Research articles

The Mannich reaction has long been used by chemists for the synthesis of stereoselective synthesis of β-amino-carbonyl compounds. Here, the authors show a catalytic homo-Mannich reaction of cyclopropanols with in situ-formed imines, furnishing chiral 2,6-disubstituted piperidines in good yields with high diastereoselectivities due to the use of a diketiminate-complexed copper.

Darwinian evolution has shaped life on our planet through natural selection. Here, the authors report on the combination of self-replication, mutation and protometabolism in an out-of-equilibrium abiotic chemical system that can lead to natural selection for protometabolic activity.

Deuterated bioactive compounds are important as diagnostic tools and pharmaceuticals, but current methods of development are limited. Here the authors report how a silicon Lewis acid and a tertiary amine base act as a frustrated Lewis pair to catalyse the hydrogen exchange reaction for the deuteration of amides and esters.

Artificial photobiocatalytic reactions are appealing but sometimes suffer from non-enzymatic side reactions. Now a photoenzyme for enantioselective [2 + 2] photocycloaddition of 2-naphthyl derivatives is reported and combined with designed quenchers that shut down the competing enzyme-free racemic reaction.

Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.

Methylthio-alkane reductases are recently discovered enzymes that can produce methanethiol and small hydrocarbons from methylated sulfur compounds. Now the cryo-EM structure of a methylthio-alkane reductase complex is solved, revealing large metalloclusters previously observed only within nitrogenases.

CO adsorption free energy has been suggested as a descriptor to explain and predict CO₂ reduction activity across various electrocatalysts, but methods for determining it experimentally under operating conditions are lacking. Here a kinetic model is combined with rotating ring-disk voltammetry to estimate this parameter.

Prime editing is a CRISPR methodology whose efficiency declines with distance from the target sequence. Here the authors demonstrate prime editing with prolonged editing window, proPE, which extends the editing distance, enabling the use of prime editing for therapeutic interventions.

Delocalized radical systems are appealing for controlling stereoselectivity in organic synthesis. Here the authors report on a Co(II)-based enantioselective radical system for the dearomative 1,7-conjugate amination of readily available 4-vinylphenols with aryl azides.

Tandem electro-biocatalytic systems present a versatile platform for producing a variety of synthetic products using CO₂ as a starting material. Here direct ocean carbon capture is incorporated into an electrolysis scheme to produce formic acid from CO₂ dissolved in seawater that is subsequently converted to succinate in a bioreactor.

The activity and stability of supported metal catalysts is in large part influenced by their interaction with the support. Now, neural network molecular dynamics simulations are combined with interpretable machine learning to reveal the governing factors of metal–support interactions for Pt nanoparticles on various oxide supports, identifying key features and proposing sinter-resistant supports.

Hexopyranose cleavage is a crucial step in carbon metabolism. Here the authors report the discovery and characterization of metalloenzyme Art22, which is involved in the sugar moiety modification of aurantinin B, an antibacterial agent from Bacillus.

It is challenging to design machine learning potentials for heterogeneous catalysis that are universal, reactive and have high accuracy. Now, an element-based machine learning potential relying on a random exploration via an imaginary chemicals optimization sampling strategy is put forward, and is successfully demonstrated for a range of applications.

Molecular organometallic catalysts typically struggle to activate only one of two identical C–H bonds in arenes for mono-selective C–H activation. Now mono-selectivity has been achieved for Pd(II)-catalysed ortho- or meta-C–H activations using commercial proteins or designed peptides as ligands.

Strategies for asymmetric control in electrosynthesis involving radicals are sought after. Now asymmetric Lewis base catalysis is combined with electrochemistry, enabling the oxidative radical cross-coupling of esters with silyl enol ethers and affording γ-keto esters in high enantiomeric excess.

Optimizing devices for electrochemical CO₂ reduction requires a comprehensive and quantitative understanding of the microenvironments where the reactions occur. Now, a multiscale modelling approach that explicitly accounts for electrolyte effects at all scales is developed and showcased for the electroreduction of CO₂ on silver.

Azetidines are four-membered saturated N-heterocycles that are of interest in drug discovery and medicinal chemistry. Here the authors report how sulfamoyl fluoride substituents tune the reactivity of acyclic imine-derived triplet intermediates for the synthesis of azetidines via a [2 + 2] photocycloaddition reaction with alkenes.

Directing group strategies for selective dearomatization of unactivated aromatic π-systems have remained elusive. Now a homogeneous ruthenium catalyst, aided by a removable directing group, enables the site-selective hydrogenation of less reactive arene moieties in polyaryl compounds.

Electrocatalytic CO₂ conversion offers opportunities for producing sustainable fuels and chemicals, but achieving strong performance with realistic CO₂ sources remains a challenge. Here a system is designed to use high-pressure captured CO₂, and achieves 85% Faradaic efficiency and high-purity C₂H₄ for over 1,500 h.

The O-alkylation of tertiary alcohols with racemic tertiary electrophiles to access chiral hindered dialkyl ethers has remained elusive. Now this synthetic challenge has been accomplished by copper-catalysed C–O cross-coupling between tertiary haloamides and alcohols using designed ligands.