LongLarf

Nature Catalysis, Published online: 18 March 2020; doi:10.1038/s41929-020-0435-z

The introduction of single abiological catalytic groups enables enzymes to catalyse new-to-nature chemical transformations. Now, this concept is extended to two abiological groups in a single protein scaffold to allow synergistic catalysis in a stereoselective Michael addition reaction.

Publication date: 24 April 2020

Source: Tetrahedron, Volume 76, Issue 17

Author(s): Jens Holz, Gudrun Wenzel, Anke Spannenberg, Mark Gandelman, Armin Börner

The field of chemical modification of proteins has been dominated by random modification of lysines or more site-specific labeling of cysteines, each with attendant challenges. Recently, we have developed oxaziridine chemistry for highly selective modification of methionine called redox-activated chemical tagging (ReACT) but have not broadly tested the molecular parameters...

An operationally simple, metal‐free, and site‐selective aromatic C−H alkylation under photoredox catalysis that utilizes equimolar quantities of coupling partners is reported. Experimental and computational studies suggest a unique mechanism, involving cyclopropanation of arene cation radicals and subsequent oxidative ring opening, that allows this transformation to be compatible with a range of aromatic substrates.

Abstract

Expanding the toolbox of C−H functionalization reactions applicable to the late‐stage modification of complex molecules is of interest in medicinal chemistry, wherein the preparation of structural variants of known pharmacophores is a key strategy for drug development. One manifold for the functionalization of aromatic molecules utilizes diazo compounds and a transition‐metal catalyst to generate a metallocarbene species, which is capable of direct insertion into an aromatic C−H bond. However, these high‐energy intermediates can often require directing groups or a large excess of substrate to achieve efficient and selective reactivity. Herein, we report that arene cation radicals generated by organic photoredox catalysis engage in formal C−H functionalization reactions with diazoacetate derivatives, furnishing sp²–sp³ coupled products with moderate‐to‐good regioselectivity. In contrast to previous methods utilizing metallocarbene intermediates, this transformation does not proceed via a carbene intermediate, nor does it require the presence of a transition‐metal catalyst.

Abstract

An imidazolium catalyst supported on thermomorphic polyethylene (PE) was prepared from 1‐methylimidazole and polyethylene iodide (PE−I). The catalyst was characterized by ¹H and ¹³C NMR, SEC and MALDI‐ToF mass spectrometry. Its catalytic activity was evaluated in the ring‐opening of epoxides with carbon dioxide to give cyclic carbonates under solvent‐free conditions. The catalyst proved to be active at low catalyst loading (down to 0.1 mol%) and allows the reaction to occur at low CO₂ pressure (1–5 bar) and moderate temperature (100 °C). A range of terminal and internal epoxides was converted to the corresponding cyclic carbonates with high yields and selectivities. The recyclability of the catalyst was studied and no significant loss of activity was observed after 5 runs.

Nature Catalysis, Published online: 16 March 2020; doi:10.1038/s41929-020-0441-1

Nonlinear effects in catalysis have been shown to allow for asymmetric amplification. Here the authors report a particularly intriguing case whereby a catalytic asymmetric reaction gives a significantly higher product e.e. when run with a non-enantiopure catalyst compared to the enantiopure version.

Nature, Published online: 16 March 2020; doi:10.1038/s41586-020-2137-8

Late-stage oxidative C(sp³)–H methylation

Synlett
DOI: 10.1055/s-0040-1708000

We report the preparation of phosphiranium salts by quaternarization of phosphiranes, a class of sensitive, highly strained, and poorly nucleophilic cyclic phosphines. High-yielding introduction of a varied set of alkyl groups including methylene ester arms was accomplished under mild conditions. A Cu-catalyzed electrophilic arylation of phosphiranes using diaryl iodonium reagents was also achieved to yield unprecedented P,P-diaryl phosphiranium salts with good efficiency.
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© Georg Thieme Verlag Stuttgart · New York

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

An unprecedented perspective on photocatalytic processes is offered, with a focus on the way photocatalytic cycles are turned over. The given examples are classified according to the species responsible for photocatalyst restoration, namely: a reaction intermediate, a co‐catalyst, a reaction partner, an electrode, etc. It is demonstrated why the photocatalyst recovery is pivotal to devise an efficient synthetic protocol, showcasing how a fine tuning of this step can completely divert the reaction outcome.

