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The design of a relatively simple and efficient method to extend the π-conjugation of readily available aromatics in one-dimension is of significant value. In this paper, pyrenes, peropyrenes, and teropyrenes were synthesized through a double or quadruple benzannulation reaction of alkynes promoted by Brønsted acid. This novel method does not involve cyclodehydrogenation (oxidative aryl-aryl coupling) to arrive at the newly incorporated large arene moieties. All of the target compounds were synthesized in moderate to good yields and were fully characterized with the structures unambiguously confirmed by X-ray crystallography. As expected, photophysical characterization clearly shows increasing red-shifts as a function of extended conjugation within the fused ring systems. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) is an indispensable basic reagent in various industries, such as textile bleach, chemical synthesis, and environmental protection. However, it is challenging to prepare H2O2 in a green, safe, simple and efficient way under ambient conditions. Here, we found that H2O2 could be synthesized using a catalytic pathway only by contact charging a two‐phase interface at room temperature and normal pressure. Particularly, under the action of mechanical force, electron transfer occurs during physical contact between polytetrafluoroethylene particles and deionized water/O2 interfaces, inducing the generation of reactive free radicals (⋅OH and ⋅O2−), and the free radicals could react to form H2O2, yielding as high as 313 μmol L−1 h−1. In addition, the new reaction device could show long‐term stable H2O2 production. This work provides a novel method for the efficient preparation of H2O2, which may also stimulate further explorations on contact‐electrification‐induced chemistry process. [ABSTRACT FROM AUTHOR]

Acidic CO2 reduction (CO2R) holds promise for the synthesis of low‐carbon‐footprint chemicals using renewable electricity. However, the corrosion of catalysts in strong acids causes severe hydrogen evolution and rapid deterioration of CO2R performance. Here, by coating catalysts with an electrically nonconductive nanoporous SiC‐NafionTM layer, a near‐neutral pH was stabilized on catalyst surfaces, thereby protecting the catalysts against corrosion for durable CO2R in strong acids. Electrode microstructures played a critical role in regulating ion diffusion and stabilizing electrohydrodynamic flows near catalyst surfaces. This surface‐coating strategy was applied to three catalysts, SnBi, Ag, and Cu, and they exhibited high activity over extended CO2R operation in strong acids. Using a stratified SiC‐NafionTM/SnBi/polytetrafluoroethylene (PTFE) electrode, constant production of formic acid was achieved with a single‐pass carbon efficiency of >75 % and Faradaic efficiency of >90 % at 100 mA cm−2 over 125 h at pH 1. [ABSTRACT FROM AUTHOR]

Abstract: Long‐lifetime room‐temperature phosphorescence (RTP) materials are important for many applications, but they are highly challenging materials owing to the spin‐forbidden nature of triplet exciton transitions. Herein, a facile, quick and gram‐scale method for the preparation of ultralong RTP (URTP) carbon dots (CDs) was developed via microwave‐assisted heating of ethanolamine and phosphoric acid aqueous solution. The CDs exhibit the longest RTP lifetime, 1.46 s (more than 10 s to naked eye) for CDs‐based materials to date. The doping of N and P elements is critical for the URTP which is considered to be favored by a n→π* transition facilitating intersystem crossing (ISC) for effectively populating triplet excitons. In addition, possibilities of formation of hydrogen bonds in the interior of the CDs may also play a significant role in producing RTP. Potential applications of the URTP CDs in the fields of anti‐counterfeiting and information protection are proposed and demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: Reported is the first organocatalytic asymmetric 1,3‐alkyl shift in alkyl aryl ethers for the synthesis of chiral 3,3′‐diaryloxindoles using a chiral Brønsted acid catalyst. Preliminary results showed that each enantiomer of the 3,3′‐diaryloxindole, and a racemic mixture, showed different antiproliferative activities against HeLa cell lines by using an MTT assay. [ABSTRACT FROM AUTHOR]

