Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Kim S Mühlfenzl; Vitus J Enemærke; Sahil Gahlawat; Peter I Golbækdal; Nikoline Munksgaard-Ottosen; Karoline T Neumann; Kathrin H Hopmann; Per-Ola Norrby; Charles S Elmore; Troels Skrydstrup

doi:10.1002/anie.202412247

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Kim S Mühlfenzl, Vitus J Enemærke, Sahil Gahlawat, Peter I Golbækdal, Nikoline Munksgaard-Ottosen, Karoline T Neumann, Kathrin H Hopmann, Per-Ola Norrby, Charles S Elmore, Troels Skrydstrup^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Here we present an effective nickel-catalyzed carbonylative cross-coupling for direct access to alkyl aryl ketones from readily accessible redox-activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late-stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon-centered radical formed via nickel(I)-induced outer-sphere decarboxylative fragmentation of the redox-active ester.

Originalsprog	Engelsk
Artikelnummer	e202412247
Tidsskrift	Angewandte Chemie International Edition
Vol/bind	63
Nummer	51
Antal sider	9
ISSN	1433-7851
DOI	https://doi.org/10.1002/anie.202412247
Status	Udgivet - 16 dec. 2024

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Mühlfenzl, K. S., Enemærke, V. J., Gahlawat, S., Golbækdal, P. I., Munksgaard-Ottosen, N., Neumann, K. T., Hopmann, K. H., Norrby, P.-O., Elmore, C. S., & Skrydstrup, T. (2024). Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones. Angewandte Chemie International Edition, 63(51), Artikel e202412247. https://doi.org/10.1002/anie.202412247

@article{950043b7d2824b63ad12dac3e221c199,

title = "Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones",

abstract = "Here we present an effective nickel-catalyzed carbonylative cross-coupling for direct access to alkyl aryl ketones from readily accessible redox-activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late-stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon-centered radical formed via nickel(I)-induced outer-sphere decarboxylative fragmentation of the redox-active ester.",

keywords = "Carbon isotope labeling, Carbonylation, Catalysis, Ketones, Nickel",

author = "M{\"u}hlfenzl, {Kim S} and Enem{\ae}rke, {Vitus J} and Sahil Gahlawat and Golb{\ae}kdal, {Peter I} and Nikoline Munksgaard-Ottosen and Neumann, {Karoline T} and Hopmann, {Kathrin H} and Per-Ola Norrby and Elmore, {Charles S} and Troels Skrydstrup",

note = "{\textcopyright} 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

year = "2024",

month = dec,

day = "16",

doi = "10.1002/anie.202412247",

language = "English",

volume = "63",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

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Mühlfenzl, KS, Enemærke, VJ, Gahlawat, S, Golbækdal, PI, Munksgaard-Ottosen, N, Neumann, KT, Hopmann, KH, Norrby, P-O, Elmore, CS & Skrydstrup, T 2024, 'Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones', Angewandte Chemie International Edition, bind 63, nr. 51, e202412247. https://doi.org/10.1002/anie.202412247

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones. / Mühlfenzl, Kim S; Enemærke, Vitus J; Gahlawat, Sahil et al.
I: Angewandte Chemie International Edition, Bind 63, Nr. 51, e202412247, 16.12.2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

AU - Mühlfenzl, Kim S

AU - Enemærke, Vitus J

AU - Gahlawat, Sahil

AU - Golbækdal, Peter I

AU - Munksgaard-Ottosen, Nikoline

AU - Neumann, Karoline T

AU - Hopmann, Kathrin H

AU - Norrby, Per-Ola

AU - Elmore, Charles S

AU - Skrydstrup, Troels

PY - 2024/12/16

Y1 - 2024/12/16

N2 - Here we present an effective nickel-catalyzed carbonylative cross-coupling for direct access to alkyl aryl ketones from readily accessible redox-activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late-stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon-centered radical formed via nickel(I)-induced outer-sphere decarboxylative fragmentation of the redox-active ester.

AB - Here we present an effective nickel-catalyzed carbonylative cross-coupling for direct access to alkyl aryl ketones from readily accessible redox-activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late-stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon-centered radical formed via nickel(I)-induced outer-sphere decarboxylative fragmentation of the redox-active ester.

KW - Carbon isotope labeling

KW - Carbonylation

KW - Catalysis

KW - Ketones

KW - Nickel

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U2 - 10.1002/anie.202412247

DO - 10.1002/anie.202412247

M3 - Journal article

C2 - 39145496

SN - 1433-7851

VL - 63

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 51

M1 - e202412247

ER -

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

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