Transition-metal-catalyzed allylic substitution is one of the most powerful and frequently used methods in organic synthesis. In particular, palladium-catalyzed allylic functionalization has become a well-established strategy to construct carbon-carbon or carbon-heteroatom bonds, and its utility has been demonstrated in natural product synthesis, drug discovery and materials science. Several methods have been developed to generate -allylpalladium complexes through ionic mechanisms; however, these methods typically require either prefunctionalized starting materials or stoichiometric oxidants, which naturally limits their scope. Here we show a radical approach for the generation of -allylpalladium complexes by employing N-hydroxyphthalimide esters as bifunctional reagents in combination with 1,3-dienes. Using this strategy, we report the 1,4-aminoalkylation of dienes. The remarkable scope and functional group tolerance of this redox-neutral and mild protocol was demonstrated across > 60 examples. The utility of this strategy was further demonstrated in radical cascade reactions and in the late-stage modification of drugs and natural products.

During the last decade,m odern machine learning has found its wayinto synthetic chemistry.Some long-standing challenges,s uch as computer-aided synthesis planning (CASP), have been successfully addressed, while other issues have barely been touched. This Viewpoint poses the question of whether current trends can persist in the long term and identifies factors that may lead to an (un)productive development. Thereby, specific risks of molecular machine learning (MML) are discussed. Furthermore,p ossible sustainable developments are suggested, such as explainable artificial intelligence (exAI) for synthetic chemistry.This Viewpoint will illuminate chances for possible newcomers and aims to guide the community into adiscussion about current as well as future trends.

Asymmetric Pd II -catalyzed intramolecular aminotrifluoromethoxylation of unactivated alkenes using readily accessible and stable CsOCF 3 as at rifluoromethoxide source has been developed, which affords aw ide variety of enantiomerically enriched b-substituted OCF 3 -containing piperidines in good yields.I ntroducing as terically bulky group into pyridine-oxazoline (Pyox) ligands is crucial to increasing both reactivity and enantioselectivity for the reaction. Additionally, the reaction features good functional group compatibility and mild reaction conditions. Scheme 1. Catalytic asymmetric trifluoromethoxylation.

Hydrofunctionalization of unactivated alkenes is an indispensable mean in synthetic chemistry. Given that addition of electrophilic species into alkenes intrinsically follows the Markovnikov rule, a regioselectivity switch presents a major challenge. Herein, we present a visible-light-promoted strategy for the selective anti-Markovnikov hydrooxygenation of unactivated alkenes. Therefore, an innovative reagent was carefully designed to release a highly reactive and strongly underdeveloped alkoxycarbonyloxyl radical upon reduction, which selectively adds into alkenes. Hydrogen atom abstraction from 2-phenylmalononitrile is the key to form the product. We believe that this methodology enlarges the toolbox for regioselective hydrofunctionalization and could serve as a complementary strategy to the established hydroboration/ oxidation protocol.

Asymmetric Pd II -catalyzed intramolecular aminotrifluoromethoxylation of unactivated alkenes using readily accessible and stable CsOCF 3 as at rifluoromethoxide source has been developed, which affords aw ide variety of enantiomerically enriched b-substituted OCF 3 -containing piperidines in good yields.I ntroducing as terically bulky group into pyridine-oxazoline (Pyox) ligands is crucial to increasing both reactivity and enantioselectivity for the reaction. Additionally, the reaction features good functional group compatibility and mild reaction conditions. Scheme 1. Catalytic asymmetric trifluoromethoxylation.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Im letzten Jahrzehnt hat das moderne maschinelle Lernen Einzug in die Synthesechemie gehalten. Einige seit langem bestehende Herausforderungen, wie die computergestützte Syntheseplanung (Computer-Aided Synthesis Planning, CASP), wurden erfolgreicha ngegangen, während andere Themen kaum berührt wurden.D ieser Standpunkt-Beitrag wirft die Frage auf,o ba ktuelle Trends langfristig bestehen kçnnen, und identifiziert Faktoren, die zu einer (un)produktiven Entwicklung führen werden. Dabei werden die spezifi-schenRisiken des molekularen maschinellen Lernens (MML) diskutiert. Ferner werden mçglichen achhaltige Entwicklungen, wie erklärbare künstliche Intelligenz (Explainable Artificial Intelligence,E xAI), fürd ie Synthesechemie vorgeschlagen und Chancen fürm çglicheN eueinsteiger beleuchtet. Generell zielt dieser Standpunkt darauf ab,d ie wissenschaftliche Gemeinschaft in eine Diskussion über aktuelle wie auchz ukünftige Trends zu führen.