Synthetic and computational assessment of a chiral metal-organic framework catalyst for predictive asymmetric transformation.

Jérôme Canivet,Elise Bernoud,Tanya K Todorova,Jonathan Bonnefoy,Elsje Alessandra Quadrelli,Alexandre Legrand,Caroline Mellot-Draznieks

doi:10.1039/d0sc03364b

Abstract

Understanding and controlling molecular recognition mechanisms at a chiral solid interface is a continuously addressed challenge in heterogeneous catalysis. Here, the molecular recognition of a chiral peptide-functionalized metal–organic framework (MOF) catalyst towards a pro-chiral substrate is evaluated experimentally and in silico. The MIL-101 metal–organic framework is used as a macroligand for hosting a Noyori-type chiral ruthenium molecular catalyst, namely (benzene)Ru@MIL-101-NH-Gly-Pro. Its catalytic perfomance toward the asymmetric transfer hydrogenation (ATH) of acetophenone into R- and S-phenylethanol are assessed. The excellent match between the experimentally obtained enantiomeric excesses and the computational outcomes provides a robust atomic-level rationale for the observed product selectivities. The unprecedented role of the MOF in confining the molecular Ru-catalyst and in determining the access of the prochiral substrate to the active site is revealed in terms of highly face-specific host–guest interactions. The predicted surface-specific face differentiation of the prochiral substrate is experimentally corroborated since a three-fold increase in enantiomeric excess is obtained with the heterogeneous MOF-based catalyst when compared to its homogeneous molecular counterpart.

Highlights

Among marketed drugs, 56% contain a chiral center.[1]
Aiming at synthesizing a novel class of chiral porous solids, we have previously designed a family of peptide-functionalized metal–organic framework (MOF) capable of performing asymmetric transformations such as asymmetric aldol catalysis.[20,21]
Gly-Pro solid (Gly)–Pro gra, the glycine spacer was found to be essential in placing the Pro residue towards the center of the cavity rather than folded towards the MOF hydroxyl groups

Summary

Introduction

56% contain a chiral center.[1]. Asymmetric catalysis plays a key role in lowering the environmental impact of the synthetic routes of pure chiral molecules for pharmaceuticals, agrochemicals and avors,[2] allowing the elimination, for example, of environmentally costly separation steps between the desired and unwanted enantiomers or between different diastereoisomers. The catalytic activity of the MOF-supported chiral benzene ruthenium complexes, (benzene)Ru@MIL-101-NH-Gly-Pro, was evaluated for the ATH of acetophenone into phenylethanol in isopropanol using chiral HPLC analysis (Table 1, Fig. S19 and S20†).

Results

Conclusion