A Site-Selective C(sp³)‑H Chlorination Boosted by an Imidazolium-Functionalized Cage in Water

The utilization of a confined cavity in a coordination cage to manipulate the reaction pathways can nicely complement the synthetic shortage of site-selective reactions. However, harmonization of the transition state in the cavity is a significant challenge. To address this issue, we have designed an imidazolium-functionalized cage with a regular octahedral geometry composed of 12 imidazolium linkers and 6 Cu4-calix[4]arene nodes. As a catalyst, the diisopropylphenylimidazolium functionality enables an efficient N-chlorination, and the created cavity favors a six-membered cyclic transition state for chlorine atom transfer, boosting the site-selective C(sp3)–H chlorination of amides/sulfonamides in the water. Our mechanistic investigations have disclosed the rate-determining N–Cl activation mode within the cavity for the chlorine atom transfer pathways

A Site-Selective C(sp³)‑H Chlorination Boosted by an Imidazolium-Functionalized Cage in Water

The utilization of a confined cavity in a coordination cage to manipulate the reaction pathways can nicely complement the synthetic shortage of site-selective reactions. However, harmonization of the transition state in the cavity is a significant challenge. To address this issue, we have designed an imidazolium-functionalized cage with a regular octahedral geometry composed of 12 imidazolium linkers and 6 Cu4-calix[4]arene nodes. As a catalyst, the diisopropylphenylimidazolium functionality enables an efficient N-chlorination, and the created cavity favors a six-membered cyclic transition state for chlorine atom transfer, boosting the site-selective C(sp3)–H chlorination of amides/sulfonamides in the water. Our mechanistic investigations have disclosed the rate-determining N–Cl activation mode within the cavity for the chlorine atom transfer pathways

A Site-Selective C(sp³)‑H Chlorination Boosted by an Imidazolium-Functionalized Cage in Water

The utilization of a confined cavity in a coordination cage to manipulate the reaction pathways can nicely complement the synthetic shortage of site-selective reactions. However, harmonization of the transition state in the cavity is a significant challenge. To address this issue, we have designed an imidazolium-functionalized cage with a regular octahedral geometry composed of 12 imidazolium linkers and 6 Cu4-calix[4]arene nodes. As a catalyst, the diisopropylphenylimidazolium functionality enables an efficient N-chlorination, and the created cavity favors a six-membered cyclic transition state for chlorine atom transfer, boosting the site-selective C(sp3)–H chlorination of amides/sulfonamides in the water. Our mechanistic investigations have disclosed the rate-determining N–Cl activation mode within the cavity for the chlorine atom transfer pathways

Multivariate Metal–Organic Frameworks as Multifunctional Heterogeneous Asymmetric Catalysts for Sequential Reactions

The search for versatile heterogeneous catalysts with multiple active sites for broad asymmetric transformations has long been of great interest, but it remains a formidable synthetic challenge. Here we demonstrate that multivariate metal–organic frameworks (MTV-MOFs) can be used as an excellent platform to engineer heterogeneous catalysts featuring multiple and cooperative active sites. An isostructural series of 2-fold interpenetrated MTV-MOFs that contain up to three different chiral metallosalen catalysts was constructed and used as efficient and recyclable heterogeneous catalysts for a variety of asymmetric sequential alkene epoxidation/epoxide ring-opening reactions. Interpenetration of the frameworks brings metallosalen units adjacent to each other, allowing cooperative activation, which results in improved efficiency and enantioselectivity over the sum of the individual parts. The fact that manipulation of molecular catalysts in MTV-MOFs can control the activities and selectivities would facilitate the design of novel multifunctional materials for enantioselective processes

Design and Assembly of Chiral Coordination Cages for Asymmetric Sequential Reactions

Supramolecular nanoreactors featuring multiple catalytically active sites are of great importance, especially for asymmetric catalysis, and are yet challenging to construct. Here we report the design and assembly of five chiral single- and mixed-linker tetrahedral coordination cages using six dicarboxylate ligands derived-from enantiopure Mn­(salen), Cr­(salen) and/or Fe­(salen) as linear linkers and four Cp₃Zr₃ clusters as three-connected vertices. The formation of these cages was confirmed by a variety of techniques including single-crystal and powder X-ray diffraction, inductively coupled plasma optical emission spectrometer, quadrupole-time-of-flight mass spectrometry and energy dispersive X-ray spectrometry. The cages feature a nanoscale hydrophobic cavity decorated with the same or different catalytically active sites, and the mixed-linker cage bearing Mn­(salen) and Cr­(salen) species is shown to be an efficient supramolecular catalyst for sequential asymmetric alkene epoxidation/epoxide ring-opening reactions with up to 99.9% ee. The cage catalyst demonstrates improved activity and enantioselectivity over the free catalysts owing to stabilization of catalytically active metallosalen units and concentration of reactants within the cavity. Manipulation of catalytic organic linkers in cages can control the activities and selectivities, which may provide new opportunities for the design and assembly of novel functional supramolecular architectures

