Article
Multidisciplinary Sciences
Taiga Kodo, Kazunori Nagao, Hirohisa Ohmiya
Summary: This paper reports a new method of semipinacol rearrangement using photochemical approach, enabling the synthesis of compounds with sp(3)-rich scaffolds.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Applied
Shivani Sharma, Jitender Singh, Anuj Sharma
Summary: The novel concept of radical-polar crossover (RPCO) and polar-radical crossover (PRCO) reactions has emerged in recent years as a valuable tool bridging the gap between polar and radical reactions, overcoming their limitations, and improving the green quotient of reactions. The development and transformation of this area into synthetically important reactions is summarized in this review.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Review
Chemistry, Applied
Serena Pillitteri, Prabhat Ranjan, Erik V. Van der Eycken, Upendra K. Sharma
Summary: The chemistry of boron compounds has been extensively studied and applied in synthetic and biologically active molecules. The advent of photoredox catalysis has led to a surge in the discovery of suitable radical precursors, with boron playing a prominent role. However, the use of boronic acids and esters in photocatalyzed reactions has received less attention, and methods to enable their involvement have only recently been developed. Nonetheless, this review summarizes novel strategies to unlock their potential as radical precursors in photochemical reactions by exploiting their intrinsic chemical properties.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Multidisciplinary Sciences
Kenji Ota, Kazunori Nagao, Dai Hata, Haruki Sugiyama, Yasutomo Segawa, Ryosuke Tokunoh, Tomohiro Seki, Naoya Miyamoto, Yusuke Sasaki, Hirohisa Ohmiya
Summary: This study demonstrates a light-driven radical-polar crossover mechanism for the tertiary alkylation of phosphorus atoms in nucleotides, enabling the synthesis of alkylphosphonate structures that are difficult to obtain using existing methods.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Sufal Paul, Piyush Kumar Verma, Anubhab Kashyap, Rahul Mondal, K. Geetharani
Summary: A new method has been developed for sequentially gem-thioborylating readily available aldehydes through cobalt-catalyzed diboration reaction. The N-heterocyclic carbene (NHC)-cobalt complex serves as a catalyst for the diboration of aldehydes to generate alpha-oxyl boronic esters, which react with lithium thiolates to form a tetracoordinate boronate species undergoing 1,2-metalate rearrangement in the presence of trifluoroacetic anhydride. The stepwise functionalization of the boryl and thiol moiety of the products enriches the chemical toolbox of diverse organic synthesis.
Article
Chemistry, Organic
Xianrong Zeng, Feng-Hua Zhang, Zhaobin Wang
Summary: The Nozaki-Hiyama-Kishi (NHK) reaction is a powerful tool in chiral alcohol synthesis and finds broad application in the total synthesis of biologically important molecules. However, synthesizing chiral ketones in NHK reactions remains a challenge. This study describes a chromium-catalyzed enantioconvergent synthesis of chiral 2,3-allenones, providing a new tool for chiral ketone synthesis.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Chemistry, Multidisciplinary
Zhoumei Tan, Haonan Zhang, Kun Xu, Chengchu Zeng
Summary: RPC reaction bridges the gap between radical and polar chemistry, providing a solution to overcome their limitations. Organic electrochemistry offers a facile strategy to access a diverse array of radical intermediates, expanding the chemical space of RPC concept. This review highlights the synthetic advances in electrochemical RPC reactions since 2020, focusing on substrate scope, reaction limitation, and mechanistic aspects.
SCIENCE CHINA-CHEMISTRY
(2023)
Article
Chemistry, Organic
Siwei Wang, Chaochao Xie, Yu Zhu, Guofu Zi, Zhanbin Zhang, Guohua Hou
Summary: An efficient Ni-(S,S)-Ph-BPE complex has been developed for the asymmetric hydrogenation of cyclic N-acyl hydrazones, leading to the formation of various chiral cyclic hydrazines with high yields and enantioselectivities of over 99%. The hydrogenation reaction can proceed smoothly on a gram scale with low catalyst loading (S/C = 3000) without a decrease in enantioselectivity, and it can be applied to the asymmetric synthesis of a RIP-1 kinase inhibitor.
Article
Chemistry, Organic
Yifan Zhang, Yuxin Jiang, Yi Wang, Tianyi Sun, Yuanjie Meng, Yueyan Huang, Xiaoqing Lv, Jinlai Gao, Xiaoqin Zhang, Shilei Zhang, Shihui Liu
Summary: In this study, a distinctive photoredox/copper dual-catalyzed esterification of benzylic C-H bonds was reported, which involves the combination of photoredox-mediated hydrogen atom transfer and Cu(II)-mediated radical-polar crossover. The methodology shows a high functional group tolerance (>40 examples) and moderate to good yields with structurally diverse benzylic C-H substrates. Notably, stoichiometric amounts of carboxylic acids are used as coupling partners, enabling the synthesis of structurally diverse benzylic esters and the late-stage functionalization of pharmaceuticals.
