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Bijvoet's method, which makes use of anomalous x-ray diffraction or dispersion, is the standard means of directly determining the absolute (stereochemical) configuration of molecules, but it requires crystalline samples and often proves challenging in structures exclusively comprising light atoms. Herein, we demonstrate a mass spectrometry approach that directly images the absolute configuration of individual molecules in the gas phase by cold target recoil ion momentum spectroscopy after laser ionizatior–induced Coulomb explosion. This technique is applied to the prototypical chiral molecule bromochlorofluoromethane and the isotopically chiral methane derivative bromodichloromethane.

So-called Minisci reactions have been used for decades in pharmaceutical and agrochemical synthesis to make carbon-carbon bonds. The reactions link carbon radicals to the carbon centers adjacent to nitrogen in pyridine rings. Proctor et al. devised a method to steer these reactions to just one of two possible mirror-image products. To make the radicals, they prepared derivatives of widely available amino acids and then activated them with an iridium photocatalyst. At the same time, a chiral phosphoric acid catalyst was used to activate the pyridine and bias the reaction geometry. Science , this issue p. 419 Pairing a photocatalyst with a chiral acid renders a widely used carbon-carbon bond-forming reaction asymmetric. Basic heteroarenes are a ubiquitous feature of pharmaceuticals and bioactive molecules, and Minisci-type additions of radical nucleophiles are a leading method for their elaboration. Despite many Minisci-type protocols that result in the formation of stereocenters, exerting control over the absolute stereochemistry at these centers remains an unmet challenge. We report a process for addition of prochiral radicals, generated from amino acid derivatives, to pyridines and quinolines. Our method offers excellent control of both enantioselectivity and regioselectivity. An enantiopure chiral Brønsted acid catalyst serves both to activate the substrate and induce asymmetry, while an iridium photocatalyst mediates the required electron transfer processes. We anticipate that this method will expedite access to enantioenriched small-molecule building blocks bearing versatile basic heterocycles.

An enantioselective reaction involving a molecule with two axes of stereochemical consequence produces four stereoisomers, and rather than racemizing as the system approaches equilibrium, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio. Chirality enters a new dimension Chiral molecules — those that are not identical to their mirror image — contain a stereogenic chiral centre, typically a tetrahedral atom and usually carbon, connected to four different substituents. This paper describes a novel catalytic reaction that produces a more complex type of chirality in which two axes of chirality are present within the same molecule, so that an enantioselective reaction produces four stereoisomers. Rather than racemizing as the system approaches equilibrium, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio. One of the most well-recognized stereogenic elements in a chiral molecule is an sp 3 -hybridized carbon atom that is connected to four different substituents. Axes of chirality can also exist about bonds with hindered barriers of rotation; molecules containing such axes are known as atropisomers 1 . Understanding the dynamics of these systems can be useful, for example, in the design of single-atropisomer drugs 2 or molecular switches and motors 3 . For molecules that exhibit a single axis of chirality, rotation about that axis leads to racemization as the system reaches equilibrium. Here we report a two-axis system for which an enantioselective reaction produces four stereoisomers (two enantiomeric pairs): following a catalytic asymmetric transformation, we observe a kinetically controlled product distribution that is perturbed from the system’s equilibrium position. As the system undergoes isomerization, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio. In a compensatory manner, the enantiomeric ratio of the other diastereomeric pair decreases. These observations are made for a class of unsymmetrical amides that exhibits two asymmetric axes—one axis is defined through a benzamide substructure, and the other axis is associated with differentially N , N -disubstituted amides. The stereodynamics of these substrates provides an opportunity to observe a curious interplay of kinetics and thermodynamics intrinsic to a system of stereoisomers that is constrained to a situation of partial equilibrium.

Stereochemical control in the construction of carbon-carbon bonds between an alkyl electrophile and an alkyl nucleophile is a persistent challenge in organic synthesis. Classical substitution reactions via SN1 and SN2 pathways are limited in their ability to generate carbon-carbon bonds (inadequate scope, due to side reactions such as rearrangements and eliminations) and to control stereochemistry when beginning with readily available racemic starting materials (racemic products). Here, we report a chiral nickel catalyst that couples racemic electrophiles (propargylic halides) with racemic nucleophiles (β-zincated amides) to form carbon-carbon bonds in doubly stereoconvergent processes, affording a single stereoisomer of the product from two stereochemical mixtures of reactants.

Recently, with the boosted development of radical chemistry, enantioselective functionalization of C( sp 3 )–H bonds via a radical pathway has witnessed a renaissance. In principle, two distinct catalytic modes, distinguished by the steps in which the stereochemistry is determined (the radical formation step or the radical functionalization step), can be devised. This Perspective discusses the state-of-the-art in the area of catalytic enantioselective C( sp 3 )–H functionalization involving radical intermediates as well as future challenges and opportunities. Enantioselective functionalization of ubiquitous C(sp 3 )–H bonds via radical species has witnessed a renaissance in the past years. Here, the authors summarize the main achievements in the field by identifying two main reaction pathways determining the stereochemistry and give an outlook on future challenges and opportunities.

