Ambient temperature ruthenium‐catalyzed C−H arylations were accomplished by visible light without additional photocatalysts. The robustness of the ruthenium‐catalyzed C−H functionalization protocol was reflected by a broad range of sensitive functional groups and synthetically useful pyrazoles, triazoles and sensitive nucleosides and nucleotides, as well as multifold C−H functionalizations. Biscyclometalated ruthenium complexes were identified as the key intermediates in the photoredox ruthenium catalysis by detailed computational and experimental mechanistic analysis. Calculations suggested that the in situ formed photoactive ruthenium species preferably underwent an inner‐sphere electron transfer.

Bridged nitrogen bicyclic skeletons have been accessed via unprecedented site‐ and diastereoselective orthogonal tandem catalysis from readily accessible reactants in a step economic manner. Directed Pd‐catalyzed γ‐C(sp3)‐H olefination of aminocyclohexane with gem‐dibromoalkenes, followed by a consecutive intramolecular Cu‐catalyzed amidation of the 1‐bromo‐1‐alkenylated product delivers the interesting normorphan skeleton. The tandem protocol can be applied on substituted aminocyclohexanes and aminoheterocycles, easily providing access to the corresponding substituted, aza‐ and oxa‐analogues. The Cu catalyst of the Ullmann‐Goldberg reaction additionally avoids off‐cycle Pd catalyst scavenging by alkenylated reaction product. The picolinamide directing group stabilizes the enamine of the 7‐alkylidenenormorphan, allowing further product post functionalizations. Without Cu catalyst, regio‐ and diastereoselective Pd‐catalyzed γ‐C(sp3)‐H olefination is achieved.

Rutheniumkatalysierte C‐H‐Arylierungen wurden bei Umgebungstemperatur durch sichtbares Licht ohne zusätzlichen Photokatalysator ermöglicht. Die Robustheit dieser rutheniumkatalysierten C‐H‐Funktionalisierung wurde in einer breiten Auswahl von sensitiven funktionellen Gruppen und synthetisch nützlichen Pyrazolen, Triazolen und empfindlichen Nucleosiden und Nucleotiden sowie durch mehrfache C‐H‐Funktionalisierungen verdeutlicht. Biscyclometallierte Rutheniumkomplexe wurden als Schlüsselintermeditate in der Photoredox‐Rutheniumkatalyse durch detaillierte rechnerische und experimentelle mechanistische Studien identifiziert. Berechnungen deuten darauf hin, dass eine in situ gebildete, photoaktive Rutheniumspezies vorzugsweise einen Inner‐Sphere‐Elektronentransfer durchläuft.

Bridged nitrogen bicyclic skeletons have been accessed via unprecedented site‐ and diastereoselective orthogonal tandem catalysis from readily accessible reactants in a step economic manner. Directed Pd‐catalyzed γ‐C(sp3)‐H olefination of aminocyclohexane with gem‐dibromoalkenes, followed by a consecutive intramolecular Cu‐catalyzed amidation of the 1‐bromo‐1‐alkenylated product delivers the interesting normorphan skeleton. The tandem protocol can be applied on substituted aminocyclohexanes and aminoheterocycles, easily providing access to the corresponding substituted, aza‐ and oxa‐analogues. The Cu catalyst of the Ullmann‐Goldberg reaction additionally avoids off‐cycle Pd catalyst scavenging by alkenylated reaction product. The picolinamide directing group stabilizes the enamine of the 7‐alkylidenenormorphan, allowing further product post functionalizations. Without Cu catalyst, regio‐ and diastereoselective Pd‐catalyzed γ‐C(sp3)‐H olefination is achieved.

Escape from flatland. Increased saturation (fraction of sp3) is more likely to be successful when moving compounds through the drug development pipeline. Bridged nitrogen heterocycles have a huge potential in drug discovery, although long synthetic sequences are typically required. New step‐economic and selective organic syntheses are therefore highly sought after. Bert U. W. Maes et al. describe in their Research Article on page 21988 the synthesis of the normorphan skeleton through challenging tandem catalysis. Cover design by Joris Snaet.