Article
Chemistry, Multidisciplinary
Ming Zhang, Qingyang Zhou, Heng Luo, Zi-Lu Tang, Xiufang Xu, Xiao-Chen Wang
Summary: Here, we present a method for C3-selective cyanation of pyridines by a tandem process using an in situ generated dihydropyridine and a cyano electrophile. This method is suitable for late-stage functionalization of pyridine drugs. The success of this method relies on the low reduction potential of the electrophile and effective transfer of the nitrile group. Detailed investigation of the reaction mechanism revealed that a combination of electronic and steric factors determines the regioselectivity of reactions involving C2-substituted pyridines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yixuan Chen, Yuefei Gu, Huan Meng, Qianzhen Shao, Zhenchuang Xu, Wenjing Bao, Yucheng Gu, Xiao-Song Xue, Yanchuan Zhao
Summary: A two-step strategy using unsymmetrical iodonium salts as versatile synthetic linchpins for transition-metal-free C-H functionalization of arenes is presented. The success relies on the identification of the 3,5-dimethyl-4-isoxazolyl (DMIX) group as a superior dummy ligand, enabling site-selective C-H functionalization and highly selective aryl transfer. Diverse structural elaboration is achieved through metal-free C-N, C-C, C-S, and C-O coupling.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Zhibin Du, Shiwen Liu, Yuke Li, Junjie Peng, Yanji Sun, Yanshan Song, Yuxuan Liu, Xiaojun Zeng
Summary: In this study, we achieved alpha- and delta-C(sp(3))-H alkylation of nitroalkanes with switchable regioselectivity by exploiting different activation modes of fluoroamides. Cu catalysis enabled the interception of a distal C-centered radical by a N-centered radical, allowing the coupling of nitroalkanes and unactivated delta-C-H bonds. Additionally, imines generated in situ by fluoroamides were trapped by nitroalkanes to realize the alpha-C-H alkylation of amides. Both of these scalable protocols have broad substrate scopes and good functional group tolerance.
Article
Chemistry, Multidisciplinary
Mingda Li, Yangbin Jin, Yupeng Chen, Wanqing Wu, Huanfeng Jiang
Summary: This paper reports a new catalytic system for the efficient oxidative amination of unactivated olefins with primary aliphatic amines, leading to the formation of secondary allylic amines. The reaction proceeds through allylic C(sp3)-H activation and nucleophilic amination. The utility of this method is demonstrated in the late-stage modification and streamlined synthesis of drug molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Youhao Wei, Zheng Wang, Kaifeng Wang, Jiang-Kai Qiu, Zhaoshan Wang, Haotian Li, Xiu Duan, Kai Guo, Xiaoguang Bao, Xinxin Wu
Summary: This study reports a copper-catalyzed allenic C(sp(2))-H cyanation with exceptional site-selectivity, addressing the challenge in synthetic chemistry of functionalizing allenic C(sp(2))-H bonds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Ashley Dang-Nguyen, Kristine C. Legaspi, Connor T. McCarty, Diane K. Smith, Jeffrey Gustafson
Summary: We present a practical, light-mediated perfluoroalkylation method using Langlois' reagent that does not require any photocatalyst or additives. This method allows for easy functionalization of pyridones and related N-heteroarenes such as azaindole. The protocol is straightforward, utilizes readily available materials, and is compatible with both electron-neutral and -rich pyridones.
