Ruthenium-Catalyzed Oxidative Cyanation of Tertiary Amines with Molecular Oxygen or Hydrogen Peroxide and Sodium Cyanide: sp3 C−H Bond Activation and Carbon−Carbon Bond Formation

Ruthenium-catalyzed oxidative cyanation of tertiary amines with molecular oxygen in the presence of sodium cyanide and acetic acid gives the corresponding α-aminonitriles, which are highly useful intermediates for organic synthesis. The reaction is the first demonstration of direct sp3 C−H bond activation α to nitrogen followed by carbon−carbon bond formation under aerobic oxidation conditions. The catalytic oxidation seems to proceed by (i) α-C−H activation of tertiary amines by the ruthenium catalyst to give an iminium ion/ruthenium hydride intermediate, (ii) reaction with molecular oxygen to give an iminium ion/ruthenium hydroperoxide, (iii) reaction with HCN to give the α-aminonitrile product, H2O2, and Ru species, (iv) generation of oxoruthenium species from the reaction of Ru species with H2O2, and (v) reaction of oxoruthenium species with tertiary amines to give α-aminonitriles. On the basis of the last two pathways, a new type of ruthenium-catalyzed oxidative cyanation of tertiary amines with H2O2 to give α-aminonitriles was established. The α-aminonitriles thus obtained can be readily converted to α-amino acids, diamines, and various nitrogen-containing heterocyclic compounds.