Tomas Horsten

The past several years has witnessed an exciting renaissance of the field of organic electrosynthesis and electrocatalysis. As an unconventional reaction tool with many unique features, electrochemistry has enabled synthetic chemists to invent novel transformations, advance new synthetic strategies, and improve the sustainability of organic synthesis. In this Guest Editorial, Song Lin and Lutz Ackermann introduce the special collection on organic electrocatalysis.

A radiosynthetic method for [¹¹C]aryl nitriles via nickel-mediated carbon-fluorine bond activation is reported. This method enables the efficient ipso-¹¹C-cyanation of a broad range of aryl fluorides, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies indicate that LiCl greatly promotes the oxidative addition of aryl fluorides to a nickel(0) complex, affording aryl(chloro)nickel(II) complexes at room temperature.

Abstract

Aryl fluorides are expected to be useful as radiolabeling precursors due to their chemical stability and ready availability. However, direct radiolabeling via carbon-fluorine (C−F) bond cleavage is a challenging issue due to its significant inertness. Herein, we report a two-phase radiosynthetic method for the ipso-¹¹C-cyanation of aryl fluorides to obtain [¹¹C]aryl nitriles via nickel-mediated C−F bond activation. We also established a practical protocol that avoids the use of a glovebox, except for the initial preparation of a nickel/phosphine mixture, rendering the method applicable for general PET centers. This method enabled the efficient synthesis of diverse [¹¹C]aryl nitriles from the corresponding aryl fluorides, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies indicated a significant promotion effect of lithium chloride on the oxidative addition, affording an aryl(chloro)nickel(II) complex, which serves as a precursor for rapid ¹¹C-cyanation.

Publication date: 25 May 2023

Source: European Polymer Journal, Volume 190

Author(s): Lauren De Grave, Celeste Di Meo, Coralie Gréant, Bo Van Durme, Melanie Gérard, Annalisa La Gatta, Chiara Schiraldi, Lieven Thorrez, Katrien V. Bernaerts, Sandra Van Vlierberghe

A mechanochemical Birch reduction is reported for the first time. The newly developed ball-milling method does not require an inert atmosphere or other special precautions. Notably, the reaction reached completion within one minute for most of the investigated substrates. The present study thus provides a novel, operationally simple, rapid, and scalable alternative to conventional solution-based Birch reduction.

Abstract

Birch reduction has been widely used in organic synthesis for over half a century as a powerful method to dearomatize arenes into 1,4-cyclohexadiene derivatives. However, the conventional Birch reduction reaction using liquid ammonia requires laborious procedures to ensure inert conditions and low temperatures. Although several ammonia-free modifications have been reported, the development of an operationally simple, efficient, and scalable protocol remains a challenge. Herein, we report an ammonia-free lithium-based Birch reduction in air without special operating conditions using a ball-milling technique. This method is characterized by its operational simplicity and an extremely short reaction time (within 1 min), probably owing to the in situ mechanical activation of lithium metal, broad substrate scope, and no requirement for dry bulk solvents. The potential of our flash Birch reaction is also demonstrated by the efficient reduction of bioactive target molecules and gram-scale synthesis.

The Front Cover visually represents our review “The Last Fortress of Tin′s Tyranny – Protodenitration of Nitroalkanes“. ”Once upon a time, in a small corner of a faraway land full of nitroalkanes, a small town called “Protodenitrations” started coming to life. Unfortunately, a sneaky tin, hungry for power, soon took the opportunity and overtook the small, still fragile community, establishing himself as the king. The kingdom ruled by Tin The Tyrant has expanded since then, spreading its roots all over the continent. Despite a few attempts to dethrone the Tyrant, he remains undefeated. However, rumors are starting to spread that an army of reagents is beginning to gather. Could the end of the last fortress of the tyranny of tin be in sight?“ This review provides the historical development and highlights the governing position of the Ono–Tanner reaction employing tributyltin hydride. Due to the unchallenged dominance of the toxic tributyltin hydride, the current situation was dubbed “the last fortress of tin′s tyranny.” The authors would like to thank Katarína R. Detková for the graphic project and creation. More information can be found in the Review by P. Jakubec et al.

