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Keywords:

  • hydrogenation;
  • palladium;
  • heterogeneous catalysis;
  • ruthenium;
  • homogeneous catalysis

Abstract

A stepwise catalytic reduction of ketone 1 to alcohol 2 and subsequently to aryl(imidazo[1,2-b]pyridazinyl)methane 3 is described, which provides synthetically useful chemoselectivity at acceptably low catalyst loadings. Undesired reactive sites include an aryl chloride, heteroarylchloride and benzylic amine group. The presence of these functional groups presents a significant challenge to chemoselectivity for both reduction steps. For selective C[DOUBLE BOND]O reduction of highly functionalised 1, high chemoselectivity was observed at low catalyst loading by using Wills’ tethered Ru transfer-hydrogenation catalyst 13. The selective hydrogenolysis of 2 was then accomplished under acidic hydrogenation conditions by using a Pd/C catalyst in the presence of Cu salts. This procedure has been demonstrated on a multi-gram scale, which makes this approach a viable method to use a combination of homogeneous and heterogeneous catalysis.