LongLarf

Synlett
DOI: 10.1055/s-0037-1611890

This account summarizes our recent work on the pK a scales of some frequently used organocatalysts, especially those of hydrogen-bond-donor catalysts and stronger Brønsted acid catalysts. Most of these pK a values were obtained by the Bordwell overlapping indicator method, which is known to provide high accuracy. Linear free-energy relationships associated with pK a values are discussed in relation to understanding of reaction mechanisms.1 Introduction2 Single Hydrogen-Bonding Donors2.1 Proline-Type Organocatalysts2.2 Cinchona Alkaloids Bearing a Hydrogen-Bonding Donor in the 6′-Position3 Double-Hydrogen-Bonding Donors3.1 Thioureas3.2 Squaramides3.3 BINOLs4 Stronger Brønsted Acids5 N-Heterocyclic Carbenes6 Summary and Outlook
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© Georg Thieme Verlag Stuttgart · New York

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Synlett
DOI: 10.1055/s-0037-1610721

The isothiourea-catalysed acylative kinetic resolution of a range of acyclic (±)-1,2-diols using 1 mol% of catalyst under operationally simple conditions is reported. Significantly, the bifunctional nature of (±)-1,2-diols was exploited in a sequential double kinetic resolution, in which both kinetic resolutions operate synergistically to provide access to highly enantioenriched products. The principles that underpin this process are discussed, and selectivity factors for the individual kinetic resolution steps are reported in a model system.
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© Georg Thieme Verlag Stuttgart · New York

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Asymmetric C−As bond formation: Key catalytic steps were examined for the PCP Ni^II pincer complex‐catalyzed asymmetric hydroarsination reaction. This was investigated with catalytic screening, DFT calculations, conductivity measurements and NMR spectroscopic studies. A unique Ni–Cl–As interaction was identified in the key catalytic intermediate which was not previously reported in other closely related hydrofunctionalization reactions (see scheme).

Abstract

Synthetic challenges have significantly slowed the development of the catalytic asymmetric hydroarsination reaction despite it being a highly attractive C−As bond formation methodology. In addition, there is a poor understanding of the main reaction steps in such reactions which limit further development in the field. Herein, key intermediates of the hydroarsination reaction catalyzed by a PCP Ni^II‐Cl pincer complex are presented upon investigating the reaction with DFT calculations, conductivity measurements, NMR spectroscopy, and catalytic screening. The novel Ni–Cl–As interaction proposed was then contrasted against known Ni^II‐catalyzed hydrophosphination reactions to highlight dissimilarities between them even though P and As share a close group relationship. Lastly, the asymmetric hydroarsination of nitroolefins was further developed to furnish a library of chiral organoarsines in up to 99 % yield and 80 % ee under mild conditions (−20 °C to RT) between 5 to 210 mins.

Sweet chemistry. A catalytic transfer hydrogenation using biomass‐derived carbohydrates as reagent is developed. Stereoselective and chemoselective hydrogenation of alkynes, alkenes, and carbonyl compounds is demonstrated. This work provides an operationally simple method for transfer hydrogenation and represents a new concept for the application of renewable biomass.

Abstract

We developed an operationally simple method for the direct use of biomass‐derived chemical entities in a fundamentally important process, such as hydrogenation. Various carbohydrates, starch, and lignin were used for stereoselective hydrogenation. Employing a transition metal catalyst and a novel catalytic system, the reduction of alkynes, alkenes, and carbonyl groups with high yields was demonstrated. The regioselective hydrogenation to access different stereoisomers was established by simple variations in the reaction conditions. This work is based on an unprecedented catalytic system and represents a straightforward application of biomass as a reducing reagent in chemical reactions.

Alcohol upgrading: A well‐defined Mn pincer complex, stabilized by a PNN ligand, catalyzes the β‐alkylation of secondary alcohols with primary alcohols without the need for further stochiometric reagents. Almost equimolar ratios of substrates are sufficient to achieve good yields of the corresponding alkylated alcohols and water is liberated as the only byproduct in this sustainable reaction.

Abstract

A new Mn‐catalyzed alkylation of secondary alcohols with non‐activated alcohols is presented. The use of a stable and well‐defined manganese pincer complex, stabilized by a PNN ligand, together with a catalytic amount of base enabled the conversion of renewable alcohol feedstocks to a broad range of higher‐value alcohols in good yields with water as the sole byproduct. The strategy eliminates the need for exogenous and detrimental alkyl halides as well as the use of noble metal catalysts, making the C‐alkylation through double hydrogen autotransfer a highly sustainable and environmentally benign process. Mechanistic investigations support a hydrogen autotransfer mechanism in which a non‐innocent ligand plays a crucial role.

The Front Cover shows the transfer dehydrogenation of secondary alcohols with a well‐defined iron–PNP‐pincer complex. In this study, acetone is used as inexpensive hydrogen acceptor. This enables the oxidation under mild conditions with good‐to‐excellent yields of the corresponding ketones. More information can be found in the Communication by Budweg et al on page 2988 in Issue 13, 2019 (DOI: https://doi.org/10.1002/cssc.20190030810.1002/cssc.201900308).

“The best advice I have ever been given is ‘Don't listen to everyone else's advice!' My favorite quote is ‘Simplicity is the ultimate sophistication’ …” Find out more about M. Kevin Brown in his Author Profile.

