Chiral S(VI) platform unifies selective C–H amination of complex molecules and alkane feedstocks.
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| Title: | Chiral S(VI) platform unifies selective C–H amination of complex molecules and alkane feedstocks. |
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| Authors: | Trinh, Tuan Anh (AUTHOR), Hu, Derek B. (AUTHOR), Kenny, Anna J. (AUTHOR), Warrington, Ethan M. (AUTHOR), Cherempei, Stanislav (AUTHOR), Guzei, Ilia A. (AUTHOR), Schomaker, Jennifer M. (AUTHOR) |
| Source: | Science. 4/23/2026, Vol. 392 Issue 6796, p421-428. 8p. |
| Subjects: | Silver catalysts, Alkanes, Pharmaceutical chemistry, Chemical reagents, Molecules |
| Abstract: | Complex molecules and simple alkanes pose distinct challenges for catalyst-controlled carbon-hydrogen (C–H) functionalizations. Whereas densely functionalized scaffolds require precise targeting among multiple reactive sites while tolerating sensitive functionalities, unactivated substrates that lack directing groups require selective activation of exceptionally inert, nearly identical C–H bonds. In this work, we addressed both challenges by repurposing a classic chiral auxiliary into a unified, selective, and predictable C–H amination platform mediated by silver catalysis and chiral sulfur(VI) nitrene precursors. This system enables stereodivergent, late-stage aminations of activated C–H bonds with broad functional group tolerance and compatibility with aqueous conditions while also mediating mild, selective aminations of chemical feedstocks. The sulfur(VI) motif functions as a modular, stereodefined, and medicinally relevant synthetic linchpin for rapid library diversification, enabling both target- and diversity-oriented synthesis. Editor's summary: Replacing carbon-hydrogen bonds with carbon-nitrogen bonds is one of the most productive reactions in organic chemistry. Nitrogen functionality is common in both commodity-scale chemicals and intricately structured pharmaceuticals, and carbon-hydrogen bonds are prevalent in nearly every class of precursor. Trinh et al. report a high-valent sulfur reagent that pairs with a silver catalyst to substitute nitrogen at alkyl sites in a broad range of simple and complex molecules (see the Perspective by Hrdina). Because the sulfur center is chiral, the reagent is stereoselective. —Jake S. Yeston [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Complex molecules and simple alkanes pose distinct challenges for catalyst-controlled carbon-hydrogen (C–H) functionalizations. Whereas densely functionalized scaffolds require precise targeting among multiple reactive sites while tolerating sensitive functionalities, unactivated substrates that lack directing groups require selective activation of exceptionally inert, nearly identical C–H bonds. In this work, we addressed both challenges by repurposing a classic chiral auxiliary into a unified, selective, and predictable C–H amination platform mediated by silver catalysis and chiral sulfur(VI) nitrene precursors. This system enables stereodivergent, late-stage aminations of activated C–H bonds with broad functional group tolerance and compatibility with aqueous conditions while also mediating mild, selective aminations of chemical feedstocks. The sulfur(VI) motif functions as a modular, stereodefined, and medicinally relevant synthetic linchpin for rapid library diversification, enabling both target- and diversity-oriented synthesis. Editor's summary: Replacing carbon-hydrogen bonds with carbon-nitrogen bonds is one of the most productive reactions in organic chemistry. Nitrogen functionality is common in both commodity-scale chemicals and intricately structured pharmaceuticals, and carbon-hydrogen bonds are prevalent in nearly every class of precursor. Trinh et al. report a high-valent sulfur reagent that pairs with a silver catalyst to substitute nitrogen at alkyl sites in a broad range of simple and complex molecules (see the Perspective by Hrdina). Because the sulfur center is chiral, the reagent is stereoselective. —Jake S. Yeston [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.aee3321 |
