I desperately need this reaction I am running now to work (a reductive detriflation). It is the last step in a long linear sequence. There were way too many hits in the literature on similar transformations, so I dissolved my starting material in DMF and added 22 equivalents of triethylamine and 20 equivalents of formic acid, which appeared to be common.

I then… heh… eyeballed dashes of Pd(OAc)2, PdCl2(dppf), PdCl2(PPh3)2 and finally a sprinkle of Pd/C into the mix. And cranked the temperature up to 90 °C. Ha!

If that -OTf is still around by LCMS by tomorrow, I do not have the slightest idea what the next logical step is :), so help me God.

 

9 Responses to Screw theory

  1. henry says:

    whatever happened with that sonogashira you were running ?

    i am running into similar problems, so an update post would definitely be appreciated !

  2. Chemjobber says:

    Ni(cod)2?

  3. drfreddy says:

    henry, The Sonogashira worked surprisingly well after adjusting to conditions mentioned by milkshake, here http://syntheticremarks.com/?p=2746

    • milkshake says:

      Not that I would like to brag about it but that Sonogashira system is particularly lovely, and happens to be my own.

      (I actually found a paper about “facile room temperature aryl bromide Sonogashira that used THF, NEt3, CuI, PdCl2.2PPh3 plus one extra PPh3 to make the catalyst more stable, run at room temp. It needed heating for my substrates and worked fine, then I found that PdCl2(dppf) was slightly better and needed no external ligand added… So I wrote it up in Org Prep Daily and told you about it. And the rest is history. It will be one day called Sonogashira-Milkshake, long after people will have forgotten names like Castro and Stephens..)

  4. Paul says:

    Can I suggest to switch from a Pd-based catalyst to a Nickel one ? On sp2 carbons I heard H2/Ni/C works pretty well. Maybe a freshly prepared Raney Nickel would work as well.

  5. Paul says:

    Also, I just remembered you can change a OTf to methyl by MeMgBr and Fe(acac)3, maybe it is worth to try with a hydride source like dibal ?

  6. Daniel says:

    Stille-style coupling with Pd(PPh3)4/Bu3SnH might do the trick would your “every palladium source hail mary” fails.

  7. Ckellz says:

    I got three less common alternatives (maybe one will work?)

    1. Pd/C, NH4OAc, Mg, MeOH
    Method
    http://pubs.acs.org/doi/abs/10.1021/ol060045q

    Mechanistic Study
    http://onlinelibrary.wiley.com/doi/10.1002/chem.200601184/abstract;jsessionid=F0B812960B97045CD486EA4DE461B70C.d02t03

    2. Not sure how well this would work but…

    Indium
    http://pubs.acs.org/doi/abs/10.1021/jo702279t

    They noticed that they got some of the detriflated product in their reaction along with coupling. I was thinking that if you just simply didn’t add the allyl acetate you would get strictly reductive detriflation. If you look at entry 6 in their table, that was mostly what they got

    3. Personal favorite because I <3 silicon:

    Et3SiH Mediated Reduction

    http://pubs.acs.org/doi/pdfplus/10.1021/ol200422p

    Seems to work well even with a sterically congested system (scheme 1) plus it seems relatively fast and easy to do.

    hope that helps…maybe? 😛

    3.

    • drfreddy says:

      First I wanted to die, because the conversion was 0 % the day after. I then extracted and evaporated the crude, and used your suggestion no. 1 – and it worked! Good isolated yield too.

      Yet another final compound: check.

      Thanks a lot, again, dude.

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