Robby Vroemans

This study focuses on the mechanochemical pathway for α-bromination of β-functionalized naphthalenes. This uses N-bromosuccinimide as a mild brominating precursor and highlights the tolerance and limitations of functional groups used. This applies on gram scale synthesis and production of various useful intermediates.

Abstract

This study is the exploration of a solvent-free, mechanochemically enabled sustainable pathway for rapid and preferential selective α-bromination of β-functionalized naphthalenes using N-bromosuccinimide. Gram-scale synthesis and diverse post-functionalizations demonstrate the versatility of the α-brominated β-functionalized naphthalenes in organic synthesis, pharmaceuticals, materials, and catalysis. This green and environment-benign approach, having E-factor of 0.5, offers high yields up to 98% within 30 minutes and highlights broad functional electron-donating groups (EDGs) along with limitations of electron-withdrawing groups (EWGs).

Nature, Published online: 20 August 2025; doi:10.1038/d41586-025-02616-5

A solvent-free mechanochemical reduction of nitro compounds using hydrogen gas is presented. In addition to enabling the synthesis of a variety of functionalized aniline derivatives, the method has been scaled up to gram quantities, evaluated for trace metal impurities, and applied to the synthesis of pharmaceutical compounds and their precursors.

A solvent-free mechanochemical method for the catalytic hydrogenation of nitro compounds is reported, requiring only the substrate, low catalyst loading, and molecular hydrogen. The approach avoids the use of additional base additives or solvents for liquid-assisted grinding. The transformation proceeds under mild conditions using palladium on carbon and hydrogen gas in pressurizable stainless steel jars operated in a planetary ball mill. A variety of functionalized nitro compounds are converted to the corresponding anilines and amines in good to excellent yields. The method displays chemoselectivity, tolerating functional groups such as halogens, benzylic ketones, and nitriles. In addition, scale-up to multigram quantities is achieved, and an analysis of trace metal impurities from abrasion revealed only minor concentrations, all below the limits established by ICH guidelines. The protocol's practicality is demonstrated by synthesizing intermediates and active ingredients used in pharmaceuticals and agrochemicals. To quantify the sustainability of the protocol, green metrics are calculated and compared with those of other mechanochemical and solution-phase nitro compound reduction methods.

This review highlights dual Cu/photoredox-catalysis for the direct transformation of C─H bonds. The synergistic interplay between visible-light photoredox activation and Cu catalysis, enabling diverse C─C and Cheteroatom bond formations is discussed. Detailed mechanistic insights from experimental and theoretical studies are presented, underscoring the current scope and future potential of this exciting research field.

Abstract

The rapid development of photo-synergistic transition metal catalysis has emerged as a green paradigm to complement thermal transition metal catalytic strategies. The interplay between photoredox and transition metal catalytic cycles allows for precise control over reactivity and selectivity, facilitating the construction of complex molecules, with the formation of diverse C─C, C–heteroatom bonds. Among different transition metal catalysts, copper, abundant in the Earth's crust, is particularly notable for its unique electronic structure and light-absorbing properties. This has spurred considerable interest in utilizing Cu in combination with an appropriate photocatalyst to enable chemical transformations that are otherwise inaccessible or require harsh reaction conditions. Over the years, dual copper and photoredox catalysis has emerged as a powerful approach for C–H functionalizations, enabling the direct modification of inert C─H bonds under mild conditions. This synergistic strategy leverages copper catalysts to activate specific substrates or intermediates, while photoredox catalysts generate reactive radical species under visible-light-induced processes. This facilitates the introduction of diverse functional groups into C─H bonds without the need for pre-functionalized starting precursors, making it an attractive approach in organic synthesis. In this review, we aim to summarize dual Cu/photoredox-catalyzed C–H functionalizations, emphasizing detailed mechanistic insights from reported experimental and theoretical studies. The present and future potential of this exciting research field is highlighted as well.

The intensification of electrochemical hydrocarboxylation reaction employing a spinning cylinder electrode reactor is presented. The optimized system provides high reaction scale for the synthesis of valuable compounds, incorporating CO₂ gas in organic molecules in an efficient way.

