Monday, October 15, 2012

I am trying to plan a reaction in which I incorporate a sulfonamide in the last step of the reaction. I need the conditions to be mild and the yields to be good. I found a paper by Mayer et al. in which the reaction conditions I want may be used:

Sulfonamide/aniline, KOt-Bu, NMP, allylchloro{1,3-bis(2,6-di-propylphenyl)imidazol-2- yilidine]
palladium(II) (IPr•HCl•Pd), Pd(dppf)Cl2•CHCl2,

What I see as a problem is the imidazol Pd(II) salt that is used. Is actually the first time I see it and they use it in 20% amounts along with Pd(dppf)Cl2•CHCl2 and I have a hard time understanding why. I have to find something more general or an explanation for this...

On the other hand, there are many other methods to go. Wang et al recently (2012) published a paper were mild reaction conditions were used. This method is very similar to an older paper by Wei et al (2005) in which they use an aminoacid as a ligand stabilizing the copper reagent.

Of course, the group of Buchwald et al. have Pd-methods that can be used, and in an earlier paper, they stress the importance of using a bulky P-ligand for the reaction to work (here are some examples with amides, and one example with sulfonamide working with chlorides).

An update. Tried out all these reactions, but the one that worked best was an old protocol using Pd(OAc)2 and the ligand Xantphos and Cs2CO3 (s) as the base in THF:Toluene (1:1) at 120 °C. Got almost 80 % product after a very easy purification procedure.

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