Article
Chemistry, Organic
Haonan Zhang, Ting Wang, Kun Xu, Chengchu Zeng
Summary: The electrochemical denitrogenation of aroylhydrazides using NHPI as a mediator for the first time results in efficient synthesis of fluorenones with intramolecular trapped acyl radicals, under conditions free of external oxidants and transition metals. The addition of a catalytic amount of 2,4,6-collidine as the base enhances the attractiveness of this method for the synthesis of fluorenones.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Applied
Hui-Min Jiang, Qing Sun, Jin-Peng Jiang, Jing-Hao Qin, Xuan-Hui Ouyang, Ren-Jie Song
Summary: We have described a method for the dicarbofunctionalization of alkenes, which allows for the introduction of alkyl and electron-rich aryl groups across the C=C bond of styrenes. This is achieved under copper catalyst and oxidative conditions, resulting in the construction of C(sp(3))-C(sp(2))/C(sp(3))-C(sp(3)) bonds via dual C-H functionalization. The method enables the synthesis of 1,1-diarylalkanes, which are important scaffolds found in natural products and drug molecules, by grafting electron-rich aromatics such as indoles, pyrroles, and trisubstituted aromatics.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Peter Angyal, Andras M. Kotschy, Adam Dudas, Szilard Varga, Tibor Soos
Summary: This study reports a widely applicable and scalable synthetic method for efficiently double oxidation of alkenes using a two-step alkenyl thianthrenium umpolung/Kornblum-Ganem oxidation strategy. The chemo- and stereoselective procedure allows easy access to various α,β-unsaturated carbonyls, which are usually difficult to synthesize by conventional methods. The strategy also enables streamlined synthesis of distinct butadienyl pheromones and kairomones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Souradip Sarkar, Aniruddha Biswas, Sarbojit Das, Bortika Sanyal, Rajkumar Sahoo, Rajarshi Samanta
Summary: A rhodium(III)-catalyzed C4-selective cyanation of indole using N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as a coupling partner is described. The protocol showed a broad scope and achieved site selectivity by utilizing a weakly coordinating tert-amide group. The photophysical properties of the C4-cyanated indole frameworks were studied.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Souradip Sarkar, Aniruddha Biswas, Sarbojit Das, Bortika Sanyal, Rajkumar Sahoo, Rajarshi Samanta
Summary: This study describes a rhodium(III)-catalyzed indole C4-selective cyanation using the bench-stable and user-friendly electrophilic cyanation agent N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as a coupling partner. The selective site was achieved by utilizing a suitable weakly coordinating tert-amide group. The protocol developed in this study has a wide scope and [Cp*Rh(MeCN)(3)][SbF6](2) was identified as an effective Rh(III) catalyst. The photophysical properties of the C4-cyanated indole frameworks were also investigated.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Hongliang Zhao, Chao-Yue Zhao, Lili Chen, Chungu Xia, Xin Hong, Senmiao Xu
Summary: We report the iridium-catalyzed enantioselective C-H borylation of aryl chlorides, which could afford axially chiral biaryls with high enantioselectivities. The method demonstrates high turnover number (TON) and shows potential for synthetic applications in C-B, ortho-C-H, and C-Cl bond functionalization.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yufei Li, Xin Liang, Kaikai Niu, Jun Gu, Fang Liu, Qing Xia, Qingmin Wang, Weihua Zhang
Summary: An attractive, versatile, and operationally simple visible-light-induced trifluoromethylation method has been demonstrated, which is transition-metal-free, photocatalyst-free, and oxidant-free. Inexpensive and readily available triflic anhydride (Tf2O) was chosen as the radical trifluoromethyl source, and thianthrene was used as a recyclable Tf2O-activating reagent, achieving a high-yielding and scalable trifluoromethylation reaction. Density functional theory and mechanistic studies revealed that the reaction involves a free radical homolytic process excited by visible light, generating a key trifluoromethyl radical intermediate.
Article
Chemistry, Organic
Lei Liang, Ge Guo, Chen Li, Song-Lin Wang, Yue-Hui Wang, Hai-Ming Guo, Hong-Ying Niu
Summary: The study demonstrates Cu-catalyzed intermolecular alkynylation and allylation of unactivated C(sp(3))-H bonds with SOMO-philes via HAT, using N-fluoro-sulfonamide as a reagent, resulting in high yields, good regioselectivity, and functional-group compatibility. Late-stage functionalization of natural products and drug molecules is also shown in the research.
