Finn Moeller

A straightforward protocol for the electrochemical oxidation of the primary hydroxy group in glycopyranosides is presented. It uses aqueous ammonia as a base and electrolyte, reticulated vitreous carbon (RVC) electrodes, and TEMPO as a mediator. The ammonium salts of the corresponding uronic acids are obtained in excellent yield upon evaporation of the volatiles.

An operationally simple protocol for the electrochemical oxidation of the primary hydroxy group in glycopyranosides is presented. The strategy uses aqueous ammonia as a base and electrolyte, reticulated vitreous carbon (RVC) electrodes, and TEMPO as a mediator. Under these conditions, the ammonium salts of the corresponding uronic acids are obtained in excellent yield upon evaporation of the volatiles, rendering an exceptionally simple protocol.

Red light-absorbing bichromophores with straightforward preparation and superior photocatalytic activity were developed. Spectroscopic studies provided deep insights into the intra-ion-pair energy transfer key step and the novel approach.

Abstract

Photoactive osmium complexes are widely used sensitizers for the generation of singlet oxygen because they can be excited directly into their triplet states with low-energy red light. However, their short-lived excited states reduce quenching efficiencies and reaction quantum yields significantly. To elongate the excited state lifetime, osmium complexes have been linked to organic chromophores to form molecular dyads. This approach, although effective, is time- and resource-consuming, hampering larger-scale applications. Here, we demonstrate a straightforward approach by directly mixing a readily available cationic osmium complex and an anionic perylene derivative in solution. Strong Coulombic interactions facilitate rapid energy transfer (∼100 ps) from the excited osmium complex to the perylene derivative, mimicking a dyad-like system. Detailed spectroscopic investigations revealed an increased singlet oxygen formation rate by over one order of magnitude at sub-millimolar perylene concentrations, attributed to i) the three orders of magnitude longer lifetime of the perylene triplet state produced via intra-ion-pair energy transfer and ii) an inherently high singlet oxygen quantum yield of that key species. The novel catalyst system enables highly productive photooxygenations in water and in a MeOH/H₂O 10:1 mixture, highlighting the broad applicability and versatility of the Coulombic dyad approach for photocatalytic synthesis and wastewater treatment.

Nature, Published online: 22 June 2025; doi:10.1038/d41586-025-01855-w

Nature, Published online: 23 June 2025; doi:10.1038/s41586-025-09284-5

Several N2-substituted indazole derivatives efficiently undergo photorearrangement to benzimidazoles with UVB irradiation. Motivated by the difference between the wavelength at which the phototransposition is most efficient and the substrate absorbance λ _max, a photochemical action plot was constructed. Wavelength-dependent quantum yields were measured, and a photoflow protocol was established to perform the phototransposition on preparative scale.

Abstract

Herein, we report a detailed investigation of the photomediated transformation of indazoles to benzimidazoles through a nitrogen–carbon transposition. This phototransposition is known to occur in low yield when 1H-indazoles are subjected to high-energy UVC irradiation. The 2H-tautomer of indazole absorbs light more strongly than the 1H-tautomer at longer wavelengths. We leveraged this improved absorbance profile to develop a general system for the high-yielding conversion of N2-derivatized indazoles (prepared from the corresponding 1H-indazoles) to the corresponding benzimidazoles under UVB or UVA irradiation in up to 98% yield. Investigation of the substrate scope revealed a strong correlation between reaction yield and electron density at N2 of the indazole substrate, suggesting the importance of the availability of the lone pair at this position for reaction efficiency. In addition, evaluation of wavelength-dependent reactivity through the generation of a photochemical action plot revealed that the highest conversion does not only occur at the substrate's maximum absorbance wavelength but also on its red-side, enabling the use of longer wavelength irradiation to achieve high yields. Building on these insights, a continuous flow protocol was established that enables the phototransposition on preparative scale.

We present a photochemical strategy for transforming 1H- and 2H-indazoles into benzimidazoles, enabling heteroaromatic interconversion under mild conditions. This approach, grounded in a two-step mechanism of excited-state tautomerization and photochemical rearrangement, offers broad scope, high yields, and functional group tolerance, expanding the diversity of heterocycle-based libraries for fragment-based drug discovery.

Abstract

Fragment-based drug discovery relies on preparing diverse libraries of advanced building blocks, often incorporating heteroaromatic motifs. Altering the core of heteroaromatics to maximize library diversity typically requires de novo synthesis of each system. This can be often challenging when specific substitution patterns are needed. Here, we introduce a photochemical strategy for the direct permutation of 1H- and 2H-indazoles into benzimidazoles. This transformation exploits the distinct photochemical properties of these heteroaromatics and proceeds under mild conditions. Through systematic experimental and computational studies, we have elucidated a two-step mechanism involving excited-state tautomerization of 1H-indazoles, followed by photochemical rearrangement of the resulting 2H-isomers. This approach demonstrates broad substrate scope, high yields, and compatibility with a variety of functional groups. This method can expand the structural diversity of heterocycle-based libraries through the concept of chemical permutation for heteroaromatic interconversion.

Nature, Published online: 10 June 2025; doi:10.1038/d41586-025-01225-6

Short text: The first synthesis of hexa-arylborazines with ortho-substituted aryl groups expands their three-dimensional structure. By selecting the appropriate ortho-substituent, the ArLi adds to the BN-core in a controlled manner, guiding the stereochemical outcome of the three-substitution reaction. This stereoselective approach enables the synthesis of multichromophoric borazine derivatives, demonstrating how the stereochemical arrangement influences their redox behavior.

