Tag Archives: biomimetic oxidation

Publication of the week, number 64, 13th February 2015

Oxidation is an important process in many facets of chemistry, here is a copper based catalyst mimicking the oxygen activating, Cu based enzyme tyrosinase. The new catalyst system was developed by Lumb etal at the McGill University in Montreal. They use a [CuCH3CN)4]PF6  at 5 mol% activated with various ligands and additives.

Studying the aerobic oxidation of octan-1-ol to the aldehyde they found that the best ligand was N,N’-di-tert-butyl-ethylenediamine (DBED) and the best additive DMAP. Using 5 mol% of the Cu complex, 5 mol% of the ligand and 20 mol% of the additive they obtained a 92% yield of the aldehyde when the reaction was carried out in dichloromethane containing 4Å sieves under 1 atmosphere of oxygen at room temperature.

From the authors”Furthermore, no aldehyde was observed when DMAP was used in the absence of DBED. These results demonstrate the high reactivity of the Cu2/O2 adducts that were formed with this ligand,and underscores the unique ability of the Cu/DBED catalyst system to affect the rapid oxidation of unactivated alcohols without the use of any external radical co-oxidant.” 

Of course this system demonstrated good functional group tolerability. How does it fare against the normal TEMPO based oxidations? They ran competition experiments which octanol and a substituted 1-phenyl alcohols and found some selectivity for the secondary alcohols. The best that was observed was 9:1 in favour of the secondary alcohol. Steric effects were similar for both systems, perhaps the new system being somewhat less sensitive.

OK, this system does show some preference for secondary alcohols, but there are better ways to produce ketones. The authors promote it as a replacement for TEMPO oxidations but is it really a viable replacement? I don’t think so. You have copper, lots of an additive and oxygen atmospheres (the reaction works in air but much more slowly). So I don’t see this as being a reagent of choice for large(er) scale synthesis. What is easier to do? TEMPO/bleach or this system? I know what I would choose.

They also claim this is cheaper than the TEMPO method. Well a quick look in the Aldrich catalogue shows that TEMPO is about £90 for 25 g, the starting copper acetonitrile complex is £230 for 25 g! So the statement “reliance upon N- oxides imposes certain limitations, as it is frequently the most expensive component of the catalyst system, which becomes a significant concern for industrial-scale applications” does not really apply. And it’s not even “green”.

So a useful replacement if you are studying enzymatic oxidations and require a chemical comparison, but otherwise more or less useless.

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