Article
Chemistry, Organic
Kuan-Lin Chen, Fujie Tanaka
Summary: The study developed organocatalytic asymmetric Mannich reactions and kinetic resolutions of the products through retro-Mannich reactions, which resulted in enantiomerically enriched tetrasubstituted alpha-amino acid derivatives. Furthermore, the combination of Mannich reaction and retro-Mannich reaction allowed the access to products with almost perfect enantiopurities.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Purui Zheng, Pan Zhou, Dong Wang, Wenhao Xu, Hepan Wang, Tao Xu
Summary: The authors reported a mild Ni/photoredox-catalyzed reductive cross-coupling of aryl iodides and alpha -chloroboranes, enriching the metallaphotoredox chemistry. This method enables the access to versatile benzylic boronic esters with good functional group tolerance and excellent enantioselectivities under mild conditions.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Yang Zhang, Dan Ye, Lei Shen, Kangjiang Liang, Chengfeng Xia
Summary: A photochemical protocol is developed for the synthesis of chiral 3-hydroxyoxindoles by coupling diarylamines and alpha-ketoesters using tandem photoredox and chiral phosphoric acid catalysis. The chiral phosphoric acid plays a crucial role in controlling the stereochemistry of the downstream radical-radical cross-coupling process.
Article
Chemistry, Physical
Steve H. Park, Jieun Jang, Kwangmin Shin, Hyunwoo Kim
Summary: We disclose a general electrocatalytic hydroetherification method for modular synthesis of alkyl aryl ethers. This method involves an electrochemically instigated cobalt-hydride-catalyzed radical-polar crossover of alkenes, resulting in the generation of cationic intermediates that react with nucleophilic phenols. Precise control of reaction potential by electrochemistry and the use of hexafluoro-2-propanol (HFIP) as the co-solvent are crucial for achieving optimal and exclusive chemoselectivity. This method is important for the late-stage functionalization of pharmacophores containing alkyl aryl ethers, which has been a challenge using traditional unconventional methods.
Article
Chemistry, Multidisciplinary
Sheng-Qiang Guo, Hui-Qing Yang, Yu-Zhen Jiang, Ai-Lian Wang, Guo-Qiang Xu, Yong-Chun Luo, Zhao-Xu Chen, Haixue Zheng, Peng-Fei Xu
Summary: In this study, a green and reliable strategy for the diastereoselective synthesis of beta-amido sulfones through organophotoredox catalytic four-component radical-polar crossover cascade reactions was reported. The transformation exhibited excellent atom-, step-, and redox economy as well as diastereoselectivity.
Article
Chemistry, Organic
Stephen Bolgunas, Ehecatl Paleo, Embarek Alwedi, Yunjing Wei, Taylor M. Keller, Fraser F. Fleming
Summary: Naphthalene converts magnesiated omega-alkenylnitriles into bi- and tricyclic ketones via a polar-radical addition-cyclization cascade. The one-electron oxidation of magnesiated nitriles generates nitrile-stabilized radicals, which then cyclize onto a pendant olefin and rebound onto the nitrile through a reduction-cyclization sequence, followed by hydrolysis to obtain a diverse array of bicyclo[3.2.0]heptan-6-ones. Combining the polar-radical cascade with a 1,2:1,4-carbonyl-conjugate addition results in the synthesis of complex cyclobutanones containing four new carbon-carbon bonds and four chiral centers.
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, 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
Florian Lind, Armido Studer
Summary: Acylsilanes, a class of organosilicon compounds, have been gaining increased attention due to their ability to generate carbenes and their usefulness as reagents in organic synthesis. In this study, a novel and efficient route for the synthesis of acylsilanes was reported through alkene hydrosilylation. By using acylhydrosilanes as silylation reagents in rhodium catalyzed alkene hydrosilylations, a wide range of acylsilanes can be accessed in good to excellent yields under mild conditions with high functional group tolerance and atom economy.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Till Drennhaus, Dirk Leifert, Jessika Lammert, Jan Philipp Drennhaus, Klaus Bergander, Constantin G. Daniliuc, Armido Studer
Summary: In this study, enantioenriched chiral indoles were synthesized through a mild and efficient radical cascade reaction using a chiral copper-bisoxazoline complex. The targeted 2-fluoroalkylated 3-(alpha-cyanobenzy-lated) indoles were accessed with excellent enantioselectivity and good yields. Mechanistic studies revealed a negative nonlinear effect which explained the stereochemical outcome. The enantioenriched 3-(alpha-cyanobenzylated) indoles demonstrated scalability and potential utility as hubs for chiral tryptamines, indole-3-acetic acid derivatives, and triarylmethanes, and a formal synthesis of a natural product analogue was disclosed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(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
Chemistry, Multidisciplinary
Hui Cao, Debkanta Bhattacharya, Qiang Cheng, Armido Studer
Summary: Selective C-H functionalization of pyridines is of great value but not well developed. In this study, a redox-neutral dearomatization-rearomatization strategy was used to achieve meta-C-H functionalization of pyridines through oxazino pyridine intermediates. Notably, by switching to acidic conditions, these intermediates underwent highly selective para-functionalization. A broad range of para-alkylated and arylated pyridines were prepared using both radical and ionic pathways. These mild and catalyst-free methods were also applied in the late-stage para-functionalization of drugs. Furthermore, the regioselective meta,para-difunctionalization of pyridines was achieved by exploiting the pH-dependent reactivity of oxazino pyridines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
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.