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

Abstract

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 Y[N(SiMe₃)₂]₃ (1) and Y[N(SiMe₃)₂]₂(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.