Design, Synthesis and Evaluation of Metal-Organic Framework Catalysts for Stereoselective Hydrogenation

Thesis Abstract

The rapid development of heterogeneous catalysis for stereoselective hydrogenation demands catalysts with tunable active sites, high activity, and robust recyclability; Metal-Organic Frameworks (MOFs) offer a modular platform to engineer chiral environments and metal centers, yet systematic design principles linking framework topology, metal coordination chemistry, and enantioselective performance remain underdeveloped. This study aims to design, synthesize, and evaluate MOF-based catalysts endowed with stereocontrolled active sites capable of enantioselective hydrogenation of prochiral alkenes and ketones under mild conditions. Specific objectives are (i) to construct a library of MOFs incorporating chiral linkers, bi-axial metal nodes, and post-synthetic modifications to generate defined chiral pockets; (ii) to synthesize at least four distinct MOF catalysts with reproducible procedures and to characterize them comprehensively using PXRD, BET surface area analysis, thermogravimetric analysis, SCXRD where feasible, solid-state NMR, and infrared spectroscopy to verify structural integrity and chiral environment; (iii) to evaluate catalytic performance in stereoselective hydrogenation of representative substrates (trans-4-phenyl-3-butenoic acid derivatives, acetophenone, and 4-aminostyrene) under 1–5 MPa H2, at 25–80°C, employing in-situ IR and in-situ X-ray absorption spectroscopy to monitor active-site dynamics; (iv) to quantify enantioselectivity and conversion using chiral GC and chiral HPLC with appropriate internal standards, and (v) to develop a structure–activity relationship (SAR) model correlating MOF topology, metal–ligand environment, and post-synthetic modifications with enantiomeric excess (ee) and turnover frequency (TOF). The methodology adopts a Design of Experiments (DoE) approach combined with mechanistic insights from density functional theory (DFT) calculations to rationalize observed selectivities, and employs a mixed-methods analysis integrating quantitative catalytic metrics with qualitative assessments of framework robustness under reaction conditions. Population and sample comprise MOF catalysts synthesized in triplicate per design and tested across three substrate classes, with kinetic data collected from triplicate runs to ensure statistical reliability; data collection instruments include powder X-ray diffractometers, N2 sorption analyzers, FTIR spectrometers, solid-state NMR, GC-FID for product quantification, and chiral GC/MS for ee determination. Data analysis utilizes regression analysis to model activity and ee as functions of structural descriptors, ANOVA to assess the significance of design factors, and multivariate principal component analysis (PCA) to identify dominant SAR features; DFT calculations at the B3LYP-D3/def2-TZVP level will explore substrate–catalyst interactions within representative pore environments to support or contest experimental findings. The anticipated findings include identifiable MOF design rules where specific cluster geometries and chiral pore architectures yield ee values exceeding 95% for selected substrates and TOFs in the 10–100 h?1 range under 2 MPa H2. The study is expected to advance knowledge by establishing quantitative links between MOF topology, chiral environment engineering, and stereocontrol in hydrogenations, enabling predictive screening of MOF catalysts for enantioselective transformations and highlighting the stability of designed frameworks under hydrogenation conditions. The contributions include a validated SAR model, a robust synthetic protocol for reproducible MOF catalysts with demonstrated enantioselectivity, and a set of design guidelines for future MOF-based asymmetric hydrogenations. Conclusions will emphasize the practical potential of MOF catalysts in pharmaceutical and fine-chemical synthesis, with recommendations for optimizing catalyst life cycle, scalability of synthesis, and integration with continuous-flow processes to enhance industrial applicability.