Direct ortho-C–H Aminoalkylation of 2-Substituted Pyridine Derivatives Catalyzed by Yttrium Complexes with N,N′-Diarylethylenediamido Ligands

A mixed ligated amidoyttrium complex, Y(NBn2)(L1)(THF)2 (8, L1 = N,N’-bis(2,6-diisopropylphenyl)ethylenediamine), served as a catalyst for addition of the ortho-pyridyl C(sp2)—H bond of 2-substituted pyridines to nonactivated imines; complex 8 showed superior catalytic performance compared with YN(SiMe3)23 (1) and YN(SiMe3)22(NBn2)(THF) (2). Concerning the reaction mechanism, we conducted a stoichiometric reaction of an alkylyttrium complex, Y(CH2SiMe3)(L1)(THF)2 (7), with 2-ethylpyridine (4e), giving a mixture of (η3-pyridylmethyl)yttrium complex 9 and (η2-pyridyl)yttrium complex 10 along with elimination of SiMe4. Furthermore, addition of N-(tert-butyl)-2-methylpropan-1-imine (5i) to the mixture of 9 and 10 afforded (pyridylmethylamido)yttrium complex 11 as a single product, and the catalytic activity of 11 was comparable to that of complex 8. Kinetic analysis of the aminoalkylation reaction in the presence/absence of HNBn2 revealed that the reaction rate in the presence of HNBn2 was four times faster than that without HNBn2 due to acceleration of the product-eliminating step from complex 11 by HNBn2 to regenerate amidoyttrium complex 8 and the product. In addition, we determined that the catalytic reaction obeyed a first-order rate dependence on the catalyst concentration, independent of the imine concentration, and a second-order rate dependence on the concentration of the pyridine substrate in the reaction system, both with and without HNBn2. An enantiomerically pure N,N’-diaryl-1,2-diphenylethylenediamido ligand was applied for the C(sp2)—H aminoalkylation reaction in combination with Lu(CH2SiMe3)3(THF)2 to give chiral aminoalkylated products in moderate yield with good enantioselectivity.