Propylene gas is produced worldwide by steam cracking on million‐metric‐ton scale per year. It serves as a valuable starting material for π‐bond functionalization but is rarely applied in transition metal‐catalyzed allylic C−H functionalization for fine chemical synthesis. Herein, we report that a newly‐developed cationic cyclopentadienyliron dicarbonyl complex allows for the conversion of propylene to its allylic C−C bond coupling products under catalytic conditions. This approach was also found applicable to the allylic functionalization of simple α‐olefins with distinctive branched selectivity. Experimental and computational mechanistic studies supported the allylic deprotonation of the metal‐coordinated alkene as the turnover‐limiting step and led to insights into the multifaceted roles of the newly designed ligand in promoting allylic C−H functionalization with enhanced reactivity and stereoselectivity. [ABSTRACT FROM AUTHOR]

A direct spirocyclization approach for the chemical synthesis of spiro[cyclohexane‐2‐indoline] alkaloids is reported. The absolute stereochemistry was introduced by a desymmetrizing Dieckmann condensation, and the relative stereochemistry was controlled by the manipulation of the kinetic and thermodynamic pathways of the spirocyclization. By contrast to the biogenetic proposal involving the diester‐type alkaloid as the precursor, we demonstrate that chemically a common lactone‐type intermediate could bridge the chemical synthesis of this class of natural products. [ABSTRACT FROM AUTHOR]

This Review provides a summary of the use and the role of coordination complexes as precursors for the generation of heterogeneous catalysts for oxidation reactions of interest for fine chemical synthesis. Specific attention is paid to the comprehension of phenomena explaining the formation of active sites in heterogeneous catalysts. Different families of coordination precursors are considered. For each example, a brief critical description of the synthesis, characterization, and catalytic performance is reported. Special attention is paid to the chemical environment of the first coordination sphere of the active metal centre. The catalysts obtained by heterogenization, grafting, or anchoring of homogeneous catalysts can therefore exhibit enhanced catalytic performance by merging advantages of both homogeneous and heterogeneous systems. The deposition of coordination complexes over a preformed support is indeed a conceptually versatile strategy to design novel catalysts with tuned and controlled properties. [ABSTRACT FROM AUTHOR]

Enantioselective reactions are at the core of chemical synthesis. Their development mostly relies on prior knowledge, laborious product analysis and post‐rationalization by theoretical methods. Here, we introduce a simple and fast method to determine enantioselectivities based on mass spectrometry. The method is based on ion mobility separation of diastereomeric intermediates, formed from a chiral catalyst and prochiral reactants, and delayed reactant labeling experiments to link the mass spectra with the reaction kinetics in solution. The data provide rate constants along the reaction paths for the individual diastereomeric intermediates, revealing the origins of enantioselectivity. Using the derived kinetics, the enantioselectivity of the overall reaction can be predicted. Hence, this method can offer a rapid discovery and optimization of enantioselective reactions in the future. We illustrate the method for the addition of cyclopentadiene (CP) to an α,β‐unsaturated aldehyde catalyzed by a diarylprolinol silyl ether. [ABSTRACT FROM AUTHOR]

Benzoxazole scaffolds feature prominently in diverse synthetic and natural product‐derived pharmaceuticals. Our understanding of their bacterial biosynthesis is, however, limited to ortho‐substituted heterocycles from actinomycetes. We report an overlooked biosynthetic pathway in anaerobic bacteria (typified in Clostridium cavendishii) that expands the benzoxazole chemical space to meta‐substituted heterocycles and heralds a distribution beyond Actinobacteria. The first benzoxazoles from the anaerobic realm (closoxazole A and B) were elucidated by NMR and chemical synthesis. By genome editing in the native producer, heterologous expression in Escherichia coli, and systematic pathway dissection we show that closoxazole biosynthesis invokes an unprecedented precursor usage (3‐amino‐4‐hydroxybenzoate) and manner of assembly. Synthetic utility was demonstrated by the precursor‐directed biosynthesis of a tafamidis analogue. A bioinformatic survey reveals the pervasiveness of related gene clusters in diverse bacterial phyla. [ABSTRACT FROM AUTHOR]

