Article
Chemistry, Multidisciplinary
Jingwen Wei, Yangyang Xing, Xiaohan Ye, Bao Nguyen, Lukasz Wojtas, Xin Hong, Xiaodong Shi
Summary: In this study, a new synthetic strategy for enantioselective 1,2-dihydropyridine synthesis was reported. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, the synthesis was achieved through a formal [3+2+1] fashion with up to 95% yield and up to 99% enantiomeric excess (e.e.).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Wang Yao, Chuan-Jun Lu, Li-Wen Zhan, Yi Wu, Jia Feng, Ren-Rong Liu
Summary: In this study, a palladium-catalyzed enantioselective C-H activation method for pyrroles was reported, which successfully synthesized structurally diverse indole-pyrrole atropisomers with a chiral N-N axis, showing high yields and enantioselectivities. Furthermore, the kinetic resolution of trisubstituted N-N heterobiaryls with more sterically demanding substituents was also achieved. This versatile method enables the rapid and selective functionalization of pyrroles, facilitating the synthesis of valuable and complex N-N atropisomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Wenzhong Li, Ran Shi, Sen Chen, Xuesi Zhang, Wei Peng, Si Chen, Jiazhu Li, Xin-Ming Xu, Yan-Ping Zhu, Xueyuan Wang
Summary: This article introduces an efficient Au(I)-catalyzed intramolecular cascade reaction, which utilizes propargyl Claisen rearrangement and 5-exo-dig cyclization to prepare a variety of pentasubstituted pyrrole derivatives with excellent yields and functional group tolerance. Scale-up experiments and chemical transformations of the products demonstrate the versatility of tertiary enamides in organic synthesis.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Baofu Zhu, Jiaming He, Kai Zou, Anquan Li, Chen Zhang, Jiaji Zhao, Hua Cao
Summary: This study established a three-component reaction catalyzed by base, involving ynals, isocyanates, amines, and alcohols. The strategy enables a wide range of substrates and provides a simple process for the preparation of diverse pyridine derivatives with good yields and high regioselectivities.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
T. Ghosh, S. Bhakta
Summary: This review summarizes recent developments (from 2006 to 2022) in the synthesis of important and efficient carbo- and heterocycles using gold-catalyzed cascade protocols. The methodologies discussed in this paper involve controlling selectivity, cost-effectiveness, and ease of product formation through the ligand, counter anion, catalyst, substrate, and reaction conditions. Gold-catalyzed cascade reactions encompass different strategies, including cyclization, hydroarylation, intermolecular and intramolecular cascade reactions, and more. This type of reaction is valuable for the synthesis of spiro, fused, bridged carbo- and heterocycles.
Article
Chemistry, Multidisciplinary
Rinat R. Gubaidullin, Anna Yu Spivak, Valery N. Maistrenko, Lyudmila Parfenova
Summary: Gold(I) chloride complex with triphenylphosphine and metal triflates catalyze the formation of novel [3,2-b]pyrrole-fused pentacyclic triterpenoids from accessible 2-alkynyl derivatives of betulonic, ursonic and oleanonic acids. The reactions proceed in the presence of 5 mol% of the catalyst and provide pyrrole-containing triterpenoids with the isolated yield of 60-86%.
Article
Chemistry, Physical
Omar Portilla-Zuniga, Oscar M. Bautista-Aguilera, Jose J. Martinez, Hugo Rojas, Mario A. Macias, Isabel Iriepa, Adrian Perez-Redondo, Angel Sathicq, Juan-Carlos Castillo, Gustavo P. Romanelli
Summary: The Paal-Knorr reaction of acetonylacetone with primary amines catalyzed by CATAPAL 200 under conventional heating at 60 degrees C for 45 min resulted in N-substituted pyrroles in yields of 68-97%. CATAPAL 200, with its high percentage of Bronsted-Lewis acid sites (23%) and pore diameter (37.8 nm), promotes the formation of pyrrole ring by facilitating condensation and dehydration processes. This protocol offers simplicity, high yields, reduced reaction time, solvent-free conditions, stoichiometric amounts of reactants, low catalyst loading, and clean reaction profile. Furthermore, CATAPAL 200 is inexpensive and readily available, making it a cost-effective option for chemical transformations. The catalyst can be reused for up to five cycles without significant loss of catalytic activity, making this protocol sustainable and advantageous compared to conventional methods.
Article
Chemistry, Physical
Peter E. Simm, Prakash Sekar, Jeffery Richardson, Paul W. Davies
Summary: The research demonstrates the controlled access to (3+2) annulation by Au(I) catalysis of isoxazole-based nitrenoids with alkynyl thioethers, resulting in the synthesis of sulfenylated pyrroles and indoles as single regioisomers bearing useful functional groups and structural variety. This offers a new strategy for achieving varied heterocycle-substitution patterns by maintaining the same reaction pathways across different alkynes.
Article
Chemistry, Multidisciplinary
Hitomi Tsuno, Jingfeng Shen, Hiroki Komatsu, Norihito Arichi, Shinsuke Inuki, Hiroaki Ohno
Summary: A gold-catalyzed cascade cyclization of naphthalene-tethered allenynes leads to strained fused phenanthrene derivatives. The reaction involves the nucleophilic reaction of an alkyne with an activated allene to generate a vinyl cation intermediate, followed by arylation with a tethered naphthalene ring to form the 4H-cyclopenta[def]phenanthrene (CPP) scaffold. The gold-catalyzed reaction of aryl-substituted substrates on the alkyne terminus also produces dibenzofluorene derivatives alongside the CPP derivatives, depending on the reaction conditions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Sidi Cheng, Yu Luo, Ting Yu, Jing Li, Chunfang Gan, Shuang Luo, Qiang Zhu
Summary: An unactivated alkene was successfully subjected to 1,2-difunctionalization through a palladium-catalyzed four-component cascade reaction, leading to the convenient synthesis of acetamides with various substituents and pyrrolo-fused heterocycles.
