Marnix van der Kolk

Nature, Published online: 28 November 2024; doi:10.1038/d41586-024-03928-8

What dinosaurs ate reveals how they adapted climate change-induced shifts in vegetation. Plus, antimatter goes on the road and India’s solar-observation mission tracks fireball from the sun.

Nature, Published online: 20 November 2024; doi:10.1038/s41586-024-08327-7

Photocatalytic C–F bond activation in small molecules and polyfluoroalkyl substances

Abstract

The combination of palladium and silver complexes has emerged as a bimetallic catalytic system in C−H activation, frequently outperforming palladium-only systems. Beyond the conventional roles of silver (I) salts serving as oxidants, halide scavengers, and Lewis acids, Pd−Ag bimetallic synergism has been shown to facilitate C−H cleavage. In this study, we explore the incorporation of a pyrazolopyridone (PzPyOH) ligand into a Pd−Ag bimetallic catalytic system, which together promote both C−H cleavage and migratory insertion processes. This synergistic approach enables dehydrogenative C−H alkenylations at the C4 position of 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, and 2,1,3-benzotriazole with alkenes. These results demonstrate the potential of combining novel ligands with heterobimetallic systems to facilitate other elementary steps beyond C−H cleavage, suggesting their broader applicability in C−H functionalization.

Nature, Published online: 13 November 2024; doi:10.1038/s41586-024-08125-1

Fluorochemicals are obtained directly from fluorspar activated in water at low temperature, without the requirement to manufacture hydrogen fluoride, a toxic and hazardous gas that is central to the current industrial process.

Here, we present the late-stage nucleophilic 18F-fluorination of (hetero)aryls under low-base conditions using triflyl [¹⁸F]fluoride. This method avoids the application of base and cryptand and enabled the efficient radiolabeling of a broad scope of (hetero)arenes and the successful production of clinical doses of [¹⁸F]mFBG, [18F]SynVesT-1 and [¹⁸F]FPEB in improved radiochemical yields (RCY) and/or shorter preparation times.

Abstract

Fluorine-18 is the predominant radionuclide used to label Positron Emission Tomography (PET) tracers. One outstanding challenge in nucleophilic aromatic radiofluorination reactions is the sensitivity of precursors and catalysts for basic reaction conditions, which are necessary for the work-up of [¹⁸F]fluoride, resulting in limited reproducibility. Triflyl [¹⁸F]fluoride is a new [¹⁸F]fluoride source that allows freedom in choice of type and amounts of base and cryptand. The aim of the current work is to explore the scope and limitations of triflyl [¹⁸F]fluoride in the late-stage nucleophilic aromatic ¹⁸F-fluorination of various functionalized precursors, exploring reduced amounts of base and cryptand. The assessment allowed for the application of this new nucleophilic [¹⁸F]fluoride reagent to the successful radiosynthesis of boron, stannane, hypervalent iodonium ylide and phenol substrates bearing electron-deficient, -neutral and -rich functional groups as well as the clinically relevant PET tracers [¹⁸F]FPEB, [¹⁸F]mFBG and [¹⁸F]SynVesT-1.

Cyclobutanes have attracted significant interest in medicinal chemistry because of their unique structure and potential advantages in pharmacological properties. In this study a two-diversification-point library of cyclobutanesulfonamides with either carbamates or triazoles was synthesized through a hyperbaric [2+2] cycloaddition reaction between ethenesulfonyl fluoride and tert-butyl vinyl ether as the key step.

Abstract

Cyclobutanes have attracted significant interest in medicinal chemistry because of their unique structure and potential advantages in pharmacological properties. Nevertheless, 1,2-disubstituted cyclobutanes remain underrepresented, both in the general chemical space and in fragment-based drug discovery libraries. In this study, a two-diversification-point library of cyclobutanesulfonamides was synthesized through a hyperbaric [2+2] cycloaddition reaction between ethenesulfonyl fluoride and tert-butyl vinyl ether as the key step. The sulfonyl fluoride was subsequently transformed into various sulfonamides, whereas the tert-butyl ether was converted into carbamates and triazoles to synthesize a fragment library. Overall, this synthesis contributes to addressing the underrepresentation of 1,2-disubstituted cyclobutane fragments, making a valuable addition to the field of fragment-based drug discovery.

Psychedelic therapies are promising, but they often miss a key ingredient: social connection. By integrating the 'social cure', we can enhance the power of psychedelics. This shift could lead to not just individual transformation, but collective healing.

Nature, Published online: 22 October 2024; doi:10.1038/d41586-024-03311-7

In 2004, physicists reported something remarkable: they had isolated ultrathin films of carbon atoms using sticky tape alone, and found that the films had astounding properties. The finding would forever change condensed-matter physics.

By identifying when HIV-positive individuals are most at risk of dropping out, healthcare providers can create better strategies to keep more people engaged in their treatment—and ultimately, help reduce the spread of HIV.

N-Alkylation of amines is a vital reaction in the synthesis of numerous bioactive compounds and materials. Among transition metals, palladium has emerged as a particularly effective catalyst for these transformations. The unique advantages of palladium arise from its superior catalytic efficiency, ability to operate under mild conditions, high selectivity and recyclability. Additionally, palladium facilitates the borrowing hydrogen methodology, offering sustainable and environmentally friendly alternatives. This review covers advancements in palladium-catalyzed N-alkylation reactions. The mechanistic insights and practical applications are discussed, providing a comprehensive overview of the current state of research and future directions in this field, covering literature up to 2024.