LongLarf

Hype in science is commonplace, compounded by the hypocrisy of those who engage in or tolerate it while disapproving of the consequences. These are first steps along a slippery slope of hype, hypocrisy, data falsification, and dissemination of fake science, encouraged by systemic drivers in the contemporary structure of the science establishment. Collective, concerted intervention is required to discourage entry to this dangerous pathway; chemists must play and active role.

Abstract

In chemistry and other sciences, hype has become commonplace, compounded by the hypocrisy of those who tolerate or encourage it while disapproving of the consequences. This reduces the credibility and trust upon which all science depends for support. Hype and hypocrisy are but first steps down a slippery slope towards falsification of results and dissemination of fake science. Systemic drivers in the contemporary structure of the science establishment encourage exaggeration and may lure the individual into further steps along the hype‐hypocrisy‐falsification‐fakery continuum. Collective, concerted intervention is required to effectively discourage entry to this dangerous pathway and to restore and protect the probity and reputation of the science system. Chemists must play and active role in this effort.

Photochemistry with potential : The synergy of photochemistry and electrochemistry in organic synthesis is beneficial not only for synthetic sustainability and chemical selectivity, but also in the accumulation of energy for accessing super‐oxidizing or ‐reducing single electron transfer agents. Examples of synthetic organic photoelectrochemistry are dissected into three categories: electrochemically mediated photoredox catalysis, decoupled photoelectrochemistry, and interfacial photoelectrochemistry.

Abstract

Photoredox catalysis (PRC) and synthetic organic electrochemistry (SOE) are often considered competing technologies in organic synthesis. Their fusion has been largely overlooked. We review state‐of‐the‐art synthetic organic photoelectrochemistry, grouping examples into three categories: 1) electrochemically mediated photoredox catalysis (e‐PRC), 2) decoupled photoelectrochemistry (dPEC), and 3) interfacial photoelectrochemistry (iPEC). Such synergies prove beneficial not only for synthetic “greenness” and chemical selectivity, but also in the accumulation of energy for accessing super‐oxidizing or ‐reducing single electron transfer (SET) agents. Opportunities and challenges in this emerging and exciting field are discussed.

Photochemistry: A mild, metal‐free and easy‐to‐execute protocol for the direct photochemical hydroacylation of unactivated olefins was developed using phenylglyoxylic acid as the photoinitiator.

Abstract

Direct alkylation of C(sp²)−H bonds to convert an aldehyde into a ketone is a notorious transformation, due to the laborious challenge of the formation of ketyl or acyl radicals. Herein, we report a green, cheap, metal‐free and efficient method for the hydroacylation of olefins in water. This photochemical protocol utilizes phenylglyoxylic acid, a commercially available small organic molecule, as the photoinitiator, water as the solvent and household fluorescent lamps as the irradiation source, leading to a broad substrate scope of products in moderate to good yields. A wide range of aromatic and aliphatic aldehydes, terminal and non‐terminal alkenes and pharmaceutically relevant molecules can be employed, without the need of directing groups and additives or metal catalysts.

Publication date: Available online 5 December 2019

Source: Chem

Author(s): Alastair McMillan, Daniele Leonori

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.

The life‐science bias in the selection of the Nobel Prize in Chemistry is quantified in this Essay. Bibliographic citation analyses explore the intellectual relationship between “chemistry” and “biochemistry.” A correlation is found between the disciplines of the members of the Nobel Committee for Chemistry and the disciplines honored by the Nobel Prize in Chemistry.

Abstract

Over the past several decades, the Nobel Prize program has slowly but steadily been modified in both transparent and opaque ways. A transparent change has been the creation of the Nobel Prize in Economic Sciences, officially known as the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel. An opaque change has been the mutation of the Nobel Prize in Chemistry into what is effectively the “Nobel Prize in Chemistry or Life Sciences.” This paper presents a detailed study of this opaque change, including evidence that the disciplines of chemistry and biochemistry cover, today, intellectually quite distinct and generally scientifically‐unrelated intellectual territory. This paper supports the evolution of the Nobel Prizes, and encourages the Nobel Prize program to move from opaque to transparent change processes for the next generations of achievement in the sciences.

Adhesives are going green! 1,4‐Pentanediol obtained through hydrogenation of γ‐valerolactone can be efficiently converted to 100 % biobased polyester polyols. These oligomers provide added value beyond renewability in adhesive and polyurethane applications.

