Potassium Alkoxide/Disilane-Mediated Dehalogenative Deuteration

Wang, Xin; Zhu, Minghui; Liu, Wenbo

doi:10.1055/s-0037-1610699

Cited by 10 publications

(2 citation statements)

References 12 publications

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“…Deuterodehalogenation of organohalides is a straightforward strategy with which to incorporate deuterium atoms at specific positions. However, the available methods often rely on transition-metal catalysis and suffer from harsh reaction conditions, narrow substrate scope, and the use of toxic and expensive deuterium sources 38 . Achieving a high level of deuterium incorporation is also a challenging task 39 .…”

Section: Introductionmentioning

confidence: 99%

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides

Lin

et al. 2021

Nat Commun

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Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.

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Section: Introductionmentioning

confidence: 99%

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides

Lin

et al. 2021

Nat Commun

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“…During our studies of a dehalogenative deuteration of aromatic halides, we unexpectedly found that 5-Br- N -tosylindole ( 1d ) was rapidly converted into 5-Br- N -methylindole ( 2d ) upon treatment with potassium methoxide (see Scheme S1 and Scheme d). Two consecutive displacement steps are involved in this transformation, namely, addition of methoxide (with R = Me for example) to the sulfonamide to generate an anionic species ( I ) and methyl 4-methylbenzenesulfonate ( II ) and a subsequent S N 2 substitution reaction between II and I delivering the methylated product 2 .…”

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confidence: 99%

Detosylative (Deutero)alkylation of Indoles and Phenols with (Deutero)alkoxides

Zhu

Feng

et al. 2019

Org. Lett.

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An efficient strategy for N/O-(deutero)alkylation of indoles and phenols with alkoxides/alcohols as the alkylation reagents is described. The consecutive detosylation/alkylation transformations feature mild reaction conditions, high ipso-selectivity, and good functional group tolerance (>50 examples). A one-pot selective N-alkylation of unprotected indoles with alcohols and TsCl is also realized. The application of this method is demonstrated by the introduction of isotope-labeled (CD3 and 13CH3) groups using the readily accessible labeled alcohols and the synthesis of pharmaceuticals.

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Mechanical‐Force‐Induced Non‐spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst

Qu,

Wan,

Zhang

et al. 2024

Angewandte Chemie

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The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid‐phase system under ball‐milling conditions. This non‐spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D‐ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro.

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Potassium Alkoxide/Disilane-Mediated Dehalogenative Deuteration

Cited by 10 publications

References 12 publications

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides

Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides

Detosylative (Deutero)alkylation of Indoles and Phenols with (Deutero)alkoxides

Mechanical‐Force‐Induced Non‐spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst

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