Abstract

Borazine and its derivatives can be considered critical doping units for engineering hybrid C(sp²)-based molecules with tailored optoelectronic properties. Herein, we report the first synthesis of hexa-arylborazines that, bearing ortho-substituted aryl moieties, extend three-dimensionally. Using a one-pot protocol, we first form an electrophilic chloroborazole and then react it with an aryl lithium (ArLi). By selecting the appropriate ortho-substituent, we can guide the ArLi to add to the BN-core in a specific way, ultimately controlling the stereochemical outcome of the three-substitution reaction. Rationalization of the stereochemical model through computational analysis allowed us to show that when aryl lithium nucleophiles bearing rigid long-range ortho-substituents are used, i.e., stiff substituents. The ortho-substituent shields its side of the electrophilic B₃N₃ core, biasing the incoming ArLi to add anti at each addition step, forming the final tri-aryl borazine exclusively as cc-isomer. Leveraging this stereoselective approach, prototypical multichromophoric borazine derivatives were prepared, and we showcased how the stereochemical arrangement of these chromophores distinctly influences their redox behavior. This methodology paves the way for previously inaccessible borazines to serve as privileged precursors to transcend the conventional bidimensionality associated with graphenoid systems and pioneer the construction of new forms of three-dimensional C(sp²)-based architectures.

The first asymmetric total synthesis of bonnadiene and ent-polytrichastrene B has been accomplished. An enantioselective redox-relay Heck alkenylation was used to form the stereocenter at C7. The unique [6,7,5] spirotricyclic structure was constructed via [5+2] cycloaddition. The functionalities in the spirotricycle have been strategically utilized to append the remaining moieties present in the natural product in a sequential manner. Moreover, two Fe-catalyzed hydrogen atom transfer (HAT) processes were employed to reduce the unactivated tetrasubstituted olefin and to construct the tetrasubstituted cyclopropane ring.

Abstract

We report herein the first asymmetric total synthesis of bonnadiene and ent-polytrichastrene B, two diterpenoids that share a common spirotricyclic skeleton. Notably, ent-polytrichastrene B also features a highly strained, sterically congested tetrasubstituted cyclopropane moiety, presenting significant synthetic challenges in both its construction and stereochemical control. The synthesis features: (1) palladium-catalyzed enantioselective redox-relay Heck alkenylation between electron-withdrawing alkenyl triflate and primary alkenol to form the stereocenter at C7; (2) diastereoselective intramolecular [5+2] cycloaddition to rapidly assemble the unique [6,7,5] spirotricyclic skeleton; (3) sequential installation of the requisite alkyl groups and alkenes present in the targeted molecule by leveraging the functionalities positioned on the tricycle; (4) Fe-catalyzed hydrogen atom transfer (HAT)-initiated hydrogenation to stereospecifically reduce the tetrasubstituted Δ^10,11 olefin and install the contiguous stereocenters; (5) Fe-mediated HAT-initiated 3-exo-trig radical cyclization to rapidly forge the tetrasubstituted cyclopropane ring with excellent stereoselectivity.

Photochemical anaerobic oxidation of sulfides, using nitroarenes as bifunctional reagents, enables the formal manipulation of the C─S bond. The method allows direct and selective access to versatile carbonyl compounds from largely inert sulfides by C–H oxidation, thus avoiding multistep activation by sulfur oxidation. The mild photo-induced protocol has been engaged in telescoped procedures to convert sulfides into amines, alcohols, and alkenes.

Abstract

The sulfide motif is distributed widely across chemical and biological space. In synthesis, its installation often marks the end point of a sequence, due to its relative inertness; sulfides typically require direct oxidation of sulfur before they are receptive toward transformation. Unfortunately, selective S-oxidation is not always straightforward, with the need for oxidants lacking chemoselectivity in the presence of functionality and delivering mixtures of oxidation products. This multistep manipulation of the sulfide motif, initiated by direct S-oxidation, limits the use of sulfides as synthetic handles for downstream manipulation. Herein, we describe a direct activation of sulfides by C–H oxidation alpha to sulfur—rather than traditional oxidation at sulfur—that facilitates efficient formal C─S bond manipulation. The mild nature of the photo-induced anaerobic oxidation protocol enables its merger with high-value transformations in telescoped or one-pot protocols that deliver branched amines, secondary alcohols, and alkenes from aldehyde and ketone intermediates. The method expands the chemistry of sulfides by diverting reactivity away from sulfur (oxidation, alkylation) and instead targeting directly the alpha position, resulting in formal manipulation of the C─S bond, and redefining sulfides as latent synthetic handles to be “switched on” at will.

Nature Chemistry, Published online: 20 June 2025; doi:10.1038/s41557-025-01848-2

An electrochemically driven deoxygenative C─Si bond formation strategy was developed for the synthesis of organosilicon compounds. The reactions operate under mild conditions without transition metal catalysts and sacrificial electrodes, providing an efficient avenue for the direct conversion of feedstock alcohols (1°, 2°, and 3°) and ketones directly to valuable organosilanes.

Abstract

Alcohols and ketones are abundant and structurally diverse feedstocks, yet their direct transformation into organosilicon compounds remains challenging due to the difficulty in selective cleaving C─OH and C═O bonds. Here, we report an electrochemically driven deoxygenative C─Si bond formation strategy that converts alcohols and ketones directly to organosilicon compounds. The reactions operate under mild conditions without external redox reagents and sacrificial electrodes. A wide range of alcohols, including primary, secondary, and tertiary alcohols, as well as ketones, are efficiently converted to the corresponding organosilane products. Overall, this study provides a step-economical, highly efficient, and synthetically versatile platform for the direct conversion of feedstock chemicals into valuable organosilicon compounds.