Explore the vast range of titles available.

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.

Pharmaceutical synthesis often requires the formation of adjacent carbon-carbon and carbon-nitrogen bonds. Monos et al. present a method that delivers the carbon and nitrogen components in a single reagent, specifically, an aryl ring tethered through sulfur dioxide to an amide. A light-activated catalyst primes an olefin to react with the nitrogen, which in turn leads to migration of the aryl ring and loss of the sulfur bridge. The efficient room-temperature process is applicable to a variety of different arenes, including heterocycles. Science , this issue p. 1369 Photoredox catalysis activates alkenes to form adjacent C–C and C–N bonds through coupling with a single reagent. Alkene aminoarylation with a single, bifunctional reagent is a concise synthetic strategy. We report a catalytic protocol for the addition of arylsulfonylacetamides across electron-rich alkenes with complete anti-Markovnikov regioselectivity and excellent diastereoselectivity to provide 2,2-diarylethylamines. In this process, single-electron alkene oxidation enables carbon-nitrogen bond formation to provide a key benzylic radical poised for a Smiles-Truce 1,5-aryl shift. This reaction is redox-neutral, exhibits broad functional group compatibility, and occurs at room temperature with loss of sulfur dioxide. As this process is driven by visible light, uses readily available starting materials, and demonstrates convergent synthesis, it is well suited for use in a variety of synthetic endeavors.

Although organic compounds consist mostly of carbon and hydrogen atoms, strategies for chemical synthesis have traditionally targeted the handful of more reactive interspersed oxygens, nitrogens, and halogens. Modifying C–H bonds directly is a more appealing approach, but selectivity remains a challenge. Saint-Denis et al. review recent progress in using transition metal catalysis to break just one of two mirror-image C–H bonds and then append a more complex substituent in its place. Ligand design has proven crucial to differentiate these otherwise similar bonds in a variety of molecular settings. Science , this issue p. eaao4798 Organic molecules are rich in carbon-hydrogen bonds; consequently, the transformation of C–H bonds to new functionalities (such as C–C, C–N, and C–O bonds) has garnered much attention by the synthetic chemistry community. The utility of C–H activation in organic synthesis, however, cannot be fully realized until chemists achieve stereocontrol in the modification of C–H bonds. This Review highlights recent efforts to enantioselectively functionalize C(sp 3 )–H bonds via transition metal catalysis, with an emphasis on key principles for both the development of chiral ligand scaffolds that can accelerate metalation of C(sp 3 )–H bonds and stereomodels for asymmetric metalation of prochiral C–H bonds by these catalysts.

Preparation of single atom catalysts (SACs) is of broad interest to materials scientists and chemists but remains a formidable challenge. Herein, we develop an efficient approach to synthesize SACs via a precursor-dilution strategy, in which metalloporphyrin (MTPP) with target metals are co-polymerized with diluents (tetraphenylporphyrin, TPP), followed by pyrolysis to N-doped porous carbon supported SACs (M 1 /N-C). Twenty-four different SACs, including noble metals and non-noble metals, are successfully prepared. In addition, the synthesis of a series of catalysts with different surface atom densities, bi-metallic sites, and metal aggregation states are achieved. This approach shows remarkable adjustability and generality, providing sufficient freedom to design catalysts at atomic-scale and explore the unique catalytic properties of SACs. As an example, we show that the prepared Pt 1 /N-C exhibits superior chemoselectivity and regioselectivity in hydrogenation. It only converts terminal alkynes to alkenes while keeping other reducible functional groups such as alkenyl, nitro group, and even internal alkyne intact. The general synthesis of single atom catalysts (SACs) is of broad interest to chemists but remains a formidable challenge. Here, with the precursor-dilution strategy, the authors successfully prepare 24 different SACs and the Pt SACs exhibit superior chemo- and regio-selectivity in hydrogenation.

Hydroformylation is an industrial process for the production of aldehydes from alkenes 1 , 2 . Regioselective hydroformylation of propene to high-value n -butanal is particularly important, owing to a wide range of bulk applications of n -butanal in the manufacture of various necessities in human daily life 3 . Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited 4 . Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n -butanal 5 – 8 . Here we show that proper encapsulation of Rh species comprising Rh(I)- gem -dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n -butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h −1 , surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n -butanal. Rhodium catalysts confined in zeolite pores exhibit high regioselectivity in the hydroformylation process of propene to high-value n -butanal, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far.

Building molecular complexity from simple feedstocks through precise peripheral and skeletal modifications is central to modern organic synthesis. Nevertheless, a controllable strategy through which both the core skeleton and the periphery of an aromatic heterocycle can be modified with a common substrate remains elusive, despite its potential to maximize structural diversity and applications. Here we report a carbene-initiated chemodivergent molecular editing of indoles that allows both skeletal and peripheral editing by trapping an electrophilic fluoroalkyl carbene generated in situ from fluoroalkyl N -triftosylhydrazones. A variety of fluorine-containing N-heterocyclic scaffolds have been efficiently achieved through tunable chemoselective editing reactions at the skeleton or periphery of indoles, including one-carbon insertion, C3 gem -difluoroolefination, tandem cyclopropanation and N1 gem -difluoroolefination, and cyclopropanation. The power of this chemodivergent molecular editing strategy has been highlighted through the modification of the skeleton or periphery of natural products in a controllable and chemoselective manner. The reaction mechanism and origins of the chemo- and regioselectivity have been probed by both experimental and theoretical methods. The rapid generation of molecular complexity from a given molecular scaffold is crucial to drug discovery and development. Now the chemodivergent molecular editing of indoles using fluoroalkyl carbenes has been developed to modularly access four different types of fluorine-containing N-heterocyclic compound with high molecular complexity.

