Extending the Substrate Scope for the Asymmetric Iridium-Catalyzed Hydrogenation of Minimally Functionalized Olefins by Using Biaryl Phosphite-Based Modular Ligand Libraries

Abstract

Asymmetric hydrogenation is one of the most efficient and atom-economical tools to prepare chiral molecules. However, the enantiodiscrimination of simple, minimally functionalized olefins is still challenging and requires more sophisticated ligand design. Herein, we discuss our progress in the successful development of ligand design for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins.

Catalytic Homogeneous Asymmetric Hydrogenation: Successes and Opportunities

“…This progress will be driven by even more productive experiments enabled by the following: new metal precursors for screening and synthesis, especially those of the earth-abundant 3d metals particularly manganese, iron, cobalt, nickel, and copper; ,, better mechanistic understanding of 3d metal catalysis ,, and the general causes of catalyst poisoning by dioxygen, , substrate functionality (e.g., nitrile, pyridyl, carboxylic acid, halogen, etc. ), and common impurities; modular components for rapid ligand covalent synthesis with diverse electronic and steric properties in a few steps from commercially available homochiral compounds; ,,,,,,,,,,, modular self-recognizing monodentate ligands for combinatorial catalyst synthesis; ,, combinatorial ligand and substrate libraries for screening; new, commercially available catalyst precursors and ligands in both enantiomeric forms in quantities suitable for OS applications; computational guidance in catalyst, substrate, and experiment design, increasingly with the application of artificial intelligence techniques; , on-stream optimization in flow; ,,− new catalyst supports for flow applications; ,, and further advances in biotechnology and the directed evolution of enzymes (Nobel Prize, 2018) …”

Mechanistically Guided One Pot Synthesis of Phosphine‐Phosphite and Its Implication in Asymmetric Hydrogenation

“…However, the notion that bidentate ligands require multiple synthetic steps is being challenged and innovative synthetic strategies are being devised to minimize the preparative steps. [27,28] Three strategies are being mainly explored that include i) the use of supramolecular ligands, ii) accelerated synthesis via high throughput screening and, iii) one pot ligand synthesis. The straightforward 1-2 step synthesis of supramolecular ligands has been developed in the last decade and these ligands have been successfully applied in asymmetric hydrogenation.…”

“…However, the notion that bidentate ligands require multiple synthetic steps is being challenged and innovative synthetic strategies are being devised to minimize the preparative steps [27,28] . Three strategies are being mainly explored that include i) the use of supramolecular ligands, ii) accelerated synthesis via high throughput screening and, iii) one pot ligand synthesis.…”

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

“…[13] Other groups as well have developed efficient ligand systems for Ir-catalyzed asymmetric hydrogenation. [14][15][16][17][18][19][20][21] Selected examples are shown in Figure 1. In addition to chiral P,N ligands, also other heterodonor ligands were successfully applied, such as P-thioether ligands [22 -24] and C,N ligands derived from N-heterocyclic carbenes.…”

“…Other groups as well have developed efficient ligand systems for Ir‐catalyzed asymmetric hydrogenation [14–21] . Selected examples are shown in Figure 1.…”