Functionalization of dicarboxylate linkers with proline was used to generate catalytically active metal−organic frameworks (MOFs) for diastereoselective aldol addition. Due to high robustness and chemical stability, zirconium based MOFs, namely UiO-67 and UiO-68, were chosen as catalyst hosts. During the MOF synthesis, utilizing Boc protected proline functionalized linkers H 2 bpdc-NHProBoc and H 2 tpdc-NHProBoc, in situ deprotection of the Boc groups without racemization is achieved, enabling direct application of the enantiopure, homochiral MOFs in catalytic reaction, without further postsynthetic treatment. Solvent screening and kinetic studies as well as cycling tests were used to evaluate the conditions for diastereoselective aldol addition using a model reaction of 4nitrobenzaldehyde and cyclohexanone. High yields (up to 97%) were achieved in reasonable reaction time using ethanol as solvent. In comparison to homocatalytic reactions catalyzed by Lproline and its derivatives, MOFs showed opposite diastereoselectivity attributed to the catalytic sites in confined pore space rendering this class of materials as promising catalysts for fine chemicals production.

The linker functionalization strategy was applied to incorporate proline moieties into a metal−organic framework (MOF). When 4,4′-biphenyldicarboxylic acid was replaced with a Boc-protected proline-functionalized linker (H 2 L) in the synthesis of DUT-32 (DUT = Dresden University of Technology), a highly porous enantiomerically pure MOF (DUT-32-NHProBoc) was obtained, as could be confirmed by enantioselective high-performance liquid chromatography (HPLC) measurements and solid-state NMR experiments. Isotope labeling of the chiral side group proline enabled highly sensitive one-and two-dimensional solid-state 13 C NMR experiments. For samples loaded with (S)-1-phenyl-2,2,2-trifluoroethanol [(S)-TFPE], the proline groups are shown to exhibit a lower mobility than that for (R)-TFPE-loaded samples. This indicates a preferred interaction of the shift agent (S)-TFPE with the chiral moieties. The high porosity of the compound is reflected by an exceptionally high ethyl cinnamate adsorption capacity. However, postsynthetic thermal deprotection of Boc−proline in the MOF leads to racemization of the chiral center, which was verified by stereoselective HPLC experiments and asymmetric catalysis of aldol addition. ■ INTRODUCTIONIt has been widely accepted that enantiomers of the same chiral compound may show quite different bioactivities, as well as different physical, chemical, pharmacological, and toxicological properties. Therefore, their preparation and especially analysis are important in many fields of science. To obtain a chiral heterogeneous selector/catalyst, usually the porous substrates are coated or immobilized with proteins, enzymes, oligosaccharides, or polysaccharides. Because important progress has been made in the field of porous materials through the development of metal−organic frameworks (MOFs), this material class is also considered to be very promising for the design and development of a new generation of chiral porous materials. The incorporation of chiral groups by ligand or cluster functionalization or the synthesis of chiral MOFs from achiral building blocks generates homochiral materials. Inspired by homogeneous chiral catalysis, the implementation of wellestablished chiral catalytically active groups as linkers or as side groups of the framework backbone has been reported for a variety of MOFs. 1−5 One common organocatalytic group for a wide range of asymmetric reactions is proline. Up to now, there are only a few homochiral MOFs with proline functionalities reported. So far, the incorporation of proline could be performed by coordination on open metal sites in MIL-101, 6 postsynthetic click reaction, 7 or postsynthetic amide coupling. 8 Furthermore, the incorporation of proline by chiral functionalization of the linker before MOF synthesis was carried out by Telfer et al. 9 The reported homochiral material could be used as heterogeneous chiral catalysts in asymmetric aldol reactions. The important point in the synthesis of enantiopure (prolinecontaining) MOFs is to avoid the racemization that can ...

DUT-67, an 8-connected zirconium and 2,5-thiophenedicarboxylate-based metal-organic framework (MOF), was postsynthetically functionalized by l-proline via solvent-assisted linker incorporation to obtain a chiral base catalyst. The parent monocarboxylate could be almost completely exchanged by l-proline after 5 days of treatment. The resulting chiral DUT-67 was demonstrated to be a promising heterogeneous catalyst for the asymmetric Michael addition of cyclohexanone to trans-β-nitrostyrene with excellent yield (up to 96%) and enantioselectivity comparable to that of l-proline in homogeneous reaction (ee of approximately 38%). The Zr-MOF could be reused at least five times without substantial degradation in the crystallinity or catalytic activity. No leaching of catalytically active species into the liquid phase was detected over five cycles.

The crucial impact of metal coordination on selectivity and leaching is elucidated by comparing MOFs constructed from different clusters and linkers.