Regioselective synthesis is a crucial concept in organic chemistry, enabling the selective formation of different regioisomers from the same type of starting materials. This approach is particularly valuable in pharmaceutical and materials sciences, where the arrangement of functional groups influences the biological activities and properties of the molecule. Pyridines are ubiquitous in organic chemistry due to their prevalence in natural products and pharmaceuticals. In addition, the introduction of boron substituents into pyridine rings enables subsequent functionalization further enhancing their utility. Herein, we present a synthetic strategy for the selective formation of either 2‐ and 3‐polysubstituted borylated pyridines via Ru‐ and Co‐catalyzed [2 + 2 + 2] cyclotrimerization reactions. Efficient synthesis and utilization of functionalized diynes allow the exploration of their reactivity in cyclotrimerization reactions with a wide variety of nitriles. The broad applicability of the methods to form pyridines with high efficiency and regioselectivity based on the used type of boronic acid derivative is shown. The application includes successful photocatalyzed cyclizations as well as the implementation of one‐pot cyclotrimerization‐coupling protocols. The findings not only provide a practical route to valuable borylated pyridines but also offer insights into the mechanistic aspects governing selectivity in these reactions. Ring the boron, not the bell: cyclotrimerization of borylated diynes with nitriles using Co and Ru catalysts allows the efficient synthesis of a wide variety of borylated pyridines with high regioselectivity, paving the way for multiple post‐functionalizations.

β-Amino acids are frequently found as important components in numerous biologically active molecules, drugs and natural products. In particular, they are broadly utilized in the construction of bioactive peptides and peptidomimetics, thanks to their increased metabolic stability. Despite the number of methodologies established for the preparation of β-amino acid derivatives, the majority of these methods require metal-mediated multistep manipulations of prefunctionalized substrates. Here we disclose a metal-free, energy-transfer enabled highly regioselective intermolecular aminocarboxylation reaction for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. A bifunctional oxime oxalate ester was developed to simultaneously generate C-centred ester and N-centred iminyl radicals. This mild method features a remarkably broad substrate scope (up to 140 examples) and excellent tolerance of sensitive functional groups, and substrates that range from the simplest ethylene to complex (hetero)arenes can participate in the reaction, thus offering a general and practical access to β-amino acid derivatives. The majority of methods to prepare β-amino acid derivatives require metal-mediated multistep manipulations of pre-functionalized substrates. Now, a metal-free, energy-transfer enabled, highly regioselective aminocarboxylation reaction has been developed, for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. An oxime oxalate ester is used as a bifunctional reagent, supplying C-centred ester and N-centred iminyl radicals.

Frustrated Lewis pairs (FLPs) are well documented for the activation of small molecules such as dihydrogen and carbon dioxide 1 – 4 . Although canonical FLP chemistry is heterolytic in nature, recent work has shown that certain FLPs can undergo single-electron transfer to afford radical pairs 5 . Owing to steric encumbrance and/or weak bonding association, these radicals do not annihilate one another, and they have thus been named frustrated radical pairs (FRPs). Notable preliminary results suggest that FRPs may be useful reagents in chemical synthesis 6 – 8 , although their applications remain limited. Here we demonstrate that the functionalization of C( sp 3 )–H bonds can be accomplished using a class of FRPs generated from disilazide donors and an N -oxoammonium acceptor. Together, these species undergo single-electron transfer to generate a transient and persistent radical pair capable of cleaving unactivated C–H bonds to furnish aminoxylated products. By tuning the structure of the donor, it is possible to control regioselectivity and tailor reactivity towards tertiary, secondary or primary C–H bonds. Mechanistic studies lend strong support for the formation and involvement of radical pairs in the target reaction. Regioselective functionalization of aliphatic carbon–hydrogen bonds is achieved using frustrated radical pairs generated from disilazide donors and an N -oxoammonium acceptor.

The cobalt complexes HCo(CO)4 and HCo(CO)3(PR3) were the original industrial catalysts used for the hydroformylation of alkenes through reaction with hydrogen and carbon monoxide to produce aldehydes. More recent and expensive rhodium-phosphine catalysts are hundreds of times more active and operate under considerably lower pressures. Cationic cobalt(II) bisphosphine hydrido-carbonyl catalysts that are far more active than traditional neutral cobalt(I) catalysts and approach rhodium catalysts in activity are reported here. These catalysts have low linear-to-branched (L:B) regioselectivity for simple linear alkenes. However, owing to their high alkene isomerization activity and increased steric effects due to the bisphosphine ligand, they have high L:B selectivities for internal alkenes with alkyl branches. These catalysts exhibit long lifetimes and substantial resistance to degradation reactions.