Design of Iridium N-Heterocyclic Carbene Amino Acid Catalysts for Asymmetric Transfer Hydrogenation of Aryl Ketones

Abstract

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of -amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

Computational (DFT) and Experimental (NMR) Study of the Chelation of an Iridium Hyperpolarization Transfer Catalyst by Amino Acids

“…[22] Structural and computational studies on the binding properties of amino acid coordination complexes have been reported in literature. [23,24] We decided to undertake a computational study using Density Function Theory (DFT), including dispersion empirical corrections, to clarify the reasons for the relative stabilities and interconversions of the complexes of the hyperpolarization catalyst with a series of amino acids (Gly, Ala, Val) of increasing side chain bulk. As in the case of our earlier DFT study, [13] the relative energies of the complexes can be used to calculate populations that can be validated with the experimental NMR abundances.…”

Transition Metal Complexes with Amino Acids, Peptides and Carbohydrates in Catalytic Asymmetric Synthesis: A Short Review

“…The new ligands represent N-Boc-Data taken from ref. [98,99]. It was shown that the nature of R in Cp* R dramatically affects both selectivity and the rate of the reaction.…”

“…Later, the same research team [99] synthesized new complexes Ir(NHC) 2 (L)(H)(X) (20), which were active in ATH of ketones. The maximum enantioselectivity was achieved in the presence of the Ir(IMe) 2 (L-Pro)(H)(I) Ir(IMe) 2 (L-Pro)(H)(I) catalyst, which reduced some acetophenone derivatives with ee up to 95%.…”

10th Anniversary of Catalysts: Molecular Catalysis

“…For example, the Special Issue summarizes efforts in the area of homogeneous catalysts concerning iridium catalysts containing NHC ligands applied to the asymmetric transfer hydrogenation of ketones [4], synthesis of quinoxalines from glycerol and diamines [5], cross coupling for natural product synthesis [6], and palladium-catalyzed reductive carbonylation of nitro-styrene [7]. This Special Issue also introduces efforts entitled "Immobilization of Rh(I)-N-Xantphos and Fe(II)-C-scorpionate onto magnetic nanoparticles [8]" and "5-(2-Pyridyl)tetrazolate complex of molybdenum(VI)" as precursors for reusable molybdenum oxide-based hybrid heterogeneous catalyst [9].…”