Organic chemistry

  • Article
    | Open Access

    Spirocycles are traditionally difficult structures to synthesize due to the congested nature of the central atom. Here the authors show a method to synthesize quaternary carbon spirocycles in one step from 1,3-enynes and pyrazolidine-type heterocycles, both relatively unactivated structures, proceeding via palladium catalysis.

    • Long Li
    • , Shan Wang
    •  & Zhihui Shao
  • Article
    | Open Access

    Sequential alkene isomerization and cross-coupling enables remote functionalization, but coupling has been limited to positions at a carbon chain terminus or proximal to a functional group. Here the authors show a method to interrupt isomerization with a nickellacycle, which enables coupling at an atypical, unreactive position.

    • Changseok Lee
    • , Huiyeong Seo
    •  & Sungwoo Hong
  • Article
    | Open Access

    Alkene isomerizations and asymmetric C–H functionalizations have been independently studied, but their combination in one protocol is uncommon. Here the authors show a palladium-catalyzed method to iteratively “walk” a terminal alkene along a carbon chain to a position next to styrenes where a soft nucleophile is added asymmetrically.

    • Ye-Wei Chen
    • , Yang Liu
    •  & Zhi-Tao He
  • Article
    | Open Access

    Isopropenyl ethers (IPPEs) are essential intermediates for obtaining ketal-based prodrugs and biomaterials, but traditional approaches for their synthesis are limited by poor functional group compatibility and harsh reaction conditions. Here, the authors report an organocatalytic transisopropenylation approach for IPPE synthesis in mild reaction conditions and with wide range of substrates, and use it to prepare acid-sensitive ketal-linked prodrugs and biomaterials.

    • Na Yu
    • , Yang Xu
    •  & Shutao Guo
  • Article
    | Open Access

    The “anti-branching rule”, introduced in 1950, excludes branched polyphosphates from biological relevance due to their supposedly rapid hydrolysis. Here, the authors synthesize monodisperse branched polyphosphates and demonstrate their unexpected stability in water, as well as provide evidence for their competence in phosphorylation.

    • Tobias Dürr-Mayer
    • , Danye Qiu
    •  & Henning J. Jessen
  • Article
    | Open Access

    The generation of alkyl radicals through deoxygenation of abundant alcohols via photoredox catalysis is of interest. In this study, the authors report a one-pot strategy for visible-light-promoted photoredox coupling of alcohols with electron-deficient alkenes, assisted by carbon disulfide and triphenylphosphine.

    • Hong-Mei Guo
    •  & Xuesong Wu
  • Article
    | Open Access

    Unlike other halogen atoms, the ability for fluorine to exist in a [C–X–C]+ connectivity pattern has only been shown in spectroscopic studies. Here the authors present a single crystal structure of a fluoronium cation, characterized by X-ray diffraction.

    • Kurt F. Hoffmann
    • , Anja Wiesner
    •  & Sebastian Riedel
  • Article
    | Open Access

    Sulfinyl radicals are an underexplored synthon in organic chemistry due to the fact that they reversibly add to pi systems and undergo homodimerization. Here the authors synthesize sulfonyl sulfones, previously thought to be unstable, and demonstrate their broad use as sulfinyl radical precursors in disulfurizations of alkenes and alkynes.

    • Zikun Wang
    • , Zhansong Zhang
    •  & Xihe Bi
  • Article
    | Open Access

    The transformation of planar aromatic molecules into non-planar structures is a challenging task and has not been realized by mechanochemistry before. Here, the authors demonstrate that mechanochemical forces can transform a planar polyarene into a curved geometry by creating new C-C bonds along the rim of the molecular structure.

    • Teoh Yong
    • , Gábor Báti
    •  & Mihaiela C. Stuparu
  • Article
    | Open Access

    Synthesizing complex structures of high enantiomeric excess from racemic feedstock is an enduring challenge. Here, the authors couple racemic secondary alcohols with pyrroles to form enantioenriched 2-substituted heteroarenes, via a borrowing hydrogen mechanism using the combination of an iridium catalyst and chiral phosphoric acid.

