4 where they used a different solvent system. Assuming that the same amount of heat went into the system (the oil bath samples being kept in the bath 2 minutes longer than the microwave samples), what could account for this deviation for bromotoluene when only the heating method was changed? With only two data points, it could be a coincidence, or a workup problem for this product when working at such small scales, but it is interesting enough to look in to further.

  3. Josh Ellsworth Says:

    Apart from feeling horribly betrayed, I’m curious as to why Table 6 is even included in the paper. No indication is given that the phenylboronic acids used in the first paper were purified. If that’s the case then those reactions should not have given the reported yields at the assumed Palladium concentration in the Sodium Carbonate. The methodology of testing a sample that, given the two year gap in publication can be assumed to be at least 2-3 years old, is tenuous at best. How was the sample stored? Was it exposed to any more contaminants on its incredible journey across the Atlantic? How did it differ from the rest of the phenylbornic acid For that matter, exactly what are the contaminants that were removed from the new batch of phenylboronic acid?

  4. Porter Marsh Says:

    The paper said that even in very small amounts, impurities in the boronic acid can shut down the reaction. So one question is what constitues very small amounts. The paper deals with Pd concentrations at the ppb or fractions of that. When they refer to a quantity as “very small” is that on the ppb scale? My second question is how an impurity in the boronic acid effectively shuts down the reaction?

  5. Adam Settimo Says:

    I still don’t really understand the use of the “ICP-AA,” what researcher doing this kind of work doesn’t have access to the proper instrumentation.

    That being said, I think that it is still interesting that a similar result can be done without the extra purchase of Pd. Besides the Nobel Prize, wasn’t the exciting idea the reduction in use of Pd? Both the cost of it and the impact on the environment? So isn’t this still a good thing? You don’t have to buy your Pd, you get it free with your sodium carbonate, kind of a two for one deal.

    Next there is mention of the use of small amount of Pd being inconsistent with regard to the yield. I am seeing a lot of yields in the 90 percent range right? this seems pretty consistent.

    My last and I guess major question here is with regard to the microwave use over conventional heating. Before they were hesitant to use above 60W and now they’re using 150W? 250%? What happened to being concerned about deactivating the catalyst?

  6. Daniel Begay Says:

    Wow, this paper is filled with a lot of intense twists and turns. I’m wondering how Leadbeater felt when they decided to do a reassessment of his original paper, I’m sure there was blood, sweat and tears involved. These new results seem to be bittersweet. Sure, they found out that even these trace amount of Pd was enough to push this reaction forward, but now they know they can do this Suzuki coupling reaction with very little Pd to catalyze the reaction, with the same non-extreme conditions. It seems to me, a win situation. Do you think that Leadbeater will still receive SOME credit for at least making this discovery?

    My question pertains to Adam’s question about the deactivation of the catalyst. It seems to me by looking at Table 4, that the deactivation of the catalyst runs true when it comes to conventional techniques. Entry 10 shows that you can get pretty decent results using conventional techniques.

    Lastly, in hindsight, I’m sure Leadbeater’s use ICP-AA was caused by a number a variables that any lab would go by. The ICP-AA, being a crude tool compared to the ICP-MS, was dramatically less expensive to quantify Pd. The sample prep to use didn’t “require” as much care and consideration as does the Almighty ICP-MS. I could go on. And also, the fire was under his feet to publish quick before someone steals his golden ticket.

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