Abstract

Novel polyester polyols were prepared in high yields from biobased 1,4‐pentanediol catalyzed by non‐toxic phosphoric acid without using a solvent. These oligomers are terminated with hydroxyl groups and have low residual acid content, making them suitable for use in adhesives by polyurethane formation. The thermal behavior of the polyols was studied by differential scanning calorimetry, and tensile testing was performed on the derived polyurethanes. The results were compared with those of polyurethanes obtained with fossil‐based 1,4‐butanediol polyester polyols. Surprisingly, it was found that a crystalline polyester was obtained when aliphatic long‐chain diacids (>C₁₂) were used as the diacid building block. The low melting point of the C₁₂ diacid‐based material allows the development of biobased shape‐memory polymers with very low switching temperatures (<0 °C), an effect that has not yet been reported for a material based on a simple binary polyester. This might find application as thermosensitive adhesives in the packaging of temperature‐sensitive goods such as pharmaceuticals. Furthermore, these results indicate that, although 1,4‐pentanediol cannot be regarded as a direct substitute for 1,4‐butanediol, its novel structure expands the toolbox of the adhesives, coatings, or sealants formulators.

Artificial lipidation: Within cells, lipidated proteins are important regulators for signal pathways. Therefore, the development of chemical and enzymatic synthetic strategies to prepare a range of lipid–protein conjugates, which can be used to analyze lipidated proteins, is of great importance. Previous developments are summarized in this Minireview.

Abstract

Biosynthesis of natural lipidated proteins is linked to important signal pathways, and therefore analyzing protein lipidation is crucial for understanding cellular functions. Artificial lipidation of proteins has attracted attention in recent decades as it allows modulation of the amphiphilic nature of the protein of interest, and is used in the design of drug‐delivery systems containing antibodies anchored on a lipid bilayer carrier. However, the intrinsic hydrophobicity of lipids makes the synthesis of lipid–protein conjugates challenging with respect to the yield and selectivity of the lipidation. In this Minireview, the development of chemical and enzymatic synthetic strategies for the preparation of a range of lipid–protein conjugates that do not compromise the functions of the proteins are discussed as well as applications of the conjugates.

Getting a hold of unfunctionalized alkenes: Optimization of the ligand in the iridium catalyst enables the asymmetric hydrogenation (AH) of unfunctionalized tetrasubstituted acyclic olefins, which installs two vicinal stereocenters with excellent stereoselectivies.

Abstract

Asymmetric hydrogenation has evolved as one of the most powerful tools to construct stereocenters. However, the asymmetric hydrogenation of unfunctionalized tetrasubstituted acyclic olefins remains the pinnacle of asymmetric synthesis and an unsolved challenge. We report herein the discovery of an iridium catalyst for the first, generally applicable, highly enantio‐ and diastereoselective hydrogenation of such olefins and the mechanistic insights of the reaction. The power of this chemistry is demonstrated by the successful hydrogenation of a wide variety of electronically and sterically diverse olefins in excellent yield and high enantio‐ and diastereoselectivity.

Two birds, one stone: Oxime esters of aliphatic carboxylic acids were used as a bifunctional source of both C‐ and N‐radicals. The persistency of the N‐radicals enables highly selective intermolecular radical carboaminations of alkenes.

Abstract

An intermolecular, two‐component vicinal carboimination of alkenes has been accomplished by energy transfer catalysis. Oxime esters of alkyl carboxylic acids were used as bifunctional reagents to generate both alkyl and iminyl radicals. Subsequently, addition of the alkyl radical to an alkene generates a transient radical for selective radical–radical cross‐coupling with the persistent iminyl radical. Furthermore, this process provides direct access to aliphatic primary amines and α‐amino acids by simple hydrolysis.

Tune the pincer: A solid‐phase synthesis approach is described to prepare a diverse library of nonsymmetrical PNP pincer ligands. The heterogenized library is applied in ruthenium‐catalyzed hydrogenation of esters and lactones under mild conditions. Catalyst recovery and recyclability are facilitated by covalent attachment to solid supports.

Abstract

In contrast to their symmetrical analogues, nonsymmetrical PNP‐type ligand motifs have been less investigated despite the modular pincer structure. However, the introduction of mixed phosphorus donor moieties provides access to a larger variety of PNP ligands. Herein, a facile solid‐phase synthesis approach towards a diverse PNP‐pincer ligand library of 14 members is reported. Contrary to often challenging workup procedures in solution‐phase, only simple workup steps are required. The corresponding supported ruthenium‐PNP catalysts are screened in ester hydrogenation. Usually, industrially applied heterogeneous catalysts require harsh conditions in this reaction (250–350 °C at 100–200 bar) often leading to reduced selectivities. Heterogenized reusable Ru‐PNP catalysts are capable of reducing esters and lactones selectively under mild conditions.

