A cascade, fifteen or so step, one-pot reaction yielding one freak heterocycle as the main product, with more sulfurs in it than … I dunno what.

freak heterocycle

Angew. Chem. Int. Ed. 1997, 36, 281-283. (DOI: 10.1002/anie.199702811)

Listen to this. Hünig’s base acts as a reactant and electrophilic sulfurs play the main characters. I love it. This is the crème de la crème of heterocyclic chemistry.

I can’t resist the temptation to once again mock retrosynthetic analysis. How many of you (yeah, you too, Corey), upon beeing presented with structure 1, would stand up and say

‘Hm… maybe if I treated Hünigs base with sulfur dichloride in the presence of DABCO…’?

 

5 Responses to THIS is heterocyclic chemistry

  1. milkshake says:

    I don’t want to brag but I have seen these “sulfur – on imine/enamine action” things happening, and the final 5-member sulfuorous-rich ring is a quite common product because it is stabilized by its high degree of aromaticity.
    By the way, the Wilgerodt-Kindler reaction (acetophene zipper with S8 and morpholine) also produces spectacular isolable cyclic intermediates with 4 or 5 sulfurs incorporated in the ring if you run the reaction at room temperature (as opposed to reflux).

    Btw, are you still looking for the Sonogashira conditions? I had one very tough class of el. rich substrates, 2,4-bis-(alkylamino)-5-bromopyrimidines, and the best way to do those was wth alkyne 1.5 eq. in THF + NEt3(2 eq.) with PdCl2(dppf) 5mol% and CuBr 1.5% (added last as a solid), in a closed vial at 60-80C. No degassing required, the reaction progress is monitored by precipitation of NEt3.HBr

    • drfreddy says:

      Ah… the Wilgerodt-Kindler again. Bittersweet memories…

      Thanks for your Sonogashira recipe. I still suffer from irreproducible results over here. Will try your kung fu.

      • milkshake says:

        the procedure is here:

        http://orgprepdaily.wordpress.com/2006/11/16/sonogashira-on-24-diamino-5-bromopyrimidine/

        the trick is to run the reaction in a tightly capped narrow/tall vial or tube filled near up the top so as to limit the headspace, then it does not need deoxygenation (the precatalyst reduction and O2 consumption happens with the alkyne and NEt3, you should see the colors changing from red to greyish to pale yellow as soon as you add CuI). CuI or CuBr work equally well but the important thing is to use the minimum feasible amount of Cu (Cu acetylide formation is not rate controling ) and avoid overloading the reaction with Cu (too much copper causes side-reactions, people add too much because it is so hard to weight out tiny quantities of CuI) and the CuI must be added last immediately before capping the vial.

  2. Paul says:

    This is crazy, I love it. It will make a good group meeting problem I have to say.

  3. milkshake says:

    since these things are so stable and aromatic, they might be a decent isoster of phenothiazine; it would be fun to take N,N-diisopropyl-3-propanol-1-amine and take the product into a a thorazine analog, to vulcanise the psychotic patients

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