Achieving site selectivity in C–H functionalization reactions is a significant challenge, especially when the target C–H bond is distant from existing functional groups.1–5 Coordination of a functional group to a metal catalyst is often a key driving force and control element in many important reactions including asymmetric hydrogenation,6 epoxidation7, 8, and lithiation9. Exploitation of this effect has led to the development of a broad range of directed C–H activation reactions.10–14 However, such C–H activation methods are limited to proximal C–H bonds, which are spatially and geometrically accessible from the directing functional group. Development of meta-selective C–H functionalizations remains a significant challenge.1–5,15–17 We recently developed a U- shaped template that can be used to overcome this constraint and have shown that it can be used to selectively activate remote meta-C–H bonds.1, 2 While this approach has proven applicable for a diverse set of substrates and catalytic transformations,3–5 the need for a covalently attached complex template is a significant drawback for synthetic applications. In this manuscript, we report an alternative approach, one that employs norbornene as a transient mediator to achieve meta-selective C–H activation with a simple and common ortho-directing group. The use of a newly developed pyridine-based ligand is crucial for relaying the palladium catalyst to the meta position by norbornene following initial ortho- C–H activation. Thus, this catalytic reaction demonstrates the feasibility of switching ortho-selectivity to meta-selectivity in C–H activation of the same substrate by catalyst control.

In the past two decades, metal–organic frameworks (MOFs) or porous coordination polymers (PCPs) assembled from metal ions or clusters and organic linkers via metal–ligand coordination bonds have captivated significant scientific interest on account of their high crystallinity, exceptional porosity, and tunable pore size, high modularity, and diverse functionality. The opportunity to achieve functional porous materials by design with promising properties, unattainable for solid-state materials in general, distinguishes MOFs from other classes of materials, in particular, traditional porous materials such as activated carbon, silica, and zeolites, thereby leading to complementary properties. Scientists have conducted intense research in the production of chiral MOF (CMOF) materials for specific applications including but not limited to chiral recognition, separation, and catalysis since the discovery of the first functional CMOF (i.e., d- or l-POST-1). At present, CMOFs have become interdisciplinary between chirality chemistry, coordination chemistry, and material chemistry, which involve in many subjects including chemistry, physics, optics, medicine, pharmacology, biology, crystal engineering, environmental science, etc. In this review, we will systematically summarize the recent progress of CMOFs regarding design strategies, synthetic approaches, and cutting-edge applications. In particular, we will highlight the successful implementation of CMOFs in asymmetric catalysis, enantioselective separation, enantioselective recognition, and sensing. We envision that this review will provide readers a good understanding of CMOF chemistry and, more importantly, facilitate research endeavors for the rational design of multifunctional CMOFs and their industrial implementation.

The development of catalytic enantioselective C(sp3)–H metal insertion reactions has been a significant challenge. Moderate success has recently been achieved via Pd-catalyzed desymmetrization of prochiral C–H bonds located on two different carbon centers. Herein, we report the discovery of chiral acetyl-protected aminoethyl quinoline (APAQ) ligands that enables Pd(II)-catalyzed enantioselective arylation of prochiral methylene C–H bonds on the same carbon center. The feasibility of performing asymmetric Pd insertion into ubiquitous β-methylene C–H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is essential for accelerating the C(sp3)–H activation thereby achieving enantioselectivity.

Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp3)–H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C–H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp3)–H activation toward postsynthetic modification of a broader range of peptides.

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.