    • Yongbing Liu
    • , Ran Tao
    •  & Yu Zhao
  • Article
    | Open Access

    2-Fluoroindoles are an important structural scaffold in many bioactive or therapeutic agents, but efficient constructions of 2-fluoroindole derivatives are very sparce. Here the authors report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity.

    • Jianke Su
    • , Xinyuan Hu
    •  & Qiuling Song
  • Article
    | Open Access

    Converting a carboxylic acid into a boronic acid, which makes a useful chemical handle from a feedstock chemical, currently relies on decarboxylation and requires metal catalysts and prior functionalization. Here the authors show a simplified procedure via deoxygenation, using diboron and free carboxylic acids.

    • Jianbin Li
    • , Chia-Yu Huang
    •  & Chao-Jun Li
  • Article
    | Open Access

    General and stereoselective synthesis of tetracyclic isochroman-containing polyketide oligomers is challenging. Here, the authors report on an Au(I)/chiral Sc(III) bimetallic catalyst for a biomimetic asymmetric hetero-Diels–Alder reaction for in-situ generation of isochromene and ortho-quinonemethide.

    • Xiangfeng Lin
    • , Xianghui Liu
    •  & Can Li
  • Article
    | Open Access

    C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins of great therapeutic potential, but their chemical synthesis is challenging. Here, the authors report a protocol for the synthesis of vinyl C-glycosyl amino acids and peptides, via a Ni-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with glycosyl bromides.

    • Yan-Hua Liu
    • , Yu-Nong Xia
    •  & Biao Yu
  • Article
    | Open Access

    The chromone scaffold is present in drugs and bioactive natural products, but conventional approaches to access chromones require stoichiometric amounts of oxidants. Here, the authors report rhodaelectro-catalyzed assembly of chromones by electrochemical formyl C–H activations, providing the basis for late-stage peptide diversification.

    • Maximilian Stangier
    • , Antonis M. Messinis
    •  & Lutz Ackermann
  • Article
    | Open Access

    Catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. Here the authors show an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by FeI2, P(V)/P(III) and photoredox catalysis that avoids the production of byproducts.

    • Yunyun Ning
    • , Shuaishuai Wang
    •  & Jin Xie
  • Article
    | Open Access

    The generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here, the authors show the treatment of S-(alkyl) thianthrenium salts, which can generate non-stabilized alkyl radicals as key intermediates that enable controlled and selective reactions under mild photoredox conditions.

    • Cheng Chen
    • , Zheng-Jun Wang
    •  & Zhuangzhi Shi
  • Article
    | Open Access

    PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

    • Chengxi Li
    • , Alex J. Callahan
    •  & Bradley L. Pentelute
  • Article
    | Open Access

    Transition metal-catalyzed regioselective difunctionalizations of alkenes with two different functional groups are useful for preparing organic compounds, but the construction of two new C–C bonds is challenging. Here, the authors report cobalt-catalyzed regioselective difluoroalkylarylation of alkenes with solid arylzinc pivalates and difluoroalkyl bromides, through a cascade Csp3 ‒Csp3/Csp3 ‒Csp2 bond formation.

    • Xinyi Cheng
    • , Xingchen Liu
    •  & Jie Li
  • Article
    | Open Access

    Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here the authors show copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions.

    • Zhe Chang
    • , Jialin Huang
    •  & Depeng Zhao
  • Article
    | Open Access

    2-(hetero)aryl N-heteroarenes are ubiquitously applied in numerous fields of science and useful for the development of bioactive molecules and drugs, but there is a lack of general methods for their synthesis. Here, the authors report an iridium(III)-catalyzed method for direct α-arylation of N-heteroarenes with aryl and heteroaryl boronic acids, by a H2O-mediated H2-evolution cross-coupling strategy.

