Finn Moeller

Nature, Published online: 08 January 2025; doi:10.1038/s41586-024-08373-1

A method to produce wireless microelectronic devices powered by light using standard nanofabrication techniques is described to convert any traditional 96-well or 384-well plate into an electrochemical reactor that can drive reactions in high throughput.

Nature, Published online: 08 January 2025; doi:10.1038/d41586-024-04106-6

Electrochemical reactions for organic synthesis typically require intricate, specialized equipment, slowing progress in this field. Minuscule electric generators now enable faster reaction discovery and development.

Arylthianthrenium salts were converted into aryl diazoesters via palladium catalysis. This strategy enables the efficient and site-selective late-stage functionalization of advanced substrates with an α-diazoester functionality. The thus introduced diazo moiety can subsequently undergo various C−C and C-heteroatom bond-forming reactions.

Abstract

By leveraging the fast oxidative addition of arylthianthrenium salts (aryl-TT⁺) to palladium(0), a regioselective diazoester installation has been developed. This approach enables the introduction of a diazo moiety to densely functionalized arenes at a late stage. The installed diazo group is amenable to facile further derivatization.

Nature, Published online: 06 January 2025; doi:10.1038/d41586-024-04218-z

Those recovering from drug or alcohol misuse speak up — and say they wish more researchers could do so freely at work.

Nature Chemistry, Published online: 06 January 2025; doi:10.1038/s41557-024-01691-x

Heavier analogues of unsaturated organic molecules are of interest because of their bonding situation and their potential use in synthesis. Now, a Bi(I)-based allyl cation, which can be seen as a heavy congener of all-carbon π-allyl cations, has been reported. This complex serves as a synthon for Bi(I) transfer, enabling access to low-valent organobismuth compounds.

A dearomative functionalization approach of abundant N-heteroarenes has been developed to harvest valued 3D N-heterocyclic skeletons. This robust method is enabled by the in situ generation of highly reactive non-symmetric iodane from bench-stable hypervalent iodane, PhI(OAc)₂, and BF₃ ⋅ OEt₂ A wide range of N-heteroarenes were transformed into their corresponding 3D analog via the installation of a highly versatile cyano group as a new vector.

Abstract

The rapid construction of three-dimensional (3D) heterocyclic frameworks is a key challenge in contemporary medicinal chemistry. The molecules with three-dimensional complexity hold a greater probability to improve clinical outcomes, solubility, selectivity for target proteins, and metabolic stability. However, the prevalence of flat molecules persists among new drug candidates, primarily owing to the multitude of chemical methods available for their synthesis. In principle, the dearomative functionalization of N-heteroarene allows for the conversion of readily available planar molecules into partially or fully saturated nitrogen heterocycles, which are most significant structural motifs of pharmaceuticals and natural products. Unfortunately, these reactions are very rare because of the inherent challenge imposed by heteroarenes’ poor reactivity, rendering the process thermodynamically unfavorable. Herein, we report a modular approach for accessing 3D chemical space in translating planar heteroarenes into valuable 3D heterocycles via the installation of a highly versatile cyano group as a new vector. This approach is enabled by the in situ generation of reactive, non-symmetric iodane by combining cyanide anion and bench-stable PhI(OAc)₂. This reaction represents a rare example of 1,2-dicyanation of N-heteroarenes that meets the numerous requirements for broad implementation in drug and agrochemical discovery. The transformation is highly selective and amenable to a wide range of N-heteroarenes and late-stage partial saturation of drugs and agrochemicals.

The electrochemical oxidation of multifunctional catechols represents a “green” and clean alternative pathway to ortho-quinones, which are used to form oligomer networks with branched multi-thiols. In these networks, the catechols are restored and represent adhesive points, which can establish transient interactions with enzymes. These oligomer/enzyme-conjugates are shielding the enzymes from heat stress, thus preventing denaturation.

Abstract

Multifunctional ortho-quinones are required for the formation of thiol-catechol-connectivities (TCC) but can be delicate to handle. We present the electrochemical oxidation of the dipeptide DiDOPA, achieving up to 92 % conversion efficiency of the catechols to ortho-quinones. Graphite and stainless steel could be employed as cost-efficient electrodes. The electrochemical activation yields quinone-solutions, which are free of undesired reactive compounds and eliminates the challenging step of isolating the reactive quinones. The DiDOPA quinones were employed in polyaddition reactions with multi-thiols, forming oligomers that functioned as transient enzyme stabilizers (TES). These TCC-TES-additives improved the thermal stability and the activity of tyrosinase in heat stress assays.

In this work, we have developed a current-regulated selective nickel-catalyzed electroreductive cross-electrophile carbonylation, which offers a direct convergent synthesis of β/γ-hydroxy ketones. A diverse range of multi-substituted β/γ-hydroxyketones can be accessed with high chemo- and regioselectivity from epoxides, aryl iodides, and a simple CO source (ClCO₂Pr). This electroreductive carbonylation strategy exhibits high functional group tolerance and can be applied in late-stage derivatization of drugs and natural products.

Abstract

The nickel catalyzed multi-component cross-electrophile carbonylation which emerges as a powerful and efficient method for constructing diverse ketones has attracted increasing attention of organic chemists. However, the selectivity of this reaction poses a significant challenge. In this work, we have developed a current-regulated selective nickel-catalyzed electroreductive cross-electrophile carbonylation, which offers a direct convergent synthesis of β/γ-hydroxy ketones, which represent pivotal structural motifs found in numerous natural products, bioactive molecules, pharmaceutical compounds, and essential building blocks. A diverse range of multi-substituted β/γ-hydroxyketones can be accessed with high chemo- and regioselectivity from epoxides, aryl iodides, and a simple CO source (ClCO₂Pr). This electroreductive carbonylation strategy exhibits high functional group tolerance and can be applied in late-stage derivatization of drugs and natural products. Notably, chiral epoxides can be employed as reactants with chirality retention, enabling the synthesis of asymmetric β-hydroxy ketones. Our approach demonstrates a novel electrochemical selectivity-controlled strategy in multi-component cross-electrophile coupling.