The first electrochemical Co^II-catalyzed enantioselective C−H alkoxylation is reported. A broad range of alkoxylated phosphinamides were obtained in good yields with excellent enantioselectivities (up to 98 % yield and >99 % ee). A cobalt(III) alcohol complex was prepared and characterized, and was found to be a key intermediate in this reaction. Mechanistic studies revealed that the oxidation of Co^III to Co^IV was facilitated by a base.

Abstract

Metalla-electrocatalyzed C−H oxygenation represents one of the most straightforward and sustainable approaches to access valuable oxygenated molecules. Despite the significant advances, the development of enantioselective electrochemical C−H oxygenation reaction is very challenging and remains elusive. Herein, we described the first electrochemical Co^II-catalyzed enantioselective C−H alkoxylation. A broad range of enantioenriched alkoxylated phosphinamides were obtained in good yields with excellent enantioselectivities (up to 98 % yield and >99 % ee). An unusual cobalt(III) alcohol complex was prepared and fully characterized, which was proven to be a key intermediate of this C−H alkoxylation reaction. Mechanistic studies revealed that the oxidation of Co^III to Co^IV was facilitated by a base and the whole process proceeded through a cobalt(III/IV/II) catalytic cycle.

Salt metathesis and BFX (boron–fluoride exchange) of BF₄ ⁻ with boronic acids generates RBF₃ ⁻ derivatives, thus showing the solvolytic lability of BF₄ ⁻ that enables its use as a fluorinating agent, even though many highly reactive reagents employ BF₄ ⁻ as a non-reactive counteranion. In their Research Article (e202215371), David M. Perrin and co-workers report the synthesis of RBF₃ ⁻ derivatives via a salt metathesis reaction using a series of MBF₄ salts in methanol. This work highlights the proclivity of BF₄ ⁻, generally considered weakly coordinating and unreactive, to rapidly fluorinate boronic acids.

The deborolative hydroxylation of arenes and alkenes using the green and largely under-explored oxidizer peroxodicarbonate is reported. Accessible through state-of-the-art electrolysis of aqueous carbonate solutions at low temperature and high current density, highly concentrated solutions of this green and sustainable oxidizer lead to a simple and straightforward protocol using only green solvents and allowed for scale-up reactions to multi-gram batch sizes.

Abstract

Peroxodicarbonate represents a green and largely underexplored oxidizer generated electrochemically from aqueous carbonate solutions. Through state-of-the-art electrolyzer technology, highly concentrated solutions have now become accessible. These were successfully employed as green oxidizer in deborolative hydroxylations. A plethora of phenols and alcohols have thus been synthesized in up to 99 % from organoboron compounds using only green and non-toxic solvents. This transformation was successfully scaled-up to multi-gram batch sizes.

Single-atom catalysts, featuring atomically dispersed metals on solid carriers, offer limitless possibilities for new, sustainable transformations in the chemical sector. These materials bridge the gap between organometallic and nanoparticle catalysis and are opening exciting avenues for mimicking metalloenzymes. This Review summarizes the impressive progress and potential knowledge gaps in the use of single-atom catalysts in organic synthesis.

Abstract

Single-atom catalysts hold the potential to significantly impact the chemical sector, pushing the boundaries of catalysis in new, uncharted directions. These materials, featuring isolated metal species ligated on solid supports, can exist in many coordination environments, all of which have shown important functions in specific transformations. Their emergence has also provided exciting opportunities for mimicking metalloenzymes and bridging the gap between homogeneous and heterogeneous catalysis. This Review outlines the impressive progress made in recent years regarding the use of single-atom catalysts in organic synthesis. We also illustrate potential knowledge gaps in the search for more sustainable, earth-abundant single-atom catalysts for synthetic applications.