Transition Metal‐Catalysed Direct C−H Bond Functionalizations of 2‐Pyridone Beyond C3‐Selectivity

2‐Pyridone is a ubiquitous motif in natural products, drug molecules, ligands in catalysis and organic materials. There is a necessity of direct step‐economic methods for the construction of 2‐pyridone based molecules. Strategically, the primary developments have led to the C3‐functionalizations due to the inherent reactivity of this center. Despite this, many elegant transition metal‐catalysed methods have been established to introduce versatile functional groups at the C4, C5 and C6‐position via direct C?H bond functionalizations. This minireview focuses on the categorized introduction of different functional groups at the 2‐pyridone scaffolds beyond C3‐selectivity and discusses substrate scope, limitations and plausible mechanistic details.     

Enzyme Activity by Design: An Artificial Rhodium Hydroformylase for Linear Aldehydes

Artificial metalloenzymes (ArMs) are hybrid catalysts that offer a unique opportunity to combine the superior performance of natural protein structures with the unnatural reactivity of transition‐metal catalytic centers. Therefore, they provide the prospect of highly selective and active catalytic chemical conversions for which natural enzymes are unavailable. Herein, we show how by rationally combining robust site‐specific phosphine bioconjugation methods and a lipid‐binding protein (SCP‐2L), an artificial rhodium hydroformylase was developed that displays remarkable activities and selectivities for the biphasic production of long‐chain linear aldehydes under benign aqueous conditions. Overall, this study demonstrates that judiciously chosen protein‐binding scaffolds can be adapted to obtain metalloenzymes that provide the reactivity of the introduced metal center combined with specifically intended product selectivity.     

Chemistry of and with Highly Reactive Metals

Today, the synthetic chemist has a large repertoire of metal activation methods at his disposal. After a first breakthrough was made at the beginning of the seventies with the introduction of the Rieke metals, a series of further, in part more efficient methods were describes, based on which not only classical metal-induced reactions could be substantially improved but also completely new reactions could be discovered. In this article the individual activation methods are discussed and compared as far as is possible using the currently available data. Especially noteworthy are the metal–graphite combinations because of their unsurpassed reactivity and concomitant easy preparation and manipulation. As shown by numerous applications of these reagents on polyfunctional substrates, particularly natural products, high reactivity of the metal and excellent selectivity are by no means precluded. Besides the purely preparative aspects also insights gained so far into the general principles and limits of metal activation are outlined, and attempts at determining the morphology of highly dispersed systems are reported.     

Protein‐Based Capacitive Biosensors: a New Tool for Structure‐Activity Relationship Studies

The present work reports a new application of a protein‐based capacitive biosensor as an in vitro assay for the selectivity study of the bacterial periplasmic protein MerP and four MerP variants. The modified MerP proteins were produced by site‐directed mutagenesis of the heavy metal associated motif (HMA). The MerP and modified MerPs selectivity for copper, zinc, cadmium and mercury bivalent ions were investigated and compared. The variations in the proteins affinity were related to the primary structure of the HMA motifs. Key amino acids for copper coordination of metalloproteins that contain the metal binding sequence Gly‐Met‐Thr‐Cys‐xxx‐xxx‐Cys were identified. The results brought insights valid for Menkes and Wilson ATPases. The protein‐based capacitive biosensors were a simple and useful tool for studying structure‐activity relationships of proteins.     

A Naturally Encoded Dipeptide Handle for Bioorthogonal Chan–Lam Coupling

Manipulation of biomacromolecules is ideally achieved through unique and bioorthogonal chemical reactions of genetically encoded, naturally occurring functional groups. The toolkit of methods for site‐specific conjugation is limited by selectivity concerns and a dearth of naturally occurring functional groups with orthogonal reactivity. We report that pyroglutamate amide N?H bonds exhibit bioorthogonal copper‐catalyzed Chan–Lam coupling at pyroglutamate‐histidine dipeptide sequences. The pyroglutamate residue is readily incorporated into proteins of interest by natural enzymatic pathways, allowing specific bioconjugation at a minimalist dipeptide tag.     