Publication date: 16 August 2019

Source: Tetrahedron, Volume 75, Issue 33

Author(s): Tahar Ayad, Aurélie Gernet, Jean-Luc Pirat, David Virieux

Graphical abstract

Synlett
DOI: 10.1055/s-0039-1690107

We report studies on the photocatalytic formation of C–S bonds to form benzothiazoles via an intramolecular cyclization and sulfenylated indoles via an intermolecular reaction. Cyclic voltammetry (CV) and density functional theory studies suggest that benzothiazole formation proceeds via a mechanism that involves an electrophilic sulfur radical, while the indole sulfenylation likely proceeds via a nucleophilic sulfur radical adding into a radical cationic indole. These conditions were successfully extended to several thiobenzamides and indole substrates.
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© Georg Thieme Verlag Stuttgart · New York

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The front cover picture, provided by Burkhard König et al., illustrates how iodine solutions block most of the incoming light with the exception of a small part at the edge of the visible light spectral region. This spectral window (385–415 nm) with low absorptivity allows irradiation of an inexpensive anthraquinone photocatalyst, which can promote the iodination of electron‐rich arenes and heteroarenes with high regioselectivity and good to excellent yields. Details are reported in the full paper on pages 3998–4004 (R. Narobe, S. J. S. Düsel, J. Iskra, B. König, Adv. Synth. Catal. 2019, 361, 3998–4004; DOI: https://doi.org/10.1002/adsc.20190029810.1002/adsc.201900298).

Which one is the most sensitive? Seventeen common oxidants were evaluated in the context of impact, thermal and electrostatic sensitiveness, and ranked as a guide for synthetic utility and de novo reaction design.

Abstract

Common oxidants used in chemical synthesis, including newly developed perruthenates, were evaluated in the context of understanding (and better appreciating) the sensitiveness and associated potential hazards of these reagents. Analysis using sealed cell differential scanning calorimetry (scDSC) facilitated Yoshida correlations, which were compared to impact sensitiveness and electrostatic discharge experiments (ESD), that enabled sensitiveness ranking. Methyltriphenylphoshonium perruthenate (MTP3, 8), isoamyltriphenylphosphonium perruthenate (ATP3, 7) and tetraphenylphosphonium perruthenate (TP3, 9) were found to be the most sensitive followed by 2‐iodoxybenzoic acid (IBX, 2) and benzoyl peroxide (BPO, 10), whereas the most benign were observed to be Oxone (12), manganese dioxide (MnO₂, 13), and N‐bromosuccinimide (NBS, 17).

Publication date: 26 July 2019

Source: Tetrahedron, Volume 75, Issue 30

Author(s): Zsolt Rapi, Tamás Nemcsok, Péter Bagi, György Keglevich, Péter Bakó

Graphical abstract

Sun‐safe: Urea, an abundant and cheap substance, blocks access to a key site on the Methylene Blue backbone and thereby protects the dye against the deleterious photobleaching effects of sunlight.

Abstract

Methylene Blue has a long history as a photochemical reagent and is known to undergo photofading on exposure to visible light in aqueous solution. Under aerobic conditions, photobleaching occurs by way of a two‐step process involving intermediary formation of singlet oxygen. The first step is ascribed to regio‐selective addition of singlet oxygen within the precursor complex. This geminate reaction ultimately leads to formation of the leuco‐dye via a slower second step. Urea forms a weak ground‐state complex with Methylene Blue which affects the optical properties of the dye but is not evident by NMR spectroscopy. This complex is weakly fluorescent and undergoes intersystem crossing to the triplet manifold. The presence of urea decreases the rate of photobleaching of the dye and, at high concentrations of urea, the bleaching kinetics are consistent with an equilibrium mixture of complexed and free dye. The complexed dye does not bleach on the timescale of the experiment. Such protection might arise from urea blocking access to the site where geminate addition of O₂ takes place.

Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C–H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (¹⁸F)–fluorination of aromatic C–H bonds by an [¹⁸F]F^– salt via organic photoredox catalysis under blue light illumination. This strategy was applied to the synthesis of a wide range of ¹⁸F-labeled arenes and heteroaromatics, including pharmaceutical compounds. These products can serve as diagnostic agents or provide key information about the in vivo fate of the labeled substrates, as showcased in preliminary tracer studies in mice.

The stabilization of peptide secondary structure via stapling is a ubiquitous goal for creating new probes, imaging agents, and drugs. Inspired by indole‐derived crosslinks found in natural peptide toxins, we employed ortho‐phthalaldehydes to create isoindole staples, thus transforming inactive linear and monocyclic precursors into bioactive monocyclic and bicyclic products. Mild, metal‐free conditions give an array of macrocyclic α‐MSH derivatives, of which several isoindole‐stapled α‐MSH analogs (Ki ~ 1 nM) are found to be as potent as α‐MSH. Analogously, late‐stage intra‐annular isoindole stapling furnished a bicyclic peptide mimic of α‐amanitin that is cytotoxic to CHO cells (IC50 = 70 µM). Given its user‐friendliness, we have termed this approach FlICk (fluorescent isoindole crosslink) chemistry.

α‐alkylidene cyclic carbonates (αCCs) recently emerged as attractive CO2‐sourced synthons for the construction of complex organic molecules. Herein, we report the transformation of αCCs into novel families of sulfur‐containing compounds by organocatalyzed chemoselective addition of thiols, following a domino process that is switched on/off depending on the desired product. The process is extremely fast, versatile in substrate scope, provides selectively linear thiocarbonates or elusive tetrasubstituted ethylene carbonates with high yields following a 100% atom economy reaction, and valorizes CO2 as a renewable feedstock. It is also exploited to produce a large diversity of unprecedented functional polymers. It constitutes a robust platform for the design of new sulfur‐containing organic synthons and important families of polymers.