Dries De Vos

A novel 1,2,5-trifunctionalization of unactivated alkenes is established by merging dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp³)−H functionalization. This transformation was triggered by XAT followed by a cascade of 1,5-HAT and intermolecular fluorine atom transfer. With this method, a broad spectrum of valuable β-hydroxyl-ϵ-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Abstract

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp³)−H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable β-hydroxyl-ϵ-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Nature Chemistry, Published online: 05 August 2024; doi:10.1038/s41557-024-01594-x

We present herein some experimental results, including NMR and x-ray, which have led to the recent retraction of a Nature Communications article claiming to feature a metal-free cross-dehydrogenative N−N coupling of primary amides with amines under the action of a hypervalent iodine oxidant. These findings should help the chemical research community to avoid such pitfalls in the future.

Abstract

The oxidative formation of N−N bonds from primary amides has been recently reported and then retracted in the journal Nature Communications by Kathiravan, Nicholls, and co-authors, utilizing a hypervalent iodane reagent. Unfortunately, the authors failed to recognize the Curtius reaction taking place under the described reaction conditions. Thus, the claimed N−N coupling products were not formed. Instead, the Curtius rearrangement urea coupling products were obtained. We demonstrate this herein by means of NMR and x-ray analysis, as well as with the support of an alternative synthetic route.

Nature Chemistry, Published online: 01 March 2024; doi:10.1038/s41557-024-01472-6

A palladium photocatalytic method is reported for the successful synthesis of primary anilines by the cross-coupling of aryl halides and sodium azide under open-air conditions at room temperature. For the first time, diverse divalent palladium complexes are shown to undergo photoexcitation to give carbon-nitrogen (C−N) cross-coupled product under air without using sophisticated ligands.

Abstract

The development of metal complexes that function as both photocatalyst and cross-coupling catalyst remains a challenging research topic. So far, progress has been shown in palladium(0) excited-state transition metal catalysis for the construction of carbon-carbon bonds where the oxidative addition of alkyl/aryl halides to zero-valent palladium (Pd⁰) is achievable at room temperature. In contrast, the analogous process with divalent palladium (Pd^II) is uphill and endothermic. For the first time, we report that divalent palladium can act as a light-absorbing species that undergoes double excitation to realize carbon-nitrogen (C−N) cross-couplings under air. Differently substituted aryl halides can be applied in the mild, and selective cross-coupling amination using palladium acetate as both photocatalyst and cross-coupling catalyst at room temperature. Density functional theory studies supported by mechanistic investigations provide insight into the reaction mechanism.

An unprecedented strategy has been proposed, using electrocatalysis to selectively depolymerize lignin into valuable aliphatic compounds in an aqueous solvent system under ambient conditions. Our innovative approach breaks down lignin‘s aromatic structure, yielding sodium levulinate, sodium 4-hydroxyvalerate, sodium formate, and sodium acetate as major products, representing an important milestone into lignin valorization and sustainability.

Abstract

Replacing crude oil as the primary industrial source of carbon-based chemicals has become crucial for both environmental and resource sustainability reasons. In this scenario, wood arises as an excellent candidate, whilst depolymerization approaches have emerged as promising strategies to unlock the lignin potential as a resource in the production of high-value organic chemicals. However, many drawbacks, such as toxic solvents, expensive catalysts, high energy inputs, and poor product selectivity have represented major challenges to this task. Herein, we present an unprecedented approach using electrocatalysis for the simultaneous depolymerization and dearomatization of lignin in aqueous medium under ambient conditions. By employing water/sodium carbonate as a solvent system, we demonstrated a pathway for selectively depolymerizing lignin under reductive electrochemical conditions using carbon as an electrocatalyst. After reductive electrocatalysis, the presence of aromatic compounds was no longer detected via nuclear magnetic resonance (NMR) spectroscopy. Further characterization by NMR, FTIR spectroscopy, and mass spectrometry revealed the major presences of sodium levulinate, sodium 4-hydroxyvalerate, sodium formate, and sodium acetate as products. By achieving a complete dearomatization, valuable aliphatic intermediates with enhanced reactivity were selectively obtained, opening new avenues for further synthesis of many different organic chemicals, and contributing to a more sustainable and circular economy.

