Iridium-catalyzed C-H activation and deuteration of primary sulfonamides: an experimental and computational study

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.
LanguageEnglish
Pages402–410
Number of pages9
JournalACS Catalysis
Volume5
Issue number1
Early online date2 Dec 2014
DOIs
Publication statusPublished - 2 Jan 2015

Fingerprint

Iridium
Sulfonamides
Chemical activation
Celecoxib
Complexation
Substrates
Hydrogen
Catalysts
Cyclooxygenase 2 Inhibitors
Isotopes
Ion exchange
Derivatives
Molecules
Pharmaceutical Preparations

Keywords

  • iridium
  • C-H activation
  • ortho-deuteration
  • hydrogen-isotope exchange
  • sulfonamide

Cite this

@article{b5c5032e820b418193907d64de873936,
title = "Iridium-catalyzed C-H activation and deuteration of primary sulfonamides: an experimental and computational study",
abstract = "Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.",
keywords = "iridium, C-H activation, ortho-deuteration, hydrogen-isotope exchange, sulfonamide",
author = "Kerr, {William J.} and Marc Reid and Tell Tuttle",
year = "2015",
month = "1",
day = "2",
doi = "10.1021/cs5015755",
language = "English",
volume = "5",
pages = "402–410",
journal = "ACS Catalysis",
issn = "2155-5435",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Iridium-catalyzed C-H activation and deuteration of primary sulfonamides

T2 - ACS Catalysis

AU - Kerr, William J.

AU - Reid, Marc

AU - Tuttle, Tell

PY - 2015/1/2

Y1 - 2015/1/2

N2 - Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.

AB - Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.

KW - iridium

KW - C-H activation

KW - ortho-deuteration

KW - hydrogen-isotope exchange

KW - sulfonamide

UR - http://pubs.acs.org/journal/accacs

U2 - 10.1021/cs5015755

DO - 10.1021/cs5015755

M3 - Article

VL - 5

SP - 402

EP - 410

JO - ACS Catalysis

JF - ACS Catalysis

SN - 2155-5435

IS - 1

ER -