Copper-Mediated Domino Cyclization/Trifluoromethylation of Propargylic <i>N</i>-Hydroxylamines: Synthesis of 4-Trifluoromethyl-4-isoxazolines

Wang, Quan‐De; Tsui, Gavin Chit

doi:10.1021/acs.joc.7b03191

Cited by 17 publications

(9 citation statements)

References 57 publications

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“…More direct C–H trifluoromethylation of indoles using transition-metal-catalyzed, − photoredox catalysis, − and radical − methods has overcome this disadvantage. At the same time, the control of regioselectivity (2-CF 3 vs 3-CF 3 ) was generally difficult with substrates not containing a blocking group, therefore limiting the reaction scope. − In the context of our interest in developing novel trifluoromethylation methods for synthesizing trifluoromethylated heterocycles, we herein describe the preparation of 2-(trifluoromethyl)indoles via a domino trifluoromethylation/cyclization strategy.…”

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confidence: 99%

Synthesis of 2-(Trifluoromethyl)indoles via Domino Trifluoromethylation/Cyclization of 2-Alkynylanilines

Cheung

et al. 2018

Org. Lett.

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A new method for the synthesis of 2-(trifluoromethyl)indoles using easily accessible 2-alkynylanilines and a well-established fluoroform-derived CuCF reagent is described. This method utilizes a domino trifluoromethylation/cyclization strategy to construct the indole cores with no ambiguity of the CF position. The intriguing 3-formyl-2-(trifluoromethyl)indoles can also be synthesized by this protocol, which are useful intermediates for the preparation of trifluoromethylated drug analogues. The ultimate CF source is the inexpensive industrial byproduct fluoroform.

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confidence: 99%

Synthesis of 2-(Trifluoromethyl)indoles via Domino Trifluoromethylation/Cyclization of 2-Alkynylanilines

Cheung

et al. 2018

Org. Lett.

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“…The effects of different solvents were compared, and the desired trifluoromethylated product was obtained in a 62% total yield in DMA (dimethylacetamide) (entries 9-15). Moreover, we were pleased to find that the presence of a base slightly improved the yield of this reaction, and KF provided a satisfying yield (entries [16][17][18]. Additionally, by carefully adjusting the amount of KF, the yield was further improved, and the reaction gave desired product 3a in 86% isolated yield (entry 19).…”

Section: Resultsmentioning

confidence: 94%

“…However, this method is limited to dry solvents and expensive trifluoromethyl sources, and it requires long reaction times. Therefore, the identification of an alternative inexpensive and readily available trifluoromethylation agent is actively being pursued in current research [15][16][17][18][19][20][21]. A seminal advance in this area was developed by Langlois who reported a novel trifluoromethyl source, CF 3 SO 2 Na (Langlois reagent).…”

Section: Introductionmentioning

confidence: 99%

Cu(II)-Catalyzed Oxidative Trifluoromethylation of Indoles with KF as the Base

Shi

2019

Catalysts

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This paper offers an efficient copper-catalyzed oxidative trifluoromethylation of indoles with low-cost CF3SO2Na via C–H activation. Notably, the use of a base is crucial for the trifluoromethylation of indoles. This reaction proceeds efficiently in good to excellent yields and is tolerance of a broad range of functional groups. Furthermore, melatonin, a medicine for sleep disorders, is converted to its 2-CF3 analogue in 68% yield. Studies of possible reaction pathways suggest that this reaction proceeds through a radical process.

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“…[55] Alternatively, propargyl hydroxylamines could be used as starting materials in the isoxazoline-forming oxy-trifluoromethylation, affording isoxazolines with the CF 3 group directly attached to the heterocyclic core (Scheme 40). [56] In this case, Ruppert-Prakash reagent was used as a trifluoromethylation agent along with stoichiometric amounts of copper and silver compounds and excess amounts of several additives. The reaction is limited to the use of aryl substituents at the propargylic position but shows broader tolerance at the distal alkyne position.…”

Section: Intramolecular Oxy-trifluoromethylationsmentioning

confidence: 99%

Evolution and Future of Hetero‐ and Hydro‐Trifluoromethylations of Unsaturated C−C Bonds

et al. 2023

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The difunctionalizative trifluoromethylation of unsaturated CÀ C bonds is a highly useful and efficient method for the synthesis of trifluoromethyl compounds with attractive architectures from simple feedstocks, allowing the introduction of the CF 3 group along with a wide variety of substituents either inter-or intramolecularly. Given that trifluoromethyl molecules are increasingly used as promising bioactive species in the design of new drugs and agrochemicals, difunctionalizative trifluoromethylation has been extensively studied during the last decade. This review focuses on reactions proceeding via the simultaneous formation of CÀ heteroatom (O, N, S, Se, B) and CÀ H bonds, as these reactions provide useful CF 3 group-containing building blocks. To identify the trends and prospects of the evolution of this methodology, we systematically describe the variants of these types of reactions and provide a more general view of reaction conditions, modes, and mechanisms. The presented comprehensive survey enables the categorization of reactions into those that are synthetically mature and those with room for further development. 1.Shintaro Kawamura completed his Ph.D. at Kyoto University in 2013 under the supervision of Prof. Masaharu Nakamura. Since 2012, he has worked in Prof. Mikiko Sodeoka's group at RIKEN. He was promoted from a postdoctoral researcher to a Research Scientist (2017) and then to a Senior Research Scientist (2021) at RIK-EN. Dr. Kawamura's research interests include fluoroalkylation reactions based on the precise reactivity control of radical species. Pablo Barrio completed his Ph.D. at the University of Oviedo in 2007 under the supervision of Prof. Barluenga. After a postdoctoral role in the group of Prof. Carreira at ETH Zurich, he joined the group of Prof. Fustero in 2009 as a Juan de la Cierva Fellow, working for several years in the field of organofluorine chemistry. In 2018, he moved to Oviedo as a Ramón y Cajal Fellow, joining the Selective Organic Synthesis (SOS) group. Dr. Barrio's research interests include gold catalysis. Santos Fustero studied Chemistry at the University of Zaragoza, where he obtained his B.S. and Ph.D. under the supervision of Prof. Barluenga and Prof. Gotor. He spent two years as a postdoctoral research associate at Prof. Lehmkuhl's laboratory at Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr, Germany. In 1983, he became Associate Professor at the University of Oviedo, Spain, and was promoted to Full Professor at the University of Valencia in 1990. In 2005, he became a research group leader at Centro de Investigación Príncipe Felipe in Valencia. Prof. Fustero's research interests include organofluorine and medicinal chemistry, organocatalysis, heterocyclic chemistry, and new reaction methodologies. Jorge Escorihuela received his Ph.D. in Chemistry at Universitat Jaume I (Castellon, Spain) in 2009. After a postdoctoral stage at Universitat Politècnica de València (UPV), he worked at Wageningen University and Research (the Netherlands) with Prof. Zuilho...

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Copper-Mediated Domino Cyclization/Trifluoromethylation of Propargylic N-Hydroxylamines: Synthesis of 4-Trifluoromethyl-4-isoxazolines

Cited by 17 publications

References 57 publications

Synthesis of 2-(Trifluoromethyl)indoles via Domino Trifluoromethylation/Cyclization of 2-Alkynylanilines

Synthesis of 2-(Trifluoromethyl)indoles via Domino Trifluoromethylation/Cyclization of 2-Alkynylanilines

Cu(II)-Catalyzed Oxidative Trifluoromethylation of Indoles with KF as the Base

Evolution and Future of Hetero‐ and Hydro‐Trifluoromethylations of Unsaturated C−C Bonds

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