Joanna Wencel-Delord

Cyclopropanes with a gem-substitution pattern are of significant structural importance, with key applications in the fields of drug design and agrochemistry. However, despite substantial progress in 4d- and 5d-metal-catalyzed C–H activation of cyclic alkanes, direct functionalization of gem-dimethyl substituted cyclopropanes remained an unmet challenge. In this paper, we set out a preliminary general strategy to address this challenge. Not only abundant and inexpensive Ni-catalyst can be used, but also the uncommon trans-selectivity can be attained under the optimized reaction conditions. This direct arylation reaction demonstrates a broad substrate scope in terms of aryl-iodide coupling partner. In addition to this, it can be directly applied to the functionalization of other cyclic alkanes, including adamantyl cores, which are notoriously challenging to process. The experimental mechanistic studies, in combination with DFT calculations, provide a rational explanation for the mechanism of this transformation and the uncommon trans-selectivity.

The direct arylation of fluoroarenes is a powerful but sustainability‐limited transformation, as most established protocols rely on organic solvents and stoichiometric silver additives. Here, we report the first silver‐free palladium‐catalyzed C–H arylation of fluoroarenes in water containing self‐assembled surfactant structures (micelles) as reaction medium. Using the designer surfactant PS‐750‐M, this sustainable method enables the coupling of diverse pyridines and fluoroarenes under mild conditions, displaying broad functional‐group tolerance while fully eliminating organic co‐solvents. Mechanistic studies, including kinetics, FT‐IR spectroscopy, dynamic light scattering (DLS), and freeze‐fracture combined transmission electron microscopy (FF‐TEM), reveal the nature of interactions between the catalyst, substrates and distinct micellar domains, providing insight into microenvironmental effects on reactivity and selectivity. The robustness of the catalytic system further allows tandem one‐pot sequences, such as C–H arylation/S _N Ar reactions, without intermediate workup or adding an additional catalyst. This work demonstrates how merging micellar catalysis with C–H activation unlocks a practical, environmentally responsible platform for cross‐coupling chemistry, expanding the utility of aqueous media for sustainable synthesis.

Kurzzusammenfassung: Hiermit präsentieren wir das erste Beispiel einer intermolekularen, enantioselektiven, Ni(II)‐katalysierten C(sp ³ )–H Arylierung, die einen direkten Zugang zu vollständig kohlenstoffsubstituierten, quartären Stereozentren liefert. Der Erfolg beruht auf der Verwendung eines speziell entwickelten BINOL‐Derivats als Ligand, das eine effiziente Desymmetrisierung der gem‐Dimethylgruppen in einem geschwindigkeits‐ und enantioselektivitätsbestimmenden C–H Aktivierungsschritt ermöglicht. Das Katalysatorsystem zeigt eine bemerkenswerte Toleranz gegenüber funktionellen Gruppen und liefert eine Vielzahl arylierter Produkte in hohen Ausbeuten (bis zu 85 %) und mit exzellenten Enantioselektivitäten (bis zu 95:5 e.r.). Mechanistische Studien, eine Kombination aus Messungen des kinetischen Isotopen‐Effekts, Markierungen mit Deuterium und DFT‐Rechnungen, zeigen, dass der Ni‐BINOL Komplex einen einzigartigen, konzertierten Metallierungs‐Deprotonierungs‐Pfad ermöglicht, welcher durch die Koordination des Liganden und durch π–π Wechselwirkungen unterstützt wird. Diese Arbeit etabliert Nickel als eine wirkungsvolle und nachhaltige Alternative zu Edelmetallen für die asymmetrische C–H Aktivierung und eröffnet neue Perspektiven zur Konstruktion von enantiomerenangereicherten, quartären Kohlenstoffzentren, die eine hohe Relevanz in der Wirkstoffentwicklung sowie den Materialwissenschaften besitzen.