Article
Chemistry, Organic
Fangyuan Yu, Sen Yang, Zihao Xie, Dengfu Lu, Yuefa Gong
Summary: This article reports an iron-catalysed selective C-((sp3))-H alkylation method for glycine derivatives, which converts N-aryl glycinates into a series of pyrroline-containing amino esters using gamma,delta-unsaturated oxime esters as both the alkylation reagent and terminal oxidant. The ligand plays a key role in tuning the chemoselectivity, and a radical-polar crossover pathway is proposed according to the mechanistic studies. Additionally, the products obtained with this method can be transformed into various valuable building blocks.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Ruairi O. McCourt, Armido Studer
Summary: A 1,2-difunctionalization reaction of cyclic enol ethers mediated by bis(arylsulfonyl) peroxides is reported. Bis(nosyl) peroxide selectively adds a sulfonyl group at the 3-position of enol ethers, generating an oxocarbenium ion that is trapped by a carboxylic acid nucleophile at the 2-position. The reaction proceeds with good yield and tolerates a variety of cyclic enol ethers as well as different carboxylic acids as the oxocarbenium ion trapping reagents.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Yongjing Wang, Kang Ma, Tiantong Zhang, Philipp Alexander Held, Armido Studer, Harald Fuchs, Zhixin Hu, Zhixiang Sun, You Han, Hong-Ying Gao
Summary: The effect of iodine on modulating the self-assembly structures of organic molecules on metal surfaces was systematically studied. By using low-temperature scanning tunneling microscopy and density functional theory, the transformation of molecular self-assembly structures induced by iodine dosing on the Ag(111) surface was explored. It was found that iodine can modulate the self-assembly structure of organic molecules with weak intermolecular interaction, while those with stronger intermolecular hydrogen bonding are not affected. These findings were confirmed by density functional theory calculations.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Article
Chemistry, Multidisciplinary
Huihui Kong, Lena Viergutz, Lacheng Liu, Alexander Sandvoss, Xinchen Peng, Henning Klaasen, Harald Fuchs, Armido Studer
Summary: Aryl propiolic acids can be used as new monomers in on-surface chemistry to synthesize poly(arylenebutadiynylenes) via decarboxylative Glaser coupling. Compared to aryl alkynes, the decarboxylative coupling occurs at slightly lower temperature and with better selectivity. The activation of propiolic acids is achieved through decarboxylation, while the classical Glaser coupling involves alkyne C-H activation and shows poor selectivity. The successful polymerization of bis(propiolic acids) as monomers demonstrates the efficiency of the decarboxylative coupling. Additionally, the new activation mode is compatible with aryl bromide functionalities, allowing the formation of unsymmetric metal-organic polymers on the surface through chemoselective sequential reactions.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Niklas Radhoff, Constantin G. G. Daniliuc, Armido Studer
Summary: The design, synthesis, and application of benzene bioisosteres have been a subject of great interest in the past two decades. Recently, bicyclo[2.1.1]hexanes have been established as highly attractive bioisosteres for ortho- and meta-substituted benzenes. In this study, we present a mild, scalable, and transition-metal-free method for constructing highly substituted bicyclo[2.1.1]hexan-2-ones through Lewis acid-catalyzed (3+2)-cycloaddition of bicyclo[1.1.0]-butane ketones with disubstituted ketenes. The reaction exhibits high functional group tolerance, as evidenced by the successful synthesis of various 3-alkyl-3-aryl and 3,3-bisalkyl bicyclo[2.1.1]hexan-2-ones (26 examples, up to 89% yield). Additionally, postfunctionalization of the exocyclic ketone moiety is demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jannik Reimler, Xiao-Ye Yu, Nico Spreckelmeyer, Constantin G. Daniliuc, Armido Studer
Summary: The Friedel-Crafts acylation reaction has been a valuable and versatile reaction, but a new radical approach for the acylation of arenes and heteroarenes is presented in this study. By using cooperative photoredox/NHC radical catalysis, C-H acylation is achieved with regiodivergent outcomes. Aroyl fluorides act as the acylation reagents in both the ionic and radical processes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Hui Cao, Qiang Cheng, Armido Studer
Summary: The pyridine moiety is widely used in the synthesis of drugs, agrochemicals, catalysts, and functional materials. While direct functionalization of ortho- and para-positions is well-established, meta-selective pyridine C-H functionalization presents more challenges due to the inherent electronic properties of pyridines. In this review, we summarize the current methods for meta-C-H functionalization of pyridines, including the use of directing groups, non-directed metalation, and temporary dearomatization strategies. Recent advances in ligand control and temporary dearomatization are highlighted, while the advantages and limitations of these techniques are discussed, aiming to inspire further developments in this important area.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Zhe Wang, Nick Wierich, Jingjing Zhang, Constantin G. Daniliuc, Armido Studer
Summary: In this study, a method for direct generation of alkyl radicals from alkylboronic pinacol esters (APEs) through reaction with aminyl radicals is reported. Aminyl radicals are readily generated by visible-light-induced homolytic cleavage of the N-N bond in N-nitrosamines, and C radical generation occurs through nucleohomolytic substitution at boron. As an application, the highly efficient photochemical radical alkyloximation of alkenes with APEs and N-nitrosamines under mild conditions is presented. Various primary, secondary, and tertiary APEs can be used in this scalable transformation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Jonas Elfert, Anup Bhunia, Constantin G. Daniliuc, Armido Studer
Summary: In this study, a radical transformation that enables intramolecular oxygen atom transfer to alkenes using the nitro functionality in nitroarenes as an oxygen donor is disclosed. The reaction proceeds via iron-catalyzed metal hydrogen atom transfer to alkenes and subsequent oxygenation, resulting in alkene hydration. Compared to intermolecular radical oxygenation, the intramolecular variant offers advantages, particularly in terms of diastereoselective radical hydration of conformationally flexible alkenes. The aryl moiety connecting the reactive NO2-functionality to the alkene substrate can be cleaved after oxygen transfer, yielding products derived from a formal diastereoselective intermolecular alkene hydration. Additionally, the resulting aniline entity after oxygen transfer can be used for the construction of nitrogen-containing heterocycles.