Article
Chemistry, Organic
Antonia Rinaldi, Vittoria Lange, Dina Scarpi, Ernesto G. Occhiato
Summary: In this study, the synthesis of (+/-)-epi-jungianol was successfully achieved through a gold(I)-catalyzed propargyl Claisen rearrangement/hydroarylation cascade reaction of suitably substituted propargyl vinyl ethers. Two different routes were compared, with the one involving substrates with less substitution on the vinyl moiety providing a higher overall yield despite requiring two additional steps. Additionally, a method for preparing acid-sensitive propargyl vinyl ethers with an alpha-alkyl-substituted vinyl moiety and their reactivity under gold catalysis was reported.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Organic
Sayantika Bhakta, Tapas Ghosh
Summary: Nickel-catalyzed cascade reactions have become a valuable tool in the field of organic synthesis, providing comprehensive coverage of different strategies such as photoredox decarboxylative vinylation and asymmetric reductive arylalkynation. These reactions are useful for synthesizing pharmaceutical compounds and bioactive molecules with high selectivity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Applied
Junying Wang, Jianghui Du, Tao Wang
Summary: The synthesis of 2-aminopyrrolo[1,2-b]pyridazines from 1,3-diynamides and 1-aminopyrroles via gold(I)-catalyzed chemoselective hydroamination/hydroarylation cascade was successfully achieved. A total of 26 examples were conducted to investigate the substrate scope, and a plausible reaction mechanism was proposed. Moreover, the fluorescence properties of the resulting products in both solution and solid states were explored.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
Biao Zhang, Xu-Heng Yang, Jian Huang, Cheng-an Tao, Jianfang Wang
Summary: A cobalt-catalyzed cyclization reaction was achieved using various 1,3-dicarbonyl compounds and halogenated N-allyl ynamides under alkaline conditions, leading to the synthesis of N-heterocycles of different sizes. The reaction exhibited broad substrate scope and tolerance towards various functional groups, enabling the selective synthesis of 5-, 6-, and 7-membered ring N-heterocycles via cobalt catalysis.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Dan-Bi Sung, Jong Seok Lee
Summary: This study describes a gold(I)-catalyzed intermolecular formal [2 + 2 + 2] cycloaddition reaction, which selectively synthesizes highly substituted 2H-pyrans using different metal triflate additives. This method provides a new opportunity for the synthesis of other heterocyclic compounds.
Article
Chemistry, Organic
Atsushi Umehara, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: By transforming melodinine E via 6-hydro-21-dehydroxyleuconolam, the synthesis of monoterpene indole alkaloids leuconoxine, leuconodine B, and rhazinilam was successfully established. The pivotal intermediate, 6-hydro-21-dehydroxyleuconolam, was prepared from melodinine E through a series of reactions, showcasing its potential as a useful synthetic precursor for these related alkaloids. This study provides new insights and methods for the synthesis of related monoterpene indole alkaloids.
Article
Chemistry, Organic
Kenji Sugimoto, Ami Kobayashi, Aki Kohyama, Haruka Sakai, Yuji Matsuya
Summary: This novel strategy achieved successful asymmetric total syntheses of two chiral hydroxylated fatty acid derivatives, providing assistance in stereochemical elucidations of natural products.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Kenji Sugimoto, Shuto Kosuge, Takae Sugita, Yuka Miura, Kiyoshi Tsuge, Yuji Matsuya
Summary: A gold(I) autotandem catalysis protocol is reported for the highly regioselective synthesis of densely substituted pyrazolines and dihydropyridines from imine derivatives via a one-pot aza-enyne metathesis/6 pi-electrocyclization sequence. The reaction pathways are controlled by the substituents on the nitrogen atom of the imine, leading to the formation of different products.
Article
Biochemistry & Molecular Biology
Takuto Fujii, Kenji Sugimoto, Takafumi Noda, Takahiro Shimizu, Yuji Matsuya, Hideki Sakai
Summary: A newly synthesized dihydropyrazole derivative KYY-008 was found to selectively inhibit the activity of gastric H+,K+-ATPase, with no effect on other P2-type ATPases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Chemistry, Medicinal
Hidetoshi Tokuyama
Summary: This study presents a benzyne-mediated cyclization/functionalization protocol for highly substituted benzene derivatives fused with N-heterocyclic rings, allowing the synthesis of various alkaloids.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2021)
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
Chemistry, Organic
Kenji Sugimoto, Ryoga Yoshida, Yuji Matsuya
Summary: This work presents the use of a combination of weak acids, namely, 2,20-biphenol and B(OH)3, as organocatalysts for the 2-aza-Cope rearrangement. Aldehydes and 1,1-diphenyl homoallylamine were successfully converted into the corresponding homoallylamines with moderate-to-high yields using 10 mol% 2,20-biphenol and 30 mol% B(OH)3. Unlike the conventional strong activator-catalyzed systems, this organocatalytic system is cost-effective, user-friendly, environmentally friendly, and uses stable reagents.
TETRAHEDRON LETTERS
(2022)
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, 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, 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)
Article
Chemistry, Organic
Kohta Ide, Miyu Furuta, Hidetoshi Tokuyama
Summary: A mild photoredox-catalyzed intramolecular cyclopropanation of alkenes with alpha-bromo-beta-keto esters in an aqueous medium was developed. The reaction proceeds in one-pot under exceptionally mild conditions at room temperature, yielding a wide range of functionalized bicyclic cyclopropanes. A broad range of substrates consisting of various alkenes and both base- and acid-sensitive functionalized esters were feasible under the reaction conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
