Copper-catalyzed one-pot functionalization of styrenes: application towards pharmaceutically relevant phenylethylamine triazole scaffolds

Timothy A. Hilton; Thomas M. Richardson; Aidan P. McKay; Allan J. B. Watson

doi:10.1021/acs.joc.5c01782

Copper-catalyzed one-pot functionalization of styrenes: application towards pharmaceutically relevant phenylethylamine triazole scaffolds

Timothy A. Hilton, Thomas M. Richardson, Aidan P. McKay, Allan J. B. Watson^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

A Cu-catalyzed, one-pot synthesis of 1,2,3-triazolyl phenylethylamine scaffolds is reported. This method utilizes a single copper catalyst to promote aziridination via nitrene addition, ring-opening with azide, and copper-catalyzed azide–alkyne cycloaddition to afford 1,4-disubstituted 1,2,3-triazole phenylethylamine scaffolds. The utility of this process is demonstrated in the synthesis of pharmaceutically relevant cores from simple styrene motifs.

Original language	English
Pages (from-to)	13774–13778
Number of pages	5
Journal	The Journal of Organic Chemistry
Volume	90
Issue number	38
Early online date	15 Sept 2025
DOIs	https://doi.org/10.1021/acs.joc.5c01782
Publication status	Published - 26 Sept 2025

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@article{2be21a75727d405aaddd16392bef5c14,

title = "Copper-catalyzed one-pot functionalization of styrenes: application towards pharmaceutically relevant phenylethylamine triazole scaffolds",

abstract = "A Cu-catalyzed, one-pot synthesis of 1,2,3-triazolyl phenylethylamine scaffolds is reported. This method utilizes a single copper catalyst to promote aziridination via nitrene addition, ring-opening with azide, and copper-catalyzed azide–alkyne cycloaddition to afford 1,4-disubstituted 1,2,3-triazole phenylethylamine scaffolds. The utility of this process is demonstrated in the synthesis of pharmaceutically relevant cores from simple styrene motifs.",

author = "Hilton, \{Timothy A.\} and Richardson, \{Thomas M.\} and McKay, \{Aidan P.\} and Watson, \{Allan J. B.\}",

note = "Funding: T.A.H. thanks the University of St Andrews for a PhD studentship. T.M.R. thanks the University of St Andrews and the EPSRC for a PhD studentship. A.J.B.W. thanks the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517/1) for support.",

year = "2025",

month = sep,

day = "26",

doi = "10.1021/acs.joc.5c01782",

language = "English",

volume = "90",

pages = "13774–13778",

journal = "The Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society (ACS)",

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TY - JOUR

T1 - Copper-catalyzed one-pot functionalization of styrenes

T2 - application towards pharmaceutically relevant phenylethylamine triazole scaffolds

AU - Hilton, Timothy A.

AU - Richardson, Thomas M.

AU - McKay, Aidan P.

AU - Watson, Allan J. B.

N1 - Funding: T.A.H. thanks the University of St Andrews for a PhD studentship. T.M.R. thanks the University of St Andrews and the EPSRC for a PhD studentship. A.J.B.W. thanks the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517/1) for support.

PY - 2025/9/26

Y1 - 2025/9/26

N2 - A Cu-catalyzed, one-pot synthesis of 1,2,3-triazolyl phenylethylamine scaffolds is reported. This method utilizes a single copper catalyst to promote aziridination via nitrene addition, ring-opening with azide, and copper-catalyzed azide–alkyne cycloaddition to afford 1,4-disubstituted 1,2,3-triazole phenylethylamine scaffolds. The utility of this process is demonstrated in the synthesis of pharmaceutically relevant cores from simple styrene motifs.

AB - A Cu-catalyzed, one-pot synthesis of 1,2,3-triazolyl phenylethylamine scaffolds is reported. This method utilizes a single copper catalyst to promote aziridination via nitrene addition, ring-opening with azide, and copper-catalyzed azide–alkyne cycloaddition to afford 1,4-disubstituted 1,2,3-triazole phenylethylamine scaffolds. The utility of this process is demonstrated in the synthesis of pharmaceutically relevant cores from simple styrene motifs.

UR - https://www.scopus.com/pages/publications/105017116636

U2 - 10.1021/acs.joc.5c01782

DO - 10.1021/acs.joc.5c01782

M3 - Article

SN - 0022-3263

VL - 90

SP - 13774

EP - 13778

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

IS - 38

ER -

Copper-catalyzed one-pot functionalization of styrenes: application towards pharmaceutically relevant phenylethylamine triazole scaffolds

Abstract

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Allan Watson Programme Grant: Boron: Beyond the Reagent

Dataset underpinning "Copper-Catalyzed One-Pot Functionalization of Styrenes: Application towards Pharmaceutically Relevant Phenylethylamine Triazole Scaffolds"

Catalytic approaches towards heterocyclic aziridine and aryl ethylamine scaffolds

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Copper-catalyzed one-pot functionalization of styrenes: application towards pharmaceutically relevant phenylethylamine triazole scaffolds

Abstract

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Other files and links

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Projects

Allan Watson Programme Grant: Boron: Beyond the Reagent

Datasets

Dataset underpinning "Copper-Catalyzed One-Pot Functionalization of Styrenes: Application towards Pharmaceutically Relevant Phenylethylamine Triazole Scaffolds"

Student theses

Catalytic approaches towards heterocyclic aziridine and aryl ethylamine scaffolds

Cite this