Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports, which gen...

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Main Authors: Alexander S. Budnikov, Igor B. Krylov, Fedor K. Monin, Valentina M. Merkulova, Alexey I. Ilovaisky, Liu Yan, Bing Yu, Alexander O. Terent’ev
Format: Article
Language:English
Published: Beilstein-Institut 2025-06-01
Series:Beilstein Journal of Organic Chemistry
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Online Access:https://doi.org/10.3762/bjoc.21.96
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author Alexander S. Budnikov
Igor B. Krylov
Fedor K. Monin
Valentina M. Merkulova
Alexey I. Ilovaisky
Liu Yan
Bing Yu
Alexander O. Terent’ev
author_facet Alexander S. Budnikov
Igor B. Krylov
Fedor K. Monin
Valentina M. Merkulova
Alexey I. Ilovaisky
Liu Yan
Bing Yu
Alexander O. Terent’ev
author_sort Alexander S. Budnikov
collection DOAJ
description Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports, which generally employed stoichiometric amounts of oxidants or more expensive transition metal catalysts, the present protocol employs only cheap copper sulfate pentahydrate as a catalyst under mild reaction conditions. The achieved phosphorylation proceeds via the formation of P-centered radicals produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert.
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institution Kabale University
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series Beilstein Journal of Organic Chemistry
spelling doaj-art-779e397a779c4a418d618fa8591ac6832025-08-20T03:28:17ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972025-06-012111192120010.3762/bjoc.21.961860-5397-21-96Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetatesAlexander S. Budnikov0Igor B. Krylov1Fedor K. Monin2Valentina M. Merkulova3Alexey I. Ilovaisky4Liu Yan5Bing Yu6Alexander O. Terent’ev7N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation College of Chemistry, Zhengzhou University, Zhengzhou 450001, China College of Chemistry, Zhengzhou University, Zhengzhou 450001, China N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports, which generally employed stoichiometric amounts of oxidants or more expensive transition metal catalysts, the present protocol employs only cheap copper sulfate pentahydrate as a catalyst under mild reaction conditions. The achieved phosphorylation proceeds via the formation of P-centered radicals produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert.https://doi.org/10.3762/bjoc.21.96c–p couplingcopperenol acetatesβ-ketophosphonatesphosphorylation
spellingShingle Alexander S. Budnikov
Igor B. Krylov
Fedor K. Monin
Valentina M. Merkulova
Alexey I. Ilovaisky
Liu Yan
Bing Yu
Alexander O. Terent’ev
Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
Beilstein Journal of Organic Chemistry
c–p coupling
copper
enol acetates
β-ketophosphonates
phosphorylation
title Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
title_full Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
title_fullStr Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
title_full_unstemmed Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
title_short Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
title_sort synthesis of β ketophosphonates through aerobic copper ii mediated phosphorylation of enol acetates
topic c–p coupling
copper
enol acetates
β-ketophosphonates
phosphorylation
url https://doi.org/10.3762/bjoc.21.96
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