A Phosphite‐Pyridine/Iridium Complex Library as Highly Selective Catalysts for the Hydrogenation of Minimally Functionalized Olefins

Abstract

A modular library of readily available phosphite‐pyridine ligands has been successfully applied for the first time in the iridium‐catalyzed asymmetric hydrogenation of a broad range of minimally functionalized olefins. The modular ligand design has been shown to be crucial in finding highly selective catalytic systems for each substrate. Excellent enantioselectivities (ees up to 99%) have therefore been obtained in a wide range of E‐ and Z‐trisubstituted alkenes, including more demanding triaryl‐substituted olefins and dihydronaphthalenes. This good performance extends to the very challenging class of terminal disubstituted olefins, and to olefins containing neighbouring polar groups (ees up to 99%). Both enantiomers of the reduction product can be obtained in excellent enantioselectivities by simply changing the configuration of the carbon next to the phosphite moiety. The hydrogenations were also performed using propylene carbonate as solvent, which allowed the iridium catalyst to be reused and maintained the excellent enantioselectivities.magnified image

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

“…To benefit from the advantages of phosphite and pyridine moieties, we took the first generation of Pfaltz's phosphinite-pyridine ligands 40 and replaced the phosphinite moiety with a biaryl phosphite group to provide ligands 41-52a-g ( Figure 15). [16] With Ir/41-52a-g catalysts, we could reach excellent enantioselectivities (ee values up to 99%) over a wide range of E-and Z-trisubstituted alkenes, including more demanding triaryl-substituted olefins, dihydronaphthalenes, and disubstituted substrates (Figure 16). A range of allylic alcohols, acetates, a,b-unsaturated esters and ketones, allylic silanes, vinylboronates, and trifluoromethyl olefins were also hydrogenated with high enantioselectivities.…”

“…Although the number of substrates that could be successfully reduced was increased with this second generation, high enantioselectivities were mainly limited to trisubstituted substrates. To benefit from the advantages of phosphite and pyridine moieties, we took the first generation of Pfaltz's phosphinite–pyridine ligands 40 and replaced the phosphinite moiety with a biaryl phosphite group to provide ligands 41 – 52a – g (Figure ) 16…”

“…Mixed phosphite-oxazoline/thiazoline ligands are exceptionally effective, providing better substrate versatility than earlier Ir-phosphinite/phosphine-oxazoline catalysts. [12][13][14] Then our research has progressed to heterodonor biaryl phosphite, X-ligands bearing more robust Xdonor groups than oxazolines (thiazoles, [15] oxazoles, [15] pyridines, [16,17] and thioethers [18][19][20] ). We have also performed mechanistic studies to explain the origin of enantioselectivity; this allows the rationalization of the modifications required of the ligand for improved selectivity.…”

Adaptable P–X Biaryl Phosphite/Phosphoroamidite‐Containing Ligands for Asymmetric Hydrogenation and C–X Bond‐Forming Reactions: Ligand Libraries with Exceptionally Wide Substrate Scope

“…We next decided to take one further step in the design of new ligand libraries using phosphite–pyridines L36 – L47 12 and phosphite–amine L48 – L53 13 ligand libraries (Figure ), which incorporated the advantages of the heterodonor, the robustness of the pyridine/amine moieties, and the extra control provided by the flexibility of the chiral pocket through the presence of a biaryl phosphite group.…”

“…We next decided to synthesize and screen a library of 84 potential new phosphite–pyridine ligands ( L36 – L47c – g , j – k ; Figure ) 12a. These ligands incorporate the advantages of the heterodonor, the robustness of the pyridine moiety, and the extra control of the chiral pocket through the presence of biaryl phosphite groups.…”