Article
Chemistry, Multidisciplinary
Andreas Boelke, Thomas J. Kuczmera, Enno Lork, Boris J. Nachtsheim
Summary: The article explores the application of N-heterocyclic iod(az)olium salts (NHISs) as highly reactive organocatalysts, particularly as potent XB-donors in halogen-bond catalysis. Among the variety of NHISs tested, N-methylated dicationic NHISs exhibited the highest reactivity in all investigated catalytic applications, surpassing previously described monodentate XB-donors based on iodine(I) and (III) as well as the strong Lewis acid BF3.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Loic Habert, Kevin Cariou
Summary: In this study, the aerobic iodoarene catalysis was achieved by using a pyrylium photocatalyst under blue light irradiation, allowing for the use of low catalytic loading of both catalysts under very mild operating conditions. This unprecedented dual organocatalytic system provides a powerful and efficient methodology for spiro-cyclization of amides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Jessica C. Bieniek, Boris Mashtakov, Dieter Schollmeyer, Siegfried R. Waldvogel
Summary: This study presents an electrocatalytic method using hypervalent iodine(III) as a mediator to synthesize 1H-N-aryl-3,4-dihydroquinolin-2-ones by C-N bond formation. The method features a low catalyst loading, recycling of the solvent, and is a sustainable alternative to conventional approaches.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Applied
Yuna Nishiguchi, Katsuhiko Moriyama
Summary: A new synthetic method was developed with the use of aniline-type hypervalent iodine(III) for direct cyclizations, resulting in high yields of the corresponding products.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Thibaut Duhail, Jorna Kalim, Jerome Marrot, Bruce Pegot, Emmanuel Magnier, Elsa Anselmi
Summary: This study describes hypervalent iodine compounds with specific ligands, investigating the influence of these groups on the stability of cyclic structure and highlighting the crucial role of the trifluoromethyl chain as an efficient ligand. The structure and reactivity of the new skeletons are discussed in detail.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Yuchen Wu, Takuma Sasayama, Takahiro Gotoh, Mamoru Ito, Takanori Shibata
Summary: In this study, hexaazatruxenes were successfully synthesized and their potential as light-emitting materials and building blocks was demonstrated.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Fabio Cuzzucoli, Leanne Racicot, John F. Valliant, Graham K. Murphy
Summary: A new class of fluorinated, cyclic N-methoxyimidates was synthesized through intramolecular fluorocyclization. The reaction achieved efficient cyclization at room temperature using unsaturated amides, a mono-fluoroiodane, and HFIP as the activator, resulting in products with up to 81% yield in a single step. Two product isomers were selectively obtained depending on the presence of an α-arene substituent.
Review
Chemistry, Applied
Akira Yoshimura, Akio Saito, Viktor V. Zhdankin
Summary: Hypervalent iodine compounds, particularly those based on the benziodoxole heterocyclic system, are widely used as reagents and catalysts in modern organic chemistry. These cyclic hypervalent iodine reagents exhibit higher stability compared to their acyclic analogues, allowing for the safe handling and preparation of reagents with special ligands such as azido, cyano, and trifluoromethyl groups. They have been utilized for the transfer of substituents on hypervalent iodine to organic substrates under various reaction conditions. This review focuses on the recent synthetic applications of cyclic hypervalent iodine(III) reagents with different ligands, including N-3, NHR, CN, CF3, SCF3, OR, OAc, ONO2, and C(=N-2)CO2R, mainly in the past 5 years.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Michael T. Shea, Gregory T. Rohde, Yulia A. Vlasenko, Pavel S. Postnikov, Mekhman S. Yusubov, Viktor V. Zhdankin, Akio Saito, Akira Yoshimura
Summary: Hypervalent iodine heterocycles are an important class of reagents in organic synthesis, and this paper presents a simple and convenient method for the synthesis of benziodazolones using readily available iodobenzamides and m-chloroperoxybenzoic acid. The new iodine heterocycles were confirmed by X-ray analysis and shown to react more efficiently than analogous benziodoxolone reagents in esterification reactions.