    • Liang Cao
    • , He Zhao
    •  & Min Zhang
  • Article
    | Open Access

    Organochlorides are widespread in natural products, therefore the methods for site-selective chlorination at specific C–H bonds are of great interest. Here, the authors report a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature.

    • Jianwen Jin
    • , Yichao Zhao
    •  & Philip Wai Hong Chan
  • Article
    | Open Access

    Nanographenes and polycyclic aromatic hydrocarbons (PAHs) are important classes of compounds with numerous applications, but challenging to access due to a lack of programmable and diversity-oriented methods. Here, the authors report a diversity-oriented, growth-from-template synthesis of nanographenes enabled by iterative annulative π-extension reactions from small PAH starting materials.

    • Wataru Matsuoka
    • , Hideto Ito
    •  & Kenichiro Itami
  • Article
    | Open Access

    The current biorefineries yield lignin with inadequate fractionation for bioconversion, yet substantial changes of these biorefinery designs could jeopardize carbohydrate efficiency and increase capital costs. Here the authors resolve the dilemma by designing ‘plug-in processes of lignin’ to enable economic waste valorization.

    • Zhi-Hua Liu
    • , Naijia Hao
    •  & Joshua S. Yuan
  • Article
    | Open Access

    Organohalides are widely used as synthetic precursors and target products, but for various halogenation reactions there is a need for effective catalysts to activate commercially available haleniums. Here, the authors report that TEMPO and its derivatives are active catalysts for electrophilic halogenation of olefins, alkynes and aromatics, under mild reaction conditions and with good functional group tolerance.

    • Weijin Wang
    • , Xinyao Li
    •  & Song Song
  • Article
    | Open Access

    Use of aryl halides as coupling precursors typically occurs through transition metal catalysis and/or photoredox chemistry, which requires some combination of light, metals, and oxidants or reductants. Here, the authors show a method to generate aryl radicals from halides using only an NHC organocatalyst.

    • Yuki Matsuki
    • , Nagisa Ohnishi
    •  & Hirohisa Ohmiya
  • Article
    | Open Access

    Mitragynine (MG) is an indole alkaloid from kratom plant that binds opioid receptors and as such presents a scaffold for the development of atypical opioid receptor modulators. Here, the authors report a synthetic method for selective functionalization of the C11 position of MG, and show that this position is essential for fine-tuning opioid receptor signaling efficacy.

    • Srijita Bhowmik
    • , Juraj Galeta
    •  & Dalibor Sames
  • Article
    | Open Access

    Allylic amines are versatile building blocks in organic synthesis and exist in bioactive compounds, but efficient catalytic systems for hydroaminoalkylation of alkynes are needed. Here, the authors report a late transition metal‐catalyzed hydroaminoalkylation of alkynes with N‐sulfonyl amines, providing a series of allylic amines in up to 94% yield.

    • Wei-Wei Yao
    • , Ran Li
    •  & Mengchun Ye
  • Article
    | Open Access

    Chiral alkyne motifs bearing an α stereocentre are often found in many bioactive compounds, chemical probes, and functional materials. Here the authors show NiH-catalysed reductive migratory hydroalkynylation of olefins with bromoalkynes that form benzylic alkynylation products in high yield and with excellent regioselectivity.

    • Xiaoli Jiang
    • , Bo Han
    •  & Shaolin Zhu
  • Article
    | Open Access

    Oxidative allylic C–H functionalizations minimise the need for functional group activation and generate alkenyl-substituted products amenable to further chemical modifications. Here the authors report an oxidant-free, electrocatalytic approach to achieve intramolecular oxidative allylic C–H amination and alkylation by employing tailored cobalt-salen complexes as catalysts.

    • Chen-Yan Cai
    • , Zheng-Jian Wu
    •  & Hai-Chao Xu
  • Article
    | Open Access

    A large number of enantiopure substances, such as those with tetrasubstituted carbon centres bearing several similar substituents, are inaccessible due to the incapability of chiral catalysts/ligands to recognize those substrates. Here, the authors develop kinetic resolution of auxiliary adjacent alcohols (KRA*) strategy to access various optically enriched compounds with two, three or four spatially and electronically similar groups.

