Finn Moeller

Nature Reviews Chemistry, Published online: 04 October 2024; doi:10.1038/s41570-024-00652-9

Dilithium tetraalkinyl palladates formed in situ from palladium salts and lithium alkynyls effectively promote the coupling of non-activated aryl chlorides with various nucleophiles with C−C or C−N bond formation. The applicability of the protocol has been demonstrated by the synthesis of 49 molecules, including pharmaceutically relevant compounds. The lithium alkinyls act as highly electron rich ligands that seem to be widely inert under the basic reaction conditions.

Abstract

Palladium-catalyzed cross-couplings of aryl chlorides usually call for bulky, electron-rich ligands such as phosphines or heterocyclic carbenes. We have now found that similarly powerful cross-coupling catalysts are obtained by the reaction of palladium salts with alkynyllithium reagents. The species initially formed in this process was characterized as a dilithium tetraalkinyl palladate complex. It catalyzes the coupling of aryl chlorides with the lithium salts of various terminal alkynes to give alkynyl arenes. The isolated Li-alkynyl-Pd complex also efficiently promotes the reaction of aryl, and allyl chlorides with (hetero)aryl-, alkyl-, and allyllithium compounds as well as lithium amides. None of these reactions proceeded in the presence of palladium salts alone. The preparative utility of this approach was demonstrated by the synthesis of 49 molecules, including pharmaceutically relevant compounds.

Dearomative construction of triply-fused 2D/3D frameworks was achieved from quinolines via nucleophilic addition and borate-mediated photocycloaddition in a chemo-, regio-, diastereo-, and enantioselective manner. The borate complex accelerates the photocycloaddition and suppresses rearomatization in the excited state. Based on mechanistic analysis, further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene are also developed.

Abstract

Dearomative construction of multiply-fused 2D/3D frameworks, composed of aromatic two-dimensional (2D) rings and saturated three-dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions of quinolines in the presence of photocatalysts usually afford 5,6,7,8-tetrahydroquinoline (THQ)-based polycycles, and dearomative access to 1,2,3,4-THQ-based structures remains limited. Herein, we present a chemo-, regio-, diastereo-, and enantioselective dearomative transformation of quinolines into 1,2,3,4-THQ-based 6–6–4-membered rings without any catalyst, through a combination of nucleophilic addition and borate-mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that the photoexcited borate complex, generated from quinoline, organolithium, and HB(pin), accelerates the cycloaddition and suppresses the rearomatization that usually occurs in conventional photocycloaddition. Based on our mechanistic analysis, we also developed further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene.

Nature Communications, Published online: 01 October 2024; doi:10.1038/s41467-024-52807-3

The furfural to cyclopentanone reaction network exhibits varying reaction conditions for each step. This disparity makes it difficult to achieve selective conversion to cyclopentanone in a single step. Therefore, a two-step strategy is proposed to optimize cyclopentanone yields.

Abstract

This work addresses catalytic strategies to intensify the synthesis of cyclopentanone, a bio-based platform chemical and a potential SAF precursor, via Cu-catalyzed furfural hydrogenation in aqueous media. When performed in a single step, using either uniform or staged catalytic bed configuration, high temperature and hydrogen pressures (180 °C and 38 bar) are necessary for maximum CPO yields (37 and 49 %, respectively). Parallel furanic ring hydrogenation of furfural and polymerisation of intermediates, namely furfuryl alcohol (FFA), limit CPO yields. Employing a two step configuration with optimal catalyst bed can curb this limitation. First, the furanic ring hydrogenation can be suppressed by using milder conditions (i. e., 150 °C and 7 bar, and 14 seconds of residence time). Second, FFA hydrogenation using tandem catalysis, i. e., a mix of β-zeolite and Cu/ZrO₂, at 180 °C, 38 bar and 0.6, allows sufficient time for CPO formation and minimises polymerisation of FFA, thereby resulting in 60 % CPO yield. Therefore, this work recommends a split strategy to produce CPO from furfural. Such modularity may aid in addressing flexible market needs.

An earth-abundant iron catalyst enabled efficient electrochemical recycling of post-consumer polystyrene with molecular hydrogen as the sole by-product, highlighting its potential for a circular carbon economy with a scalable green hydrogen evolution.

Abstract

Plastics are omnipresent in our everyday life, and accumulation of post-consumer plastic waste in our environment represents a major societal challenge. Hence, methods for plastic waste recycling are in high demand for a future circular economy. Specifically, the degradation of post-consumer polymers towards value-added small molecules constitutes a sustainable strategy for a carbon circular economy. Despite of recent advances, chemical polymer degradation continues to be largely limited to chemical redox agents or low energy efficiency in photochemical processes. We herein report a powerful iron-catalyzed degradation of high molecular weight polystyrenes through electrochemistry to efficiently deliver monomeric benzoyl products. The robustness of the ferraelectrocatalysis was mirrored by the degradation of various real-life post-consumer plastics, also on gram scale. The cathodic half reaction was largely represented by the hydrogen evolution reaction (HER). The scalable electro-polymer degradation could be solely fueled by solar energy through a commercially available solar panel, indicating an outstanding potential for a decentralized green hydrogen economy.

