A Theoretically‐Guided Optimization of a New Family of Modular P,S‐Ligands for Iridium‐Catalyzed Hydrogenation of Minimally Functionalized Olefins

Abstract

A library of modular iridium complexes derived from thioether-phosphite/phosphinite ligands has been evaluated in the asymmetric iridium-catalyzed hydrogenation of minimally functionalized olefins. The modular ligand design has been shown to be crucial in finding highly selective catalysts for each substrate. A DFT study of the transition state responsible for the enantiocontrol in the Ir-catalyzed hydrogenation is also described and used for further optimization of the crucial stereodefining moieties. Excellent enantioselectivities (enantiomeric excess (ee) values up to 99 %) have been obtained for a range of substrates, including E- and Z-trisubstituted and disubstituted olefins, α,β-unsaturated enones, tri- and disubstituted alkenylboronic esters, and olefins with trifluoromethyl substituents.

Extending the Substrate Scope of Bicyclic P‐Oxazoline/Thiazole Ligands for Ir‐Catalyzed Hydrogenation of Unfunctionalized Olefins by Introducing a Biaryl Phosphoroamidite Group

“…13c, 22 Our results show that by correctly choosing the N‐donor group (thiazole rather than oxazoline) and the configuration of the biaryl group ( R for S21 and S for S22 ) of the ligand, excellent enantioselectivities can be achieved for the reduction of two types of alkenylboronic esters containing either one or two (pinacolato)boron groups. The enantioselectivities achieved are among the best reported, and they surpass those obtained with the first generation of ligands 11d. 13c, 22…”

“…The synthesis of chiral organoboron compounds has recently received considerable attention; they are valuable organic intermediates because the CB bond can be readily transformed into chiral CN, CO, and CC bonds. In this field, the reduction of alkenylboronic esters has been less investigated, and only a few catalytic systems have been used effectively 11d. 13c, 22 Our results show that by correctly choosing the N‐donor group (thiazole rather than oxazoline) and the configuration of the biaryl group ( R for S21 and S for S22 ) of the ligand, excellent enantioselectivities can be achieved for the reduction of two types of alkenylboronic esters containing either one or two (pinacolato)boron groups.…”

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

“…Then, we decided to focus our research on developing new simple P‐thioether ligand libraries and optimize their application using DFT calculations. We therefore next applied a new highly modular P‐thioether ligand library (Figure ; ligands L71 – L80 ) 19. In a simple three‐step procedure, several ligand parameters were easily tuned to maximize the enantioselectivities for each substrate.…”

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

“…Next, in collaboration with Pericas's group, we applied a new highly modular phosphite/phosphinite–thioether ligand library (Figure ; ligands 68 – 77a – g ) 19. In a simple three‐step procedure, several ligand parameters were easily tuned to maximize the enantioselectivities for each substrate.…”

“…Then our research has progressed to heterodonor biaryl phosphite, X‐ligands bearing more robust X‐donor groups than oxazolines (thiazoles,15 oxazoles,15 pyridines,16,17 and thioethers18–20). 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 14b,19,20…”