Article
Chemistry, Organic
Wenqi Liu, Meng Zang, Jian Zhang, Quannan Wang, Yang-Zi Liu, Wei-Ping Deng
Summary: An efficient method for the construction of 1,5-di/ox-azonanes via Pd-catalyzed [5 + 4] cycloaddition has been developed. This reaction demonstrates a high tolerance towards various functional groups and shows exclusive regioselectivity, resulting in a series of nine-membered heterocycles in moderate to excellent yields. The synthetic utility of the method has been further demonstrated by a gram-scale reaction.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Enrique Gil de Montes, Matteo A. Tallarida, Ana T. Carmona, Claudio D. Navo, Inmaculada Robina, Pilar Elias-Rodriguez, Gonzalo Jimenez-Oses, Antonio J. Moreno-Vargas
Summary: This study highlights the regioselective rearrangement of aminyl radicals, leading to the formation of novel bicyclic diazabicyclic compounds. The research explores the impact of different bridgehead atoms and substituents on the rearrangement reaction, while providing a detailed mechanistic proposal supported by computational studies.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Bing Yuan, Decai Ding, Chuan Wang
Summary: In this study, we have successfully implemented a reductive strategy for the ring opening reaction of aryl cyclopropylketones with unactivated alkyl bromides. The nickel-catalyzed reductive Csp3-Csp3cross-coupling reaction proceeds with complete regioselectivity, bypassing the need for pregenerated organometallics and allowing for efficient synthesis of alkylated ketones with high step economy and functionality tolerance.
Article
Chemistry, Organic
Yanfeng Gao, Hui Wang, Xiaoquan Chen, Yiyang Qiao, Zhiwei Miao
Summary: We present a highly efficient and diastereoselective gold and palladium sequential relay catalysis system for the synthesis of furan-fused eight-membered heterocycles. By utilizing a one-pot procedure, readily available enynamides undergo cyclization to generate azadienes in situ, which then engage in diastereoselective formal[4 + 4] cycloadditions with gamma-methylene-delta-valerolactones. This method enables the rapid and efficient construction of a range of furan-fused azacyclooctanes with diverse substituents in good yields (63-97%) and a high level of diastereoselectivity (7:1 → 20:1 dr).
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Maximilian P. Mueller, Alexander Hinz
Summary: Silacycles are widely used building blocks in organic synthesis. In this study, small silacycles were expanded catalytically to form larger cyclic compounds. The reactivity and reaction mechanisms of these silacycles were investigated, showing that they can undergo ring expansion reactions and subsequent isomerization reactions. This research provides insights into the reactivity patterns of silacycles and their potential applications.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Malte Leverenz, Guillaume Masson, Domingo Gomez Pardo, Janine Cossy
Summary: Alpha-trifluoromethyl azocanes were synthesized efficiently from 2-(trifluoropropan-2-ol) piperidines via metal-free ring-expansion with a bicyclic azetidinium intermediate. The opening of the azetidinium intermediate was achieved with various nucleophiles in excellent regio-, diastereo- and enantioselectivity and good yields. The relative configuration of the piperidines and azocanes was determined, providing opportunities for further derivatization of the deprotected azocanes.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Multidisciplinary Sciences
Julia C. Reisenbauer, Ori Green, Allegra Franchino, Patrick Finkelstein, Bill Morandi
Summary: Reliable strategies for directly editing the core skeleton of pharmaceutical lead compounds are still scarce despite recent developments in the field. This study presents a method for skeletal editing of indoles through nitrogen atom insertion, demonstrating its utility in late-stage skeletal editing of several commercial drugs.
Article
Chemistry, Multidisciplinary
Tushar Singha, Ganesh Arjun Kadam, Durga Prasad Hari
Summary: The Dowd-Beckwith reaction is a powerful method for synthesizing medium to large-sized carbocyclic scaffolds by ring-expansion of carbonyl compounds via alkoxy radicals. However, its synthetic applications are hampered by the dominating pathway of Dowd-Beckwith ring-expansion followed by H-atom abstraction, and there is currently no report on the functionalization of ring-expanded radicals using non-carbon based nucleophilic reagents.
Article
Chemistry, Organic
Fuchao Yu, Daniel A. Valles, Weijie Chen, Scott D. Daniel, Ion Ghiviriga, Daniel Seidel
Summary: Secondary alicyclic amines are converted to alpha-aminonitriles by adding TMSCN to their corresponding imines, which are generated in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing a-substituent undergo regioselective alpha'-cyanation, even if the C-H bonds at that site are less activated. Amine alpha-arylation can be combined with alpha'-cyanation to produce difunctionalized products in a single step.
