Review
Chemistry, Multidisciplinary
Jiarong Shi, Lianggui Li, Yang Li
Summary: Arynes are highly active organic intermediates used in the rapid synthesis of substituted arenes, with o-silylaryl triflates being the most frequently employed precursors. The resurgence in aryne chemistry over the past 20 years is largely attributed to the widespread use of Kobayashi's method, which involves fluoride-induced removal of the TMS group with concomitant departure of its ortho OTf group. This review provides an overview of the history, achievements, and applications of Kobayashi's method in the synthesis of natural products, bioactive molecules, and polycyclic aromatic hydrocarbons.
Article
Chemistry, Multidisciplinary
Yuncong Luo, Shengjie Jiang, Xin Xu
Summary: This work reports a novel site-selective C-H borylation reaction of pyridines at the ortho-position using a yttrocene catalyst, enabling the introduction of boronate groups. The resulting boronates exhibit a broad substrate scope and high atom efficiency, and can undergo various transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Bo Li, Ke Wang, Huifeng Yue, Alwin Drichel, Jingjing Lin, Zhenying Su, Magnus Rueping
Summary: In this study, a mild and visible-light-induced method for the synthesis of aryl borates without the use of base, transition metal-ligand complex, or photoredox catalyst was reported. The reaction showed excellent functional group tolerance and was successfully applied to the late-stage modification of natural products and the synthesis of a drug intermediate.
Article
Chemistry, Organic
Jairus L. Lamola, Paseka T. Moshapo, Cedric W. Holzapfel, Banothile C. E. Makhubela, Munaka Christopher Maumela
Summary: The study investigates the influence of ligand steric bulk on the Pd-catalyzed borylation of ortho-substituted aryl bromides and chlorides under mild conditions (25 - 80 degrees C). Catalysts derived from the less hindered biaryl phobane[3.3.1] 1 (cone angle = 178.5 degrees) exhibited high efficiency for borylation of various ortho-substituted aryl bromides. Dialkylbiaryl phosphine 5 (cone angle = 181.3 degrees) and biaryl phosphacycle 2 (cone angle = 220.0 degrees) possessed suitable ligand steric bulk for facile Pd-catalyzed borylation of ortho-substituted aryl chlorides.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Kai Kang, Nathan L. Loud, Tarah A. DiBenedetto, Daniel J. Weix
Summary: A new, general approach to biheteroaryls through Ni- and Pd-catalyzed multimetallic cross-Ullmann coupling has been developed, demonstrating successful synthesis of a variety of heteroaryl halides and triflates. This method showed high generality and >90% hit rate in a 96-well plate format.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Jyoti Dhankhar, Micha D. Hofer, Anthony Linden, Ilija Coric
Summary: This article presents a new selectivity mode for C-H arylation reactions, which is the preference for C(sp(2))-H activation next to alkyl groups. The study results indicate that this preference is related to the non-covalent interactions between the catalyst and the substrate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Daniel Marcos-Atanes, Cristian Vidal, Claudio D. Navo, Francesca Peccati, Gonzalo Jimenez-Oses, Jose L. Mascarenas
Summary: Iridium-catalyzed borylations of aromatic C-H bonds allow for the synthesis of a wide variety of ortho-borylated derivatives. A subtle change in the bipyridine ligand, introducing a CF3 substituent at position 5, enables a complete change of regioselectivity in the borylation of aromatic amides. Computational studies suggest that this regio- and chemoselectivity is due to unusual outer-sphere interactions between the amide group of the substrate and the CF3-substituted aryl ring of the bipyridine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Shuai Mao, Bo Yuan, Xinyu Wang, Yahao Zhao, Lu Wang, Xue-Yan Yang, Yi-Ming Chen, San-Qi Zhang, Pengfei Li
Summary: This study presents a regioselective ortho,ortho'-diborylation of aromatic triazenes catalyzed by [Ir(OMe)(cod)](2) in near-quantitative yields without an additional ligand. The synthesized products can undergo a variety of transformations, providing a short entry to densely functionalized arenes.
