Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

Loh, Yong Yao; Nagao, Kazunori; Hoover, Andrew J.; Hesk, David; Rivera, Nelo R.; Colletti, Steven L.; Davies, Ian W.; MacMillan, David W. C.

doi:10.1126/science.aap9674

Cited by 460 publications

(308 citation statements)

References 50 publications

Supporting

Mentioning

300

Contrasting

Unclassified

Order By: Relevance

“…We speculated that thiols or ascorbic acid (AscH 2 )m ight be suitable reaction partners for hydrogen atom transfer (HAT), particularly in view of the recently reported hydroamination of unactivated olefins by photoredox catalysis with thiol HATco-catalysts. [14] Compared to traditional (thermal) reductive amination methods, [7] our photoredox catalysis procedure offers the advantage of enabling spatial and temporal reaction control, as demonstrated by the photopatterning of ac ellulose surface by light-driven reductive amination using an anthracene fluorophore.T he concept of polarity-matched HATapplied in our study should be transferrable to other types of photoredox reactions in which electron-rich radical intermediates need to be reduced. [6] Very recently,t he concept of polarity-matched HATt oi ntercept a-aminoalkyl radicals was exploited for photoredox deuteration and tritiation.…”

mentioning

confidence: 99%

Reductive Amination by Photoredox Catalysis and Polarity‐Matched Hydrogen Atom Transfer

Guo

Wenger

2018

Angew Chem Int Ed

View full text Add to dashboard Cite

The excitation of a Ru photosensitizer in the presence of ascorbic acid leads to the reduction of iminium ions to electron-rich α-aminoalkyl radical intermediates, which are rapidly converted into reductive amination products by thiol-mediated hydrogen atom transfer (HAT). As a result, the reductive amination of carbonyl compounds with amines by photoredox catalysis proceeds in good to excellent yields and with broad substrate scope and good functional group tolerance. The three key features of this work are 1) the rapid interception of electron-rich α-aminoalkyl radical intermediates by polarity-matched HAT in a photoredox reaction, 2) the method of reductive amination by photoredox catalysis itself, and 3) the application of this new method for temporally and spatially controlled reactions on a solid support, as demonstrated by the attachment of a fluorescent dye on an activated cellulose support by photoredox-catalyzed reductive amination.

show abstract

mentioning

confidence: 99%

Reductive Amination by Photoredox Catalysis and Polarity‐Matched Hydrogen Atom Transfer

Guo

Wenger

2018

Angew Chem Int Ed

View full text Add to dashboard Cite

show abstract

“…In 2017, MacMillan and co‐workers developed an efficient photocatalyzed deuterium‐ and tritium‐labeling method, and achieved the modification of 18 drug molecules with thiols as important H/D‐ or H/T‐atom transfer reagents [Eq. (83)] . For deuteration, D 2 O was used as the hydrogen isotope source, which helped to achieve the corresponding transformations on a gram scale.…”

Section: Sulfur‐containing Hat Reagentsmentioning

confidence: 99%

Sulfur‐Center‐Involved Photocatalyzed Reactions

Wang

Jiang

2018

Chemistry An Asian Journal

View full text Add to dashboard Cite

Sulfur-containing compounds (SCCs) exist widely in, for example, natural sources, pharmaceuticals, materials, and foods. Their multifarious functions have stimulated scientists to construct them in greener and more efficient ways and further exploit their properties. Different photosensitizers with sulfur atoms have been developed and exploited. Furthermore, SCCs display excellent ability in hydrogen-atom-transfer reactions. In addition to acting as catalysts, SCCs can also be efficiently transformed under visible-light-promoted conditions. Bond dissociation and oxygenation reactions that involve sulfur centers are emphasized here.

show abstract

“…The visualization of synthetized or isolated natural compounds is a fundamental aspect for studies of their action, affinity, and toxicity. Tritium, the most versatile radionuclide, readily labels small organic molecules of interest and is traditionally used in ligand‐biological receptor‐structure‐activity studies or in administration, distribution, metabolism, and excretion (ADME) studies …”

Section: Introductionmentioning

confidence: 99%

Frustrated Lewis pairs: A real alternative to deuteride/tritide reductions

Doubková

Marek

2019

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Deuterium‐ and tritium‐labeled compounds play a principal role in tracing of biologically active molecules in complicated biochemical systems. The state‐of‐the‐art techniques using noble metal catalysts or strong reducing agents often suffers from low functional group tolerances, poor selectivity, tricky or multistep synthesis of reagents, and low specific activity of the labeled product. Herein, we demonstrate a mild and nonmetallic technique of deuteration and tritiation of polarized double bonds, such as carbonyl compounds, yielding labeled alcohols of high specific activities. This one‐pot synthesis uses carrier‐free hydrogen gas in situ activated by a freshly prepared frustrated Lewis pair, generating reducing reagents. This labeling strategy shows better selectivity and functional group tolerances compared with current reductive methods. Reported is an example of the selective reduction of the aldehyde moiety of 3‐acetylbenzaldehyde. What makes this technology groundbreaking is its mildness, selectivity, and generation of limited amount of radioactive waste as almost no byproducts were generated after use of (B(C6F5)33H)(3HTMP) reducing reagent. Radiochemical purity of desired 3H‐labeled product in a crude reaction mixture was determined of over 94%. This work provides, to the community of radiochemists, a practical protocol for frustrated Lewis pairs (FLP)‐assisted deuterium/tritium labeling technology.

show abstract

Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

Cited by 460 publications

References 50 publications

Reductive Amination by Photoredox Catalysis and Polarity‐Matched Hydrogen Atom Transfer

Reductive Amination by Photoredox Catalysis and Polarity‐Matched Hydrogen Atom Transfer

Sulfur‐Center‐Involved Photocatalyzed Reactions

Frustrated Lewis pairs: A real alternative to deuteride/tritide reductions

Contact Info

Product

Resources

About