Mild, aqueous α-arylation of ketones: towards new diversification tools for halogenated metabolites and drug molecules

Enrico Marelli; Yohann Renault; Sunil V. Sharma; Steven P. Nolan; Rebecca J. M. Goss

doi:10.1002/chem.201700680

Mild, aqueous α-arylation of ketones: towards new diversification tools for halogenated metabolites and drug molecules

Enrico Marelli, Yohann Renault, Sunil V. Sharma, Steven P. Nolan, Rebecca J. M. Goss

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

Abstract

The palladium-catalyzed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/ alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.

Original language	English
Pages (from-to)	3832-3836
Number of pages	5
Journal	Chemistry - A European Journal
Volume	23
Issue number	16
Early online date	6 Mar 2017
DOIs	https://doi.org/10.1002/chem.201700680
Publication status	Published - 17 Mar 2017

Keywords

Palladium
Aqueous coupling
Halogenated compounds
Ketone arylation
Amino acids

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10.1002/chem.201700680

Marelli_2017_CEJ_HalogenatedMetabolites_AAM
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1002/chem.201700680
Accepted author manuscript, 1.36 MB

GCGXC: EU FP7 ERC Consolidator Grant 2013 GCGXC
Goss, R. (PI)
European Research Council
1/06/14 → 30/04/20
Project: Standard
FUNCAT: EU FP7 ERC Advanced Grant - FUNCAT - Fundamental Studies in Organometallic Chemistry and Homogeneous Catalysis
Nolan, S. P. (PI)
European Research Council
1/01/09 → 31/12/14
Project: Standard

Cite this

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title = "Mild, aqueous α-arylation of ketones: towards new diversification tools for halogenated metabolites and drug molecules",

abstract = "The palladium-catalyzed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/ alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.",

keywords = "Palladium, Aqueous coupling, Halogenated compounds, Ketone arylation, Amino acids",

author = "Enrico Marelli and Yohann Renault and Sharma, {Sunil V.} and Nolan, {Steven P.} and Goss, {Rebecca J. M.}",

note = "The authors thank the European Research Council (FP7/2007-2013/ERC grant agreement no 614779 to RJMG) and (FP7 2009-2014/ERC agreement no 227817 to SPN) for generous funding. ",

year = "2017",

month = mar,

day = "17",

doi = "10.1002/chem.201700680",

language = "English",

volume = "23",

pages = "3832--3836",

journal = "Chemistry - A European Journal",

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TY - JOUR

T1 - Mild, aqueous α-arylation of ketones

T2 - towards new diversification tools for halogenated metabolites and drug molecules

AU - Marelli, Enrico

AU - Renault, Yohann

AU - Sharma, Sunil V.

AU - Nolan, Steven P.

AU - Goss, Rebecca J. M.

N1 - The authors thank the European Research Council (FP7/2007-2013/ERC grant agreement no 614779 to RJMG) and (FP7 2009-2014/ERC agreement no 227817 to SPN) for generous funding.

PY - 2017/3/17

Y1 - 2017/3/17

N2 - The palladium-catalyzed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/ alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.

AB - The palladium-catalyzed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/ alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.

KW - Palladium

KW - Aqueous coupling

KW - Halogenated compounds

KW - Ketone arylation

KW - Amino acids

U2 - 10.1002/chem.201700680

DO - 10.1002/chem.201700680

M3 - Article

SN - 1521-3765

VL - 23

SP - 3832

EP - 3836

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 16

ER -

Mild, aqueous α-arylation of ketones: towards new diversification tools for halogenated metabolites and drug molecules

Abstract

Keywords

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Projects

GCGXC: EU FP7 ERC Consolidator Grant 2013 GCGXC

FUNCAT: EU FP7 ERC Advanced Grant - FUNCAT - Fundamental Studies in Organometallic Chemistry and Homogeneous Catalysis

Cite this