Morphinans are essential medicines derived entirely from poppy supply chains rendered increasingly volatile by climate change. Here, we report a seven‐step, asymmetric chemical synthesis of (−)‐codeine from simple materials that requires a total combined reaction time of fewer than 24 hours. The efficiency of our approach arises from a double‐Heck cyclization reaction that generates two rings and two contiguous stereogenic carbon centres in the one pot. A subsequent photo‐redox hydroamination protocol provides a novel, atom‐economical means for assembling the piperidine D‐ring of codeine. Simple modifications to the closing stages of our sequence offer effective access to pharmacologically valuable derivatives of N‐demethyl codeine. Our work highlights the capacity for contemporary, stand‐alone chemical synthesis regimes to diversify access to essential opiate medicines. [ABSTRACT FROM AUTHOR]

This section presents abstracts of research papers on chemistry, including "Synthesis and Thermal Responses of Polygonal Poly(ethylene glycol) Analogues," by S. Kawasaki et al., "A Three-Enzyme Pathway With an Optimised Geometric Arrangement to Facilitate Substrate Transfer," by M. Liu et al. and "Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A," by A. G. Waterson.

Vicinal oxygen‐containing tetra‐ and tri‐substituted stereocenters exist widely in chromanone lactone and tetrahydroxanthone natural products. Their enantioselective construction in a single step remains elusive and poses a formidable challenge for chemical synthesis. Here, we report the first copper(I)‐catalyzed asymmetric vinylogous additions of siloxyfurans to 2‐ester‐substituted chromones, which enable concise and enantioselective assembly of chromanone lactones. Both syn and anti adducts can be accessed with excellent diastereo‐ and enantioselectivity by judicious choice of the chiral ligands. Our approach allowed for the efficient synthesis of (−)‐blennolide B with precise stereochemical control, which provides a formal synthesis of secalonic acid A. [ABSTRACT FROM AUTHOR]

Chemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well‐defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well‐defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki–Miyaura coupling reaction, and synthesis of the drug sulfanilamide. [ABSTRACT FROM AUTHOR]

The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis‐electrophiles, carbenoids, bis‐nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris‐electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective. [ABSTRACT FROM AUTHOR]

Abundant and affordable methane is not only a high‐quality fossil fuel, it is also a raw material for the synthesis of value‐added chemicals. Solar‐energy‐driven conversion of methane offers a promising approach to directly transform methane to valuable energy sources under mild conditions, but remains a great challenge at present. In this Review, recent advances in the photocatalytic conversion of methane are systematically summarized. Insights into the construction of effective semiconductor‐based photocatalysts from the perspective of light‐absorption units and active centers are highlighted and discussed in detail. The performance of various photocatalysts in the conversion of methane is presented, with the photooxidation classified according to the oxidant systems. Lastly, challenges and future perspectives in the photocatalytic oxidation of methane are described. [ABSTRACT FROM AUTHOR]

Recombinant human erythropoietin (EPO) is the main therapeutic glycoprotein for the treatment of anemia in cancer and kidney patients. The in‐vivo activity of EPO is carbohydrate‐dependent with the number of sialic acid residues regulating its circulatory half‐life. EPO carries three N‐glycans and thus obtaining pure glycoforms provides a major challenge. We have developed a robust and reproducible chemoenzymatic approach to glycoforms of EPO with and without sialic acids. EPO was assembled by sequential native chemical ligation of two peptide and three glycopeptide segments. The glycopeptides were obtained by pseudoproline‐assisted Lansbury aspartylation. Enzymatic introduction of the sialic acids was readily accomplished at the level of the glycopeptide segments but even more efficiently on the refolded glycoprotein. Biological recognition of the synthetic EPOs was shown by formation of 1:1 complexes with recombinant EPO receptor. [ABSTRACT FROM AUTHOR]

The first chemical total synthesis of the highly oxygenated polyketide enterocin has been accomplished. The key step of the synthesis was a late‐stage biomimetic reaction cascade involving two intramolecular aldol reactions in which each step proceeded in 52 % yield (averaged) and which established four of the seven stereogenic centers. The pivotal precursor for the cascade reaction was assembled from three readily available building blocks. A chiral dithioacetal with two stereogenic centers originating from L‐arabinose represented the core fragment to both ends of which the other building blocks were attached by aldol reactions. The remaining stereogenic center was installed by Davis oxygenation immediately prior to the key step. [ABSTRACT FROM AUTHOR]