Chemical reactions such as Heck and Suzuki coupling facilitate access to an enormous range of relatively flat molecules. This geometrical constraint is associated with the comparative ease of linking together aryl and alkenyl carbons. Choi and Fu review recent developments in forming bonds between the more abundant alkyl carbon centers that underlie diverse molecules with complex three-dimensional structures. Nickel catalysis in particular has emerged as a powerful method to access individual mirror-image isomers selectively and thereby tune the biological properties of the targeted products. Science , this issue p. eaaf7230 Because the backbone of most organic molecules is composed primarily of carbon-carbon bonds, the development of efficient methods for their construction is one of the central challenges of organic synthesis. Transition metal–catalyzed cross-coupling reactions between organic electrophiles and nucleophiles serve as particularly powerful tools for achieving carbon-carbon bond formation. Until recently, the vast majority of cross-coupling processes had used either aryl or alkenyl electrophiles as one of the coupling partners. In the past 15 years, versatile new methods have been developed that effect cross-couplings of an array of alkyl electrophiles, thereby greatly expanding the diversity of target molecules that are readily accessible. The ability to couple alkyl electrophiles opens the door to a stereochemical dimension—specifically, enantioconvergent couplings of racemic electrophiles—that substantially enhances the already remarkable utility of cross-coupling processes.

Naturally evolved enzymes, despite their astonishingly large variety and functional diversity, operate predominantly through thermochemical activation. Integrating prominent photocatalysis modes into proteins, such as triplet energy transfer, could create artificial photoenzymes that expand the scope of natural biocatalysis 1 – 3 . Here, we exploit genetically reprogrammed, chemically evolved photoenzymes embedded with a synthetic triplet photosensitizer that are capable of excited-state enantio-induction 4 – 6 . Structural optimization through four rounds of directed evolution afforded proficient variants for the enantioselective intramolecular [2+2]-photocycloaddition of indole derivatives with good substrate generality and excellent enantioselectivities (up to 99% enantiomeric excess). A crystal structure of the photoenzyme–substrate complex elucidated the non-covalent interactions that mediate the reaction stereochemistry. This study expands the energy transfer reactivity 7 – 10 of artificial triplet photoenzymes in a supramolecular protein cavity and unlocks an integrated approach to valuable enantioselective photochemical synthesis that is not accessible with either the synthetic or the biological world alone. Triplet photoenzymes developed through genetic encoding and directed evolution result in excited-state photocatalysts that provide a valuable approach to enantioselective photochemical synthesis.

Chirality arises universally across many different fields. Recent advancements in artificial nanomaterials have demonstrated chiroptical responses that far exceed those found in natural materials. Chiroptical phenomena are complicated processes that involve transitions between states with opposite parities, and solid interpretations of these observations are yet to be clearly provided. In this review, we present a comprehensive overview of the theoretical aspects of chirality in light, nanostructures, and nanosystems and their chiroptical interactions. Descriptions of observed chiroptical phenomena based on these fundamentals are intensively discussed. We start with the strong intrinsic and extrinsic chirality in plasmonic nanoparticle systems, followed by enantioselective sensing and optical manipulation, and then conclude with orbital angular momentum-dependent responses. This review will be helpful for understanding the mechanisms behind chiroptical phenomena based on underlying chiral properties and useful for interpreting chiroptical systems for further studies.Towards an extended understanding of chiroptical phenomenaStrengthening the theoretical understanding of chirality is necessary for developing applications based on its phenomena. Junsuk Rho of Korea’s Pohang University of Science and Technology (POSTECH) reviewed with colleagues the theoretical aspects of chirality, a symmetry property that describes mirror-image objects or systems that cannot be superimposed. Chiral materials have attracted much attention due to their interesting interactions. Scientists are familiar with how geometrically chiral objects and systems interact with light. However, such ‘chiroptical effects’ can also be found in achiral systems, Rho and his colleagues explain. Also, globally achiral light can be locally chiral near nanostructures. Scientists need to extend their concepts and theoretical understandings of chiroptical systems in order to be able to further develop applications based on their phenomena, such as in metamaterials, sensing, spintronics and stereochemistry.

The past decade has seen unprecedented growth in the development of new chemical methods that proceed by mechanisms involving radical intermediates. This new attention has served to highlight a long-standing challenge in the field of radical chemistry — that of controlling absolute stereochemistry. This Review will examine developments using a strategy that offers enormous potential, in which attractive non-covalent interactions between a chiral catalyst and the substrate are leveraged to exert enantiocontrol. In a simplistic sense, such an approach mimics the modes of activation and control in enzyme catalysis and the realization that this can be achieved in the context of small-molecule catalysts has had sizable impact on the field of asymmetric catalysis in recent years. This strategy is now starting to quickly gather pace as a powerful approach for control of enantioselectivity in radical reactions and we hope that this focused survey of progress so far will inspire future developments in the area.The past decade has seen unprecedented growth in the development of chemical methods that proceed by mechanisms involving radical intermediates, but controlling absolute stereochemistry has been a longstanding challenge in this area. This Review Article examines how attractive non-covalent interactions between a chiral catalyst and the substrate can exert enantiocontrol in radical reactions.