The regio- and site-selectivity of organic reactions is one of the most important aspects when it comes to synthesis planning. Due to that, massive research efforts were invested into computational mo...

Jules  Schleinitz,  Alba  Carretero-Cerdán, Anjali  Gurajapu, Yonatan  Harnik, Gina  Lee, Amitesh  Pandey, Anat  Milo, and Sarah Reisman (20...

The development of machine learning models to predict the regioselectivity of C(sp3)–H functionalization reactions is reported. A data set for dioxirane oxidations was curated from the literature and ...

Herein, we present a comprehensive computational study of the reaction mechanism and regioselectivity patterns of the phosphine-catalyzed Heine reaction involving N-benzoylaziridines. Density function...

The regio- and site-selectivity of organic reactions is one of the most important aspects when it comes to synthesis planning. Due to that, massive research efforts were invested into computational mo...

Sulfinate-mediated radical C–H functionalisation reactions are widely used for the modification and diversification of scaffolds in drug discovery. However, prediction of the regiochemistry can be cha...

Regioselectivity models are of key importance to the implementation of C–H functionalisations in synthetic route planning. In structure- and fragment-based drug discovery (SBDD/FBDD), ligand-target affinity is enhanced by elaborating weak hits into potent ...

Olefins are common starting points for syntheses as they are widely available and can often be functionalized twice in one step, but controlling the regioselectivity of these difunctionalizations rema...

Directed, metal-catalysed C–H activation reactions rely on the binding of a Lewis basic functional group to the metal centre to ensure precise control of regioselectivity. However, groups that bind th...

The regio- and site-selectivity of organic reactions is one of the most important aspects when it comes to synthesis planning. Due to that, massive research efforts were invested into computational mo...

The mild and selective functionalization of carbon-hydrogen (C-H) bonds remains a pivotal challenge in organic synthesis, crucial for developing complex molecular architectures in pharmaceuticals, polymers, and agrochemicals. Despite advancements in directing group (DG) methodologies and computational approaches, predicting accurate regioselectivity in C-H activation poses significant difficulties due to the diversity and complexity of organic compounds. This study introduces a novel quantum mechanics-based computational workflow tailored for the regioselective prediction of C-H activation in the presence of directing groups. Utilizing (semi-empirical) quantum calculations hierarchically, the workflow efficiently predicts outcomes by considering concerted metallation deprotonation mechanisms mediated by common catalysts like Pd(OAc)2. Our methodology not only identifies potential activation sites but also addresses the limitations of existing models by including a broader range of directing groups and reaction conditions while maintaining moderate computational cost. Validation against a comprehensive dataset reveals that the workflow achieves high accuracy, significantly surpassing traditional models in both speed and predictive capability. This development promises substantial advancements in the design of new synthetic routes, offering rapid and reliable regioselectivity predictions that are essential for accelerating innovation in material science and medicinal chemistry.

Nature Synthesis, Published online: 16 September 2026; doi:10.1038/s44160-026-01151-zAlthough catalyst development has transformed alkene hydrogenation into a reliable synthetic tool, controlling regioselectivity between closely related alkenes continues to challenge even the most sophisticated catalytic systems. Now, a multifunctional phosphorus-mediated proton relay directs priority towards more substituted alkenes, delivering divergent products under exceptionally mild conditions

Olefins are common starting points for syntheses as they are widely available and can often be functionalized twice in one step, but controlling the regioselectivity of these difunctionalizations rema...