Synthesis and Characterization of Chiral Iridium Complexes Bearing Carbohydrate Functionalized Pyridincarboxamide Ligands and Their Application as Catalysts in the Asymmetric Transfer Hydrogenation of α-Ketoacids in Water

Abstract

[Cp*IrLnCl] complexes [L1 = (methyl-β-d-glucopyranosid-2-yl)picolinamide, 1; L2 = (methyl-3,4,6-tri-O-acetyl-β-d-glucopyranosid-2-yl)picolinamide, 2; L3 = (2,3,4,6-tetra-O-acetyl-β-d-glucopyranosid-1-yl)picolinamide, 3] have been synthesized and completely characterized in solution, by 1D- and 2D-NMR spectroscopy, and in the solid state, by X-ray single crystal diffractometry. Despite the chirality of the Ln-moiety and metal, a single diastereoisomer is observed for L1 (1) and L2 (2) having a (R)-iridium configuration: the pyranose moiety is oriented in a way to minimize the interactions of the axial protons, vicinal to the amide moiety, and Cp*, with the OMe-group pointing toward the Cp*-ligand and away from Ir–Cl. Such a diastereoisomer is also favored by the establishment of an O–H···Cl–Ir hydrogen bond (2.356 Å) and by the minimization of the steric repulsion between one acetyl moiety of L2 and Cp* and picolinamide ligands in 1 and 2, respectively. DFT calculations computed a stabilization by more than 5.9 and 3.1 kcal/mol of this diastereoisomer with respect to other possible ones. Two interconverting diastereoisomers with different chirality at iridium are instead observed in solution for complex 3 in which −CH2OAc [3a, 63%, (R)] and −OAc [3b, 37%, (S)] moieties, respectively, are oriented toward Cp* and N-arm of picolinamide ligands. Consistently, DFT calculations indicate that 3a and 3b have a comparable stability (ΔE = 1.2 kcal/mol). Complexes 1–3 catalyze the asymmetric transfer hydrogenation of RC(O)C(O)OH to RCH(OH)C(O)OH [R = Ph (PGA), CH2Ph (PPA), CH2(4-OH)C6H4 (HPPA)], using both HCOOH and H3PO3 as hydrogen donor, in water at pH 7 (by phosphate buffer), with excellent chemoselectivity and efficiency (conversion >99%) and moderate to good enantioselectivity (30–70% ee). Utilizing catalyst 3 instead of 2, bearing the pseudoenantiomeric L3 of L2 ligand, causes a reduction of the percentage of the major enantiomer (R) with PGA and an inversion of stereoselectivity from (R) to (S) with PPA and HPPA substrates.