Origin of enantioselectivity in palladium-catalyzed asymmetric allylic alkylation reactions using chiral N,N-ligands with different rigidity and flexibility

Abstract

The chiral bidentate-N,N ligands, (S_a)-1, (S_a)-2, (S,S)-3 and (S,S)-4, were synthesized. They were shown to contain rigid 2-pyridinyl or 8-quinolinyl building blocks and the C₂-symmetric chiral frameworks trans-2,5-dimethylpyrrolidinyl or (S)-(+)-2,2′-(2-azapropane-1,3-diyl)-1,1′-binaphthalene. In the (S_a)-2, and (S,S)-4 ligands pair, the 8-quinolinyl skeleton is directly bonded to the C₂-symmetric chiral frameworks (S)-(+)-2,2′-(2-azapropane-1,3-diyl)-1,1′-binaphthalene or trans-2,5-dimethylpyrrolidinyl. This feature induces rigidity in this pair of ligands upon the N,N-framework. However, this does not occur for the (S_a)-1 and (S,S)-3 ligands, in which the presence of the –CH₂– spacer between the frameworks bearing the nitrogen atom donors gives greater flexibility to the ligand. A further difference between the pairs of ligands is significant from the electronic properties of the chiral framework N-donor atom. The coordinating properties and the specific steric structural features of the (S_a)-1, (S_a)-2, (S,S)-3, and (S,S)-4 ligands are explained by their reactions with the [Pd(PhCN)₂Cl₂] and [Pd(η³-PhCHCHCHPh)(µ-Cl)]₂ substrates, in which the reported ligands form chelate complexes, with the exception of (S_a)-2, which failed to react with [Pd(η³-PhCHCHCHPh)(µ-Cl)]₂. The ligands were used in the palladium–allyl catalyzed substitution reaction of 1,3-diphenylallyl acetate with dimethylmalonate, with the best result being obtained using the (S_a)-1 ligand, giving the substitution product 2-(1,3-diphenylallyl)dimethylmalonate with an enantiomeric excess of 82% in the S form and a yield of 96%. The work demonstrates that in the presence of a steric ligand control, the electronic properties of the ligand donor atoms play a role though not significant in determining the enantioselectivity of palladium(II) catalyzed allylic substitution reactions. The results of the catalytic reaction do not provide a convincing explanation considering the coordinated chiral ligand features, as rigidity or flexibility and electronic properties of the N-donor atoms. A rationalization of the results is proposed on the basis of NMR studies and DFT calculation on the cationic complexes [Pd(η³-PhCHCHCHPh)(N-N*)]CF₃SO₃, (N-N* = (S_a)-1, 9; (S,S)-3, 10; (S,S)-4, 11).