Ligation auxiliaries are used in chemical protein synthesis to extend the scope of native chemical ligation (NCL) beyond cysteine. However, auxiliary‐mediated ligations at sterically demanding junctions have been difficult. Often the thioester intermediate formed in the thiol exchange step of NCL accumulates because the subsequent S→N acyl transfer is extremely slow. Here we introduce the 2‐mercapto‐2‐(pyridin‐2‐yl)ethyl (MPyE) group as the first auxiliary designed to aid the ligation reaction by catalysis. Notably, the MPyE auxiliary provides useful rates even for junctions containing proline or a β‐branched amino acid. Quantum chemical calculations suggest that the pyridine nitrogen acts as an intramolecular base in a rate‐determining proton transfer step. The auxiliary is prepared in two steps and conveniently introduced by reductive alkylation. Auxiliary cleavage is induced upon treatment with TCEP/morpholine in presence of a MnII complex as radical starter. The synthesis of a de novo designed 99mer peptide and an 80 aa long MUC1 peptide demonstrates the usefulness of the MPyE auxiliary. [ABSTRACT FROM AUTHOR]

After more than 70 years since their discovery, Criegee intermediates (CIs) are back at the forefront of modern chemistry of short‐lived reactive intermediates. They play an important role in the mechanistic context of chemical synthesis, total synthesis, pharmaceuticals, and, most importantly, climate‐controlling aerosol formation as well as atmospheric chemistry. This Minireview summarizes key aspects of CIs (from the mechanism of formation, for example, by ozonolysis of alkenes and photolysis methods employing diiodo and diazo compounds, to their electronic structures and chemical reactivity), highlights the most recent findings and some landmark results of gas‐phase kinetics, and detection/measurements. The recent progress in synthetic and mechanistic studies in the chemistry of CIs provides a guide to illustrate the possibilities for further investigations in this exciting field. [ABSTRACT FROM AUTHOR]

“What I look for first in a publication is the abstract and schemes. The most important thing I learned from my parents is to work hard. …︁” This and more about Janine Cossy can be found on page 7634–7635. [ABSTRACT FROM AUTHOR]

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2‐alkylphenolic precursors into 6‐alkyl‐6‐hydroxycyclohexa‐2,4‐dienones. These so‐called ortho‐quinols cyclodimerize via a remarkably selective bispericyclic Diels–Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho‐quinols can be chemically reproduced in the laboratory with the same strict level of site‐specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho‐quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)‐maytenone. [ABSTRACT FROM AUTHOR]

The first total synthesis of marine anti‐cancer meroterpenoids dysideanone B and dysiherbol A have been accomplished in a divergent way. The synthetic route features: 1) a site and stereoselective α‐position alkylation of a Wieland–Miescher ketone derivative with a bulky benzyl bromide to join the terpene and aromatic moieties together and set the stage for subsequent cyclization reactions; 2) an intramolecular radical cyclization to construct the 6/6/6/6‐tetracycle of dysideanone B and an intramolecular Heck reaction to forge the 6/6/5/6‐fused core structure of dysiherbol A. A late‐stage introduction of the ethoxy group in dysideanone B reveals that this group might come from the solvent ethanol. The structure of dysiherbol A has been revised based on our chemical total synthesis. [ABSTRACT FROM AUTHOR]

(−)‐Isoscopariusin A was isolated from the aerial parts of Isodon scoparius. Chemical synthesis and spectroscopic analysis established its structure as an unsymmetrical meroditerpenoid bearing a sterically congested 6/6/4 tricyclic carbon skeleton with seven continuous stereocenters. A gram‐scale synthesis was achieved in 12 steps from commercially available (+)‐sclareolide. A cobalt catalyzed, hydrogen atom transfer‐based olefin isomerization was used to prepare a trisubstituted alkene, which underwent stereoselective [2+2] cycloaddition with a substituted keteniminium ion generated in situ from the corresponding amide. The cyclobutanone product was further elaborated into the fully substituted cyclobutane core through face‐selective homologation, and the two side chains were installed by using nickel‐catalyzed cross‐electrophile coupling and carbodiimide‐mediated esterification, respectively. (−)‐Isoscopariusin A displayed selective inhibition of T‐cell proliferation. [ABSTRACT FROM AUTHOR]

Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co‐)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6‐fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137‐fold, and half‐life up to 3.3‐fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50–100 °C. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs‐ and/or thermal‐resistant lipases and other α/β‐hydrolases. [ABSTRACT FROM AUTHOR]

The direct dehydrogenation of alkanes is among the most efficient ways to access valuable alkene products. Although several catalysts have been designed to promote this transformation, they have unfortunately found limited applications in fine chemical synthesis. Here, we report a conceptually novel strategy for the catalytic, intermolecular dehydrogenation of alkanes using a ruthenium catalyst. The combination of a redox‐active ligand and a sterically hindered aryl radical intermediate has unleashed this novel strategy. Importantly, mechanistic investigations have been performed to provide a conceptual framework for the further development of this new catalytic dehydrogenation system. [ABSTRACT FROM AUTHOR]

Development of modulators targeting specific interactions of ubiquitin‐based conjugates with their partners is a formidable task since it requires a suitable screening assay and homogeneous ubiquitin conjugates. We developed a novel high‐throughput strategy for screening ligands for Lys48‐linked tetraubiquitin chain in a relatively simple, fast, and affordable manner. This approach combined with a state‐of‐the‐art toolbox of chemical protein synthesis and a specially optimized Cys deprotection protocol enabled us to design highly potent, Lys48‐linked tetraubiquitin chain selective "next generation" dimeric peptide modulators. The dimeric peptide exhibited cancer cell permeability and induced cell death with higher efficiency compared to its monocyclic analogue. These features make our dimeric peptide a promising candidate for further studies using in vivo models. Our assay can be adopted for other various ubiquitin chains in their free or anchored forms as well as conjugates for Ub‐like modifiers. [ABSTRACT FROM AUTHOR]

α‐Amino acids represent a valuable class of natural products employed as building blocks in biological and chemical synthesis. Because of the limited number of natural amino acids available, and of their widespread application in proteomics, diagnosis, drug delivery and catalysis, there is an increasing demand for the development of procedures for the preparation of modified analogues. Herein, we show that the use of bioinspired manganese catalysts and H2O2 under mild conditions, provides access to modified α‐amino acids via γ‐C−H bond lactonization. The system can efficiently target 1°, 2° and 3° γ‐C−H bonds of α‐substituted and achiral α,α‐disubstituted α‐amino acids with outstanding site‐selectivity, good to excellent diastereoselectivity and (where applicable) enantioselectivity. This methodology may be considered alternative to well‐established organometallic procedures. [ABSTRACT FROM AUTHOR]

New iron dinitrogen complexes are crucial to a catalytic ammonia synthesis in homogeneous solution and establish new structural motifs related to the iron–molybdenum cofactor of the enzyme nitrogenase (see scheme; BArF= B[3,5‐(CF3)2C6H3]4). These findings are put into the context of 50 years of synthetic nitrogen fixation and latest developments regarding the crystal structure and the molecular mechanism of nitrogenase. [ABSTRACT FROM AUTHOR]

This review is the sequel to the 2000 report on the recent advances in the chemistry of odorants and it summarizes the developments in fragrance chemistry over the past 20 years. Following the olfactory spectrum set out in that report, trendsetting so‐called captive odorants (patent‐protected ingredients unavailable to the market) are presented according to the main odor families: "fruity", "marine", "green", "floral", "spicy", "woody", "amber", and "musky". The design of odorants, their chemical synthesis, and their use in modern perfumery are illustrated with prominent examples. Featured are new fruity odorants that provide signature in the top note, as well as precursor technology. In the green domain, focus is on leafy notes and green pear. New benzodioxepines and benzodioxoles have modernized the marine family and required a revision of the existing olfactophore models. The replacement of Lilial and Lyral kept the industry busy in the floral domain with a plethora of new "muguets". There was continued activity in the domain of rose odorants, especially in the area of rose ketones. Biotechnology became significant, for example, with Clearwood and Ambrofix, and the principal odorants of vetiver oil in the woody family have been found. Fourth and fifth families of musk odorants were also discovered and populated. Thus, new avenues for further explorations into fragrance chemistry have been opened. [ABSTRACT FROM AUTHOR]