Heterobimetallic Catalysis: Platinum‐Gold‐Catalyzed Tandem Cyclization/C−X Coupling Reaction of (Hetero)Arylallenes with Nucleophiles

Heterobimetallic catalysis offers new opportunities for reactivity and selectivity but still presents challenges, and only a few metal combinations have been explored so far. Reported here is a Pt‐Au heterobimetallic catalyst system for the synthesis of a family of multi‐heteroaromatic structures through tandem cyclization/C?X coupling reaction. Au‐catalyzed 6‐endo‐cyclization takes place as the first fast step. Pt‐Au clusters are proposed to be responsible for the increased reactivity in the second step, that is, the intermolecular nucleophilic addition which occurs through an outer‐sphere mechanism by hybrid homogeneous‐heterogeneous catalysis.     

Switching on Supramolecular Catalysis via Cavity Mediation and Electrostatic Regulation

Synthetic supercontainers constructed from divalent metal ions, carboxylate linkers, and sulfonylcalix[4]arene‐based container precursors exhibit great promise as enzyme mimics that function in organic solvents. The capacity of these artificial hosts to catalyze Knoevenagel condensation can be switched on when the aldehyde substrate possesses a molecular size and shape matching the nanocavity of the supercontainers. In contrast, little reactivity is observed for other aldehydes that do not match the binding pocket. This substrate‐dependent catalytic selectivity is attributed to the Brønsted acidity of the metal‐bound water molecules located inside the nanocavity, which is amplified when the size/shape of the aldehyde substrate fits the binding cavity. The electrostatic environment of the binding cavity and the Brønsted acidity of the supercontainer can be further modulated using tetraalkylammonium‐based regulators, leading to higher reactivity for the otherwise unreactive aldehydes.     

Efficient Enantioselective Syntheses of Chiral Natural Products Facilitated by Ligand Design

The employment of enantioselective transition‐metal‐catalyzed transformations as key steps in asymmetric natural product syntheses have attracted considerable attention in recent years owing to their versatile synthetic utilities, mild conditions and high efficiency in chirality generation. The chiral catalysts or supporting ligands are believed to be crucial for the requisite reactivity and enantioselectivity. Therefore, the rational design of chiral ligands is at the heart of developing new asymmetric transition‐metal catalyzed reactions and provides an avenue to the asymmetric synthesis of natural products. Our group has been engaged in the development of transition‐metal‐catalyzed enantioselective cross‐coupling, cyclization and other related reactions and the application of these methodologies to natural product syntheses. In this account, we summarized our recent synthetic efforts towards the efficient total syntheses of several different types of natural products including terpenes, alkaloids and polyketides facilitated by the design of a series of versatile P‐chiral phosphorous ligands.     

Analytical application of surface-affinity polymerized vesicular membranes to trace metal analysis by electrothermal atomic absorption spectrometry

The affinity of anionic polymerized vesicular membranes for metal cations in aqueous solutions is explored in terms of metal ion extraction and preconcentration. The method is based on the coordination of metal ions on the surface of charged polymerized vesicles via intra-vesicular complexes. These are causing changes in the selectivity, reactivity and inter-vesicular bridges which facilitate the aggregation of polymerized vesicles promoting phase separation. An analytical demonstration is shown by the optimization of the experimental conditions that enable the determination of antimony (III) in natural waters. The analytical features of the method including detection limits, precision and analytical recoveries from spiked natural water samples suggest that polymerized vesicular membranes can be a promising alternative to surfactant-mediated extractions of metal ions from aqueous matrices.     

Manganese Complexes for (De)Hydrogenation Catalysis: A Comparison to Cobalt and Iron Catalysts

The sustainable use of the resources on our planet is essential. Noble metals are very rare and are diversely used in key technologies, such as catalysis. Manganese is the third most abundant transition metal of the Earth's crust and based on the recently discovered impressive reactivity in hydrogenation and dehydrogenation reactions, is a potentially useful noble‐metal “replacement”. The hope of novel selectivity profiles, not possible with noble metals, is also an aim of such a “replacement”. The reactivity of manganese complexes in (de)hydrogenation reactions was demonstrated for the first time in 2016. Herein, we summarize the work that has been published since then and especially discuss the importance of homogeneous manganese catalysts in comparison to cobalt and iron catalysts.     

