Finn Moeller

Catalytic aerobic oxidation under aqueous alkaline conditions promotes C–C cleavage in pine- and poplar-derived lignin oligomers, accessing high yields of aromatic monomers. The monomeric phenols obtained from this process then undergo effective biological conversion into cis,cis-muconic acid and 2-pyrone-4,6-dicarboxylic acid using engineered strains of Pseudomonas putida.

Abstract

Existing methods for lignin deconstruction to aromatic monomers primarily cleave carbon–oxygen bonds within the polymer, resulting in sub-optimal monomer yields and formation of oligomers that retain intact carbon–carbon bonds. Here, we demonstrate that copper-catalyzed aerobic oxidation under aqueous alkaline conditions promotes oxidative cleavage of carbon–carbon bonds in lignin oligomers derived from reductive catalytic fractionation (RCF) of pine and poplar biomass. Fundamental insights are gained from reactions of model compounds that resemble subunits present in RCF oligomers. Optimal results are achieved in a flow reactor that provides precise control over O₂ delivery, temperature, and reaction residence time. The Cu-catalyzed aerobic oxidation conditions access aromatic monomers in 19 and 34 wt% monomer yields, respectively, from pine- and poplar-derived RCF oligomers. Overall, the sequence consisting of biomass RCF into monomers and oligomers followed by oxidative deconstruction of the RCF oligomers generates substantially higher yields of aromatic monomers from lignin. Engineered strains of Pseudomonas putida support biological funneling of the oligomer-derived oxygenated aromatic compounds into cis,cis-muconic acid from pine or 2-pyrone-4,6-dicarboxylic acid from poplar.

A stereodivergent deacylative Mizoroki–Heck reaction for preparing a large variety of alkyl-tethered alkenes from methyl ketones and cyclic ketones under dual Co/photoredox catalysis has been developed. This protocol features a one-pot reaction, high ring-opening efficiency, mild reaction conditions, and broad substrate scope with excellent functional group compatibility.

Abstract

Alkene structures represent one of the most functional and widely used in organic synthesis, drug design, and material science. However, developing a practical strategy to produce such high-valued chemicals from widely abundant materials, such as ketones, remains elusive. Herein, we present a stereodivergent deacylative Mizoroki–Heck reaction of methyl ketones and cyclic ketones to furnish both E- and Z-configured alkenes via dual photoredox/cobalt catalysis. Interestingly, the tunable E/Z-selectivity is achieved by energy transfer catalysis via the judicious choice of photocatalyst. This versatile strategy features a broad substrate scope with excellent functional group tolerance and is suitable for late-stage modification of complex molecules and the one-pot operation. It also expands the reaction profiles of both deacylative transformation and photoredox/cobalt catalysis.

Electrooxidation enables tunable halocyclization of ambident amides, yielding either C–O or C–N products through ionic or radical pathways, respectively. While detailed experimental and analytical mechanistic studies highlight mode-dependent selectivity, in silico experimentation provided insight into the energetic origin of this divergence.

Abstract

Herein, we report a divergent electrochemical halocyclization of ambident amides that enables selective formation of either C–O or C–N bonds. Unique chemoselectivity is governed by anodic oxidation conditions, in which haliranium-mediated C–O bond formation proceeds via chloride oxidation, while amidyl radicals guide C–N bond formation under basic conditions. Various approaches to understanding reaction mechanisms have been performed, including cyclic voltammetric analyses, experimental kinetic studies, and in silico experimentation. The developed electrooxidative synthetic method offers broad functional group tolerance, highlighting electrochemistry as a powerful tool for selective halocyclization.

Nature Chemistry, Published online: 11 November 2025; doi:10.1038/s41557-025-01990-x

Molecular scaffolds bearing 1,1-diaryl-substituted four-membered rings remain difficult to access using traditional synthesis. Now it has been shown that a modular, nickel-electrocatalytic sequence enables the programmable, scalable and chemoselective synthesis of these high-value motifs, offering broad utility across drug discovery and showcasing strategic applications to patented intermediates.

Angewandte Chemie International Edition, Volume 64, Issue 51, December 15, 2025.

After decades of research into metal alkylidyne complexes and their extensive use as catalysts for alkyne metathesis, one might think that there is nothing fundamentally new to be discovered in this field. The present study into formally d⁴-configured Ru alkylidynes shows that this notion is incorrect: not only is a novel and convenient entry route disclosed but also an entirely unprecedented stepwise pathway for [2 + 2] cycloaddition reactions is uncovered.

