A mild, general, and metal-free method for site-specific deuteration induced by visible light using D<sub>2</sub>O as the source of deuterium atoms

Shi, Shuai; Li, Ruining; Rao, Liangming; Sun, Zhankui

doi:10.1039/c9gc04096j

Cited by 31 publications

(13 citation statements)

References 34 publications

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“…Using a combination of a phosphoric reagent and di- tert -butyl peroxide, Sun and co-workers established a specific deuterium labeling methodology based on a desulfurization-deuteration approach . Comparably high deuterium incorporations are observed following a radical process mediated by visible light.…”

Section: Miscellaneous Transformations With Deuterium Incorporationmentioning

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: Miscellaneous Transformations With Deuterium Incorporationmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…In 2020, Sun and co-workers 34 developed a metal-free desulfurizative deuteration of both sulfides and disulfides by using di- tert -butyl peroxide (DTBP) as a radical precursor under visible light and Ph 2 POEt as a desulfurization reagent. This radical approach features excellent functional group compatibility, and the use of substrates with free –OH, –COOH, and –NH groups resulted in excellent D-incorporations even though the acidic hydrogen atom may affect the deuteration.…”

Section: Radical Defunctionalization–deuterationmentioning

confidence: 99%

Radical deuteration

et al. 2022

Chem. Soc. Rev.

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“…In spite of these challenges, herein we report the realization of our hypothesis through the development of three-component radical homo Mannich reaction for the streamlined synthesis of complex tertiary amines. We chose to generate the electrophilic radical I through desulfurization of thiols 36 , 37 . We believe the mild conditions could tolerate different functionalities.…”

Section: Introductionmentioning

confidence: 99%

Three-component radical homo Mannich reaction

et al. 2021

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Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach. Here we show, by employing a radical process, we are able to utilize enolizable aldehydes as substrates and develop the three-component radical homo Mannich reaction for the streamlined synthesis of γ-amino-carbonyl compounds. The electrophilic radicals are generated from thiols via the desulfurization process facilitated by visible-light, and then add to the electron-rich double bonds of the in-situ formed enamines to provide the products in a single step. The broad scope, mild conditions, high functional group tolerance, and modularity of this metal-free approach for the synthesis of complex tertiary amine scaffolds will likely be of great utility to chemists in both academia and industry.

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A mild, general, and metal-free method for site-specific deuteration induced by visible light using D₂O as the source of deuterium atoms

Abstract: Visible light induced desulfurization–deuteration method was developed using D2O as the source of deuterium atoms. This radical approach features mild conditions, broad substrate scope, highly efficient D-incorporation and excellent functional group compatibility.

Cited by 31 publications

References 34 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Radical deuteration

Three-component radical homo Mannich reaction

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A mild, general, and metal-free method for site-specific deuteration induced by visible light using D2O as the source of deuterium atoms

Abstract: Visible light induced desulfurization–deuteration method was developed using D2O as the source of deuterium atoms. This radical approach features mild conditions, broad substrate scope, highly efficient D-incorporation and excellent functional group compatibility.

Cited by 31 publications

References 34 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Radical deuteration

Three-component radical homo Mannich reaction

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Product

Resources

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A mild, general, and metal-free method for site-specific deuteration induced by visible light using D₂O as the source of deuterium atoms