Solvent‐Enabled Radical Selectivities: Controlled Syntheses of Sulfoxides and Sulfides

Controlling selectivity is of central importance to radical chemistry. However, the highly reactive and unstable radical intermediates make this task especially challenging. Herein, a strategy for taming radical redox reactions has been developed, in which solvent‐bonding can alter the reactivity of the generated radical intermediates and thereby drastically alter the reaction selectivity at room temperature. Various β‐oxy sulfoxides and β‐hydroxy sulfides can be facilely obtained, some of which are difficult to synthesize by existing methods. Notably, neither a metal catalyst nor any further additives are necessary in these processes.     

Intramolecular Thioether Migration in the Rhodium‐Catalyzed Ene‐Cycloisomerization of Alkenylidenecyclopropanes by a Metal‐Mediated β‐Sulfide Elimination

Reported is the first example of a rhodium‐mediated β‐sulfide elimination, which represents a new mode of reactivity for late‐transition‐metal chemistry. This serendipitous discovery facilitates an ene‐cycloisomerization of allylic‐sulfide‐containing alkenylidenecyclopropanes (ACPs) to afford five‐membered carbo‐ and heterocyclic rings with concomitant intramolecular thioether migration. Interestingly, similar selectivity is obtained with both E‐ and Z‐allylic sulfides and the reaction is also feasible with an allylic selenide. Mechanistic studies are consistent with an inner‐sphere transfer of the sulfide, which is remarkable given the propensity for sulfides to poison transition‐metal catalysts. Finally, this type of atom‐economical rearrangement is envisioned to prompt the development of related processes given the utility of sulfides in target‐directed synthesis.     

Rational Control of the Selectivity of a Ruthenium Catalyst for Hydrogenation of 4‐Nitrostyrene by Strain Regulation

Tuning the selectivity of metal catalysts is of paramount importance yet a great challenge. A new strategy to effectively control the selectivity of metal catalysts, by tuning the lattice strain, is reported. A certain amount of Co atoms is introduced into Ru catalysts to compress the Ru lattice, as confirmed by aberration‐corrected high‐resolution transmission electron microscopy (HRTEM) and X‐ray absorption fine structure (XAFS) measurements. We discover that the lattice strain of Ru catalysts can greatly affect their selectivity, and Ru with 3 % lattice compression exhibits extremely high catalytic selectivity for hydrogenation of 4‐nitrostyrene to 4‐aminostyrene compared to pristine Ru (99 % vs. 66 %). Theoretical studies confirm that the optimized lateral compressive strain facilitates hydrogenation of the nitro group but impedes the hydrogenation of the vinyl group. This study provides a new guideline for designing metal catalysts with high selectivity.     

Self‐Assembled Selenium Monolayers: From Nanotechnology to Materials Science and Adaptive Catalysis

Self‐assembled monolayers (SAMs) of selenium have emerged into a rapidly developing field of nanotechnology with several promising opportunities in materials chemistry and catalysis. Comparison between sulfur‐based self‐assembled monolayers and newly developed selenium‐based monolayers reveal outstanding complimentary features on surface chemistry and highlighted the key role of the headgroup element. Diverse structural properties and reactivity of organosulfur and organoselenium groups on the surface provide flexible frameworks to create new generations of materials and adaptive catalysts with unprecedented selectivity. Important practical utility of adaptive catalytic systems deals with development of sustainable technologies and industrial processes based on natural resources. Independent development of nanotechnology, materials science and catalysis has led to the discovery of common fundamental principles of the surface chemistry of chalcogen compounds.     

Development of a General and Efficient Iron‐Catalyzed Epoxidation with Hydrogen Peroxide as Oxidant

The development of inexpensive and practical iron catalysts for the environmentally benign epoxidation of olefins with hydrogen peroxide as terminal oxidant is described. By systematic variation of ligands, metal sources, and reaction conditions, it was discovered that FeCl₃?6H₂O in combination with pyridine‐2,6‐dicarboxylic acid and different amines shows high reactivity and excellent selectivity towards the epoxidation of aromatic olefins and moderate reactivity towards that of aliphatic olefins.     

