Copper (I)‐BOX Catalyzed Asymmetric 3‐Component Reaction for the Synthesis of Trifluoromethylated Propargylic Ethers and Anilines**

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Abstract

An asymmetric 3‐component reaction between EthynylBenziodoXoles (EBXs), 2,2,2‐trifluorodiazoethane and nucleophiles catalyzed by a Cu ^I‐BOX (Bisoxazoline) catalyst is described. This protocol gives access to chiral trifluoromethylated propargyl ethers and anilines, which are valuable building blocks in synthetic and medicinal chemistry. The reaction proceeds with high enantioselectivity and yield with different nucleophiles such as primary, secondary and tertiary alcohols, as well as both electron‐rich and electron‐poor anilines. Aryl‐, alkyl‐ and silyl‐substituted alkynes can be successfully introduced as electrophiles. In case of chiral substrates, high catalyst control was observed, leading to good diastereoselectivity.

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Most cited references 71

Record: found
Abstract: found
Article: not found

Fluorine in pharmaceuticals: looking beyond intuition.

K. Müller, C. Faeh, F Diederich (2007)

Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.

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Record: found
Abstract: not found
Article: not found

The many roles for fluorine in medicinal chemistry.

William K Hagmann (2008)

0 comments Cited 615 times – based on 0 reviews      Review now

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Record: found
Abstract: found
Article: not found

Applications of Fluorine in Medicinal Chemistry.

Eric Gillis, Kyle Eastman, Matthew Hill … (2015)

The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pKa, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, (18)F has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography.

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Author and article information

Contributors

Nieves P. Ramirez: (View ORCID Profile)

Jerome Waser: (View ORCID Profile)

Journal

Title: Angewandte Chemie International Edition

Abbreviated Title: Angew Chem Int Ed

Publisher: Wiley

ISSN (Print): 1433-7851

ISSN (Electronic): 1521-3773

Publication date Created: August 07 2023

Publication date (Electronic): July 03 2023

Publication date (Print): August 07 2023

Volume: 62

Issue: 32

Affiliations

[1 ] Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering Ecole Polytechnique Fédérale de Lausanne (LCSO-ISIC-EPFL) and National Centre of Competence and Research (NCCR Catalysis) 1015 Lausanne Switzerland

Article

DOI: 10.1002/anie.202305776

SO-VID: 696b5aba-d56b-4c10-85a9-5e1ea204bd60

License:

http://creativecommons.org/licenses/by/4.0/

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