Article
Chemistry, Applied
Florian Sachse, Christoph Schneider
Summary: The Bronsted acid catalyzed method reported here allows for the efficient synthesis of thiazolo[3,4-a]indoles under mild conditions, with high yields and good functional group tolerance. Upscaling experiments and further transformations demonstrate the practicality of the process and synthetic potential of the products. Mechanistic insights into this cycloaddition were provided through additional control experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Shuang Yang, Hai-Qing Wang, Jun-Nan Gao, Wen-Xin Tan, Yu-Chen Zhang, Feng Shi
Summary: A Lewis acid-catalyzed (3+2) cycloaddition of 2-indolylmethanols with beta,gamma-unsaturated alpha-ketoesters has been developed, leading to the synthesis of a series of cyclopenta[b]indoles with high yields and excellent diastereoselectivities. This reaction represents the first C3-nucleophilic (3+2) cycloaddition of 2-indolylmethanols and provides a good example for (2+n) cycloaddition of beta,gamma-unsaturated alpha-ketoesters, enriching the chemistry of 2-indolylmethanols. Additionally, this method offers an atom-economic and useful approach for constructing biologically important cyclopenta[b]indole scaffolds.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tian-Zhen Li, Si-Jia Liu, Yu-Wen Sun, Shuang Deng, Wei Tan, Yinchun Jiao, Yu-Chen Zhang, Feng Shi
Summary: The regio- and enantioselective (3+3) cycloaddition of nitrones with 2-indolylmethanols was successfully achieved through the cooperative catalysis of hexafluoroisopropanol (HFIP) and chiral phosphoric acid (CPA). This approach resulted in the synthesis of indole-fused six-membered heterocycles with high yields, excellent enantioselectivities, and exclusive regiospecificity. The role of the cocatalyst HFIP in helping CPA control the reactivity and enantioselectivity of the reaction was elucidated through theoretical calculations, demonstrating a new mode of cooperative catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Tatsuhiro Uchikura, Irene Sanchez-Sordo, Tatsuhiko Yoshimura, Yudai Makino, Hiroto Osakabe, Takahiko Akiyama
Summary: We have developed a chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts alkylation reaction between pyrroles and indolylmethanols. Wide substrate scope was observed, and a chiral all-carbon quaternary center was constructed at the 3 position of indoles in high yields with high to excellent enantioselectivities (up to 99% ee).
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Kosuke Nakashima, Sumire Hanamura, Aoi Imamura, Yasuyuki Matsushima, Shin-ichi Hirashima, Tsuyoshi Miura
Summary: This study investigates the asymmetric Friedel-Crafts alkylation of indoles with alpha,beta-unsaturated trifluoromethyl ketones using a squaramide organocatalyst. The squaramide organocatalyst efficiently promotes the reaction, yielding products with both indole motif and trifluoromethyl group in high yields and excellent enantioselectivities (up to 99% ee). The transformation of the obtained adduct to a chiral spiro indoline 3-one is also demonstrated.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Xue-Qiang Chu, Li-Wen Sun, Yu-Lan Chen, Jia-Wei Chen, Xuan Ying, Mengtao Ma, Zhi-Liang Shen
Summary: An efficient transition-metal-free hydrodefluorination reaction of trifluoromethyl alkenes for accessing gem-difluoroalkenes is developed. It was surprising to find that the phosphoryl anion is able to mediate the defluorination. The successful realization of the reaction could also be attributed to the utility of water as an eco-friendly promoter.
Article
Chemistry, Organic
Olesya V. Khoroshilova, Irina A. Boyarskaya, Aleksander V. Vasilyev
Summary: This study investigates the reaction of TMS ethers of CF3-benzyl alcohols and their heterocyclic analogues under the catalysis of strong acids, leading to the synthesis of alpha-(trifluoromethyl)styrenes and cis-/trans- 1,3-di(trifluoromethyl)indanes with high yields. The plausible reaction mechanisms, including the formation of CF3-benzyl carbocations as intermediates, are discussed.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Xuling Pan, Qian Liu, Yingling Nong
Summary: An acid-catalyzed 2-alkylation reaction of indole molecules has been developed using traceless HI as the only reaction promoter. The reaction produces 2,3-disubstituted indole molecules bearing congested tertiary carbon centers in moderate to excellent yields.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Organic
Yingying Zhang, Yating Huang, Kewei Yu, Xiaoxiang Zhang, Wenhua Yu, Jiale Tang, Yiran Tian, Wanxing Wei, Zhuan Zhang, Taoyuan Liang
Summary: Herein, we report a novel iron and iodine cooperative catalytic system for the synthesis of diverse 2-amino-3-alkylindoles. The method exhibits good substrate and functional group compatibility, and the catalyst system and feedstocks are readily available, showing great potential for further exploration of biological activities.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Organic
Zhang Honghao, Shi Feng
Summary: Indole-based chiral heterocycles are important compounds found in natural products and pharmaceuticals. The introduction of functional groups to the indole ring and using them as building blocks has provided a new strategy for the efficient synthesis of chiral indole derivatives. 2-Indolylmethanols are versatile platform molecules that can act as electrophiles or nucleophiles in catalytic asymmetric reactions, leading to the development of new types of indole-based platform molecules.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Pandula T. Kirinde Arachchige, Suhashini Handunneththige, Marat R. Talipov, Nishantha Kalutharage, Chae S. Yi
Summary: A catalytic system formed in situ from a cationic Ru-H complex with a specific benzoquinone was discovered to mediate an alkylation reaction of ketones with amines, producing alpha-alkylated ketone products. A strong promotion effect was observed for amine substrates with electron-releasing groups. It is suggested that there may be an Ru-enamine intermediate involved in the catalytic alkylation reaction.
Article
Chemistry, Multidisciplinary
Jie Cui, Tongdao Wang
Summary: A B(C6F5)(3)-mediated direct C7-alkenylation of N-propargylindoles was achieved without the need for directing groups. This reaction proceeds via the & pi;-activation of the alkynyl group followed by Friedel-Crafts alkenylation and proton transfer. Interestingly, the C7-alkenylation products can be further transformed into fused indoles through deprotonation and ultimately into polyaromatic N-heterocycles via hydride abstraction.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Bing-Bing Wu, Jie Xu, Kang-Jie Bian, Qian Gao, Xi-Sheng Wang
Summary: Fluorinated motifs are commonly found in drugs and agrochemicals, and incorporating these motifs in drug candidates has emerged as a powerful tool in pharmaceutical research. In this study, a nickel-catalyzed asymmetric trifluoroalkylation reaction was developed for the synthesis of chiral alcohols bearing β-CF3-substituted stereogenic carbons, with high yields and enantioselectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Minghe Sun, Min Liu, Changkun Li
Summary: The chemodivergent regio- and enantioselective allylic alkylation of indoles catalyzed by Rh/bisoxazolinephosphane enables the selective formation of chiral C3- and N1-allylindoles with high branched/linear ratio and up to 99% ee by adjusting the counteranion of Rh, the allylic carbonate, reaction temperature, and the ligand.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Zhen Zhang, Yongjin Wang, Xiaojuan Chen, Xiaojuan Song, Zhengchao Tu, Yongheng Chen, Zhimin Zhang, Ke Ding
Summary: An aromatic trifluoromethyl ketone moiety was characterized as a new warhead for designing covalently reversible kinase inhibitors targeting non-catalytic cysteine residue. It successfully led to the design and synthesis of potent and selective inhibitors for FGFR4 kinase. Furthermore, this functional group was also applied to the discovery of a new JAK3 inhibitor, indicating its potential in designing other kinase inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.