Article
Chemistry, Multidisciplinary
Lizhao Zhu, Rei Kinjo
Summary: In this study, a series of boron-containing compounds were synthesized. A novel compound 4 was successfully prepared by a sequence of reactions including substitution, ring contraction, and hydride abstraction. Furthermore, compound 4 underwent reactions with azobenzene and pyridazine to afford two new compounds, 5 and 6, and also reacted with a diazo compound to yield compound 7.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Regina Drescher, Leonie Wust, Cornelius Mihm, Ivo Krummenacher, Alexander Hofmann, James Goettel, Holger Braunschweig
Summary: In this study, synthesis of five aluminafluorene derivatives with diverse aluminium substituents was reported, and their Lewis acid properties and reactivity were probed. It was found that 9-bromo-9-aluminafluorene readily forms Lewis acid-base adducts with N-heterocyclic carbenes, cyclic (alkyl)(amino)carbenes, and pyridines, and undergoes a selective ring expansion reaction with iminoborane tBuN-BMes to give a boron-nitrogen analogue of alumepins.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Organic
Alessia Petti, Philipp Natho, Kevin Lam, Philip J. Parsons
Summary: A mild electrochemical method has been developed for the regioselective preparation of 1-tetralones under environmentally friendly conditions, accessing a series of aromatic- and heteroaromatic-fused 1-tetralones through ring expansion of functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Shuo Li, Xian Xu, Qianlin Sun, Xin Xu
Summary: This study presents a intramolecular C(sp3)-H annulation of functionalized 2,6-lutidines catalyzed by an organocalcium hydride. The reaction provides a streamlined approach for the synthesis of tetrahydro-1,5naphthyridines and hexahydropyrido[3,2-b]azocines derivatives with high efficiency and broad substrate scope. The isolation and structural characterization of a calcium alkyl complex confirms its role as the catalytic intermediate.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Yuko Wakahara, Takahiro Noro, Juri Sakata, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: This study investigates the construction of tetrahydroquinolines with a spirocyclic structure at the 4-position. A five-step sequence was developed, including the synthesis of benzocyclopentanone oxime, followed by the addition of aryl Grignard Reagent, intramolecular Friedel-Crafts acylation, condensation with hydroxylamine, and reductive ring expansion reaction. The method was successfully used to construct various tetrahydroquinolines with spirocyclic rings of different sizes and adamantane and indane structures at the 4-position.
Article
Chemistry, Multidisciplinary
Peter Wonneberger, Nils Koenig, Menyhart B. Sarosi, Evamarie Hey-Hawkins
Summary: Reduction of 1-phospha-2-azanorbornene derivative leads to formation of a novel compound 1-phosphabicyclo[3.2.1]octa-2,5-diene and an unusual 2H-phosphole dimer. Additionally, 3H-phospholes were found to potentially act as dienophile in the dimerisation reaction under elevated temperatures, contrary to previous assumptions of their synthetic irrelevance.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Attila Taborosi, Oiyuan He, Yusuke Ano, Naoto Chatani, Seiji Mori
Summary: The reaction of N-8-amino-quinolinyl aromatic amides with maleimides under rhodium(I) catalysis results in C-H alkylation at the ortho position of the amide. Computational studies using density functional theory (DFT) have shown that the reaction proceeds through several steps including NH amide deprotonation, oxidative addition, migratory insertion, reductive elimination, and protonation. The oxidation number of the Rh catalyst plays a crucial role in determining the reaction path.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Yuki Yamakawa, Takashi Ikuta, Hiroki Hayashi, Keigo Hashimoto, Ryoma Fujii, Kyohei Kawashima, Seiji Mori, Tatsuya Uchida, Tsutomu Katsuki
Summary: C-H functionalization is a powerful tool for modifying bioactive compounds and creating new active molecules in late-stage transformations. However, its application is limited. This study demonstrates the efficient catalysis of an iridium-salen complex in asymmetric carbene C-H insertion reactions, achieving high stereoselectivity and regioselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Naoki Sakai, Kohei Ojima, Seiji Mori, Takeshi Oriyama
Summary: In this study, a novel chiral catalyst derived from (S)-proline was used to perform enantioselective kinetic resolution of beta-unfunctionalized primary alcohols with benzoyl chloride. Valuable chiral 2-substituted propan-1-ols were obtained with good enantioselectivities, and density functional theory calculations revealed the crucial role of noncovalent interactions, such as CH-pi interactions, in the enantioselectivity of the resolution.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Editorial Material
Chemistry, Organic
Hidetoshi Tokuyama
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2022)
Article
Chemistry, Organic
Haoran Xiong, Kei Yoshida, Kosuke Okada, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: This study presents a novel chiral catalytic system for the enantioselective 5-endo-trig bromocycloetherification, delivering high yields and enantioselectivity. The results indicate that the structure of the catalyst plays a crucial role in determining the selectivity of the products.