Review
Chemistry, Multidisciplinary
Dirk Leifert, Armido Studer
Summary: This article provides an overview of the structure, stability, and versatile applications of nitroxides, with a focus on their use in organic synthesis.
Article
Multidisciplinary Sciences
Jingjing Zhang, Christian Mueck-Lichtenfeld, Armido Studer
Summary: Chemical activation of water is a hot topic in energy research and enables the conversion of this abundant resource into valuable compounds. In this study, we demonstrate the activation of water using a photocatalytic phosphine-mediated radical process, which involves sequential heterolytic and homolytic cleavage of O-H bonds. The resulting PR3-OH radical intermediate can react with various closed-shell p systems, leading to transfer hydrogenation of the p system and incorporation of hydrogen atoms from water into the product. Experimental and theoretical studies support the importance of the hydrogen atom transfer step in this radical hydrogenation process.
Article
Chemistry, Organic
Shyam Kumar Banjare, Dirk Leifert, Frauke Weidlich, Constantin G. Daniliuc, Fatmah A. Alasmary, Armido Studer
Summary: An oxidative radical cascade addition cyclization approach using eco-friendly iron catalysis and inexpensive tert-butylhydroperoxide (TBHP) as the oxidant has been reported for the synthesis of quinoline-based p-extended polyheterocyclic compounds. This method utilizes readily available ortho-alkynylated aromatic aldehydes as radical precursors and aryl isonitriles as radical acceptors. By applying this approach, quinolines that are p-conjugated with an additional heteroarene moiety can be prepared in a single sequence using indole and thiophene-based carbaldehydes.
Article
Chemistry, Organic
Lena Lezius, Jannik Reimler, Nadine Doeben, Michael Hamm, Constantin G. Daniliuc, Armido Studer
Summary: Cooperative NHC and photoredox catalysis have emerged as an important research field. In this study, a cyclizing aminoacylation of alkenes is achieved through the combination of these two catalytic modes. The key step involves a radical/radical cross-coupling between a persistent ketyl radical and a transient benzylic or aliphatic C-radical, generated through radical cyclization of an oxidatively formed amidyl radical. Various substrates containing an alkene moiety and different acyl fluorides can be used, resulting in moderate to good yields of the products.
Article
Chemistry, Organic
Shyam Kumar Banjare, Dirk Leifert, Frauke Weidlich, Constantin G. Daniliuc, Fatmah A. Alasmary, Armido Studer
Summary: An oxidative radical cascade addition cyclization approach using eco-friendly iron catalysis and inexpensive TBHP as the oxidant has been developed for the synthesis of quinoline-based p-extended polyheterocyclic compounds. This method allows the preparation of quinolines that are p-conjugated with an additional heteroarene moiety in a single sequence.
Article
Chemistry, Multidisciplinary
Anirban Maity, Armido Studer
Summary: 1,2-Aminoxyalkylation of alkenes with alkyl iodides and TEMPONa in the presence of an aryldiazonium salt as an XAT mediator is described. Primary, secondary and tertiary alkyl iodides can serve as C-radical precursors in the 1,2-aminoxyalkylation reaction with electrophilic alkenes. The resulting alkoxyamines can be easily converted to alcohols or ketones through reduction or oxidation, respectively. Mechanistic studies reveal the involvement of aryl radicals generated through SET-reduction of the aryldiazonium salt in the XAT process, allowing the addition of alkyl radicals to alkenes. The trapping of the adduct radicals with TEMPO leads to the formation of 1,2-aminoxyalkylation products. Transition metals are not required for these mild conditions transformations. Direct 1,2-aminoxyperfluoroalkylation of alkenes with perfluoroalkyl halides can be achieved using TEMPONa without the need for an aryldiazonium salt as an XAT mediator.
Article
Chemistry, Multidisciplinary
Florian Lind, Kirill Markelov, Armido Studer
Summary: This article introduces a photocleavable alcohol protecting group based on acyl silanes, which can be easily synthesized in three concise steps with high overall yield. The protection of alcohols occurs under mild conditions and can be removed through exposure to visible light. This approach demonstrates remarkable tolerance to diverse functional groups and showcases its robustness against various transformations.