Article
Chemistry, Multidisciplinary
Eliott Le Du, Thibaut Duhail, Matthew D. Wodrich, Rosario Scopelliti, Farzaneh Fadaei-Tirani, Elsa Anselmi, Emmanuel Magnier, Jerome Waser
Summary: This study reported the synthesis of new N-heterocyclic hypervalent iodine reagents with increased structural flexibility based on amide, amidine and sulfoximine scaffolds. The alkynylation reactions of beta-ketoesters and thiols showed variable yields, with compounds with a stronger sigma-hole reacting better. In metal-mediated transformations, the N-heterocyclic hypervalent iodine reagents gave inferior results when compared to the O-based EBX reagents.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Applied
Stanislav A. Paveliev, Oleg O. Segida, Oleg Bityukov, Hai-Tao Tang, Ying-Ming Pan, Gennady Nikishin, Alexander O. Terent'ev
Summary: In this study, the electrochemical intramolecular cross-dehydrogenative C(sp(2))-H/N-H coupling of alpha,beta-unsaturated hydrazones resulting in substituted pyrazoles has been discovered. This process is catalyzed by hypervalent iodine species generated in situ through anodic oxidation of aryl iodide in fluorinated alcohol media. The formation of hypervalent iodine compound and its key role in the construction of a new C-N bond were confirmed with CV and NMR experiments. A wide range of substituted pyrazoles were obtained with yields ranging from 46% to 88%.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Chemistry, Organic
Irina A. Mironova, Stefan F. Kirsch, Viktor V. Zhdankin, Akira Yoshimura, Mekhman S. Yusubov
Summary: This review summarizes recent approaches to the direct synthesis of organic azides using hypervalent iodine reagents. The first part discusses the use of unstable azidoiodinanes generated in situ, while the second part focuses on the application of stable azidobenziodoxoles as azidating reagents. The use of azidobenziodoxoles allows for selective direct azidation of specific bonds under mild reaction conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Joel Haefliger, Olga O. Sokolova, Madina Lenz, Constantin G. Daniliuc, Ryan Gilmour
Summary: The success of saturated, fluorinated heterocycles in drug discovery has led to increased research efforts in main group catalysis. By utilizing iodine(I)/iodine(III) catalysis, selective fluorinated analogs with stereocontrol have been synthesized. Furthermore, the key stereoelectronic interactions in the products have been confirmed through X-ray crystal structures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Vasco Corti, Mathias Kirk Thaegersen, Valdemar Juel Enemaerke, Nomaan M. Rezayee, Casper L. Barlose, Karl Anker Jorgensen
Summary: The first atroposelective aminocatalytic methodology for the construction of C-N atropisomers is described. By directly coupling indole-2-carboxaldehydes to ortho-quinones, a new library of functionalized and enantioenriched C-N atropisomers was obtained using a designed and synthesized aminocatalyst. The synthetic utility of these atropisomers was demonstrated through various transformations.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Applied
Elghareeb E. Elboray, Taeho Bae, Kotaro Kikushima, Yasuyuki Kita, Toshifumi Dohi
Summary: We developed a metal catalyst-free protocol for O-arylation of benzamide hydroxamate esters. By varying the electronic and/or steric properties of the diaryliodonium salt and/or the substrate, the chemoselective O- versus N-arylation of the amides was controlled. The O-arylation reaction showed preference for sterically and electronically diverse substrates. This study demonstrates the possibility of substituent- and reagent-controlled chemoselectivity with diaryliodonium salts and may draw interest in the field of hypervalent iodine chemistry.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Koki Kawai, Hiroto Uno, Daichi Fujimoto, Norio Shibata
Summary: A stereoselective catalytic synthesis of 3-trifluoromethyl indolines was developed through the transition-metal-free [4+1] cycloaddition of benzoxazinones and sulfur ylides. The key to this catalytic transformation lies in the dual attack of sulfur ylides on substrates. This method is not only applicable to the synthesis of non-fluorinated indolines, but also achieved the synthesis of target products under stoichiometric conditions.
HELVETICA CHIMICA ACTA
(2021)
Article
Chemistry, Organic
Yumeng Liang, Zhengyu Zhao, Akihito Taya, Norio Shibata
Summary: A novel reagent system allows for the direct synthesis of acyl fluorides from carboxylic acids, aldehydes, or alcohols with high yields up to 99%. This transformation is useful for late-stage functionalization of natural products and drug molecules containing a carboxylic acid, aldehyde, or alcohol group.
Article
Multidisciplinary Sciences
Satoshi Yamanaka, Yuto Horiuchi, Saya Matsuoka, Kohki Kido, Kohei Nishino, Mayaka Maeno, Norio Shibata, Hidetaka Kosako, Tatsuya Sawasaki
Summary: This article introduces a method based on AirID to identify drug-induced neo-substrates through proximity-dependent biotinylation. The study identifies several new CRBN substrates and demonstrates that this method can serve as a general strategy for studying drug-induced protein-protein interactions in cells.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Hiroto Uno, Koki Kawai, Taichi Araki, Motoo Shiro, Norio Shibata
Summary: Gem-difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. A novel asymmetric method for their construction was developed, allowing easy access to chiral 1,3-dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center. The gem-difluoro substitution pattern promotes the reaction, and various substrates were suitable for this method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Kentaro Iwaki, Koki Maruno, Osamu Nagata, Norio Shibata
Summary: The trans-tetrafluoro-lambda 6-sulfanyl (SF4) unit is of medicinal interest due to its high electronegativity, lipophilicity, and unique hypervalent structure. Despite the difficulties in synthesis, the first synthesis of (ethynyl-trans-tetrafluoro-lambda 6-sulfanyl) pyridines and their use as versatile reagents for SF4-alkynylation to carbonyl compounds was reported. The addition reaction of t-ethynyl-SF4-pyridines to carbonyl groups in the presence of MeLi yielded pyridine-SF4-propargylic tertiary and secondary alcohols in high yields.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Kentaro Iwaki, Kazuhiro Tanagawa, Soichiro Mori, Koki Maruno, Yuji Sumii, Osamu Nagata, Norio Shibata
Summary: In this study, we reported a metal-free hydration reaction of pyridine-SF4-alkynes under acidic conditions, which synthesized pyridine-SF4-methyl ketones with yields ranging from 59% to 93%. We further demonstrated the synthetic applications of these compounds, including chlorination, NaBH4 reduction, Baeyer-Villiger oxidation, and the generation of enol triflates. These compounds show promise as useful building blocks in the synthesis of a wide range of SF4-containing drug candidates.