Chiral Covalent Organic Frameworks with High Chemical Stability for Heterogeneous Asymmetric Catalysis

Covalent organic frameworks (COFs) featuring chirality, stability, and function are of both fundamental and practical interest, but are yet challenging to achieve. Here we reported the metal-directed synthesis of two chiral COFs (CCOFs) by imine-condensations of enantiopure 1,2-diaminocyclohexane with <i>C</i>₃-symmetric trisalicylaldehydes having one or zero 3-<i>tert</i>-butyl group. Powder X-ray diffraction and modeling studies, together with pore size distribution analysis demonstrate that the Zn­(salen)-based CCOFs possess a two-dimensional hexagonal grid network with AA stacking. Dramatic enhancement in the chemical stability toward acidic (1 M HCl) and basic (9 M NaOH) conditions was observed for the COF incorporated with <i>tert</i>-butyl groups on the pore walls compared to the nonalkylated analog. The Zn­(salen) modules in the CCOFs allow for installing multivariate metals into the frameworks by postsynthetic metal exchange. The exchanged CCOFs maintain high crystallinity and porosity and can serve as efficient and recyclable heterogeneous catalysts for asymmetric cyanation of aldehydes, Diels–Alder reaction, alkene epoxidation, epoxide ring-opening, and related sequential reactions with up to 97% ee

Chiral NH-Controlled Supramolecular Metallacycles

Chiral NH functionalities-based discrimination is a key feature of Nature’s chemical armory, yet selective binding of biologically active molecules in synthetic systems with high enantioselectivity poses significant challenges. Here we report the assembly of three chiral fluorescent Zn₆L₆ metallacycles from pyridyl-functionalized Zn­(salalen) or Zn­(salen) complexes. Each of these metallacycles has a nanoscale hydrophobic cavity decorated with six, three, or zero chiral NH functionalities and packs into a three-dimensional supramolecular porous framework. The binding affinity and enantioselectivity of the metallacycles toward α-hydroxycarboxylic acids, amino acids, small molecule pharamaceuticals (l-dopa, d-penicillamine), and chiral amines increase with the number of chiral NH moieties in the cyclic structure. From single-crystal X-ray diffraction, molecular simulations, and quantum chemical calculations, the chiral recognition and discrimination are attributed to the specific binding of enantiomers in the chiral pockets of the metallacycles. The parent metallacycles are fluorescent with the intensity of emission being linearly related to the enantiomeric composition of the chiral biorelevant guests, which allow them to be utilized in chiral sensing. The fact that manipulation of chiral NH functionalities in metallacycles can control the enantiorecognition of biomolecular complexes would facilitate the design of more effective supramolecular assemblies for enantioselective processes

Chiral NH-Controlled Supramolecular Metallacycles

Chiral NH functionalities-based discrimination is a key feature of Nature’s chemical armory, yet selective binding of biologically active molecules in synthetic systems with high enantioselectivity poses significant challenges. Here we report the assembly of three chiral fluorescent Zn₆L₆ metallacycles from pyridyl-functionalized Zn­(salalen) or Zn­(salen) complexes. Each of these metallacycles has a nanoscale hydrophobic cavity decorated with six, three, or zero chiral NH functionalities and packs into a three-dimensional supramolecular porous framework. The binding affinity and enantioselectivity of the metallacycles toward α-hydroxycarboxylic acids, amino acids, small molecule pharamaceuticals (l-dopa, d-penicillamine), and chiral amines increase with the number of chiral NH moieties in the cyclic structure. From single-crystal X-ray diffraction, molecular simulations, and quantum chemical calculations, the chiral recognition and discrimination are attributed to the specific binding of enantiomers in the chiral pockets of the metallacycles. The parent metallacycles are fluorescent with the intensity of emission being linearly related to the enantiomeric composition of the chiral biorelevant guests, which allow them to be utilized in chiral sensing. The fact that manipulation of chiral NH functionalities in metallacycles can control the enantiorecognition of biomolecular complexes would facilitate the design of more effective supramolecular assemblies for enantioselective processes