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To celebrate our first anniversary, the editors of Nature Synthesis have curated a Collection of content published so far, in which we showcase the scientific areas featured in the journal.
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.
Chemical synthesis typically draws on the roughly 90 elements found in nature and transforms them into fantastic things, which serve all imaginable needs of humankind. However, there are more than just these 90 elements in the periodic table. The synthesis of the heaviest elements, one atom at a time, is discussed here.
The use of step count as a metric of synthetic efficiency carries opportunities and challenges. Here, proposals are made to standardize what constitutes a synthetic step and how steps are counted. These proposals may be beneficial in the holistic evaluation of published synthetic routes.
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.
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.
Cross-coupling reactions between aryl halides and alcohols using copper are challenging due to the energetically demanding oxidative addition of copper into aryl halides. Now, this high-barrier step is bypassed using an energy transfer or direct excitation strategy for copper-mediated cross-coupling reactions. This process enables the use of aryl chlorides as electrophiles and alcohols, amines and fluoride as nucleophilic coupling partners.
Synthetic routes to aminoglycosides are often long and rely upon the coupling of semisynthetically produced fragments. Now, an enantioselective, copper-catalysed hydroamination of benzene has been developed to enable access to the aminoglycoside antibiotic ribostamycin. This bottom-up strategy provides modular and expedient entry into the aminocyclitol class.
Ketyl radicals can be used in a range of reactions, but their generation often requires harsh conditions and a large excess of reductants. Now, a multicomponent, palladium-photocatalysed reaction between aldehydes, 1,3-butadiene and N, S, O and C nucleophiles to build architecturally complex homoallylic alcohols is reported wherein ketyl-type radicals are generated under mild conditions.
Nature evolves diverse pathways for production of acetyl-CoA, a principal biosynthetic building block. Now, through in silico thermodynamic and kinetic analyses, this study proposes an acetyl-CoA biosynthetic route from C1 compounds and implements it in gas-fermenting bacteria for effective production of C2 metabolites.
The Mizoroki–Heck reaction forms C−C bonds between aryl halides and alkenes. For electron-deficient alkenes, β-coupled products are typically formed and synthesizing α-arylated products is challenging. Now, a triple catalysis system (nickel, photoredox catalysis and sulfinate) enables regioirregular formal Mizoroki–Heck reactions for electron-deficient alkenes and styrenes to give α-arylated alkenes.
β-hydride and β-heteroatom eliminations are elementary steps in many catalytic reactions used in the synthesis of drug molecules and polymers. However, the elimination processes often compete leading to unpredictable outcomes. Here, a series of mechanistically informed selection rules are developed to selectively achieve the desired elimination.
Plastic waste poses a serious economic, ecological and environmental threat. Here, non-recyclable, post-consumer microplastics are used as an electron feedstock for biosynthetic reactions in a photoelectrocatalytic system. The microplastics are simultaneously broken down into organic fuels, meaning that this system provides valuable chemicals at both the anodic and cathodic sites.
Selective oxidation of ring C–H bonds is an attractive route to functionalized cyclic amines, which are versatile intermediates in drug synthesis. Now, engineered P450 enzymes, designed with computational guidance to disfavour undesired products, are reported to oxidize all unactivated C–H bonds in cyclic amines with high selectivity.
Controlling diastereodivergent light-driven processes remains synthetically challenging. Here, we disclose how the light source and steric parameters can be used to control the diastereoselectivity of [2 + 2] heterocycloaddition processes, such as in Paternò–Büchi reactions, and provide access to previously inaccessible stereochemical variants.
Alkaline earth elements are among the most abundant and cost-effective metals in the toolbox of synthetic chemists and investigations of their structures and bonding have led to fascinating discoveries. This Review discusses the emerging synthetic chemistry and unusual redox chemistry of low-oxidation-state Be, Mg and Ca complexes.
MXenes are 2D materials with a rich chemistry and applications in energy storage, electronics and biomedicine. This Review discusses various MXene syntheses—from layered precursors to single-layer 2D flakes—including principles behind these methods and synthesis–structure–property relationships.
