Proton‐Promoted Nickel‐Catalyzed Asymmetric Hydrogenation of Aliphatic Ketoacids

Abstract

A robust and highly active homogeneous chiral nickel–phosphine complex for the asymmetric hydrogenation of aliphatic γ‐ and δ‐ketoacids has been discovered. The hydrogenation could proceed smoothly in the presence of 0.0133 mol% catalyst loading (S/C=7500). The coordination chemistry and catalytic behavior of Ni(OTf)2 with (S,S)‐Ph‐BPE were explored by 1H NMR and HRMS. The mechanistic studies revealed that a proton promoted the activation of the substrate C=O bond and controlled the stereoselectivity through hydrogen bonds. A series of chiral γ‐ and δ‐alkyl substituted lactones were obtained in high yields with excellent enantioselectivities (up to 98 % yield and 99 % ee). In addition, this catalytic system also demonstrated that levulinic acid produced from a biomass feedstock was converted into chiral γ‐valerolactone without loss of ee value.

Ni-Catalyzed Asymmetric Hydrogenation of Aromatic Ketoacids for the Synthesis of Chiral Lactones

“…In this catalytic system, no exchange of protons with solvent or substrate was observed, which was different from our previous reports on nickel-catalyzed aliphatic ketoacids. 13 On the basis of the results of this mechanistic experiment and previous reports, 11d,e, 13 we proposed the following Finally, the hydroxy acid was subjected to cyclization and dehydration to afford the product.…”

“…More recently, our group reported the nickel-catalyzed asymmetric hydrogenation of aliphatic ketoacids with high enantioselectivity. 13 Given a few examples of nickel-catalyzed asymmetric hydrogenation of the CO bond, to the best of our knowledge, there are no cases about earth-abundant nickelcatalyzed asymmetric hydrogenation of aryl ketoacids to date. Herein, we achieved the first example of directly nickelcatalyzed asymmetric hydrogenation of aromatic γand δketoacids to chiral lactones in high yields and excellent enantioselectivities.…”

“…However, the catalytic system requires triphenylphosphine and base. More recently, our group reported the nickel-catalyzed asymmetric hydrogenation of aliphatic ketoacids with high enantioselectivity . Given a few examples of nickel-catalyzed asymmetric hydrogenation of the CO bond, to the best of our knowledge, there are no cases about earth-abundant nickel-catalyzed asymmetric hydrogenation of aryl ketoacids to date.…”

Nickel-Catalyzed Asymmetric Hydrogenation of γ-Keto Acids, Esters, and Amides to Chiral γ-Lactones and γ-Hydroxy Acid Derivatives

“…Both examples similarly investigated the nickel-catalyzed asymmetric hydrogenation of racemates and realized the dynamic kinetic resolution (DKR) with excellent results in the presence of a relatively higher catalyst loading (5–10 mol %), and when the acetophenone or methyl benzoylacetate without substituents at the α-position was evaluated, only poor to moderate enantioselectivities were achieved . Most recently, Fu and Deng developed proton-promoted Ni-catalyzed asymmetric hydrogenation of aliphatic keto acids . Therefore, developing nickel-catalyzed highly efficient asymmetric hydrogenation with a broad substrate scope is still desirable.…”

“…8a Most recently, Fu and Deng developed proton-promoted Nicatalyzed asymmetric hydrogenation of aliphatic keto acids. 9 Therefore, developing nickel-catalyzed highly efficient asymmetric hydrogenation with a broad substrate scope is still desirable. We hence report the nickel-catalyzed asymmetric hydrogenation of γ-keto acids for the first one-pot synthesis of chiral lactones with high enantioselectivity and activity.…”