Article
Chemistry, Multidisciplinary
Xinyu Chen, Na Yang, Wen Zeng, Lei Wang, Pinhua Li, Hongji Li
Summary: A mild dearomative [5+2]/[2+2] cycloaddition of 1H-indoles with ortho-(trimethylsilyl)aryl triflates was reported, leading to the synthesis of dibenzo[b,e]azepine derivatives in moderate to good yields. Increasing steric hindrance at the C2-position of 1H-indoles directs the reaction towards a [2+2] cycloaddition pathway. Mechanistic investigations suggest that the reaction proceeds through a [2+2] cycloaddition followed by a ring expansion to form the [5+2] cycloaddition product.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Zhao Wu, Guangbin Dong
Summary: A strategy for accessing diverse multisubstituted acrylamides from cyclic ketones has been developed using palladium/norbornene catalysis. Key to achieving the desired reactivity and selectivity was the development of bulky C2 secondary amide-substituted norbornene cocatalysts. This method allows for the installation of various moieties at the ipso position and can be used for the synthesis of lactam-containing polycyclic scaffolds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Mengyang Shen, Jie Zhao, Yuanshuang Xu, Xinying Zhang, Xuesen Fan
Summary: This novel synthesis method of dihydroquinolinone derivatives involves an unprecedented cascade reaction, which includes the in-situ formation of aryne and its addition with pyrazolidinone, followed by N-N bond cleavage and intramolecular C-C bond formation. Compared to existing methods, this protocol offers advantages such as multiple transformations in one pot, a broad substrate scope, mild reaction conditions, and good tolerance of various functional groups. Additionally, the products obtained from this method demonstrated significant in vitro antiproliferative activity in selected human cancer cell lines.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Polymer Science
Daijun Feng, Satish Mishra, Nuwayo E. Munyaneza, Santanu Kundu, Colleen N. Scott
Summary: C-H functionalization is utilized to transform poly(phenyl ether) into a borylated analog for further functional group transformation. The resulting polymer derivatives exhibit thermal stability and the adhesive produced has good adhesion energy due to cohesive fracture.
EUROPEAN POLYMER JOURNAL
(2021)
Article
Chemistry, Organic
Xiao-Ming Ji, Yan-Zhen Chen, Jian-Guo Fu, Shu-Sheng Zhang, Chen-Guo Feng
Summary: In this study, a palladium-catalyzed intermolecular C(sp3)-H phosphorylation reaction via 1,4-palladium migration has been reported. By carefully selecting the phosphine ligand, phosphorylation of C(sp3)-H bonds was achieved with high yields and excellent regioselectivity.
Article
Chemistry, Multidisciplinary
James E. Gillespie, Charlotte Morrill, Robert J. Phipps
Summary: The method utilizes noncovalent interactions to control positional selectivity in radical reactions, enabling direct access to ortho-phenylenediamines through amination, crucial for the synthesis of medicinally relevant compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Aitor Bermejo-Lopez, Wei-Jun Kong, Pedro J. Tortajada, Daniels Posevins, Belen Martin-Matute, Jan-E Backvall
Summary: A novel iron-catalyzed borylation reaction of propargylic acetates leading to allenylboronates has been developed. This method allows the preparation of di-, tri-, and tetrasubstituted allenylboronates at room temperature with good functional group compatibility. Stereochemical studies show that an anti-S(N)2' displacement of acetate by boron occurs, allowing chirality transfer to yield enantiomerically enriched allenylboronates.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Rika Idogawa, Akihiro Kobayashi, Youngchan Kim, Ken Shimomori, Takamitsu Hosoya, Suguru Yoshida
Summary: An efficient method for sequential C-F transformations of o-hydrosilyl-substituted benzotrifluorides was developed, allowing for the synthesis of a wide variety of organofluorine compounds through successive reactions. Key to the success was the hydride reduction of o-fluorosilyl-substituted difluoromethylenes, enabling further C-F transformations.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Jumpei Taguchi, Kota Kimura, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya
Summary: The generation of 3-azidoarynes from o-iodoaryl triflate-type precursors was achieved using a silylmethyl Grignard reagent as the activator. The azido group controls the regioselectivity of the reaction and can be further transformed into different nitrogen-containing compounds.