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.
On-surface methods can be used to synthesize organic molecules, polymers and nanomaterials, however, the diversity of conceivable products is limited by the number of known on-surface reactions. Now, a phenylene ring-forming reaction on a gold surface by intermolecular oxidative coupling of isopropyl substituents on arenes is reported. The reaction is probed using bond-resolved imaging and computational modelling.
Although dinitrogen cleavage by metal complexes is known, the subsequent formation of N–H bonds using H2 is thermodynamically challenging. Now, ammonia synthesis using an Ir photocatalyst and H2 for the hydrogenation of a N2-derived molybdenum nitride is reported. The starting molybdenum nitride can be regenerated to complete a synthetic cycle for the preparation of ammonia from N2 and H2.
The synthesis of graphynes has often been limited to using irreversible coupling reactions that are likely to result in materials that lack long-range order. Now, a periodically sp–sp2-hybridized carbon allotrope, γ-graphyne, is prepared using a reversible dynamic alkyne metathesis and managing the balance between kinetic and thermodynamic control. This material’s interlayer stacking and folding behaviour are also revealed.
Strategies for the creation of topological carbon nanostructures have greatly advanced synthetic organic chemistry and materials science. Now, the synthesis of a Möbius carbon nanobelt, a molecule with a twist on belt-shaped aromatic hydrocarbons, is reported.
Dual-atom catalysts are promising for CO2 reduction reactions; however, sluggish kinetics limit practical applications. Now, a Ni dual-atom catalyst has been synthesized, realizing efficient electrocatalytic CO2 reduction with a CO partial current density of ~1 A cm2 at >99% Faradaic efficiency.
Current synthesis of 2D crystalline superconductors mainly limits them to layered materials. Now, crystalline, non-layered 2D PdTe has been synthesized by inducing interfacial reactions at a solid–solid interface, exhibiting 2D superconductivity with a thickness-dependent onset critical temperature of ~2.56 K.
Two-dimensional materials have many desirable properties but controllable synthesis is difficult. Now, a flux-assisted growth approach has been designed to reproducibly prepare high-quality, atomically thin materials. Eighty atomically thin composite flakes have been prepared by this approach.
Torus knots are assembled in a contra-helical tubular manner by coaxially nesting a small multistranded helix within a larger reverse helix. This approach enables the near-quantitative one-step syntheses of four iron(II)-templated trefoil knots. The spin-crossover properties of the iron(II) centres in the knots are tuneable by altering the intramolecular strain.
For 3D printing to reach its full potential, materials should be designed to take advantage of the unique processing flows involved. In this Perspective, we explore the design rules for printable materials and articulate how 3D printing can direct and enhance the functionality of printed systems.
Metals in their zero-valent form offer a great deal of potential for chemical synthesis. The reliable and straightforward activation of these raw materials has perhaps inhibited the full realization of this promise. This review examines the emergence of the technique of ball milling as a reactor technology to enable mechanical activation of zero-valent metals.
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.
Quantum chemical calculations are typically used in synthetic organic chemistry to probe reaction mechanisms and propose stereochemical models. Now, a strategy to develop chemical reactions using quantum chemical calculations is reported. This study demonstrates in silico reaction screening with difluorocarbene, leading to a method for the synthesis of fluorinated N-heterocycles.
The complexity of carbohydrate structures makes their synthesis challenging. Now, an automated glycan synthesizer is reported which is capable of preparing a library of bioactive oligosaccharides, including a fully protected fondaparinux pentasaccharide. Furthermore, the synthesizer can rapidly assemble arabinans up to 1,080-mer size, starting from monosaccharide building blocks.
Automated organic synthesis is often limited to making simple molecules, requiring a small number of synthetic steps, because of the complexity and variety of organic molecules. Now, a robotic platform has been instructed to build complex structures, such as the core fragment of (+)-kalkitoxin, in a stereochemically controlled and iterative manner.