Research articles

The selective synthesis of non-symmetrical diamides and amido-esters is a challenge. Now a Pd-catalysed dicarbonylation method is reported that generates non-symmetrical diamides and amido-esters through diamino- and amino-alkoxy carbonylations of propargylic acetates using two different nucleophiles. Mechanistic studies reveal that the process occurs through a sequential carbonylation process.

Arynes are often generated using strong bases or fluoride sources, limiting functional group tolerance. Now, stable triaryloxonium salts are transformed into arynes and subsequently trapped using cycloaddition reactions by treatment with potassium phosphate at room temperature. This functional group-tolerant method proceeds by an elimination, unimolecular, conjugate base-like elimination mechanism to form the aryne.

While enzyme-mediated oligosaccharide synthesis is versatile, it is often limited by the availability of glycosyl transferases. Now a chemoenzymatic strategy is reported, comprising enzymatic assembly of a core oligosaccharide followed by chemical manipulations, to produce a library of glycans that reveal binding specificities of serum antibodies.

Centring structure-directing agents govern structure assembly to consistently obtain sodalite topology backbone, yielding more than 20 isoreticular zeolite-like metal–organic frameworks with tailored pore apertures and porosity.

Direct synthesis of nitric acid from nitrogen and oxygen is attractive but is challenging under mild conditions. Now, direct conversion of air to nitric acid is achieved under mild conditions via a hydroxyl-radical-mediated hetero-homogeneous electrochemical route at the cathode.

A chemical dedoping technique is introduced to mitigate excessive electron doping in molecular cation intercalated MoS₂, producing a stable bulk monolayer material with monolayer-like optical properties but a much larger optical cross-section.

The synthesis of polycyclic conjugated hydrocarbons with antiaromatic moieties is realized by the thermal rearrangement of dibromomethylene-functionalized molecular precursors on a hot Au(111) metal surface.

The reversible deactivation process in polymerization using chain-end hydrogen atoms remains underexplored and difficult to control. Now, deprotonation–protonation equilibrium-driven C(sp³)–H alkylation polymerization of cyclopropanes is reported using the cooperative catalysis of an organic base and a metal salt to control the polymerization.

Shape-controlled multimetallic nanoparticles remain elusive due to large existing miscibility gaps. Now, a low-temperature (≤80 °C) non-equilibrium synthesis of nanosurface alloys with tunable size, shape and composition is reported. The nanosurface alloys can be used as selective and phase-stable CO₂ reduction electrocatalysts.

Polymetallic rings are formed via the collision-induced dissociation of larger complexes. Ion mobility mass spectrometry can be used to determine whether the formed polymetallic complexes are cyclic or acyclic.

The electroreduction of CO to methanol catalysed by supported cobalt phthalocyanine molecules is hindered by low selectivity and poor mechanistic understanding. Here a mechanism-guided reaction based on systematic kinetic studies is used to achieve an improved methanol Faradaic efficiency of roughly 85%.

meta-Selective acylation of arenes typically requires directing groups or steric hindrance. Now, a combined N-heterocyclic carbene and organic photoredox catalysed of electron-rich arenes, using acyl imidazoles as acylating agents, is reported. Mechanistic studies reveal the process proceeds through single-electron oxidation and radical–radical coupling steps.

Suzuki-type cross-coupling for C(sp²)–C(sp³) bond formation with aliphatic halides remains challenging with tertiary aliphatic halides and under transition-metal-free conditions. Now, a transition-metal-free C(sp²)–C(sp³) cross-coupling of α-(pseudo)halo aliphatic ketones with boronic acids via a 1,4-metallate shift is reported which is compatible with tertiary aliphatic halides, allowing for 1,3-disubstituted products.

Developing reaction conditions for radical–radical cross-dehydrogenative amination reactions is challenging. Now a nickel-catalysed asymmetric electrochemical cross-dehydrogenative amination reaction between acylimidazoles and nitrogen nucleophiles is developed to access structurally diverse α-amino carbonyls that can be used to synthesize (+)-γ-secretase inhibitor, (+)-flamprop-methyl and (+)-flamprop-isopropyl.

N-Alkyl amines are prevalent compounds in organic synthesis and medicinal chemistry; however, their synthesis can be impeded by the availability of key reaction components and low selectivity. Now, a metallaphotocatalytic chemo- and regioselective synthesis of N-alkyl anilines is reported that uses readily available tertiary alkylamines, nitroarenes and carboxylic acids.

C(sp³)–H fluoroalkylation of bioactive molecules is a challenge. Now, a scalable and site-selective allylic fluoroalkylation of terpenes and olefins has been developed using a cobaloxime catalyst. Mechanistic studies reveal the process probably proceeds through halogen-atom transfer and hydrogen-atom transfer steps.

Multiple-component cross-coupling reactions can often be unselective and inefficient, making them difficult to develop. Now a chemoselective chromium-catalysed process is reported, forming tertiary alkane centres from benzylic ethers, a Grignard reagent and a silyl chloride, alkyl tosylate or trifluoromethyl-substituted alkene.

The combination of nickel-catalysis and sensitized electron transfer is underdeveloped. Now, a nickel-catalysed sensitized electron transfer method for the synthesis of methyl thioesters from carboxylic acids is reported. Mechanistic investigations reveal that the merger of photocatalytic electron transfer, energy transfer and nickel catalysis plays an essential role in this thioesterification reaction.

Macrocyclization with chirality induction is challenging owing to the entropic penalty associated with ring closure while maintaining chiral conformation. Now, a confinement strategy is reported to achieve chiral macrocyclization and yield an enantiopure product. The chirality of the capsule can be switched to the opposite form by sonication.

The most popular reactions used by medicinal chemists are often incompatible with nanoscale ultrahigh-throughput experimentation (ultraHTE). Now, ultraHTE-amenable reaction conditions are developed through miniaturization of four of the most important drug discovery transformations, and their generality and scalability are tested on a range of natural products and drug candidates.