Iridium-catalysed ortho-deuteration of primary sulfonamides: an experimental and computational study

Research output: Contribution to journalMeeting abstract

Abstract

Isotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule and represents a particularly industry-facing example of chemoselective organometallic catalysis. Consequently, preliminary studies from our laboratory have allowed expedient access to a series of novel iridium complexes, such as 2, that are able to catalyse the ortho-deuteration of various coordinating functionalities and pharmacophores, such as ketones, amides and nitro compounds 2 (Scheme 1). As part of our latest studies, we recently reported an efficient protocol for ortho-deuteration using more readily accessible Ir(I)chloro-carbene complexes. Turning to more challenging substrate classes, the utility of bench-stable catalysts such as 5 has now evolved to deliver the first highly effective strategy for the ortho-deuteration of primary sulfonamides at room temperature (Scheme 2). Additionally, we have used experimental and computational methods in parallel to explain the origins of observed chemoselectivity in labelling multi-functional drug molecules like 7, highlighting the importance of substrate–complex interactions during complexation. The details of all such studies will be delineated in this lecture.

Fingerprint

Iridium
Sulfonamides
Labeling
Nitro Compounds
Facings
Molecules
Organometallics
Substrates
Computational methods
Ketones
Complexation
Catalysis
Amides
Isotopes
Pharmaceutical Preparations
Hydrogen
Industry
Catalysts
Temperature
carbene

Keywords

  • isotopic labelling
  • heavy hydrogen isotopes
  • organometallic catalysis

Cite this

@article{bbbb55a85e3848e893ed6f18e2ce0acd,
title = "Iridium-catalysed ortho-deuteration of primary sulfonamides: an experimental and computational study",
abstract = "Isotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule and represents a particularly industry-facing example of chemoselective organometallic catalysis. Consequently, preliminary studies from our laboratory have allowed expedient access to a series of novel iridium complexes, such as 2, that are able to catalyse the ortho-deuteration of various coordinating functionalities and pharmacophores, such as ketones, amides and nitro compounds 2 (Scheme 1). As part of our latest studies, we recently reported an efficient protocol for ortho-deuteration using more readily accessible Ir(I)chloro-carbene complexes. Turning to more challenging substrate classes, the utility of bench-stable catalysts such as 5 has now evolved to deliver the first highly effective strategy for the ortho-deuteration of primary sulfonamides at room temperature (Scheme 2). Additionally, we have used experimental and computational methods in parallel to explain the origins of observed chemoselectivity in labelling multi-functional drug molecules like 7, highlighting the importance of substrate–complex interactions during complexation. The details of all such studies will be delineated in this lecture.",
keywords = "isotopic labelling, heavy hydrogen isotopes, organometallic catalysis",
author = "William Kerr and Marc Reid and Christopher Tuttle",
year = "2014",
month = "3",
day = "1",
doi = "10.1002/jlcr.3173",
language = "English",
volume = "57",
pages = "183--184",
journal = "Journal of Labelled Compounds and Radiopharmaceuticals",
issn = "0362-4803",
number = "3",

}

TY - JOUR

T1 - Iridium-catalysed ortho-deuteration of primary sulfonamides

T2 - Journal of Labelled Compounds and Radiopharmaceuticals

AU - Kerr, William

AU - Reid, Marc

AU - Tuttle, Christopher

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Isotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule and represents a particularly industry-facing example of chemoselective organometallic catalysis. Consequently, preliminary studies from our laboratory have allowed expedient access to a series of novel iridium complexes, such as 2, that are able to catalyse the ortho-deuteration of various coordinating functionalities and pharmacophores, such as ketones, amides and nitro compounds 2 (Scheme 1). As part of our latest studies, we recently reported an efficient protocol for ortho-deuteration using more readily accessible Ir(I)chloro-carbene complexes. Turning to more challenging substrate classes, the utility of bench-stable catalysts such as 5 has now evolved to deliver the first highly effective strategy for the ortho-deuteration of primary sulfonamides at room temperature (Scheme 2). Additionally, we have used experimental and computational methods in parallel to explain the origins of observed chemoselectivity in labelling multi-functional drug molecules like 7, highlighting the importance of substrate–complex interactions during complexation. The details of all such studies will be delineated in this lecture.

AB - Isotopic labelling with heavy hydrogen isotopes (D2 and T2) is widely used as a means to monitor the biological fate of a potential drug molecule and represents a particularly industry-facing example of chemoselective organometallic catalysis. Consequently, preliminary studies from our laboratory have allowed expedient access to a series of novel iridium complexes, such as 2, that are able to catalyse the ortho-deuteration of various coordinating functionalities and pharmacophores, such as ketones, amides and nitro compounds 2 (Scheme 1). As part of our latest studies, we recently reported an efficient protocol for ortho-deuteration using more readily accessible Ir(I)chloro-carbene complexes. Turning to more challenging substrate classes, the utility of bench-stable catalysts such as 5 has now evolved to deliver the first highly effective strategy for the ortho-deuteration of primary sulfonamides at room temperature (Scheme 2). Additionally, we have used experimental and computational methods in parallel to explain the origins of observed chemoselectivity in labelling multi-functional drug molecules like 7, highlighting the importance of substrate–complex interactions during complexation. The details of all such studies will be delineated in this lecture.

KW - isotopic labelling

KW - heavy hydrogen isotopes

KW - organometallic catalysis

UR - http://onlinelibrary.wiley.com/doi/10.1002/jlcr.3173/abstract

U2 - 10.1002/jlcr.3173

DO - 10.1002/jlcr.3173

M3 - Meeting abstract

VL - 57

SP - 183

EP - 184

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 3

ER -