Peptide Nanomaterials Designed from Natural Supramolecular Systems

Natural supramolecular assemblies exhibit unique structural and functional properties that have been optimized over the course of evolution. Inspired by these natural systems, various bio‐nanomaterials have been developed using peptides, proteins, and nucleic acids as components. Peptides are attractive building blocks because they enable the important domains of natural protein assemblies to be isolated and optimized while retaining the original structures and functions. Furthermore, the peptide subunits can be conjugated with exogenous molecules such as peptides, proteins, nucleic acids, and metal nanoparticles to generate advanced functions. In this personal account, we summarize recent progress in the construction of peptide‐based nanomaterial designed from natural supramolecular systems, including (1) artificial viral capsids, (2) self‐assembled nanofibers, and (3) protein‐binding motifs. The peptides inspired by nature should provide new design principles for bio‐nanomaterials.     

The CH Activation/1,3‐Diyne Strategy: Highly Selective Direct Synthesis of Diverse Bisheterocycles by RhIII Catalysis

The reactivity and selectivity of 1,3‐diynes in transition‐metal‐catalyzed C? H activation is exploited to quickly assemble diverse polysubstituted bisheterocycles, which are highly important but difficult to access. By using the C? H activation/1,3‐diyne strategy, we overcame the challenges of selectivity (chemo‐, regio‐, and mono‐/diannulation) and constructed seven kinds of adjacent bisheterocycles through the formation of four strategic bonds with high efficiency and high selectivity.     

基于蛋白质工程的人工金属酶——半合成金属酶在原子转移反应中的应用

近年来,随着生物技术的进步,基于蛋白质工程的人工金属酶?半合成金属酶的研究及应用取得了突飞猛进的发展.在原子转移反应中,半合成金属酶已经能够高效、高选择性地催化氧化、不对称氢化、碳-碳键偶联等多种反应.通过对蛋白质的突变和对人工辅酶的修饰与改进,可以实现对酶的功能、催化效率以及立体选择性等多方面的调控.通过对半合成金属酶的研究,能够更深入地理解二级配位环境,为设计和制备高效"绿色金属催化剂",以及为探索金属配合物与蛋白质的相互作用、发展无机金属药物提供崭新的途径.     

New Vistas in N‐Heterocyclic Silylene (NHSi) Transition‐Metal Coordination Chemistry: Syntheses,Structures and Reactivity towards Activation of Small Molecules

This account is a review on the synthesis and transition‐metal coordination chemistry of N‐heterocyclic silylenes (NHSi’s) over the last 20 years till the present time (2012). Recently, fascinating and novel synthetic methods have been developed to access transition‐metal–NHSi complexes as an emerging class of compounds with a wealth of intriguing reactivity patterns. The striking influence of coordinating NHSi’s to transition‐metal complex fragments affording different reactivities to the “free” NHSi is a connecting theme (“leitmotif”) throughout the review, and highlights the potential of these compounds which lie at the interface of contemporary main‐group and classical organometallic chemistry towards new molecular catalysts for small‐molecule activation.     

New Perspectives in Living/Controlled Anionic Polymerization

Summary: Control of the reactivity and selectivity of active species remains a major challenge in the course of living/controlled polymerizations of vinyl and heterocyclic monomers. We have found that alkyl metal derivatives such as dialkylmagnesium or trialkylaluminum derivatives or the corresponding alkoxyakyl metal derivatives, when added to conventional anionic polymerization systems, are very effective mediators for the controlled anionic polymerization of both styrenic and oxirane monomers. When used as additives to alkali metal alkyl initiators (alkyl lithium, alkyl sodium) for the styrene anionic polymerizations, they strongly retard the reactivity of the propagating species and allow controlling the polymerization in very unusual conditions (bulk, very high temperature). On the contrary, when used in combination to the same alkali metal based initiators for the anionic polymerization of ethylene oxide or propylene oxide, these additives can drastically enhance the reactivity and the selectivity of the propagating species allowing a fast living-like polymerization to proceed already at low temperature in hydrocarbon media.