There is an increasing attention in developing reactions that can incorporate CO₂ into organic molecules. In this context, electrochemistry offers a sustainable and mild approach to utilize this valuable yet elusive C1 building block in a scalable fashion. Herein, the intensification of the electrochemical hydrocarboxylation of activated alkenes is presented. The study covers the evaluation of critical chemical and electrochemical parameters to maximize the efficiency of the process in standardized small-scale batch cells, followed by the transfer to a spinning cylinder electrochemical reactor. Leveraging the enhanced mass transfer of this reactor design, the reaction can be further optimized, leading to a more efficient process. After validating the transformation across different substrates, the regioselective addition of CO₂ is further improved by tuning the current density of the process. Finally, a scale-up in recirculation mode is performed, achieving a productivity of 55 g day⁻¹ and demonstrating its potential for the efficient and scalable utilization of the electrochemical hydrocarboxylation reaction.

A simple photoredox system comprising Hantzsch ester, Cs₂CO₃, and 4DPAIPN that enables direct and site-selective deoxygenation of benzyl alcohol derivatives is described. Mechanistic studies reveal that in situ reversible acylative activation of hydroxy groups plays a pivotal role in achieving the unique selectivity, highlighting the importance of reversible activation strategies in selective molecular transformations.

A simple yet efficient method is presented for direct and site-selective deoxygenation of benzyl alcohol derivatives, including polyols, without requiring preactivation. This reaction system, consisting of Hantzsch ester, Cs₂CO₃, and a photocatalyst under photoirradiation, enables direct and site-selective deoxygenation. Mechanistic studies reveal that in situ reversible acylative activation of hydroxy groups plays a pivotal role in achieving unique selectivity. This approach offers a general and practical strategy for the selective transformation of polyols.

The first high-generation catenane-branched dendrimers with up to twenty-one [2]catenane branches have been precisely constructed through a controllable divergent approach, not only achieving the construction of novel high-order catenane dendrimers with well-defined topological arrangements, but also providing a new platform for dynamic multifunctional supramolecular materials.

Abstract

To tackle the challenge of the precise construction of catenane-based mechanically interlocked macromolecules with well-defined topological arrangements, starting from a novel [2]catenane building block with dendrimer growth sites, catenane-branched dendrimers have been precisely constructed via an efficient and controllable divergent approach. Notably, to the best of our knowledge, the third-generation dendrimer which consists of twenty-one [2]catenane branches is the most complicated discrete [2]catenane oligomer synthesized to date. Interestingly, the switchable coconformation transformations of [2]catenane branches triggered by sodium ions and cryptands lead to an integrated and amplified expansion–contraction motion of the resultant dendrimers, achieving reversible size regulation at the nanoscale. The unique recognition sites of the resultant catenane-branched dendrimers also facilitate the reversible binding of drug and dye guests. This work not only addresses the synthetic challenge of highly branched catenane dendrimers but also provides a new platform for dynamic supramolecular functional materials.

Herein, we present a scalable mechanocatalytic method for synthesizing cyclic carbonates from solid and liquid epoxides using CO₂ at 1 bar and room temperature. Employing a gallium aminotrisphenolate catalyst, this process achieves high yields, efficiently transforms multi-terminal epoxides, and outperforms solution-based methods in green metrics, setting a benchmark for sustainable synthesis.

Abstract

Over the past two decades, main group elements have gained attention as promising substitutes for precious metals in catalytic processes. Additionally, mechanochemistry is emerging as a field with the potential to promote catalytic reactions under mild conditions. Herein, we report a scalable, main-group mechanocatalytic synthesis of cyclic carbonates from both solid and liquid epoxides, using CO₂ as a renewable feedstock under mild conditions with a gallium aminotrisphenolate catalyst. Unlike solution-based methods that generally require high temperatures and/or high CO₂ pressures, this mechanocatalytic process operates at just 1 bar and room temperature. The developed mechanochemical method affords the targeted compounds in high yields while also enabling efficient transformation of multi-terminal epoxides and avoiding the conversion losses typically observed in solution. Furthermore, this scalable method outperforms solution-based approaches across all green metrics, setting a new benchmark for environmentally friendly synthesis.

Publication date: October 2025

Source: Polymer Degradation and Stability, Volume 240

Author(s): Tuan Sherwyn Hamidon, Liang Bi, M. Hazwan Hussin

Nature, Published online: 09 June 2025; doi:10.1038/d41586-025-01775-9