The dynamic evolutions of active sites are ubiquitous in electrocatalysis due to the applied potentials and reaction environments. The study on dynamic active sites deciphers the intrinsic structure–property relationships and provides more comprehensive insights into the interaction between electrocatalysts and electrochemical reactions.

Abstract

In-depth understanding of the real-time behaviors of active sites during electrocatalysis is essential for the advancement of sustainable energy conversion. Recently, the concept of dynamic active sites has been recognized as a potent approach for creating self-adaptive electrocatalysts that can address a variety of electrocatalytic reactions, outperforming traditional electrocatalysts with static active sites. Nonetheless, the comprehension of the underlying principles that guide the engineering of dynamic active sites is presently insufficient. In this review, we systematically analyze the fundamentals of dynamic active sites for electrocatalysis and consider important future directions for this emerging field. We reveal that dynamic behaviors and reversibility are two crucial factors that influence electrocatalytic performance. By reviewing recent advances in dynamic active sites, we conclude that implementing dynamic electrocatalysis through variable reaction environments, correlating the model of dynamic evolution with catalytic properties, and developing localized and ultrafast in situ/operando techniques are keys to designing high-performance dynamic electrocatalysts. This review paves the way to the development of the next-generation electrocatalyst and the universal theory for both dynamic and static active sites.

Nature Communications, Published online: 07 September 2024; doi:10.1038/s41467-024-52248-y

Nature Communications, Published online: 30 August 2024; doi:10.1038/s41467-024-52042-w

The control of enantioselectivity in radical cation reactions presents long-standing challenges. Here, we described a novel strategy of asymmetric counteranion-directed electrocatalysis to solve the enantioselectivity in radical cation chemistry. Examples of asymmetrical dehydrogenative indole-phenol [3+2] coupling and an atroposelective C−H/N−H coupling reactions with high yields and excellent enantioselectivities demonstrated the great success of this strategy.

Abstract

The control of enantioselectivity in radical cation reactions presents long-standing challenges, despite a few successful examples. We introduce a novel strategy of asymmetric counteranion-directed electrocatalysis to address enantioselectivity in radical cation chemistry. This concept has been successfully demonstrated in two reactions: an asymmetric dehydrogenative indole-phenol [3+2] coupling and an atroposelective C−H/N−H dehydrogenative coupling. These reactions have enabled the synthesis of benzofuroindolines and C−N axially chiral indoles with high yields and excellent enantiomeric excesses. Detailed mechanistic studies confirmed a radical-radical coupling mechanism. Moreover, density functional theory (DFT) calculations supported the indole radical cation as the pivotal intermediate, rather than a neutral indolyl radical, shedding new light on the underlying processes driving these reactions.

Intermolecular Homo-couplings, but especially Cross-couplings are challenging! We reported an electrochemical [2+2+2] annulation of alkynes with nitriles using triarylamine as a redox mediator to form substituted pyridines. Our process demonstrates unprecedented control of chemoselectivity, allowing both homo- and heterocouplings of alkynes and nitriles. A mechanistic rationale is proposed, supported by CV, EPR, NMR, and computational studies.

Abstract

We disclose a mediated electrochemical [2+2+2] annulation of alkynes with nitriles, forming substituted pyridines in a single step from low-cost, readily available starting materials. The combination of electrochemistry and a triarylamine redox mediator obviates the requirements of transition metals and additional oxidants. Besides the formation of diarylpyridine moieties via the homocoupling of two identical alkynes, the heterocoupling of two different alkynes depending on their electronic nature is possible, highlighting the unprecedented control of chemoselectivity in this catalytic [2+2+2] process. Mechanistic investigations like cyclic voltammetry and crossover experiments combined with DFT calculations indicate the initial oxidation of an alkyne as the key step leading to the formation of a vinyl radical cation intermediate. The utilization of continuous flow technology proved instrumental for an efficient process scale-up. The utility of the products is exemplified by the synthesis of π-extended molecules, being relevant for material or drug synthesis.

The combination of DoE with reaction automation using LABS was the key to the efficient optimization of the direct undivided multicomponent synthesis of alkyl arenesulfonates in flow. The transfer from the previously divided batch electrolysis protocol to undivided flow resulted in an increase in yield and productivity in scale-up.

Abstract

The necessary separation of anodic and cathodic compartments in the electrochemical multicomponent synthesis of alkyl arenesulfonates in batch was overcome by the transfer of this reaction in an undivided electrochemical flow cell. The yield was increased from an initial 23 % to 67 % by optimization using Design of Experiments (DoE). The experiments were carried out using an automated experimental flow electrolysis setup controlled by the automation software LABS (Laboratory Automation and Batch Scheduling), an open-source software that allows to plan and conduct experiments with an arbitrary, freely selectable experimental setup. The automated experimental setup turned out to be stable and provides reproducible results. In total, 6 examples are demonstrated with isolated yields up to 81 %. In addition, the robust scalability of the electrochemical reaction was demonstrated in a 10-fold scale-up.