Mukaiyama Thioester Synthesis

September 25th, 2011

I have made it a rule not to participate in blog carnivals. There is something disturbing about them. Perhaps it’s the association of carnivals with fun, which I try to limit in my life. Instead of organizing and participating in “carnivals”, I do exactly the same thing and call them “roundtables”. It’s so much more professional and so much less fun.

But ever since neutrinos decided to disobey the speed limit, I’ve been reconsidering my adherence to all of the rules in my life—including my self-imposed prohibition of carnivals. The good people at C&EN are hosting a blog carnival this month in honor of the International Year of Chemistry, and I feel strangely compelled to participate. The subject: “Your favorite chemical reaction”.

Fortunately, I didn’t need to conduct my usual 200 hours of background research to write this post, because I actually wrote it in January 2007. My favorite reaction is the same now as it was then:


I came across the above reaction while thumbing through a random issue of Chemical Reviews whilst consuming a carton of curry chicken from Yenching Restaurant. It looks like the reaction can be traced to this paper by Mukaiyama from 1970. Much like Charlie Brown’s obsession with a bit of cartoon strumpet known to him only as the little red-haired girl, I find myself in the predictament of having fallen in love with a reaction that has no name. But a reaction so lovely should not have to go nameless for a minute longer. Henceforth, the reaction shall be known as the Mukaiyama Thioester Synthesis in all lands and kingdoms for perpetuity. Go forth and spread the gospel. Yields are risen.

Here is what I believe to be the (shorthand) mechanism for this dandy:

What do I find so compelling about this beauty of a reaction? Perhaps it’s the involvement of my favorite compounds, thioesters? Perhaps it is the generation of a notoriously strong phosphorus-oxygen bond to serve as the driving force for the reaction? Perhaps it is the neat nucleophilic attack of the phosphine on the disulfide in a process that must be similar to thiol-disulfide interchange? Perhaps it is the fact that this single reaction has all of these things wrapped into one? I don’t know.

And that’s all I have to say about that.  Having looked over the other entries in the carnival, I find it unfortunate how far off-base the other contributors have been.  There is nothing about any other reaction that could justify its being someone’s favorite above Mukaiyama Thioester Synthesis. The reaction is clearly the greatest in history.

7 Responses to “Mukaiyama Thioester Synthesis”

  1. Ricola Says:

    Hahah a lovely (re)post. If I’m ever going to run this reaction, I too will describe it as the ‘Mukaiyama Thioester Synthesis’ in the manuscript. :-P

  2. See Arr Oh Says:

    “The reaction is clearly the greatest in history.”

    Wow, I mean, how far off was I? Once I saw the inherent beauty in the super-stoichiometric phosphine oxides and stinky thiol byproducts, I said to myself “I am going to go delete my post, and put up a page full of links to Paul’s post.”

    I’d advise all other participants to do the same. No sense in taking home 4th prize.

  3. Macdrifter » Blog Archive » Reactions (not what you think)[Link] Says:

    [...] This kind of stuff is why I fell in love with Organic Chemistry and spent half my life in school to learn it. [...]

  4. Curious Wavefunction Says:

    Jaw-dropping. Off I go to prove that a 30 step natural product synthesis can be performed using only the Mukaiyama Thioester Synthesis and no other reaction, at room temperature in a kitchen sink with only water as a solvent and traces of a snickerdoodle catalyst. Bionic Brothers here I come.

  5. Paul Says:

    @See Arr Oh: How dare you impugn the fragrant bouquet of thiols? How dare you?

  6. darksyde Says:

    One of the huge reasons why I hate Big Bang Theory is that it’s made the fucking “ferrous wheel” tee shirts really popular, and now a google search of “ferrous wheel” just puts up a bunch of bullshit. Thanks for shitting in the pool, C&EN.

  7. milkshake Says:

    there is a fairly nice Staudinger ligation version that takes advantage of Mukaiyama: RCO2H + ‘RN3 + PPh3(excess) = RCONHR’ + N2 + Ph3PO. The catalyst for this reaction is Pyr-Se-Se-Pyr that generates a somewhat more reactive RCOSePyr in situ, which then acylates the iminophosphorane. The reaction still requires strictly anhydrous conditions but it can be run at room temp overnight. (This could be actually quite useful in biopolymer and peptide chemistry.)

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