Placobranchus ocellatus is well known to produce diverse and complex γ‐pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A–D, a series of racemic non‐γ‐pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene‐substituted dimethylfuran‐3(2H)‐one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X‐ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1–4 after chiral HPLC resolution. An array of new and diversity‐generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co‐occurring γ‐pyrones (5–10). Furthermore, the successful biomimetic semisynthesis of ocellatusone A (1) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction. [ABSTRACT FROM AUTHOR]

A divergent synthetic approach to six Ganoderma meroterpenoids, namely ganocins A–C, ganocochlearins C and D, and cochlearol T, has been developed for the first time. This synthetic route features a two‐phase strategy which includes early‐stage rapid construction of a common planar tricyclic intermediate followed by highly selective late‐stage transformations into various Ganoderma meroterpenoids. Key to the strategy are a bioinspired intramolecular hetero‐Diels–Alder reaction and Stahl‐type oxidative aromatization, allowing efficient formation of the common tricyclic phenol intermediate. A nucleophilic dearomatization of the phenol unit, combined with a regioselective 1,4‐reduction of the resulting dienone, enabled rapid access to ganocins B and C. Additionally, site‐selective Mukaiyama hydration, followed by an intramolecular oxa‐Michael addition/triflation cascade, served as a key strategic element in the chemical synthesis of ganocin A. [ABSTRACT FROM AUTHOR]

Pinching molecules via chemical strain suggests intuitive consequences, such as compression at the pinched site and clothespin‐like opening of other parts of the structure. If this opening affects two spin centers, it should result in reduced communication between them. We show that for naphthalene‐bridged biscobaltocenes with competing through‐space and through‐bond pathways, the consequences of pinching are far less intuitive: despite the known dominance of through‐space interactions, the bridge plays a much larger role for exchange spin coupling than previously assumed. Based on a combination of chemical synthesis, structural, magnetic, and redox characterization, and a newly developed theoretical pathway analysis, we can suggest a comprehensive explanation for this non‐intuitive behavior. These results are of interest for molecular spintronics, as naphthalene‐linked cobaltocenes can form wires on surfaces for potential spin‐only information transfer. [ABSTRACT FROM AUTHOR]

Mechanochemical solvent‐free reactions by milling, grinding or other types of mechanical action have emerged as a viable alternative to solution chemistry. Mechanochemistry offers not only a possibility to eliminate the need for bulk solvent use, and reduce the generation of waste, but it also unlocks the door to a different reaction environment in which synthetic strategies, reactions and molecules previously not accessible in solution, can be achieved. This Minireview examines the potential of mechanochemistry in chemical and materials synthesis, by providing a cross‐section of the recent developments in using ball milling for the formation of molecules and materials based on covalent and coordination bonds. [ABSTRACT FROM AUTHOR]

The first chemical synthesis of tetravinylallene (3,5‐divinylhepta‐1,3,4,6‐tetraene) is reported. The final, key step of the synthesis involves a palladium‐catalyzed, Negishi‐type cross‐coupling involving 1,5‐transposition of a penta‐2‐en‐4‐yn‐1‐ol methanesulfonate. The unprecedented fundamental hydrocarbon is sufficiently stable to be purified by flash chromatography. A similar synthetic pathway grants access to the first substituted tetravinylallenes, which provide insights into the influence of substitution upon stability and reactivity. Tetravinylallenes are shown to break new ground in swift structural complexity creation, with three novel sequences reported. [ABSTRACT FROM AUTHOR]

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO2. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished. [ABSTRACT FROM AUTHOR]

The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (−)‐himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu‐catalyzed nitrile hydration, a Heck reaction to construct the challenging 2‐azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot‐economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency. [ABSTRACT FROM AUTHOR]

