Ckellz over at New Reactions just posted the most awesome write-up about a new oxidant ‘affectionately dubbed Bobbitt’s Salt’ and its applications in simple, effective and selective oxidations of alcohols to aldehydes, among several other fantastic things. Before you read any further, I urge everyone to check out the original post. Amazing powder. Is that salt commercially available?

I’m a big fan of oxidations for several reasons. In real life, oxidations are generally much more challenging than what the typical text books suggests. Theoretically, many of the most common oxidations are elusive; we are not sure exactly how they do their job. I therefore welcome all efforts in nailing down oxidants’ modes of action, preferably in the form of curly arrows.

To be honest I haven’t had the time to read all the cited references in Ckellz’s post, but the mechanism he proposes… I don’t like it that much.

The main problem as I see it is the first step. The typical alcohol doesn’t kick out a hydride just like that. Some carboxylic acids, most notably formic acid, may expel a hydride if the conditions are right, but a straight alcohol? Improbable.

I started thinking that perhaps I could come up with an alternative that doesn’t include the spontaneous extrusion of a hydride as the key step. I soon realized that the accepted mechanism for the Swern oxidation had all the components I needed: a super-potent electrophile (check), alcohol as the nucleophile (check), an umpolung of the alcohol to turn it into a fantastic leaving group (check), and finally a concerted rearrangement to release the aldehyde (check). Like so:

Alternative mechanism

Those who are not with me are against me! He-he. No but seriously, what does your gut feeling say? Which version do you like more?


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6 Responses to An alternative mechanism

  1. Ckellz says:

    You want to know what’s funny about all of this? I agree with you about the hydride transfer! The only reason I put that mechanism up is because of the following article (and is also the one used in the article I was reviewing): Bailey, W. F.; Bobbitt J.M.; Wiberg; K. B.J. Org. Chem., 2007, 72 (12), pp 4504 (Link: Semmelhack back in the 80s (Tet. Lett. 1986, 27, 1119) investigated the mechanism of the oxidation and Semmelhack finally suggested that it was in fact O attack by the alcohol on the nitrogen of the oxoammonium species. However those studies were performed under basic conditions where the alcohol was suspected to be in fact deprotonated. Wiberg, Bailey and Bobbitt did some computational studies on the “base free” conditions that are now used (and if anything slightly acidic from the silica gel), and they found that “the much slower oxidation of alcohols in acidic solution, wherein the concentration of alkoxide is negligible, likely involves bimolecular transfer of a hydride from the alpha carbon of alcohol to the oxygen of the oxoammonium cation”. Personally I’m much more of a fan of an H-Bonding mechanism in which the hydrogen of the alcohol H-bonds with the O of the oxoammonium salt and the H of the alpha carbon (“hydride” hydrogen) interacts with the nitrogen. If you draw it out, it results in a 6-membered transition state which for most reactions is highly favored. However, the computations disagree with me. You mechanism is also quite valid and was considered by Semmelhack in the 80s. I just have a hard time buying into the oxygen-oxygen attack. I don’t think the oxygen of the salt bares the majority of the positive charge, just based on E.N. arguments.
    I really want to thank you for posting this. I’m glad you liked the post (I put quite a bit of work into it) and if you want any help with prepping the salt and in running the reaction, just contact me.
    PS: I love making the salt. It’s not often I get to run reaction on a mole scale and, moreover, get >90% yield per step over 3 steps!

    • drfreddy says:

      I agree oxygen attacking oxygen isn’t beautiful. At least it avoids attacking the most hindered atom of the all, the nitrogen. I really like the sound of a 6-membered TS.

      I’m gonna read all the papers now. (Generally something you should do, I guess, before sticking your fingers in.) Fascinating subject, with or without computational chemistry.

      In all likelihood I will get back to you soon for the experimental details. I have a troublesome alcohol, among several other compound waiting to be oxidized, that needs to become a carboxylic acid on gram scale.

      Thank you!

  2. Free Radical says:

    This just seems like a TEMPO oxidation, doesn’t it? N should be the site of nucleophilic attack instead of the oxygen, but same idea:,2,6,6-tetramethylpiperidinyloxy.shtm

    • drfreddy says:

      Caveat: Basic conditions. In our case we have neutral/slightly acidic.

      I love the fact that your link takes me to a page where I’m personal friends with the authors of the topmost paper 🙂

  3. James Bobbitt says:

    The salt is commercially available from TCI for $20 per g. It can be easily prepared in molar amounts from 4-amino-2,2,6,6-tetramethylpiperidine for about $0.75 per gram. The piperidine is available from TCI for ca. $300 for 500 mL. The procedure is trivial and can be obtained from [email protected]. I will comment on the mechanism at a later time.

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