Article
Chemistry, Organic
Jun Zhou, Bingyao Jiang, Zhengyu Zhao, Norio Shibata
Summary: A potassium base-mediated defluoroetherification method for aryl and heteroaryl fluorides is reported, which efficiently and safely provides a wide variety of aryl ethers without the use of metal catalysts, specific ligands, and harsh conditions. This method can also be applied to the late-stage etherification of structurally complex fluorides and bioactive alcohols.
Article
Chemistry, Organic
Yuji Sumii, Hiroto Iwasaki, Yamato Fujihira, Elsayed M. Mahmoud, Hiroaki Adachi, Takumi Kagawa, Dominique Cahard, Norio Shibata
Summary: A protocol for the stereodivergent pentafluoroethylation of N-sulfinylimines has been developed using HFC-125 with KHMDS/triglyme. The presence or absence of triglyme enables the selective synthesis of both diastereomers of the pentafluoroethylated amines. This additive-controlled protocol offers a straightforward and cost-effective alternative to the previously reported base-controlled stereodivergent trifluoromethylation using potassium hexamethyldisilazide (KHMDS) versus P4-tBu.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Masahiro Sugiura, Kazuki Ishikawa, Kota Katayama, Yuji Sumii, Rei Abe-Yoshizumi, Satoshi P. Tsunoda, Yuji Furutani, Norio Shibata, Leonid S. Brown, Hideki Kandori
Summary: This study reports a novel photochemical reaction mediated by a microbial rhodopsin, leading to the selective transition from the all-trans to 7-cis form.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Norio Shibata, Dominique Cahard
Summary: From 2000, our two research groups independently and simultaneously designed and developed a novel family of electrophilic fluorinating reagents based on the use of Cinchona alkaloids. The chiral N-fluoro ammonium salts demonstrated the highest efficiency compared to prior art in enantioselective electrophilic fluorination for a wide range of substrates. In this account, we tell our respective stories, how the same idea germinated in our laboratories, the characterization of the chiral reagents, the use in stoichiometric quantity then the development of a catalytic version, the application to the synthesis of chiral fluorinated molecules of pharmaceutical interest, and finally the exploitation of our reagents by other teams and for other applications.
Review
Chemistry, Multidisciplinary
Yuji Sumii, Norio Shibata
Summary: The trifluoromethyl group is a crucial component in drugs and polymers, making the development of trifluoromethylation reactions a significant area of research in organic chemistry. Various methods, including nucleophilic and electrophilic approaches, transition-metal catalysis, photocatalysis, and electrolytic reactions have been developed over the years. Microflow versions of these reactions have shown great potential for industrial applications due to their scalability, safety, and time efficiency. This review discusses the current state of microflow trifluoromethylation, focusing on different trifluoromethylation reagents and techniques such as continuous flow, flow photochemical, microfluidic electrochemical reactions, and large-scale microflow reactions.
Letter
Chemistry, Organic
Elsayed M. Mahmoud, Soichiro Mori, Yuji Sumii, Norio Shibata
Summary: The synthesis of acyl fluorides from carboxylic acids is achieved using Selectfluor mediated by elemental sulfur. A wide range of acyl fluorides can be accessed while avoiding the formation of acid anhydrides. F-19 NMR spectra indicate that the reactive species in this deoxyfluorination reaction are the in situ generated S-8-fluoro-sulfonium cation A and neutral S-8-difluoride A'.
Article
Multidisciplinary Sciences
Jun Zhou, Zhengyu Zhao, Norio Shibata
Summary: Defluorinative cross-coupling between amines and organic fluorides is achieved via a silylboronate-mediated strategy. This method enables the room-temperature cross-coupling of C-F and N-H bonds, avoiding the high energy barriers associated with thermally induced S(N)2 or S(N)1 amination. The selective activation of the C-F bond of organic fluorides by silylboronate is a significant advantage of this transformation.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Chemistry, Multidisciplinary
Norio Shibata, Dinesh Talwar
Summary: The unique properties and applications of fluorine-containing molecules have had significant impact across different scientific fields, from small to large molecules. This special issue provides a comprehensive overview of the state-of-the-art in fluorine chemistry.
Article
Chemistry, Multidisciplinary
Jun Zhou, Zhengyu Zhao, Bingyao Jiang, Katsuhiro Yamamoto, Yuji Sumii, Norio Shibata
Summary: In this study, an efficient silylboronate-mediated cross-coupling reaction of aryl fluorides with arylalkanes was developed under transition-metal-free, room-temperature conditions. The method showed good adaptability to aryl fluorides with a C(sp(2))-F bond and can be extended to other coupling partners with a C(sp(3))-H bond. It provides a practical and convenient approach to obtain di- and triarylalkanes with tertiary or quaternary carbon centers.