Bicyclic and tricyclic peptides have emerged as promising candidates for the development of protein binders and new therapeutics. However, convenient and efficient strategies that can generate topologically controlled bicyclic and tricyclic peptide scaffolds from fully‐unprotected peptides are still much in demand, particularly for those amenable to the design of biosynthetic libraries. In this work, we report a reliable chemical and ribosomal synthesis of topologically controlled bicyclic and tricyclic peptide scaffolds. Our strategy involves the combination of selenoether cyclization followed by disulfide or thioether cyclization, yielding desirable bicyclic and tricyclic peptides. This work thus lays the foundation for developing peptide libraries with controlled topology of multicyclic scaffolds for in vitro display techniques. You'd better shape up: A reliable chemical and ribosomal synthesis of topologically controlled bicyclic and tricyclic peptide scaffolds was developed. Selenoether cyclization was combined with disulfide or thioether cyclization to yield desirable bicyclic and tricyclic peptides. This work lays the foundation for developing peptide libraries with multicyclic scaffolds of controlled topology for in vitro display techniques. [ABSTRACT FROM AUTHOR]

Rhodomyrtusials A–C, the first examples of triketone‐sesquiterpene meroterpenoids featuring a unique 6/5/5/9/4 fused pentacyclic ring system were isolated from Rhodomyrtus tomentosa, along with several biogenetically‐related dihydropyran isomers. Two bis‐furans and one dihydropyran isomer showed acetylcholinesterase (AChE) inhibitory activity. Structures of the isolates were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Bioinspired total syntheses of six isolates were achieved in six steps utilizing a reactive enetrione intermediate generated in situ from a readily available hydroxy‐endoperoxide precursor. Novel meroterpenoids were isolated from R. tomentosa and characterized, and led to a hypothesis for their biosynthesis. In situ generation of a reactive enetrione in the presence of the sesquiterpene caryophyllene led to efficient chemical syntheses of four of the five meroterpenoids, as well as two biogenetically related cycloadducts, in a biomimetic, six‐step sequence. Further evaluation of alkene reaction partners identified additional modes of reactivity for the enetrione. [ABSTRACT FROM AUTHOR]

An enantioselective Michael addition– four‐atom ring expansion cascade reaction involving cyclobutanones activated by a N‐aryl secondary amide group and ortho‐amino nitrostyrenes has been developed for the preparation of functionalized eight‐membered benzolactams using bifunctional aminocatalysts. Taking advantage of the secondary amide activating group, the eight‐membered cyclic products could be further rearranged into their six‐membered isomers having a glutarimide core under base catalysis conditions without erosion of optical purity, featuring an overall ring expansion– ring contraction strategy. A four‐atom ring expansion strategy is developed for the organocatalytic enantioselective synthesis of eight‐membered ring benzolactams. A base‐catalyzed ring contraction of these medium‐sized rings allowed the synthesis of glutarimides with retention of the optical purity. [ABSTRACT FROM AUTHOR]

The N‐iodosuccinimide‐mediated spirocyclization of tryptamine‐derived isocyanides to generate spiroindolenines is reported. The products contain both an imine and an imidoyl iodide as flexible handles for follow‐up chemistry. Nucleophilic addition typically occurs chemoselectively on the imine moiety with complete diastereoselectivity, providing opportunities for the construction of complex molecular frameworks. The synthetic potential of the method was showcased in the formal total synthesis of (±)‐aspidofractinine. I make(s) spirocycles: Iodospirocyclization of tryptamine‐derived isocyanides affords highly substituted spiroindolenine imidoyl iodides. The imine functionality can undergo a variety of diastereoselective addition reactions, including in situ reduction, while the imidoyl iodide functionality is remarkable stable. The utility of the method was demonstrated by the formal total synthesis of (±)‐aspidofractinine. [ABSTRACT FROM AUTHOR]

Abstract: The enantioselective synthesis of highly functionalized chiral cyclopent‐2‐enones by the reaction of alkynyl malonate esters with arylboronic acids is described. These desymmetrizing arylative cyclizations are catalyzed by a chiral phosphinooxazoline/nickel complex, and cyclization is enabled by the reversible E/Z isomerization of alkenylnickel species. The general methodology is also applicable to the synthesis of 1,6‐dihydropyridin‐3(2H)‐ones. [ABSTRACT FROM AUTHOR]

Abstract: The efficient, 12–14 step (LLS) total synthesis of (−)‐halenaquinone has been achieved. Key steps in the synthetic sequence include: (a) proline sulfonamide‐catalyzed, Yamada–Otani reaction to establish the C6 all‐carbon quaternary stereocenter, (b) multiple, novel palladium‐mediated oxidative cyclizations to introduce the furan moiety, and (c) oxidative Bergman cyclization to form the final quinone ring. [ABSTRACT FROM AUTHOR]