Abstract

A new entry into square-planar, formally d⁴-configured ruthenium alkylidyne complexes is disclosed, using p-tolyl(trimethylsilyl)diazomethane as a convenient and safe alkylidyne synthon. The method furnished complex 12 supported by an electron-rich PNP-pincer ligand, which undergoes remarkably facile [2 + 2] cycloaddition with electron-rich, electron-deficient, and strained alkynes; these reactions represent the first examples of metallacyclobutadiene formation by a d⁴-configured transition metal alkylidyne complex. Strikingly, however, the cycloadditions proceed by a stepwise mechanism, which stands in marked contrast to the concerted pathway entertained by all prototypical d⁰ and d² Schrock-type alkylidynes, including the molybdenum, tungsten, and rhenium complexes that currently dominate the field of alkyne metathesis. In essence, it is the non-bonding lone pair forming the largely metal-centered HOMO of significant d_z2 character that accounts for this unorthodox behavior. The newly gained insight into this key reactivity determinant also allows the few other known reactions of formally d⁴-configured alkylidene complexes previously described in the literature to be explained and will empower further explorations of their chemistry.

We report a photochemical method for oxidative γ-C─H lactonization of simple carboxylic acid substrates upon LMCT photoactivation. Intriguingly, these conditions suppress the rapid decarboxylation characteristic of oxidized carboxylates, suggesting the intermediacy of metal-stabilized acyloxy radical instead of the dissociative process typically invoked in LMCT photoactivations.

Abstract

Photoinduced ligand-to-metal charge-transfer (LMCT) activation of carboxylic acids has increasingly become recognized as a versatile platform for the development of synthetically useful new reactions. When the metal species is also capable of mediating an oxidative radical coupling process, this approach has been shown to be a powerful strategy for decarboxylative coupling of carboxylate feedstocks with diverse nucleophilic reaction partners. LMCT photoreactions that could engage the acyloxy radical intermediate in other canonical reactions of heteroatom-centered radicals such as 1,5-hydrogen atom transfer (HAT) would broaden the scope of possible reactions. The rapid intrinsic rate of decarboxylation, however, presents a formidable challenge. Herein, we report the LMCT-promoted C─H lactonization of benzoic and aliphatic carboxylic acids. Mechanistic investigations suggest that under the optimized reaction conditions, the key acyloxy radical intermediate can be stabilized by the metal center, enabling 1,5-zHAT to outcompete decarboxylation.

It is introduced in this report a unified toolbox comprising of 15 sulfonyl hydrazide reagents that enable the redox-neutral radical cross-coupling of 14 distinct C(sp³)-rich small fragments onto (hetero)arenes, providing a modular, efficient, and operationally simple platform for installing diverse small fragments. The platform has the potential to accelerate medicinal chemistry campaigns, enables late-stage modifications, and positions it as a useful resource for drug discovery.

Abstract

The hit-to-lead phase of drug discovery is frequently bottlenecked by the time-consuming, iterative synthesis of analogs, especially when incorporating small C(sp³)-rich fragments such as methyl, cyclopropyl, or oxetanyl groups—moieties known to improve drug solubility, bioactivity, and metabolic stability. Conventional approaches like Suzuki or Negishi couplings make use of unstable reagents, high costs, and harsh reaction conditions, while many modern radical-based methods rely on exogenous redox agents or costly metal catalysts. To overcome these limitations, a toolbox of 15 sulfonyl hydrazide reagents is disclosed to facilitate redox-neutral, nickel-catalyzed radical cross-coupling of 14 distinct small fragments onto (hetero)arenes under mild conditions. These crystalline, bench-stable reagents are straightforward to synthesize from accessible precursors and require no additional oxidants, reductants, or precious metals, offering a modular and operationally simple platform. Demonstrated across a diverse set of over 60 (hetero)aryl halides, the method exhibits exceptional substrate scope and functional group tolerance, accommodating complex, medicinally relevant scaffolds. Comparative studies with existing techniques underscore its advantages, including a 51% yield for trideuteromethylation of a MET kinase inhibitor precursor (versus a precedented 14% via Kumada coupling) and a streamlined one-step cyclobutylation of an NLRP3 inhibitor intermediate at 41% yield (versus a known < 5% over a four-step sequence).

It is introduced in this report a unified toolbox comprising of 15 sulfonyl hydrazide reagents that enable the redox-neutral radical cross-coupling of 14 distinct C(sp³)-rich small fragments onto (hetero)arenes, providing a modular, efficient, and operationally simple platform for installing diverse small fragments. The platform has the potential to accelerate medicinal chemistry campaigns, enables late-stage modifications, and positions it as a useful resource for drug discovery.

