Fluoroalkylated amines play a pivotal role in medicinal chemistry, yet the general and efficient synthesis of beta-difluoroalkylated amines remains elusive. Here, we developed a nickel-catalyzed umpolung strategy that enables the difluoroalkylation of 2-azaallyl anions generated from aliphatic and aromatic imines, effectively overcoming the previous limitations. By inverting the polarity of imines, this strategy allows for the coupling of a variety of readily accessible difluoroalkyl bromides and iodides. This approach is characterized by its high efficiency, broad substrate scope, high functional group tolerance, and ease of synthesis. The rapid modification of bioactive molecules by the efficient synthesis of difluorinated analogs of key amine moieties present in bioactive molecules, including amphetamine, using the current approach shows the promising potential of this protocol in advancing drug discovery and development.

Enantioselective transition metal catalysis is undoubtedly a cornerstone at the frontier of chemistry, attracting intense interest from both academia and the pharmaceutical industry. Central to this field is the strategic utilization of noncovalent interactions (NCIs), including hydrogen bonding, ion pairing, and pi-system engagements, which not only drive asymmetric synthesis but also enable precise stereochemical control in transition metal-catalyzed transformations. Recent breakthroughs have unveiled a new generation of rationally designed ligands that exploit ligand-substrate noncovalent interactions, emerging as indispensable tools for stereocontrolled synthesis and setting new paradigms in ligand engineering. These advancements establish a transformative framework for ligand engineering, bridging fundamental mechanistic insights with practical synthetic utility. In this review, the judicious design concepts and syntheses of novel ligands from the past five years were highlighted and their synthetic applications in asymmetric catalysis were detailed.

A one-pot transformation of aliphatic and aromatic tertiary amines to novel fluorinated enaminones has been developed, utilizing perfluoroalkyl ether carboxylates (PFECA salts) featuring -CF2O- units as the fluorine-containing reagents. Carbonyl fluoride, acyl fluorides and anhydrides by thermal decomposition of these PFECA salts were proposed to act as key active species that trigger the tandem oxidation-acylation process of tertiary amines, through enamine intermediates.

Thorium, a radioactive pollutant and promising nuclear fuel, is increasingly important due to its significant potential in sustainable nuclear energy applications. In this study, we designed and synthesized two imidazolebased covalent organic frameworks, AN-COF and ABI-COF, through an efficient one-pot Debus-Radziszewski reaction. Both COFs exhibit high crystallinity and large specific surface areas, which are key attributes for enhanced adsorption performance. The unique imidazole functional groups within these COFs enable highly efficient and selective capture of Th(IV) over a range of competing metal ions. Notably, ABI-COF demonstrates an impressive maximum adsorption capacity of 617 mg.g-1 for Th(IV), with adsorption equilibrium achieved within just three minutes. Furthermore, we elucidate the binding mechanism between Th(IV) and the imidazole nitrogen sites, providing valuable insights for the optimization of Th(IV) capture in future applications.

Thiopeptides, which share a macrocyclic framework characterized by a six-membered, nitrogen heterocycle central to multiple (thi)azol(in)es and dehydroamino acids, represent one of the most structurally complex groups of ribosomally synthesized and post-translationally modified peptides (RiPPs). Although post-translational modifications (PTMs) necessary for common framework formation were established, how bicyclic thiopeptides, which depend on additional specific enzyme activities to afford a side ring system, are formed remains poorly understood. Using the biosynthesis of nosiheptide as a model system, here, we report the first PTM logic to achieve a bicyclic thiopeptide based on in vivo and in vitro structural reconstitution. Eleven biosynthetic proteins are employed, processing the precursor peptide through the proper coordination of five PTM steps, of which three are common and two are specific: (1) formation of five thiazoles, (2) incorporation of an indolic moiety, (3) dehydration of five Ser/Thr residues, (4) indolic side ring closure, and (5) pyridine formation to establish the thiopeptide framework. Heterologous expression and biochemical characterization validated that the two macrocyclic ring systems are established in an interdependent and alternating manner. Distinct from tailoring PTMs, this study unveils a paradigm of a new PTM introduction for expanding the chemical and biological spaces during the establishment of the group-defining framework.

Asymmetric allylic C-H functionalization is a valuable and challenging research area. Different from the conventional direct allylic C-H cleavage strategy, transition metal-catalyzed migratory allylic substitution of remote dienes has emerged as a new route to achieve allylic C-H functionalization enantioselectively. This review provides a detailed summary of the development and advance of this strategy, introduces the related mechanistic processes, and discusses the area based on the types of catalysts and products.

The (hetero)aryl sulfoximines are important structures for developing bioactive molecules, whose synthesis relies on oxidation of (hetero)aryl sulfilimines. However, asymmetric approaches for assembling (hetero)aryl sulfilimines are still rare. Here we show that combination of CuI and NOBIN-derived amide ligands offers an effective catalytic system for enantioselective coupling of (hetero)aryl iodides with sulfenamides. A large number of functional groups and heterocycles are tolerated under the coupling conditions, providing a powerful approach for diverse synthesis of enantioenriched (hetero)aryl sulfilimines. The efficiency of the coupling reaction is highly dependent on the electronic nature of (hetero)aryl iodides and sulfenamides. Both (hetero)aryl- and some bulky alkyl-substituted sulfenamides give excellent enantioselectivities, while sulfenamides with smaller alkyl substituents lead to the formation of the (hetero)aryl sulfilimines with moderate enantioselectivities. Density functional theory (DFT) calculations reveal that proper steric repulsions in the transition states of the intramolecular SNAr reaction are crucial for achieving desirable enantioselectivity.