Abstract: Regiodivergent syntheses of indolo[3,2‐c]coumarins and benzofuro[3,2‐c]quinolinones through a controllable palladium(II)‐catalyzed carbonylative cyclization are established. The chemo‐ and regioselectivity are exclusively tuned by the ligand on the palladium catalyst. The rigid framework of the electron‐deficient ligand promotes the O‐attack/N‐carbonylation cyclization leading to benzofuro[3,2‐c]quinolinones, while a sterically bulky and electron‐rich ligand facilitates N‐attack/O‐carbonylation cyclization to generate indolo[3,2‐c]coumarins. Furthermore, various other nucleophiles are applicable for delivering a variety of indoloquinolinones, pyranoquinolones, and chromeno[3,4‐c]quinolinones in one step, and serves as a method for creating compound libraries for drug discovery. [ABSTRACT FROM AUTHOR]

Abstract: Due to a more distinct σ‐hole, BrCl is able to form stronger halogen bonds than those in polyhalogen anions based on Cl2 and Br2. This stabilization allows the crystallographic characterization of a variety of new polyinterhalides, in which chloride functions as the central ion as shown by the molecular structures of [AsPh4][Cl(BrCl)3] and [CCl(NMe2)2][Cl(BrCl)5]. Furthermore, the solid‐state structure of an octahedrally coordinated nonclassical interhalide is reported for the first time. The tridecainterhalide monoanion [Cl(BrCl)6]− consists of a central chloride ion, which is coordinated by six BrCl molecules in a slightly distorted octahedral structure. All new compounds were characterized by single‐crystal X‐ray diffraction (XRD), NMR and Raman spectroscopy, as well as quantum‐chemical calculations. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of a zig‐zag oxygen‐doped molecular rhombic ribbon has been achieved. This includes oxidative C−C and C−O bond formations that allowed the stepwise elongation and planarization of an oxa‐congener of 2,7‐periacenoacene. X‐ray diffraction analysis corroborated the flat structure and the zig‐zag topology of the O‐doped edges. Photophysical and electrochemical investigations showed that the extension of the peri‐xanthenoxanthene (PXX) into the molecular ribbon induces a noticeable shrinking of the molecular band gap devised by a rising of the HOMO energy level, a desirable property for p‐type organic semiconductors. [ABSTRACT FROM AUTHOR]

Abstract: Efficient total syntheses of the naturally occurring, potent antibiotic compounds (−)‐crinipellin A and (−)‐crinipellin B are described. The key advanced intermediate, a fully functionalized tetraquinane core, was constructed by a novel thiourea/palladium‐catalyzed Pauson–Khand reaction. This intermediate can serve as a common intermediate for the collective total synthesis of other members of the crinipellin family. [ABSTRACT FROM AUTHOR]

Abstract: Despite significant recent progress in copper‐catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N‐arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N‐arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1‐disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method. [ABSTRACT FROM AUTHOR]

Abstract: 1‐Boraphenalenes have been synthesized by reaction of BBr3 with 1‐(aryl‐ethynyl)naphthalenes, 1‐ethynylnaphthalene, and 1‐(pent‐1‐yn‐1‐yl)naphthalene and they can be selectively functionalized at boron or carbon to form bench‐stable products. All of these 1‐boraphenalenes have LUMOs localized on the planar C12B core that are closely comparable in character to isoelectronic phenalenyl cations. In contrast to the comparable LUMOs, the aromatic stabilization of the C5B ring in 1‐boraphenalenes is dramatically lower than the C6 rings in phenalenyl cations. This is due to the occupied orbitals of π symmetry being less delocalised in the 1‐boraphenalenes. [ABSTRACT FROM AUTHOR]

Polymeric VesiclesB. P. Bastakoti and J. Perez‐Mercader show in their Communication on page 12086 ff., how the oscillatory Belousov–Zhabotinsky reaction can be used to synthesize self‐assembling giant polymeric vesicles in one pot. [ABSTRACT FROM AUTHOR]