Oxygen-rich biomass-derived substrates as reducing agents with a dioxomolybdenum catalyst. Stepwise transformation of nitrobenzene to aniline through three consecutive Mo(VI)/Mo(IV) catalytic cycles. In-situ produced water provides the protons needed for nitro to amine reduction.

Abstract

Density Functional Theory is used to unravel the mechanism of the nitrobenzene to aniline reduction, catalyzed by dioxomolybdenum (VI) dichloride. The use of pinacol as an oxoaccepting reagent and the production of only acetone and water as byproducts, signals a novel and environmentally friendly way to add value to the oxygen-rich biomass-derived polyols. The reaction proceeds through three consecutive cycles, each one responsible for one of the three reductive steps needed to yield aniline from nitrobenzene, with nitrosobenzene and hydroxylamine as intermediates. Each cycle regenerates the catalyst and releases one water and two acetone molecules. The mechanism involves singlet/triplet state crossings, a crucial feature in polyoxomolibdate catalyzed processes. The role of the Mo-coordinated water as the provider of the mysterious protons needed to reduce the nitro group, was revealed. The disclosure of this challenging mechanism and its rate limiting step can contribute to the design of more effective Mo(VI) catalysts.

Lights and shadows in photocatalysis. This Review analyzes the sustainability of photoredox catalytic processes in the context of mass-based metrics, highlighting significant sustainability issues in photocatalysts synthesis and in catalytic protocols, primarily driven by energy demanding preparations and by solvent intensive work-up and purification steps. Waste generated during the preparation of a photocatalyst may severely affect the sustainability of a catalytic protocol, where solvents emerge as a pivotal key factor in waste generation. A careful analysis of the entire process, from catalyst preparation to work-up and purification stages of a catalytic protocol, is required to avoid overstated claims of greenness in photocatalysis. This approach will surely help in exploiting the full potential of photoredox catalysis in the development of environmentally friendly and sustainable chemical processes.

Abstract

In the past century, significant advancements in synthetic chemistry undeniably contributed to the wellness of mankind, from the development of new drugs to the design of materials for energy production and storage. However, this technological progress has also brought forth significant challenges, emphasizing the urgent need to rethink chemistry for more environmentally friendly approaches. In this Review a critical and comprehensive analysis of the sustainability in the preparation of commonly used photocatalysts is performed, by employing mass-based metrics. Additionally, a comparative evaluation is made between some selected photocatalytic protocols and traditional reactions not relying on light. The objective is to quantitatively evaluate claims of sustainability and greenness commonly associated with photocatalysis, by exploring the real impact of photocatalytic procedures on waste generation. This quantitative approach provides insights into the broader concept of sustainable processes, challenging assumptions and encouraging a more rigorous evaluation of green claims in catalysis. Furthermore, the toxicity of the involved species and the availability of the required chemical elements is commented on to provide a global perspective on the sustainability of the analyzed transformations. The results shed light on the true environmental footprint of photocatalysis and reveal that the notion of green chemistry can sometimes be overstated.

Julia-Kocienski olefination has been lately often used in the preparation of trisubstituted alkenes which serve as precursors of natural products and their analogs as well of pharmaceutically interesting/biologically important compounds. Significant observations regarding the stereoselectivity of those reactions are described in this reviewing work covering comprehensively the period 2016–2022.

Abstract

Julia-Kocienski olefination, a coupling reaction between a carbonyl component and a sulfone partner, has emerged as a powerful synthetic tool in the preparation of several organic compounds. A number of interesting examples involving particularly the preparation of trisubstituted alkenes along with important observations regarding the stereoselectivity of those reactions have been recently reported. This reviewing work covers the literature for the period 2016–2022 and describes in a comprehensive way the progress and developments of Julia-Kocienski olefination application in the synthesis of trisubstituted alkenes which serve as precursors of natural products and their analogs as well of pharmaceutically interesting/biologically important compounds. Moreover, key methodology results dealing with the investigation of the optimum conditions and stereoselectivities and new modifications and approaches are discussed.