Abstract

The hit-to-lead phase of drug discovery is frequently bottlenecked by the time-consuming, iterative synthesis of analogs, especially when incorporating small C(sp³)-rich fragments such as methyl, cyclopropyl, or oxetanyl groups—moieties known to improve drug solubility, bioactivity, and metabolic stability. Conventional approaches like Suzuki or Negishi couplings make use of unstable reagents, high costs, and harsh reaction conditions, while many modern radical-based methods rely on exogenous redox agents or costly metal catalysts. To overcome these limitations, a toolbox of 15 sulfonyl hydrazide reagents is disclosed to facilitate redox-neutral, nickel-catalyzed radical cross-coupling of 14 distinct small fragments onto (hetero)arenes under mild conditions. These crystalline, bench-stable reagents are straightforward to synthesize from accessible precursors and require no additional oxidants, reductants, or precious metals, offering a modular and operationally simple platform. Demonstrated across a diverse set of over 60 (hetero)aryl halides, the method exhibits exceptional substrate scope and functional group tolerance, accommodating complex, medicinally relevant scaffolds. Comparative studies with existing techniques underscore its advantages, including a 51% yield for trideuteromethylation of a MET kinase inhibitor precursor (versus a precedented 14% via Kumada coupling) and a streamlined one-step cyclobutylation of an NLRP3 inhibitor intermediate at 41% yield (versus a known < 5% over a four-step sequence).

The Pd-catalyzed aminative coupling of primary and secondary alkyl boronic esters with aryl (pseudo)halides is reported. DFT calculations and mechanistic experiments show that the first C─N bond formation may take place through an unusual dyotropic rearrangement of a LPd(Ar)NHX complex (X = OPOPh₂).

Abstract

Insertive cross-coupling reactions provide the option of repurposing widely available coupling partners for the formation of new linkages. By confronting a major limitation of the aminative Suzuki–Miyaura methods we recently reported, we achieve a general method for the Pd-catalyzed aminative coupling of primary and secondary alkyl boronic esters with aryl (pseudo)halides. Introducing a formal nitrene insertion into this Suzuki–Miyaura reaction diverts the outcome from the traditional C(sp²)─C(sp³) products to the C(sp²)─NH─C(sp³) analogues (N-aryl anilines). DFT calculations and experimental mechanistic studies indicate that C─N bond formation from the electrophilic aryl component occurs first, providing further evidence for this previously hypothetical pathway. By comparison of several transition state structures, we find that C─N bond formation likely takes place through an unusual dyotropic rearrangement of a LPd(Ar)NHX complex (X = OPOPh₂).

RETRACTION: T. Yu, X. Liu, A.-L. Bolcato-Bellemin, Y. Wang, C. Liu, P. Erbacher, F. Qu, P. Rocchi, J.-P. Behr, and L. Peng, “An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo,” Angewandte Chemie International Edition 51, no. 34 (2012): 8478-8484. https://doi.org/10.1002/anie.201203920.

The above article, published online on 24 July 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Frank Maass and Nathalie Weickgenannt; the German Chemical Society; and Wiley-VCH GmbH. A third party reported that Figure 1C contained duplicated bands, that the Naked siRNA bands in Figure 2D had been manipulated to remove data containing bands from the 0-120 (min) lanes. These concerns were confirmed by the publisher.

The authors responded to an inquiry by the publisher and stated that the bands in Figure 1C were original but agreed that Figure 2D was incorrect. The authors confirmed that all original data were no longer available, supplied data of repeated experiments for Figure 2D, and stated their intention to supply data from repeated experiments for Figure 1C. Both the editors and publisher agree that a correction with data from repeated experiments would not be appropriate.

The retraction has been agreed to because the evidence of image manipulation in Figures 1C and 2D fundamentally compromises the editor's confidence in the conclusions presented in the article. The authors were informed of the retraction.

The final challenge in the total synthesis of the caged polycyclic Daphniphyllum alkaloids was the Calyciphylline D-type alkaloid, featuring a strained 8-azatricyclo[4.2.1.0^4,8]nonane ring system. Presented herein is the total synthesis of calyciphylline F, a member of the calyciphylline D-type alkaloid family, by an intramolecular [4 + 3] cycloaddition reaction of pyrroles, an intramolecular aldol reaction, and three C─C bond-forming radical reactions.

Abstract

Calyciphylline F represents the final challenge in the total synthesis of the caged polycyclic-type of Daphniphyllum alkaloids due to the strained 8-azatricyclo[4.2.1.0^4,8]nonane ring system. Here, we report the total synthesis of calyciphylline F. We construct the ring system by applying [4 + 3] cycloaddition reaction of pyrroles with 2-oxyallyl cations to an intramolecular reaction, followed by an intramolecular aldol reaction and capture of the resulting alkoxide as the xanthate. The bridgehead quaternary carbon center is constructed by the intramolecular addition reaction of the bridgehead radical to the alkoxy-acrylate, which is designed based on the proposed mechanism of by-product formation. Finally, another 6-exo-radical cyclization reaction constructs the last remaining ring and achieves the total synthesis of calyciphylline F.