Finn Moeller

An efficient, metal-free electrochemical three-component reaction of cinnamic acids, SO₂, and amines to access (E)-β-styryl sulfonamides is reported. Utilizing graphite electrodes and SO₂ stock solutions, this decarboxylative protocol proceeds under mild conditions with high regio- and stereoselectivity. Scalability, electrode/electrolyte reusability, and renewable feedstocks underscore its sustainable synthetic potential.

An efficient, electrochemical three-component reaction for the synthesis of vinyl sulfonamides from cinnamic acids, SO₂, and amines is reported. This metal-free protocol utilizes inexpensive graphite electrodes and easy-to-use SO₂ stock solutions to facilitate a decarboxylative transformation under mild conditions. The reaction proceeds with high regio- and stereoselectivity. The use of cinnamic acid derivatives as biobased feedstocks, combined with the demonstrated scalability and electrode/electrolyte reusability, highlights the potential of this approach for a sustainable synthesis of the important vinyl sulfonamide scaffold.

Bisabosquals are unusual meroterpenoids from Stachybotrys containing a benzopyran/benzopyran core. Herein, we report the successful completion of the first enantioselective total synthesis of any bisabosqual with a 16-step synthesis of (−)-bisabosqual F. Key aspects include enantioselective N-heterocyclic carbene catalyzed (4 + 2) annulation to construct the D-ring; stereoinvertive cyclization at a tertiary alcohol to produce the benzochromene; and late stage oxidative NHC-mediated lactonization to assemble the pentasubstituted aromatic.

Abstract

In 2001, a family of meroterpenoids, the bisabosquals, were isolated from the Stachybotrys fungi during studies focused on the discovery of antifungals. Although they share biosynthetic precursors with more common Stachbotrys merotepenoids, their cyclization is reminiscent of the cannabinoid family thereby providing their unique densely functionalized benzopyran/benzofuran core. Despite interest in their total synthesis, to date only racemic bisabosqual A has been prepared, with the enantioselective total synthesis of any bisabosqual yet to be realized. Herein, we report the successful completion of the first enantioselective total synthesis of a bisabosqual with the 16-step synthesis of (−)-bisabosqual F. Key aspects include an enantioselective N-heterocyclic carbene (NHC) catalyzed (4 + 2) annulation to construct the D-ring; stereoinvertive cyclization at a tertiary alcohol to produce an advanced benzochromene; and late stage oxidative NHC-mediated lactonization to assemble the pentasubstituted aromatic.

The total synthesis of (±)-cristaxenicin A was achieved by employing a one-pot sequence of the Eschenmoser–Claisen and Cope rearrangement reactions to construct the nine-membered ring from a five-membered nitrile. After formation of the trans-fused bicyclic skeleton through an intramolecular Stetter reaction, the cyclopentene ring was transformed into a dihydropyran ring by oxidative cleavage, followed by intramolecular acetalization.

Abstract

Cristaxenicin A, a natural marine product with a skeleton consisting of a nine-membered carbocycle fused with a dihydropyran ring, displays strong antiprotozoal activity against Leishmania amazonensis and Trypanosoma congolense. The synthesis of cristaxenicin A is challenging because of its unique oxidation pattern at C11 and C20, the cis-cyclononane with a C5─C6 double bond, and the C1─C19 alkene moiety functionalized as an enol acetate. Herein, we report the first total synthesis of (±)-cristaxenicin A. The nine-membered ring was constructed from 2,2-divinylcyclopentanecarbonitrile through an addition reaction with 4-(tert-butyldimethylsilyl)oxy-2-butenal followed by a one-pot sequence of the Eschenmoser–Claisen and Cope rearrangement reactions. After the formation of a trans-fused bicyclo[7.3.0]dodecane skeleton through an intramolecular Stetter reaction, the cyclopentane ring was transformed into a dihydropyran ring by oxidative cleavage, followed by intramolecular acetalization. Two reactions described herein, namely, the formation of a cyclononadiene ring via the Cope rearrangement without using an oxy-Cope substrate and a new protocol for the construction of a dihydropyran ring from a cyclopentene derivative, provide a powerful tool for the total synthesis of natural products with highly functionalized complex structures.

Nature Communications, Published online: 26 December 2025; doi:10.1038/s41467-025-66806-5

While iron catalysis holds immense promise in organic synthesis due to the comparatively wide availability and low toxicity of the metal, modulation of the catalyst’s oxidation state still typically relies on conventional and wasteful approaches. Here, the authors integrate mechanochemistry into iron-catalyzed regiodivergent hydroarylation of alkenes with indoles, leading to an efficient generation of alkylated indoles.

After the oxidation of Ni(OH)₂, chloride ions adsorb on the NiOOH surface, leading to OCl⁻ formation through the chlorine oxidation reaction and partial Ni dissolution. In contrast, the presence of a spectator anion layer on NiOOH inhibits chloride adsorption and improves the selectivity of the oxygen evolution reaction.

Water electrolysis is a promising route to green hydrogen production, but its operation in chloride-containing electrolytes (e.g., seawater) is hindered by the competing chlorine evolution reaction (CER) that lowers oxygen evolution reaction (OER) selectivity and accelerates catalyst degradation. Here, we use a combination of electrochemical quartz crystal microbalance (EQCM) and operando Surface-Enhanced Raman spectroscopy (SERS) to directly probe chloride adsorption on Ni-based catalysts. Our study reveals that chloride ions (Cl⁻) adsorb on the Ni surface even at low potentials where Ni(OH)₂ is the predominant phase, and that this adsorption intensifies on high-valent Ni OOH during OER, leading to hypochlorite (OCl⁻) formation significantly reduce OER selectivity and catalyst stability. Importantly, introducing spectator anions such as CO₃ ²⁻, SO₄ ²⁻, or NO₃ ⁻ suppresses Cl⁻ adsorption. Among these, CO₃ ²⁻ binds strongly to Ni sites and inhibits both Cl⁻ and OH⁻ adsorption, whereas SO₄ ²⁻ and NO₃ ⁻, with their weaker binding, preferentially block Cl⁻ while still allowing OH⁻ adsorption. As a result, OCl⁻ generation is dramatically decreased even under locally acidic conditions caused by high OER current densities, thereby enhancing catalyst activity and stability by selectively favoring OER over CER. This study highlights the utility of combined EQCM–SERS analysis to unravel interfacial adsorption processes in complex electrolytes like seawater splitting and provides new insights into leveraging adsorption preferences of spectator anions.