Photocatalytic strategies have recently revolutionized the field of organic synthesis. However, while the progress has been impressive in terms of reported methodologies, less attention has been devoted to mechanistic aspects. In this regard, key to the development of efficient strategies is the recovery of the exhausted photocatalyst formed upon quenching of the excited state. This review summarizes the different ways available to turn over the photocatalyst and classifies them according to the species responsible for this step, being a reaction intermediate, a co‐catalyst, a reaction partner or an electrode. Finally, an analysis of the common aspects of the described alternatives is offered, also showcasing how the tuning of the photocatalyst turn‐over step can completely divert the reaction outcome.

Burkhard König and Géraldine Masson reflect on the current challenges and opportunities in the field of chemical photocatalysis. The illustration “Interaction” (digital painting, 2019, 59 × 42 cm) was created by Felix Bock, who currently studies Arts at the University of Regensburg. Reproduced with permission of the artist.

Abstract

The Still–Gennari olefination is a widely applied modification of the Horner–Wadsworth–Emmons reaction, allowing access to Z‐olefins by carbonyl group transformation. Its synthetic utility is undoubtedly of great significance for organic chemistry, as can be illustrated by the number of citations of the original report by W. C. Still and C. Gennari which up to date has been cited over 1000 times. In 2008 Nobel prize winner Ei‐ichi Negishi indicated the Still–Gennari olefination as one of the crucial methods for tolefin synthesis, complementary to palladium‐catalyzed alkenylations. Surprisingly, so far there is no review concerning this popular and valuable transformation. Therefore, we aim to comprehensively systematize achievements in this field and to present the scope of applications of the Still–Gennari olefination along with recent examples in the total synthesis of biologically active compounds. Our review is intended to be of interest for the general chemical community as well as to be a helpful source of information for synthetic organic chemists.

Chiral cations have been used extensively as organocatalysts, but their application to rendering transition metal–catalyzed processes enantioselective remains rare. This is despite the success of the analogous charge-inverted strategy in which cationic metal complexes are paired with chiral anions. We report here a strategy to render a common bipyridine ligand anionic and pair its iridium complexes with a chiral cation derived from quinine. We have applied these ion-paired complexes to long-range asymmetric induction in the desymmetrization of the geminal diaryl motif, located on a carbon or phosphorus center, by enantioselective C–H borylation. In principle, numerous common classes of ligand could likewise be amenable to this approach.

Nature, Published online: 11 March 2020; doi:10.1038/s41586-020-2079-1

In mouse models of cancer, a biorthogonal chemical system based on desilylation catalysed by phenylalanine trifluoroborate enables the controlled release of gasdermin to induce pyroptosis selectively in tumour cells

Getting poly(aminoborane)s : The well‐known Fe amido complex [(PNP)Fe(H)(CO)] (PNP=N(CH₂CH₂Pi Pr₂)₂) is a potent catalyst for the selective formation of poly(aminoborane)s from methylamine borane and a SiMe₃‐substituted analogue. Mechanistic studies support a chain‐growth mechanism with polymer formation by nucleophilic attack at the terminus of a growing B−N chain.

Abstract

Dehydropolymerisation of methylamine borane (H₃B⋅NMeH₂) using the well‐known iron amido complex [(PNP)Fe(H)(CO)] (PNP=N(CH₂CH₂Pi Pr₂)₂) (1 ) gives poly(aminoborane)s by a chain‐growth mechanism. In toluene, rapid dehydrogenation of H₃B⋅NMeH₂ following first‐order behaviour as a limiting case of a more general underlying Michaelis–Menten kinetics is observed, forming aminoborane H₂B=NMeH, which selectively couples to give high‐molecular‐weight poly(aminoborane)s (H₂BNMeH) _n and only traces of borazine (HBNMe)₃ by depolymerisation after full conversion. Based on a series of comparative experiments using structurally related Fe catalysts and dimethylamine borane (H₃B⋅NMe₂H) polymer formation is proposed to occur by nucleophilic chain growth as reported earlier computationally and experimentally. A silyl functionalised primary borane H₃B⋅N(CH₂SiMe₃)H₂ was studied in homo‐ and co‐dehydropolymerisation reactions to give the first examples for Si containing poly(aminoborane)s.

