Review Articles

Enantioselective synthesis of medium-sized rings by organocatalytic cycloadditions offers opportunities that are complementary to metal-catalysed cycloadditions. This Review discusses the ability of organocatalytic cycloadditions to synthesize stereodefined medium-sized ring architectures, critically evaluates current synthetic strategies, and highlights avenues for further development.

Catalytic enantioselective synthesis of all-carbon quaternary stereocentres is a long-term challenge in organic synthesis because of substantial steric repulsion and dissimilarities between the substituents around the stereocentre. This Review presents how the desymmetrization strategy plays an important role in constructing these types of motifs.

Performing enantioselective photocatalytic reactions with visible light is a challenging task that has seen substantial advances with the development of new catalysts. Although many approaches utilize dual-catalytic systems in which the photocatalyst is separate from the chirality-inducing moiety, in this Review bifunctional photocatalysts that perform both roles are discussed.

The electrocatalytic oxygen evolution reaction (OER) balances the hydrogen evolution reaction when splitting water into hydrogen and oxygen. This review highlights the need for new theory, electrochemistry and operando spectroscopy to enable knowledge-driven synthesis of new OER electrocatalysts.

Chemoenzymatic strategies that combine chemical and enzymatic transformations are becoming increasingly popular in the synthesis of complex molecules. This Review highlights notable case studies in the application of chemoenzymatic strategies for structure–activity relationship explorations of bioactive natural products.

Green ammonia synthesis is important for future sustainable manufacturing of fuels and chemicals. This Review highlights the recent progress and challenges in both fundamental research in catalysis and potential industrial scaleup using renewables.

Combinatorial synthesis has historically been the cornerstone of high-throughput experimentation. In this Review, we discuss the evolution of combinatorial synthesis and envision a future for accelerated materials science through its integration with artificial intelligence. We also evaluate the key aspects of combinatorial synthesis with respect to workflow design.

Anodic C(sp³)–H bond oxidative functionalization that involve C(sp³)–M, a C(sp³) radical or a C(sp³) cation intermediate with hydrogen evolution can be achieved by direct and indirect electrolysis. This Review discusses both strategies, and gives examples of the electrochemical methods developed for such functionalization reactions.

Intercalation-based exfoliation is a reliable strategy for preparing atomically thin sheets. This Review highlights various types of intercalation-based exfoliation methods as well as the potential applications of the exfoliated nanosheets and the challenges and prospects in this emerging field.

Self-driving labs (SDLs) combine machine learning with automated experimental platforms, enabling rapid exploration of the chemical space and accelerating the pace of materials and molecular discovery. In this Review, the application of SDLs, their limitations and future opportunities are discussed, and a roadmap is provided for their implementation by non-expert scientists.

1,4-Dicarbonyls are challenging targets owing to the natural-polarity mismatch of potential reaction partners. This Review discusses methods for 1,4-dicarbonyl synthesis based on the coupling of two carbonyl-containing fragments as well as methods that involve non-carbonyl precursors. A spotlight on 1,4-dicarbonyls in total synthesis underlines the diversity of approaches for this motif.

Nucleophiles are versatile reagents that can engage in a plethora of C–C and C–heteroatom bond-forming reactions. This Review examines their increasing role in transition metal-catalysed directed C–H functionalization, with a focus on synthetic approaches involving organometallic nucleophiles and X-based (X = N, O and S) coupling partners.

Polar effects permeate radical chemistry and control the outcome of radical reactions. This Review discusses important types of polar effects and how their interplay has been used in the synthesis and late-stage modification of complex molecules. The discussion covers hydrogen-atom transfer, halogen-atom transfer and homolytic aromatic substitution.

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.

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.

Crystal engineering of nanosized and hierarchical zeolites may improve the mass transport properties of materials at the nanoscale in various applications. In this Review, synthetic methods used to prepare different classes of zeolitic materials are summarized, with a focus on nucleation and growth mechanisms. Experimental and computational advances, as well as future challenges in the field, are discussed.

Catalytic asymmetric transformations of quinone methides and indole imine methides involve catalysts such as chiral Brønsted acids, Lewis acids and bases as well as transition metal complexes. In this Review, these asymmetric transformations are discussed with a focus on reaction pathways and activation modes.

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.

Molecular editing allows structures to be built up in terms of complexity, or changed or pruned one atom at a time using transformations which are mild and selective enough to be employed at the late stages of a synthetic sequence. In this Review, a subclass of molecular editing reactions termed ‘single-atom skeletal editing’ are described, with a particular focus on heterocycles.

Reductive coupling reactions mediated by samarium(ii) iodide are useful transformations to form C–C bonds. The unique reactivity and selectivity of SmI₂ result in its wide application in key steps in the total synthesis of natural products. This Review outlines synthetic routes using this versatility to make important C–C bonds in complex products.