Improving the Substrate Scope of the Kumada-Corriu Cross Coupling Reaction

The Ni or Pd catalysed Kumada-Corriu reaction between an aryl halide and a Grignard reagent is one of the original cross coupling reactions, and we all know that the Grignard reagent can react with suitable functional groups, such as carbonyls, on the aryl halide which limits it’s applicability.  Buchwald1 and Knochel2 have shown that by using a Pd-SPhos catalyst either at -65°C or under radical conditions in the presence of i-PrI sensitive substrates can be accommodated but this paper3 takes a different approach addition rate control.

The Grignard reagent is added at a rate to match the oxidative addition step in the catalytic cycle as the Grignard transmetalates to palladium faster than it reacts with other functional groups.  The reaction is carried out 50°C (one or two substrates work at room temperature) in THF – toluene using a Pd(OAc)2 and SPhos catalyst system (3 mol %).  Nitriles, ketones, esters, and amides all tolerated giving yields of 51-96% and works for heteroaryl chlorides as well and is also applicable to the Feringa cross-coupling of organolithium reagents.

  1. R. Martin and S.L. Buchwald,* J. Am. Chem. Soc., 2007, 129, 3844-3845.
  2. G. Manonlikakes and P. Knochel,* Angew. Chem. Int. Ed., 2009, 48, 205-209.
  3. XY. Hua, J. Masson-Makdissi, R.J. Sullivan, and S.G. Newman,* Org. Lett., 2016, 18, 5312-5325.