Article
Pharmacology & Pharmacy
Takayoshi Nakaoka, Ken-ichi Kaneko, Satsuki Irie, Aya Mawatari, Ami Igesaka, Yuta Uetake, Hidenori Ochiai, Takashi Niwa, Emi Yamano, Yasuhiro Wada, Masaaki Tanaka, Kohei Kotani, Hideki Kawahata, Joji Kawabe, Yukio Miki, Hisashi Doi, Takamitsu Hosoya, Maeda Kazuya, Hiroyuki Kusuhara, Yuichi Sugiyama, Yasuyoshi Watanabe
Summary: Uptake and efflux transporters play crucial roles in drug disposition. PET imaging is a useful tool for directly assessing drug transporter activity. A synthetic method for [18F]PTV, a PET probe for hepatobiliary transport, was developed. Rifampicin pretreatment significantly inhibited hepatic concentration and biliary excretion of the probe and decreased hepatic uptake clearance and canalicular efflux clearance. These results demonstrate the usefulness of [18F]PTV for investigating hepatobiliary transporters in humans.
DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Chemistry, Medicinal
Yuka Miyazaki, Masaki Kikuchi, Koji Umezawa, Aurelie Descamps, Daichi Nakamura, Gaku Furuie, Tomoe Sumida, Kanako Saito, Ninako Kimura, Takashi Niwa, Yuto Sumida, Takashi Umehara, Takamitsu Hosoya, Isao Kii
Summary: The study investigates DYRK1A's folding intermediate-selective inhibition and introduces a novel small molecule inhibitor termed dp-FINDY, expanding chemical options for kinase inhibitor design.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Akihiro Kobayashi, Tsubasa Matsuzawa, Takamitsu Hosoya, Suguru Yoshida
Summary: The interrupted Pummerer reaction of alkynyl sulfoxides with phenols is reported, leading to the efficient synthesis of various benz[b]furans through the unexplored electrophilic activation of the electron-deficient alkynyl sulfinyl group. Utilizing readily available alkynes, thiosulfonates, and phenols, we successfully prepared functionalized benz[b]furans.
Article
Chemistry, Multidisciplinary
Zhouen Zhang, Takashi Niwa, Kenji Watanabe, Takamitsu Hosoya
Summary: In this study, a two-phase radiosynthetic method for the ipso-C-11-cyanation of aryl fluorides was developed, using nickel-mediated C-F bond activation. A practical protocol was established that does not require a glovebox, making it applicable for general PET centers. This method enabled the efficient synthesis of diverse [C-11]aryl nitriles, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies demonstrated the significant promotion effect of lithium chloride on the oxidative addition, facilitating rapid C-11-cyanation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Takashi Niwa, Tsuyoshi Tahara, Charles E. Chase, Francis G. Fang, Takayoshi Nakaoka, Satsuki Irie, Emi Hayashinaka, Yasuhiro Wada, Hidefumi Mukai, Kenkichi Masutomi, Yasuyoshi Watanabe, Yilong Cui, Takamitsu Hosoya
Summary: This study reports the successful 11C-radiolabeling of eribulin, an approved anticancer drug, which enables the quantitative measurement of eribulin migration into tumor tissue. The optimized synthetic method provides a reproducible way to produce [35-11C]eribulin with high radiochemical purity and molar activity. PET imaging using mice shows specific accumulation of [35-11C]eribulin in tumors without significant metabolic changes.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Suguru Yoshida
Summary: We have developed selective methods for single C-F transformations of aromatic trifluoromethyl compounds, enabling us to prepare a broad range of organofluorines from simple benzotrifluorides through C-F and C-Si transformations. These methods include allylation using trityl cations, thiolation and azidation catalyzed by Yb(OTf)(3), as well as chlorination using trityl chloride. The resulting fluorosilyl group in these transformations can undergo further reactions such as protonation, halogenation, and Hiyama cross-coupling with C-Si cleavage. Additionally, benzyl fluorides can be synthesized through LiAlH4-reduction of the resulting fluorosilanes and further C-F transformations.
