Density Functional Theory-Inspired Design of Ir/P,S-Catalysts for Asymmetric Hydrogenation of Olefins

Jorge Faiges,Montserrat Diéguez,Maria Besora,Isidro M Pastor,Carlota Borràs,Oscar Pàmies

doi:10.1021/acs.organomet.1c00450

Jorge Faiges, Montserrat Diéguez + Show 4 more

Open Access

https://doi.org/10.1021/acs.organomet.1c00450

Copy DOI

Abstract

In silico-based optimization of Ir/P,S-catalysts for the asymmetric hydrogenation of unfunctionalized olefins using (E)-1-(but-2-en-2-yl)-4-methoxybenzene as a benchmark olefin has been carried out. DFT calculations revealed that the thioether group has a major role in directing the olefin coordination. This, together with the configuration of the biphenyl phosphite group, has an impact in maximizing the energy gap between the most stable transition states leading to opposite enantiomers. As a result, the optimized catalyst proved to be efficient in the hydrogenation of a range of alkenes with the same substitution pattern and olefin geometry as the benchmark olefin, regardless of the presence of functional groups with different coordination abilities (ee values up to 97%). Appealingly, further modifications at the thioether groups and at the biaryl phosphite moiety allowed the highly enantioselective hydrogenation of olefins with different substitution patterns (e.g., α,β-unsaturated lactones and lactams, 1,1′-disubstituted enol phosphinates, and cyclic β-enamides; ee values up to >99%).

Highlights

The preparation of enantiomerically enriched compounds has become central in the chemical industry in general, and in the pharmaceutical and phytopharmaceutical industry in particular, enabling the production of compounds with increased biological efficacy, less adverse effects, and less costs.[1]
In between the unfunctionalized olefins and the analogues with coordinating functional groups, there is a wide range of interesting substrates with intermediate coordinating properties, such as α,β-unsaturated esters, lactones, lactams, and ketones, for which Ir-catalysts have been superior to Rh/ Ru-catalysts.[4]
We have demonstrated that Ir-catalysts modified with chiral P,thioether ligands are good alternatives to the commonly used Ir-P,N catalysts in the asymmetric hydrogenation of olefins without coordinative groups owing to the fact that thioether groups are more stable than oxazolines and generate an additional stereogenic center near to Ir, which confers a different steric environment around the metal center.[6]

Summary

Introduction

The preparation of enantiomerically enriched compounds has become central in the chemical industry in general, and in the pharmaceutical and phytopharmaceutical industry in particular, enabling the production of compounds with increased biological efficacy, less adverse effects, and less costs.[1] Metalcatalyzed asymmetric hydrogenation with hydrogen gas has postulated itself as a key technology for the preparation of these types of chiral compounds. While Ru/Rh-diphosphines are the most suitable for the hydrogenation of functionalized substrates,[3] the catalysts of choice for the hydrogenation of unfunctionalized olefins are IrP,N catalysts.[4] In between the unfunctionalized olefins and the analogues with coordinating functional groups, there is a wide range of interesting substrates with intermediate coordinating properties, such as α,β-unsaturated esters, lactones, lactams, and ketones, for which Ir-catalysts have been superior to Rh/ Ru-catalysts.[4] the effectiveness of these Ircatalysts again depends on the geometry and substitution pattern of the olefin.[4] The identification of a catalyst useful for substrates with functional groups with varying coordination abilities and with different substitution patterns remains a central task in asymmetric hydrogenation

Methods

Results

Conclusion