Articles in 2022

Predictably activating C–H and C–C bonds for the synthesis of new materials remains a challenge within the synthetic community. A ternary catalytic dance between radicals, metals and light may unlock this puzzle.

Late-stage tritiation with high selectivity, isotopic purity and functional-group tolerance is important for the radiolabelling of drug candidates or bioactive compounds. Now, a broadly applicable protocol using aryl thianthrenium salts allows for tritiation of complex molecules by hydrogenolysis via an intermediate cationic palladium complex.

Iterative synthesis can generalize, automate and democratize the molecule-making process. Now, by using a computer algorithm to scan the depths of chemical reactivity space, thousands of iterative ways to make small molecules are discovered.

The organizing principles of click chemistry help scientists make molecules for a variety of applications. Such democratization of synthesis is challenging and rewarding, as useful simplicity is difficult to achieve. We reflect on this and look forward, hoping to continue to tie the joy of functional discovery to the challenges of synthetic chemistry.

In early 2020, scientists and medics started rummaging around the pharmacy shelves hunting for treatments that might curtail the spiralling pandemic death rates. This is the story of how they are searching and what they have found so far.

Enzymes catalyse reactions with unparalleled activity and selectivity. Using chemical insights, researchers can now direct these powerful natural catalysts to perform new-to-nature transformations that solve challenging synthetic problems. In this Perspective, we show how chemists and protein engineers have guided nature’s genetically encoded and evolvable machinery to perform new biocatalytic transformations.

Iterative sequences of organic reactions can be automated but are rare and challenging to identify. Now, a computer-driven strategy is reported for the systematic discovery and evaluation of such sequences. Several of the iterative sequences are validated experimentally and enable the syntheses of useful motifs in natural product targets.

A ternary catalytic method combining organic photoredox, hydrogen atom transfer and nickel catalysis is reported. This combination can directly arylate the allylic C(sp³)–H bonds of a broad range of readily available olefins. Mechanistic experiments, coupled with density functional theory calculations aid the elucidation of the ternary catalytic cycle and the origin of regioselectivity.

Remote functionalization through alkene isomerization is a popular strategy in organic synthesis. The dynamic nature of alkene isomerization typically leads to difficulties in controlling the stereochemistry of C(sp³) centres along the carbon skeleton. This Review outlines synthetic methods that tackle this issue and leverage alkene isomerization to control C(sp³) stereocentres in complex organic molecules.

Oximes are valuable motifs with diverse reactivity. This Review outlines the breadth of oxime reactivity including N–O bond fragmentation through transition metal catalysis and photocatalysis, [2 + 2]-cycloaddition reactions, asymmetric reduction and applications in materials science. Developments in transition metal catalysis and photocatalysis highlight the use of oximes as powerful synthetic building blocks.

A sonochemical route rapidly synthesizes covalent organic frameworks (COFs) in aqueous solutions of acetic acid. This method has operational advantages compared with conventional solvothermal routes and yields COFs of higher crystallinity and porosity, and hence improved materials properties.

In photoelectrochemical (PEC) cells, water oxidation to O₂, when coupled to CO₂ reduction, typically requires a pair of light absorbers or an applied bias voltage. Now, a bias-free PEC cell with a single sunlight absorber drives simultaneous CO₂ reduction to give formate, and the oxidation of an organic substrate in aqueous conditions.