Article
Psychiatry
Manon Dubol, Jana Immenschuh, My Jonasson, Kayo Takahashi, Takashi Niwa, Takamitsu Hosoya, Sara Roslin, Johan Wikstrom, Gunnar Antoni, Yasuyoshi Watanabe, Mark Lubberink, Anat Biegon, Inger Sundstrom-Poromaa, Erika Comasco
Summary: The study investigated the availability of aromatase in healthy women before and after nicotine exposure. The findings suggest that nicotine acutely decreases aromatase availability in the thalamic area, indicating a potential mechanism mediating the effects of nicotine on human behavior.
COMPREHENSIVE PSYCHIATRY
(2023)
Article
Chemistry, Organic
Shinya Tabata, Mai Minoshima, Akihiro Kobayashi, Takamitsu Hosoya, Suguru Yoshida
Summary: Migrative thioamination of aryne intermediates using o-iodoaryl triflates and sulfilimines leads to the formation of highly functionalized o-thioaminated diaryl sulfides. The ring expansion of cyclic sulfilimines enables the synthesis of eight- and nine-membered organosulfur compounds from dibenzothiophene- and thianthrene-type sulfilimines, respectively.
Article
Chemistry, Organic
Jumpei Taguchi, Takumi Okuyama, Satomi Tomita, Takashi Niwa, Takamitsu Hosoya
Summary: An efficient method for producing 3-triazenylarynes from ortho-iodoaryl triflate-type precursors has been developed. The resulting arynes exhibit high regioselectivity in reactions with various arynophiles due to the presence of the triazenyl group. The 3-triazenylaryne precursors can be used as intermediates for the synthesis of diverse multisubstituted aromatic compounds through the transformation of the remaining triazenyl group in the aryne adducts and triazenyl group-directed ortho-C-H functionalization.
Article
Chemistry, Organic
Keisuke Nakamura, Yukiko Kumagai, Akihiro Kobayashi, Minori Suzuki, Suguru Yoshida
Summary: A practical method for synthesizing sulfinate esters from aryl iodides is presented, involving the direct oxidation of thioesters obtained through copper-catalyzed C-S formation. This efficient synthesis enables the preparation of a wide range of sulfinate esters using readily available starting materials such as carboxylic acids and anilines.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Koyo Numata, Shinya Tabata, Akihiro Kobayashi, Suguru Yoshida
Summary: An efficient synthetic method for multisubstituted naphthalenes has been revealed, involving the cycloaddition of 4-hydroxy-2-pyrones with aryne intermediates. Highly functionalized 2-pyrones were synthesized from 4-hydroxy-2-pyrones through a short synthetic route. The resulting 2-pyrones underwent smooth reactions with a variety of aryne intermediates, generated from o-silylaryl triflates. This led to the formation of multisubstituted naphthalenes via Diels-Alder reaction and subsequent decarboxylative aromatization. The aryne reaction of 2-pyrones also played a role in the synthesis of naphthalenes with 1,2,3-triazole moieties by combining with the triazole formation of 4-azido-2-pyrones.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Kazuya Sugiyama, Yuki Sakata, Takashi Niwa, Suguru Yoshida, Takamitsu Hosoya
Summary: The iridium-catalyzed azide-thioalkyne cycloaddition proceeds faster with benzyl azide than with phenyl azide. Additionally, high azido-type selectivity is observed in other combinations of azides with different steric environments. This discovery enables efficient assembly of three azidophilic molecules to triazido platforms through three sequential triazole-forming reactions.
CHEMICAL COMMUNICATIONS
(2022)