TETRAHEDRON LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Tatsuya Joutsuka, Ryota Nanasawa, Keisuke Igarashi, Kazuki Horie, Masakazu Sugishima, Yoshinori Hagiwara, Kei Wada, Keiichi Fukuyama, Naomine Yano, Seiji Mori, Andreas Ostermann, Katsuhiro Kusaka, Masaki Unno
Summary: This study investigates the specific reduction of biliverdin by an enzyme called PcyA in Synechocystis sp. PCC 6803. Neutron crystallography and quantum chemical analysis reveal that the protonation states of biliverdin and surrounding residues correlate with the absorption spectra, providing mechanistic insights into bilin pigment biosynthesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Masatoshi Yamada, Kazuki Azuma, Iori Takizawa, Yuki Ejima, Mitsuhisa Yamano, Kimio Satoh, Takayuki Doi, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: A scalable asymmetric total synthesis of (-)-emetine, an important component in emetics, has been achieved. The synthesis involved 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and industrial deoxygenation, eliminating the need for chromatographic purification. A high yield of (-)-emetine center dot 2HCl (12%) with over 93.2% HPLC purity was obtained, and the synthesis can be easily scaled up for larger production and currently used in natural ipecac syrup for clinical application.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Multidisciplinary
Hirofumi Ueda, Soichiro Sato, Kenta Noda, Hiroyuki Hakamata, Eunsang Kwon, Nagao Kobayashi, Hidetoshi Tokuyama
Summary: A biomimetic oxidative dimerization method for tryptophan derivatives was developed using oxygen as a bulk oxidant in aqueous media catalyzed by an iron octacarboxy phthalocyanine complex. The highly active iron catalyst enables aerobic enzyme-mimetic oxidation in a flask. This method provides a facile access to a broad range of dimerized peptides with unique scaffold, which can be used as a powerful tool for creating new small- and medium-sized molecules as drug candidates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama, M. Iyag
Summary: This study conducted synthetic studies on a dimeric indole alkaloid, cimicidu-phytine, by modifying the synthesis of (+)-haplophytine. The key aspects of this synthesis included the chemoselective deallylation of an N,O-diallyl derivative of a hydroxy aniline and the copper sulfate-mediated oxidative lactonization via oxidation of the amino moiety. A highly convergent strategy successfully synthesized the originally proposed cimiciduphytine, but it proved to be unstable under air and underwent cyclization to generate a bridged derivative.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Kosuke Okada, Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The synthesis of (+)-pleiocarpamine, (+)-voacalgine A and (+)-bipleiophylline was achieved in this study. The 10-step synthesis of (+)-pleiocarpamine features the construction of stereochemistry at the C16 position by radical cyclization and the synthesis of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C-H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(CO2H)(8), the oxidative coupling of (+)-pleiocarpamine with pyrocatechuic acid produced (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or the one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Misaki Hirato, Akinari Yokoya, Yuji Baba, Seiji Mori, Kentaro Fujii, Shin-ichi Wada, Yudai Izumi, Yoshinori Haga
Summary: X-ray photoelectron spectroscopy (XPS) was used to study the mechanism of high radio-sensitisation in living cells with brominated genomic DNA. The bromine atom reduced the energy gap between the valence and conduction states, facilitating electron transfer and increasing the probability of reaction with low energy electrons. This leads to DNA damage and cytotoxic effects.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Organic
Aymen Skhiri, Attila Taborosi, Nozomi Ohara, Yusuke Ano, Seiji Mori, Naoto Chatani
Summary: A rhodium(I)-catalysed reaction was conducted using aromatic amides containing a 2-(methylthio)aniline directing group and maleimides, resulting in the formation of isoindolone spirosuccinimides under aerobic, metal oxidant-free, and solvent-free conditions. The use of a (2-methylthio)aniline directing group led to C-H oxidative alkenylation/cyclization, in contrast to a previous study with an 8-aminoquinoline directing group. Analysis using density functional theory (DFT) calculations identified the main steps involved in the reaction mechanism, including oxidative addition/migratory insertion and C-N bond formation.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Yuko Wakahara, Takahiro Noro, Juri Sakata, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: This study investigates the construction of tetrahydroquinolines with a spirocyclic structure at the 4-position. A five-step sequence was developed, including the synthesis of benzocyclopentanone oxime, followed by the addition of aryl Grignard Reagent, intramolecular Friedel-Crafts acylation, condensation with hydroxylamine, and reductive ring expansion reaction. The method was successfully used to construct various tetrahydroquinolines with spirocyclic rings of different sizes and adamantane and indane structures at the 4-position.
Article
Chemistry, Multidisciplinary
Yuto Shima, Takashi Suzuki, Hitoshi Abe, Tatsuo Yajima, Seiji Mori, Yuichi Shimazaki
Summary: Cu complexes with p-dimethylaminophenolate ligands were synthesized and characterized in this study. The complexes exhibited a valence state change from Cu-II-phenolate to Cu-I-phenoxyl radical upon loss of the coordinated solvent. The Cu-I-phenoxyl radical species showed characteristic properties and reactivities.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Kosuke Okada, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The total synthesis of (+/-)-vinoxine was achieved using Tf2O-mediated Bischler-Napieralski reaction, assembling a multi-substituted tetrahydropyrido[1,2-a]indole skeleton. The characteristic diazabicyclo[3.3.1]nonane skeleton was stereoselectively constructed via radical cyclization based on the stereochemistry of the C3 position. This methodology opens up new options for synthesizing natural products and pharmaceuticals containing the multi-substituted pyrido[1,2-a]indole skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)