Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science.

High fidelity: 1‐Iodoalkynes react rapidly and selectively with organic azides in the presence of copper(I) catalysts (see scheme; TTTA=tris((1‐tert‐butyl‐1H‐1,2,3‐triazolyl)methyl)amine). The reaction is compatible with many functional groups and solvents, and 5‐iodotriazole products were usually obtained in excellent yield. These products can be further functionalized to give fully substituted 1,2,3‐triazoles.

Discovering and optimizing commercially viable materials for clean energy applications typically takes more than a decade. Self-driving laboratories that iteratively design, execute, and learn from materials science experiments in a fully autonomous loop present an opportunity to accelerate this research process. We report here a modular robotic platform driven by a model-based optimization algorithm capable of autonomously optimizing the optical and electronic properties of thin-film materials by modifying the film composition and processing conditions. We demonstrate the power of this platform by using it to maximize the hole mobility of organic hole transport materials commonly used in perovskite solar cells and consumer electronics. This demonstration highlights the possibilities of using autonomous laboratories to discover organic and inorganic materials relevant to materials sciences and clean energy technologies.

Insights into the mechanism of attrition-enhanced deracemization and resolution of solid enantiomorphic chiral compounds are obtained by crystal size and solubility measurements and by isotopic labeling experiments. Together these results help to deconvolute the various chemical and physical rate processes contributing to the phenomenon. Crystal size measurements highlight a distinct correlation between the stochastic, transient growth of crystals and the emergence of a single solid enantiomorph under attrition conditions. The rapid mass transfer of molecules between the solution and solid phases under attrition is demonstrated, and the concept of a crystal-size-induced solubility driving force is exploited to overcome the stochastic nature of the crystal growth and dissolution processes. Extension to non-racemizing conditions provides a novel methodology for chiral resolution. Implications both for practical chiral separations and for the origin of biological homochirality are discussed.

The process of delineating the origins of the chemistry of life starts with the consideration of the molecules that might have existed on prebiotic earth and extends to the discussion of potential mechanisms for assembly of these molecules into informational polymers capable of self-replication and transmittance of genetic information. At some point along this pathway, the property of single chirality emerges as the hallmark of the amino acids and sugars present in biological molecules. In the 20th century, researchers developed abstract mathematical theses for the origin of biomolecular homochirality from a presumably racemic collection of prebiotic molecules. Before the end of that century, experimental findings corroborated a number of basic features of these theoretical models, but these studies involved chemical systems without direct prebiotic relevance. Currently researchers are examining prebiotically plausible conditions that couple chemical and physical processes leading to single chirality of sugars and amino acids with subsequent chemical reactions that enhance molecular complexity. While these studies have been conducted for the most part in the context of the RNA World hypothesis, the experimental findings remain relevant to a "metabolism first" model for the origin of life. To many chemists interested in chembiogenesis, the synthesis of activated pyrimidine ribonucleotides under potentially prebiotic conditions by Sutherland's group provided a landmark demonstration of what Eschenmoser has described as "an intrinsic structural propinquity" between certain elementary chemical structures and modern biological molecules. Even while some synthetic issues for plausible prebiotic construction of RNA remain unsolved, our work has focused on coupling these synthetic advances with concepts for the evolution of biomlolecular homochirality. Drawing on our own findings as well as those from others, we present an intriguing "chicken or egg" scenario for the emergence of single chirality of sugars and amino acids. Our work incorporates both chemical and physical phenomena that allow for the amplification of a small initial imbalance of either sugars by amino acids or amino acid by sugars, suggesting that an enantioenriched chiral pool of one type of molecule could lead to a similarly enantioenriched pool of the other.

ChemOS aims to catalyze the expansion of autonomous laboratories and to disrupt the conventional approach to experimentation.

Autonomous process optimization involves the human intervention-free exploration of a range process parameters to improve responses such as product yield and selectivity. Utilizing off-the-shelf components, we develop a closed-loop system for carrying out parallel autonomous process optimization experiments in batch. Upon implementation of our system in the optimization of a stereoselective Suzuki-Miyaura coupling, we find that the definition of a set of meaningful, broad, and unbiased process parameters is the most critical aspect of successful optimization. Importantly, we discern that phosphine ligand, a categorical parameter, is vital to determination of the reaction outcome. To date, categorical parameter selection has relied on chemical intuition, potentially introducing bias into the experimental design. In seeking a systematic method for selecting a diverse set of phosphine ligands, we develop a strategy that leverages computed molecular feature clustering. The resulting optimization uncovers conditions to selectively access the desired product isomer in high yield.

The single-handedness of biological molecules is critical for molecular recognition and replication processes and would seem to be a prerequisite for the origin of life. A drawback of recently reported synthetic routes to RNA is the requirement for enantioenriched reactants, which fails to address the puzzle of how the single chirality of biological molecules arose. Here, we report the synthesis of highly enantioenriched RNA precursor molecules from racemic starting materials, with the molecular asymmetry derived solely from a small initial imbalance of the amino-acid enantiomers present in the reaction mixture. Acting as spectators to the main reaction chemistry, the amino acids orchestrate a sequence of physical and chemical amplification processes. The emergence of molecules of single chirality from complex, multi-component mixtures supports the robustness of this synthesis process under potential prebiotic conditions and provides a plausible explanation for the single-handedness of biological molecules before the emergence of self-replicating informational polymers.