X‐ray meets magnet and chemometrics : Benefits of a new 4‐in‐one spectroscopy installed at a synchrotron and supported by chemometric evaluation of results are demonstrated using aerobic Cu/TEMPO catalyzed alcohol oxidation as model reaction.

Abstract

Operando EPR, XANES/EXAFS, UV‐Vis and ATR‐IR spectroscopic methods have been coupled for the first time in the same experimental setup for investigation of unclear mechanistic aspects of selective aerobic oxidation of benzyl alcohol by a Cu/TEMPO catalytic system (TEMPO=2,2,6,6‐tetramethylpiperidinyloxyl). By multivariate curve resolution with alternating least‐squares fitting (MCR‐ALS) of simultaneously recorded XAS and UV‐Vis data sets, it was found that an initially formed (bpy)(NMI)Cu^I‐ complex (bpy=2,2′‐bipyridine, NMI=N ‐methylimidazole ) is converted to two different Cu^II species, a mononuclear (bpy)(NMI)(CH₃CN)Cu^II‐OOH species detectable by EPR and ESI‐MS, and an EPR‐silent dinuclear (CH₃CN)(bpy)(NMI)Cu^II(μ‐OH)₂ ⋅ Cu^II (bpy)(NMI) complex. The latter is cleaved in the further course of reaction into (bpy)(NMI)(HOO)Cu^II‐TEMPO monomers that are also EPR‐silent due to dipolar interaction with bound TEMPO. Both Cu monomers and the Cu dimer are catalytically active in the initial phase of the reaction, yet the dimer is definitely not a major active species nor a resting state since it is irreversibly cleaved in the course of the reaction while catalytic activity is maintained. Gradual formation of non‐reducible Cu^II leads to slight deactivation at extended reaction times.

Transformer‐tive chemistry: High‐throughput experimentation (HTE) is changing the way we work in many fields of chemistry. A personal perspective, describing the distinctions between traditional synthetic organic chemistry and HTE from a careers and impact viewpoint.

Abstract

High‐throughput experimentation (HTE) is a growing, enabling technology that allows the execution of large, parallel sets of experiments. Often, automation is required to dose compounds on milligram to sub‐milligram scale, to run many parallel reactions, and to analyse large datasets. Unique approaches to screen design, implementation, and analysis are required, distinct from traditional synthetic organic chemistry. The discipline also presents a profitable opportunity for individual scientists to learn about and explore fields adjacent to chemistry, including data science, robotics and equipment engineering, and computer programming. This perspective presents the author's viewpoints on the field of HTE, its implementation within a chemistry career, and the automated future of organic chemistry technology.

Many disease pathologies can be understood through the elucidation of localized biomolecular networks, or microenvironments. To this end, enzymatic proximity labeling platforms are broadly applied for mapping the wider spatial relationships in subcellular architectures. However, technologies that can map microenvironments with higher precision have long been sought. Here, we describe a microenvironment-mapping platform that exploits photocatalytic carbene generation to selectively identify protein-protein interactions on cell membranes, an approach we term MicroMap (μMap). By using a photocatalyst-antibody conjugate to spatially localize carbene generation, we demonstrate selective labeling of antibody binding targets and their microenvironment protein neighbors. This technique identified the constituent proteins of the programmed-death ligand 1 (PD-L1) microenvironment in live lymphocytes and selectively labeled within an immunosynaptic junction.

Take the direct route!: A manganese‐catalyzed one‐pot conversion of nitroarenes into N‐methylarylamines has been developed. This transfer hydrogenation method employs a well‐defined bench stable Mn PN³P pincer precatalyst in combination with methanol as both the reductant and the C1 source. A selection of commercially available nitroarenes was converted into N‐methylarylamines in synthetically useful yields.

A manganese‐catalyzed one‐pot conversion of nitroarenes into N‐methylarylamines has been developed. This transfer hydrogenation method employs a well‐defined bench stable Mn PN³P pincer precatalyst in combination with methanol as both the reductant and the C1 source. A selection of commercially available nitroarenes was converted into N‐methylarylamines in synthetically useful yields.

Nature Catalysis, Published online: 24 February 2020; doi:10.1038/s41929-020-0430-4

There are very few methods for the organocatalytic aziridination of unactivated olefins. Here the authors report a simple ketone catalyst for the transfer of nitrogen to isolated carbon–carbon double bonds, with good substrate scope and in high yields.