In this work, the carbon‐carbon double bond of unsaturated carbonyl compounds is readily reduced by a phosphetane oxide catalyst in the presence of a simple organosilane as terminal reductant and water as the hydrogen source. A catalyst screening was conducted and quantitative hydrogenation was observed when 1.0 mol% of a methyl substituted phosphetane oxides was employed as the catalyst. The procedure is highly selective towards activated double bonds tolerating a variety of functional groups which are usually prone to reduction. In total, 25 alkenes and two alkynes were hydrogenated to the corresponding alkanes in excellent yields up to 99%. Notably, less active poly(methylhydrosiloxane) could also be utilized as the terminal reductant. Mechanistic investigation revealed the phosphane as the catalyst resting state and a protonation/deprotonation sequence as the crucial step in the catalytic cycle.

Synlett
DOI: 10.1055/s-0039-1691523

A convergent approach for the synthesis of (±)-myricanol, a strained diarylheptanoid isolated from Myricacae, was undertaken using a Suzuki–Miyaura coupling followed by a ring-closing metathesis (RCM). Herein, we report the unintentional formation of a 26-membered macrocycle as RCM product resulting from a head-to-tail dimerization of the seco-precursor, even in relay ring-closing metathesis (RRCM) conditions.
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© Georg Thieme Verlag Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

News on NP₃ ring systems: The reactivity of chlorinated NP₃ ring systems was investigated by experimental and computational methods. Comparisons with known N₂P₂ and P₄ congeners are drawn to obtain a systematic understanding of the reactivity of these types of compounds.

Abstract

The reactivity of the four‐membered NP₃ ring system [RN(μ‐PCl)₂PR] (R=Mes*=2,4,6‐tri‐tert‐butylphenyl) towards Lewis acids, Lewis bases, and reducing agents was investigated. Comparisons with the literature‐known, analogous cyclic compounds [ClP(μ‐NR)]₂ (R=Ter=2,6‐dimesitylphenyl) and [ClP(μ‐PR)]₂ (R=Mes*) are drawn, to obtain a better systematic understanding of the reactivity of cyclic NP species. Apart from experimental results, DFT computations are discussed to further the insight into bonding and electronic structure of these compounds.

All metal‐free: A photoinduced tandem amine dehydrogenation/Povarov cyclization/aromatization reaction leads to isocryptolepine analogues with high yields, by using molecular iodine under visible light, or by combining an organic photoredox catalyst with a halide anion (see scheme; PC=photocatalyst).

Abstract

A metal‐free, photoinduced aerobic tandem amine dehydrogenation/Povarov cyclization/aromatization reaction between N‐aryl glycine esters and indoles leads to tetracyclic 11H‐indolo[3,2‐c]quinolines under mild conditions and with high yields. The reaction can be performed by using molecular iodine along with visible light, or by combining an organic photoredox catalyst with a halide anion. Mechanistic studies reveal that product formation occurs through a combination of radical‐mediated oxidation steps with an iminium ion or N‐haloiminium ion [4+2]‐cycloaddition, and the N‐heterocyclic products constitute new analogues of the antiplasmodial natural alkaloid isocryptolepine.

Tagged: Reported is a bioinspired nitroalkylation strategy for chemoselective modification of proteins that mimics a key post‐translational modification (PTM). A variety of different tags are installed on proteins rapidly and with high conversions (99 %) under mild reaction conditions. The nitro‐peptide conjugates provide a handle for site‐selective fluorination of peptides. This strategy is applied for the stapling of peptides.

Abstract

Nitroalkanes react specifically with aldehydes, providing rapid, stable, and chemoselective protein bioconjugation. These nitroalkylated proteins mimic key post‐translational modifications (PTMs) of proteins and can be used to understand the role of these PTMs in cellular processes. Demonstrated here is the substrate scope of this bioconjugation by attaching a variety of tags, such as NMR tags, fluorescent tags, affinity tags, and alkyne tags, to proteins. The structure and enzymatic activity of modified proteins remain conserved after labeling. Notably, the nitroalkane group leads to easy characterization of proteins by mass spectrometry because of its distinct fingerprint pattern. Importantly, the nitro‐alkylated peptides provide a new handle for site‐selective fluorination of peptides, thus installing a specific probe to study peptide–protein interactions by ¹⁹F NMR spectroscopy. Furthermore, nitroalkane reagents can be used for the late‐stage diversification of peptides and for the synthesis of peptide staples.

Increasing molecular complexity: Radical precursors, dienes, and electrophilic coupling partners are transformed in a photoredox‐ and nickel‐enabled radical addition/cyclization/cross‐coupling process. The reaction takes place under mild conditions and furnishes a diverse array of saturated carbo‐ and heterocyclic scaffolds, thus providing a quick gain in C−C bond saturation.

