The Natural Product Lepidiline A as an N-Heterocyclic Carbene Ligand Precursor in Complexes of the Type [Ir(cod)(NHC)PPh3)]X: Synthesis, Characterisation, and Application in Hydrogen Isotope Exchange Catalysis

Cochrane, Alison Ruth; Kennedy, Alan R.; Kerr, William J.; Lindsay, David M.; Reid, Marc; Tuttle, Tell

doi:10.3390/catal10020161

Cited by 8 publications

(10 citation statements)

References 30 publications

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“…In principle any organic compound is amenable to HIE; however, most of the published methodologies concern HIE on arenes, often enabled by late transition-metal catalysts and directing groups with deuterium or tritium gas as the isotope source. Specifically, numerous new phosphine-coordinated iridium(I) catalysts have been developed since the early efforts using the Crabtree catalyst, − leading to the highly efficient contemporary HIE reactions which exhibit exceptionally mild conditions (ambient temperature, short reaction times, no additives). Especially, ortho -directed aromatic HIE continues to be dominated by iridium catalysis.…”

Section: Hydrogen Isotope Exchangementioning

confidence: 99%

“…Reported directing groups for transition-metal-catalyzed aromatic HIE. 56,62,63,[67][68][69][70][71][72][73][75][76][77][79][80][81]83,[85][86][87][88][89]91,[96][97][98][99][100][101][102][103][104][105][106]109,110,112,113,118 Finally, it should be noted that, depending on the substrate, more expensive calculations which include solvation models as well as thermal corrections to the electronic energies can be needed to accurately reproduce experimental results. Building on these computational results, Kerr, Reid, and co-workers were able to successfully predict catalysts with higher or inverse selectivity by changing the steric properties of the NHC ligand.…”

Section: Hie On Aromatic Compoundsmentioning

confidence: 99%

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Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017−2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

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Section: Hydrogen Isotope Exchangementioning

confidence: 99%

Section: Hie On Aromatic Compoundsmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…All samples were analysed neat unless otherwise stated, and wavenumbers are reported in cm -1 . 1 H, 13 18 were prepared according to the reported literature procedures. 4-Amino-2-[(diethylamino)methyl]phenol dihydrochloride (6297-14-9) 5 is commercially available from Fluorochem.…”

Section: Synthesismentioning

confidence: 99%

“…Catalysts 1a (1019853-00-9), 1b (1019853-03-2), 1c (1019853-01-0), 1d (1628471-64-6), and 1e (1884137-92-1) are commercially available from Strem, Inc. Catalysts 1f, 17 1g 18 and 1h 18 were prepared according to the reported literature procedures. 4-Amino-2-[(diethylamino)methyl]phenol dihydrochloride (5) (6297-14-9) is commercially available from Fluorochem.…”

Section: Special Topic Synthesismentioning

confidence: 99%

Selective Deuteration of Heterocycle N-Oxides via Iridium-Catalysed Hydrogen Isotope Exchange

et al. 2023

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An iridium(I) N-heterocyclic carbene/phosphine complex has been applied to the C-H activation and hydrogen isotope exchange of quinoline N-oxides. The isotope labelling proceeds under exceptionally low catalyst loadings of 0.25 mol%, and delivers products with high levels of deuterium incorporation selectively at the C8 position. A broad substrate scope is demonstrated, with the method tolerant of electron-poor and -rich substrates, and of substitution adjacent to the site of C-H activation. The isotope label is fully retained under standard deoxygenation conditions to give the corresponding labelled quinoline, and the labelling and deoxygenation can be combined in a one-pot procedure.

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“…For example, both compounds exhibit some activity toward the FDIGROV cell line but the latter molecule was slightly more active and showed promising activity also against the UMUC3, PACA2, and MDA231 lines. In addition to the protocols for the isolation of I from natural sources, the syntheses of lepidilines A and B via double one-pot N-benzylation of the respective parent heterocycle were also reported [15,16].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C

et al. 2020

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Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole N-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent O-benzylation afforded, depending on the type of alkylating agent, either symmetric or nonsymmetric alkoxyimidazolium salts considered as structural analogues of naturally occurring imidazole alkaloids, lepidilines A and C. Some of the obtained salts were tested as precursors of nucleophilic heterocyclic carbenes (NHCs), which in situ reacted with elemental sulfur to give the corresponding N-alkoxyimidazole-2-thiones. The cytotoxic activity of selected 4,5-dimethylimidazolium salts bearing either two benzyloxy or benzyloxy and 1-adamantyloxy groups at N(1) and N(3) atoms was evaluated against HL-60 and MCF-7 cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Notably, in two cases of alkoxyimidazolium salts, no effect of the counterion exchange (Br− → PF6−) on the biological activity was observed.

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The Natural Product Lepidiline A as an N-Heterocyclic Carbene Ligand Precursor in Complexes of the Type [Ir(cod)(NHC)PPh3)]X: Synthesis, Characterisation, and Application in Hydrogen Isotope Exchange Catalysis

Cited by 8 publications

References 30 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Selective Deuteration of Heterocycle N-Oxides via Iridium-Catalysed Hydrogen Isotope Exchange

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C

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