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Empirically observed regiochemistries indicate that the CF₂H radical has a nucleophilic character similar to alkyl radicals, but the CF₃ radical is electrophilic in reactions with heterocycles. Here, the authors report DFT calculations, reproducing experimental selectivities and leading to an explanation of this difference.

Synthetic methods to generate tertiary nitroalkanes are scarce. Now the cobalt-catalysed synthesis of tertiary nitro-containing compounds under mild conditions from easily available olefins is enabled by a nitro-transfer reagent containing an anomeric amide.

Enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene is demonstrated using a two-phase terpene synthesis strategy.

An Ni-electrocatalytic system can couple two different carboxylates using doubly decarboxylative cross-coupling, tolerating a range of functional groups, being scalable, used for the synthesis of 32 known compounds and reducing overall step counts by 73%.

Highly substituted carbon–carbon bonds are constructed using a simple iron catalyst and an inexpensive silane: more than 60 examples of this reaction — in which heteroatom-substituted olefins are reacted with electron-deficient olefins — are presented.

Members of the hapalindole, fischerindole, welwitindolinone and ambiguine families were synthesized, each constructed without the use of a single protecting group. As a consequence, molecules that have previously required 20 or more steps to synthesize racemically in milligram amounts can now be procured as single enantiomers in significant quantities in 10 steps or less.

Synthetic chemistry has long been used to prepare useful compounds — especially those that are hard to obtain from natural sources. But synthetic biology is coming of age as an alternative strategy. A biologist and two chemists debate the merits of their fields' synthetic prowess.

Although organic chemists often devise synthetic routes for molecules by mimicking enzyme reactions, such syntheses generally target individual compounds; here, a strategy is reported that targets a whole family of compounds. The approach mimics the biosynthesis of terpenes to efficiently prepare five compounds from the eudesmane family of terpenes, and provides a framework for the synthesis of other such compounds.

Molecular scaffolds bearing 1,1-diaryl-substituted four-membered rings remain difficult to access using traditional synthesis. Now it has been shown that a modular, nickel-electrocatalytic sequence enables the programmable, scalable and chemoselective synthesis of these high-value motifs, offering broad utility across drug discovery and showcasing strategic applications to patented intermediates.

Starting with alkyl carboxylic acids, a simple olefin synthesis using any substitution pattern or geometry, based on amide-bond synthesis with nickel- or iron-based catalysis, is described.

Using a combination of radical retrosynthesis, biocatalysis and C–H functionalization logic, a concise and scalable approach to the synthesis of saxitoxin and derivatives thereof in fewer than ten steps is presented.

Readily accessible enantioenriched sulfonylhydrazides and low loadings of an inexpensive achiral Ni catalyst can be used to control the stereochemical outcome of radical cross-coupling.

Nucleoside diphosphates and triphosphates impact nearly every aspect of biochemistry. Now, a modular, reagent-based platform has been developed to enable the stereocontrolled and scalable synthesis of a library of such molecules. This operationally simple approach provides access to pure stereoisomers of nucleoside α-thiodiphosphates and α-thiotriphosphates.

Amino alcohols are essential in pharmaceuticals, agrochemicals and other applications. Now, using a serine-derived chiral carboxylic acid, an electrocatalytic decarboxylative transformation enables efficient and stereoselective access to diverse amino alcohols. This method is scalable, modular and could offer rapid synthesis of medicinal compounds and key building blocks.

A scalable total synthesis of portimines enables structural reassignment of portimine B and in-depth functional evaluation of portimine A, revealing that portimine A induces translation inhibition selectively in human cancer cells and is efficacious in vivo tumour-clearance models.

The tumour-targeting activity and specificity of T cells with a CAR forming a reversible covalent bond with a hapten can be regulated by a small-molecule adapter that selectively binds to the hapten and to a chosen tumour antigen.

The use of protecting groups has been, and remains, instrumental in the development of organic synthesis. However, designing protecting-group-free strategies offers the challenge of developing useful new chemoselective processes as well as being inherently more step- and atom-economic.

The covalent capture of a ligand by its target protein(s) is important for drug-target identification. Now an electrochemically active warhead—diazetidinone—can be leveraged in a chemoproteomics platform for electroaffinity labelling of a ligand’s target protein to afford target-ligand identification in live cells.

We report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, enabling an approach to accessing complex molecular architectures, which relies on a silver additive that forms an active Ag nanoparticle-coated electrode surface along with carefully chosen ligands.

A route to the synthesis of hindered ethers is developed, in which electrochemical oxidation is used to liberate high-energy carbocations that are then captured by an alcohol.

Combining cycloaddition and carbon–carbon cross-coupling offers a way of simplifying the enantioselective preparation of chemical building blocks, natural products and medicines such as the antipsychotic asenapine.

Electrophilic halogenation approaches often suffer from low reactivity and chemoselectivity when it comes to complex compounds. Now a class of halogenating reagents based on anomeric amides that can halogenate complex bioactive molecules with diverse functional groups and heterocycles has been developed. The higher reactivity of these anomeric amide reagents is attributed to the energy stored in the pyramidalized nitrogen.

An electrochemical C–H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity is described; it uses inexpensive and readily available materials and represents a scalable allylic C–H oxidation that could be adopted in large-scale industrial settings without substantial environmental impact.

It is shown that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild, direct and operationally simple formation of medicinally relevant carbon–carbon bonds while reacting in a complementary fashion to other innate carbon–hydrogen functionalization methods.

A bench-stable, aryl sulfonyl triazene is described that can be appended to alcohols or amines and used as a directing group to effect remote desaturation of unactivated aliphatics to produce olefins. The reaction is mild, operationally simple, requires no added metals and produces unsaturated tosylates or tosylamides available for further functionalization.

A synthetic strategy has been developed that provides easy access to structurally diverse analogues of naturally occurring antibiotics, providing a fresh means of attack in the war against drug-resistant bacteria. See Article p.338

A perspective is given on how an electrocatalytic approach, inspired by decades of energy storage studies, can be used in the context of efficient cobalt-hydride generation with a variety of applications in modern organic synthesis.

Excising hydrogen adjacent to a carbonyl group—one of the most basic and widely employed transformations in organic synthesis—is traditionally achieved using metals and/or stoichiometric oxidants. Now, it has been shown that an electrochemically driven approach removes such requirements, resulting in a more sustainable and easily scalable method with wide substrate scope.

A catalyst that couples together three reactants to form just one compound out of several possibilities, as a single mirror-image isomer, should simplify the synthesis of biologically relevant molecules. See Article p.367

Compounds that are sensitive to the components of air are difficult to use in chemical reactions, requiring conditions that are tedious to set up. A simple, practical solution to this problem has finally been devised. See Letter p.208

Iodine atoms can be fitted with a chemical jacket to control the conversion of simple carbon chains into complex iodine-containing molecules. Previously, such reactions were only possible with enzymes.

The taxane diterpene family is structurally complex and exhibits a wide range of biological activities, best exemplified by the successful drug Taxol. Here, two of the least oxidized taxanes in the family, ‘taxadienone’ and taxadiene, are prepared by total synthesis on a gram scale. The concise synthetic route described herein provides a scalable, enantioselective entry to the taxane family of natural products.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Structural and functional studies reveal how the bacterial flavoenzyme EncM catalyses the oxygenation–dehydrogenation dual oxidation of a highly reactive substrate, and show that EncM maintains a stable flavin oxygenating species that promotes substrate oxidation and triggers a rarely seen Favorskii-type rearrangement.