The asymmetric ring-opening of epoxides is an important reaction in organic synthesis, since it allows for the enantioselective installation of two vicinal functional groups with specific stereochemistry within one step from a highly available starting material. An effective class of catalysts for the asymmetric ring-opening of epoxides is metal–salen complexes. This review summarizes the development of metal–salen catalyzed enantioselective desymmetrization of meso-epoxides and kinetic resolution of epoxides with various nucleophiles, including the design and application of both homogeneous- and heterogeneous epoxide-opening catalysts as well as multi-metallic covalent and supramolecular catalytic systems.
A bis(18-crown-6) Tröger's base receptor and 4substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an allanti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl-and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be À 1.7 and À 3.3 kJ mol À 1 , respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior. Results and Discussion Description of the model systemReceptor 1 consists of a Tröger's base motif with 18-crown-6 moieties fused to each end of the aromatic cavity, and is synthesized in one step by the condensation of commercially [a] A
The first examples of enantiopure catalysts that are chiral merely due to coordination of different metal ions at enantiotopic positions of an achiral meso‐ligand are reported. These catalysts exhibit a pseudo‐Cs symmetry and are able to catalyze reactions demanding simultaneous involvement of two catalytic sites. The latter was demonstrated by application in the asymmetric ring‐opening of meso‐epoxides.
The consecutive binding of two potassium ions to a bis(18-crown-6) analogue of Tröger’s base (BCETB) in water was studied by isothermal titration calorimetry using four different salts, KCl, KI, KSCN, and K 2 SO 4 . A counterintuitive result was observed: the enthalpy change associated with the binding of the second ion is more negative than that of the first (Δ H bind,2 ° < Δ H bind,1 ° ). This remarkable finding is supported by continuum electrostatic theory as well as by atomic scale replica exchange molecular dynamics simulations, where the latter robustly reproduces experimental trends for all simulated salts, KCl, KI, and KSCN, using multiple force fields. While an enthalpic K + –K + attraction in water poses a small, but fundamentally important, contribution to the overall interaction, the probability of the collapsed conformation (COL) of BCETB, where both crown ether moieties (CEs) of BCETB are bent in toward the cavity, was found to increase successively upon binding of the first and second potassium ions. The promotion of the COL conformation reveals favorable intrinsic interactions between the potassium coordinated CEs, which further contribute to the observation that Δ H bind,2 ° < Δ H bind,1 ° . While the observed trend is independent of the counterion, the origin of the significantly larger magnitude of the difference Δ H bind,2 ° – Δ H bind,1 ° observed experimentally for KSCN was studied in light of the weaker hydration of the thiocyanate anion, resulting in an enrichment of thiocyanate ions close to BCETB compared to the other studied counterions.
A model system to study interactions between aromatic cavities and non‐polar side chains was developed and studied by different NMR methods, where a weak but evident side‐chain discrimination was observed. The experimental quantitative and qualitative data was used to evaluate different computational methods, with the conclusion that, for this system, molecular mechanics gave more accurate results than density functional theory calculations. More information can be found in the Full Paper by P.‐O. Norrby, K. Wärnmark, et al. (DOI: 10.1002/chem.202100890).
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