Palladium-Catalyzed Nondirected Late-Stage C-H Deuteration of Arenes

Farizyan, Mirxan; Mondal, Arup; Mal, Sourjya; Deufel, Fritz; Gemmeren, Manuel van

doi:10.33774/chemrxiv-2021-vtsnn-v2

Cited by 4 publications

(4 citation statements)

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“…158 Further modification of the amino-acid-derived ligands by substituting the carboxylic acid functionality by a sulfonamide lead to highly active catalyst systems that prove its value in the HIE of a broad range of aromatic substrates using deuterium oxide as deuterium source. 159 While the exchange proceeds slower at more sterically hindered positions, high deuterium incorporations could generally be achieved (Scheme 38d). Remarkably, a barium amide complex was recently shown to be capable of catalyzing HIE of aromatic and, preferentially, benzylic C−H bonds in simple arenes under deuterium gas atmosphere (Scheme 38e).…”

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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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: Hie On Aromatic Compoundsmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…An array of diversely substituted acrylates served as effective coupling partners for this transformation giving excellent yields of the desired olefinated products and maintaining high degree of β-selectivity (2−6). The present catalytic system was amenable to olefins possessing free carboxylic acid (7), ketone (8), nitrile (9), phosphonate (10), and sulfone (11), with equivalent efficiency as acrylates. With a cyclic α,β-unsaturated ester, an allylic product was obtained in a synthetically useful yield and high β-regioselectivity (12).…”

Section: Resultsmentioning

confidence: 99%

Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites

et al. 2022

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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different elds, the associated reactivity and regioselectivity issues had rendered it redundant. The revival of this exemplary reaction requires the development of a mechanistic paradigm that would have simultaneous control on both the reactivity and regioselectivity. Often high thermal energy required to promote ole nation leads to multiple site functionalization. To this aim we established a photoredoxcatalytic system constituting a merger of palladium/organo-photocatalyst that forges oxidative ole nation in an explicit regioselective fashion of diverse arenes and heteroarenes. Visible light plays a signi cant role in executing 'regio-resolved' Fuijiwara-Moritani reaction without the requirement of silver salts and thermal energy. The catalytic system is also amenable towards proximal and distal ole nation aided by respective directing groups (DGs), which entails the versatility of the protocol in engaging the entire spectrum of C(sp2)-H ole nation.Furthermore, streamlining the synthesis of natural products, chiral molecules, drugs and diversi cation through late-stage functionalizations underscore the importance of this sustainable protocol. The photoinduced attainment of this regioselective transformation is mechanistically established through control reactions, kinetic studies and theoretical calculations.

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“…The increasing importance of deuteration and C-H activation in isotopic labelling inspired us to design a laboratory experiment based on a modified study from our group (Figure 1e). 12 The dual ligand-based catalyst design 13,14 is maintained, but is adapted to use exclusively commercially available equipment, starting materials, and ligands. 15…”

Section: Introductionmentioning

confidence: 99%

Deuteration of Arenes via Pd-Catalyzed C–H Activation – A Lesson in Nondirected C–H Activation, Isotopic Labelling and NMR Characterization

Deufel,

van Gemmeren

2024

Preprint

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Isotopic labelling is an important tool in medicinal research, metabolomics, and for understanding reaction mechanisms. In this context, transition metal catalyzed C–H activation has emerged as a key technology for deuterium incorporation via hydrogen isotope exchange. A detailed and easy-to-implement experimental procedure for a nondirected arene deuteration has been developed that exclusively uses commercial equipment and chemicals. The protocol is ideally suited for students and other prospective applicants who are not experts in catalysis. The degree of deuterium incorporation was analyzed via different means like mass spectrometry, 1H and 2H NMR. A hands-on understanding of quantitative NMR as well as the influence of H/D exchange on experimental spectra was conveyed by comparative NMR spin simulations. Students were measurably familiarized with the concepts of C H activation, isotope effects, and basics in experimental catalysis.

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Palladium-Catalyzed Nondirected Late-Stage C-H Deuteration of Arenes

Cited by 4 publications

References 0 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites

Deuteration of Arenes via Pd-Catalyzed C–H Activation – A Lesson in Nondirected C–H Activation, Isotopic Labelling and NMR Characterization

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