    • Shengtong Niu
    • , Hao Zhang
    •  & Xinqiang Fang
  • Article
    | Open Access

    Cyclohexadienes have been widely explored as proaromatic surrogates for group transfer reactions but limited storage stability and difficult accessibility of these compounds limits the application range. Here, the authors present a class of proaromatic bicyclo[2.2.0]hexene derivatives and demonstrate their application in alkyl transfer reactions and sensing applications.

    • Bin Wu
    • , Jianing Wang
    •  & Rong Zhu
  • Article
    | Open Access

    The direct deoxygenative coupling of aldehydes or ketones to construct C(sp3)−C(sp3) bond remains a scientific challenge. Here the authors use a nickel−catalyzed reductive homo-coupling of moisture- and air-stable hydrazones generated in-situ from naturally abundant aldehydes and ketones to construct challenging C(sp3)−C(sp3) bonds.

    • Dawei Cao
    • , Chen-Chen Li
    •  & Chao-Jun Li
  • Article
    | Open Access

    Organometallic complexes have numerous applications in chemistry and biology, but diversification of their structures is synthetically challenging. Here, the authors report a versatile platform for on-the-complex annulation reactions using transient aryne intermediates to access pi-extended polypyridyl complexes.

    • Jason V. Chari
    • , Katie A. Spence
    •  & Neil K. Garg
  • Article
    | Open Access

    In hybrid perovskites, the driving forces of an order–disorder transition that arise from the organic cation and inorganic framework cannot be easily untangled. Here, the authors introduce a cage-in-framework structure in which reorientation of the cage cation does not alter the cubic symmetry of the perovskite lattice.

    • Zhifang Shi
    • , Zheng Fang
    •  & Qixi Mi
  • Article
    | Open Access

    Chiral α-aryl ketones are versatile building blocks, and represent important pharmacophores existing in many drug molecules such as ibuprofen and naproxen. Here the authors for such ketones but using nickel and photoredox dual catalysis in asymmetric benzylic C−H acylation of alkylarenes and employing carboxylic acids as acyl surrogates.

    • Leitao Huan
    • , Xiaomin Shu
    •  & Haohua Huo
  • Article
    | Open Access

    Arene-fused siloles have attracted interest due to their promising applications in electronic and optoelectronic devices. Here, the authors report Ir(III)-catalyzed cycloaromatization of ortho-alkynylaryl vinylsilanes with arylsulfonyl azides via α-silyl radical Smiles rearrangement for accessing naphthyl-fused benzosiloles under visible-light photoredox conditions.

    • Fengjuan Chen
    • , Youxiang Shao
    •  & Wei Zeng
  • Article
    | Open Access

    Compounds bearing a carbonyl group, such as aldehydes and ketones, are important industrial chemicals and widespread in pharmaceuticals and natural products. Here, the authors report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2, to generate valuable α-hydroxycarboxylic acids.

    • Guang-Mei Cao
    • , Xin-Long Hu
    •  & Da-Gang Yu
  • Article
    | Open Access

    Compounds that contain alkyl-difluoromethyl moieties are of interest for medicinal chemistry, but their synthesis is challenging. Here, the authors report a copper-catalyzed radical relay approach for the carbodifluoromethylation of alkenes that simultaneously introduces CF2H groups and complex alkyl or aryl groups into alkenes.

    • Aijie Cai
    • , Wenhao Yan
    •  & Wei Liu
  • Article
    | Open Access

    Synthesis of fluorinated organic molecules is of high interest for agrochemistry and pharmaceutics, but efficient and general reagents for introducing -CF2- groups are lacking. Here, the authors report the synthesis of 3,3-difluoropropen-1-yl ammonium salts as stable and scalable gem-difluoromethylation reagents, which react with a range of nucleophiles under mild conditions and high regioselectivity.

    • Fei Ye
    • , Yao Ge
    •  & Matthias Beller