A domino reaction strategy for facile and modular construction of synthetically challenging functionalized ortho-fluoroanilines

Grau B, Kohlbauer S, Gu YG, Hahn F, Lösing J, Wangen C, Stangier M, Ackermann L, Marschall M, Tsogoeva S (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Organic Chemistry Frontiers Royal Society of Chemistry

Book Volume: 11

Pages Range: 6768-6777

Journal Issue: 23

DOI: 10.1039/d4qo01692k

Abstract

The selective formation of ortho-fluoroanilines, representing versatile intermediates for the pharmaceutical and fine chemical industries, relies to date on, e.g., transition-metal-catalyzed fluorination of azobenzenes, which must be preformed from aniline derivatives. While few efficient methods for aniline synthesis were reported, sustainable, straightforward, and selective synthesis of fluoroanilines, and in particular ortho-fluoroanilines, remains challenging. Herein, we describe a domino approach that involves the simultaneous construction of a benzene ring and the installation of both amine and fluorine groups in a single operation under metal-free conditions, starting from readily available acyclic compounds. The developed atom- and cost-efficient, highly convenient, selective, and environmentally friendly four-step domino process allows the formation of a variety of functionalized ortho-fluoroanilines with yields of up to 80% and bypasses the selectivity issues of transition-metal-catalyzed aniline fluorination reactions. Furthermore, we show that the new domino products can efficiently be utilized to synthesize fluorinated azo dye and (tetrahydro)quinazoline derivatives in a bioactive form, i.e., possessing a first-time proven micromolar antiviral activity and high selectivity (EC50 (HCMV) down to 1.9 ± 0.7 μM, CC50 up to >100 μM), under conventional and/or visible-light mediated conditions.

Authors with CRIS profile

Benedikt Grau Lehrstuhl für Organische Chemie I Sascha Kohlbauer Lehrstuhl für Organische Chemie I Yun Gyeong Gu Lehrstuhl für Organische Chemie I Friedrich Hahn Institute of Clinical and Molecular Virology Josephine Lösing Institute of Clinical and Molecular Virology Manfred Marschall Institute of Clinical and Molecular Virology Svetlana Tsogoeva Professur für Organische Chemie

Involved external institutions

Georg-August-Universität Göttingen DE Germany (DE)

How to cite

APA:

Grau, B., Kohlbauer, S., Gu, Y.G., Hahn, F., Lösing, J., Wangen, C.,... Tsogoeva, S. (2024). A domino reaction strategy for facile and modular construction of synthetically challenging functionalized ortho-fluoroanilines. Organic Chemistry Frontiers, 11(23), 6768-6777. https://doi.org/10.1039/d4qo01692k

MLA:

Grau, Benedikt, et al. "A domino reaction strategy for facile and modular construction of synthetically challenging functionalized ortho-fluoroanilines." Organic Chemistry Frontiers 11.23 (2024): 6768-6777.

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