Abstract

Chemical transformations based on cascade reactions have the potential to simplify the preparation of diverse and architecturally complex molecules dramatically. Herein, we disclose an unprecedented and efficient method for the cross‐coupling of radical precursors, dienes, and electrophilic coupling partners via a photoredox‐ and nickel‐enabled cascade cross‐coupling process. The cascade reaction furnishes a diverse array of saturated carbo‐ and heterocyclic scaffolds, thus providing access to a quick gain in C−C bond saturation.

Direct conversion: 43 % alanine was achieved from crude glycerol over a Ru₁Ni₇/MgO catalyst. Ni‐doped Ru remarkably promoted lactic acid amination, a key step in the reaction. The catalytic route creates new opportunities for glycerol utilization and enriches the substrate scope of renewable feedstock to access value‐added amino acids.

Abstract

Chemical synthesis of amino acids directly from biomass feedstock is rare. Reported here is a one‐step protocol to convert crude glycerol, from the biodiesel industry, into 43 % alanine over a Ru₁Ni₇/MgO catalyst. The multifunctional catalytic system promotes glycerol conversion into lactic acid, and then into alanine. X‐ray absorption spectroscopy and scanning transmission electron microscopy revealed the existence of bimetallic RuNi species, whereas density‐functional theory calculations suggested Ni‐doped Ru substantially decreased the E _a of C−H bond dissociation of lactate alkoxide to form pyruvate, which is the rate‐determining step. The catalytic route established in this work creates new opportunities for glycerol utilization and enriches the substrate scope of renewable feedstock to access value‐added amino acids.

From tetra‐ to trimerization and back: PNP ligands are responsible for the selective tetra‐ and as modified ligands for the trimerization of ethylene. The very special PNPN−H ligands are highly selective for the formation of 1‐hexene, compared to other similar PNP, PNPN and NPNPN ligands. In this minireview all published information about these PNPN−H ligands are summarized and compared to some other similar ligands. Mechanistic information are collected to explain the switch from tetra‐ to trimerization and back by substituents.

Abstract

Many examples exist for the chromium catalyzed selective ethylene oligomerization in which the influence of ligands is essential for the formation of products. Regarding the tri‐ and tetramerization to 1‐hexene or 1‐octene mostly PNP ligands are responsible for the tetra‐ and some of such modified ligands for the trimerization. A very special case in these reactions are PNPN−H ligands, showing in most cases highly selective trimerization of ethylene to 1‐hexene. In this review all existing published information about these PNPN−H ligands is accumulated and compared to some other related PNP, PNPN and NPNPN ligands in the chromium catalyzed selective ethylene oligomerization with respect to the switch from tetra‐ to trimerization and back by different substituent pattern of PNP ligand. Mechanistic information and arguments are collected to explain the switch from tetra‐ to trimerization and back by substitution of functional groups in classical PNP to PNPN−H ligands as a result of mono‐ and dinuclear catalytic species.

Poly put the CO₂ on! The present review aims to report the updates and challenges in CO₂‐based (poly)carbonate synthesis. It focuses on progress realized in the preparation of cyclic carbonate synthons and aliphatic polycarbonate preparation from CO₂/epoxide copolymerization. Furthermore, all metal‐based processes are comprehensively discussed and the rapidly developing field of organocatalytic approaches is included.

Abstract

The utilization of carbon dioxide as a comonomer to produce polycarbonates has attracted a great deal of attention from both industrial and academic communities because it promises to replace petroleum‐derived plastics and supports a sustainable environment. Significant progress in the copolymerization of cyclic ethers (e.g., epoxide, oxetane) and carbon dioxide has been made in recent decades, owing to the rapid development of catalysts. In this Review, the focus is to summarize and discuss recent advances in the development of homogeneous catalysts, including metal‐ and organo‐based complexes, as well as the preparation of carbon dioxide‐based block copolymer and functional polycarbonates.

A valuable and operationally simple experimental approach to prepare perfluoroalkylated β‐fluoroenones and related compounds is described, providing a general approach to a variety of synthetically useful perfluoroalkylated β‐fluoroenones in moderate to high yields and excellent stereoselectivities.

The synthesis of fluorinated compounds is of increasing importance for the preparation of new pharmaceuticals and agrochemicals. For this purpose, the development of general and selective synthetic methods, which allow the preparation of versatile and scalable building blocks, is required. In this respect, here we report a facile and practical method for the stereoselective synthesis of fluoroalkylated β‐fluoroenones from ubiquitous ketones. The presented transition‐metal‐free procedure makes use of an amine promoter and easily available starting materials. It features broad substrate diversity with excellent stereoselectivity. In general, this novel strategy provides a facile synthesis of structurally diverse (per)fluoroalkylated β‐fluoroenones, which can be further transformed to various potentially bioactive molecules in a straightforward manner.