We report the first example of an intermolecular, enantioselective Ni(II)‐catalyzed C(sp ³ )─H arylation, providing direct access to challenging all‐carbon quaternary stereogenic centers. Key to this success is the use of a specially designed BINOL‐derived ligand, which enables efficient desymmetrization of gem‐dimethyl groups through a rate‐ and enantio‐determining C─H activation step. This catalytic system demonstrates remarkable functional group tolerance, affording a wide variety of arylated products in high yields (up to 85%) and with excellent enantioselectivities (up to 95:5 e.r.). Mechanistic studies, combining kinetic isotope effect measurements, deuterium labeling, and DFT calculations, reveal that the Ni–BINOL complex promotes a unique concerted metalation–deprotonation pathway assisted by ligand coordination and π–π interactions. This work establishes nickel as a powerful and sustainable alternative to precious metals for asymmetric C─H activation, opening new perspectives for the construction of enantioenriched quaternary carbon centers of high relevance in drug discovery and materials science.

The synthesis of biaryl-2′-halo-2-silane derivatives via aryne insertion into the N–Si σ-bond of aminosilanes, followed by cyclization to yield diverse silacycles is described.

Abstrakt: Während in letzter Zeit wichtige Fortschritte bei der direkten Funktionalisierung von Alkanen durch photokatalytische Verfahren erzielt wurden, stellt die direkte Aminierung von aliphatischen Verbindungen nach wie vor eine große Herausforderung dar. Hier berichten wir über eine konzeptionell neue Strategie zur direkten Umwandlung von Kohlenwasserstoffen in Amine, die auf der in situ‐Erzeugung von Nitrenradikalen basiert. Die Energieübertragung zwischen dem Thioxanthon (TXO)‐Photokatalysator und Iminoiodinan liefert das Triplett‐Nitrenradikal, das eine HAT‐Reaktion (Wasserstoffatomtransfer) eingehen kann, welche die Alkan‐Aktivierung und den anschließenden Schritt der C─N‐Bindungsbildung fördert. Die Benutzerfreundlichkeit der metallfreien Umwandlung sowie die milden Reaktionsbedingungen unterstreichen zusätzlich die Nachhaltigkeit dieses skalierbaren Prozesses, der eine Vielzahl von Cycloalkylaminen liefert. Kombinierte experimentelle mechanistische Studien und quantenchemische Rechnungen stützen den ungewöhnlichen Reaktionsmechanismus.

While important progress has been achieved recently on direct functionalization of alkanes via photocatalytic methods, direct amination of aliphatic compounds remains a great challenge. Herein we report a conceptually new strategy towards direct conversion of hydrocarbons into amines, based on in situ generation of nitrene radical. Energy transfer between thioxanthone (TXO) photocatalyst and iminoiodinane furnishes the triplet nitrene radical, able to undergo HAT reaction promoting alkane activation and subsequent C─N bond formation step. The user‐friendly nature of the metal‐free transformation, along with mild reaction conditions further highlight the sustainability of this scalable process delivering a diversity of cycloalkylamines. Combined experimental and computational mechanistic studies support the unusual reaction mechanism.

We report the first example of an intermolecular, enantioselective Ni(II)-catalyzed C(sp³)–H arylation, providing direct access to challenging all-carbon quaternary stereogenic centers. Key to this success is the use of a specially designed BINOL-derived ligand, which enables efficient desymmetrization of gem-dimethyl groups through a rate- and enantio-determining C–H activation step. This catalytic system demonstrates remarkable functional group tolerance, affording a wide variety of arylated products in high yields (up to 85%) and with excellent enantioselectivities (up to 95:5 e.r.). Mechanistic studies, combining kinetic isotope effect measurements, deuterium labeling, and DFT calculations, reveal that the Ni–BINOL complex promotes a unique concerted metalation–deprotonation pathway assisted by ligand coordination and π–π interactions. This work establishes nickel as a powerful and sustainable alternative to precious metals for asymmetric C–H activation, opening new perspectives for the construction of enantioenriched quaternary carbon centers of high relevance in drug discovery and materials science.

A novel class of well‐defined rhodium and iridium complexes containing various chiral cyclic(alkyl)(amino)carbene ( ^Chi CAAC) ligands has been synthesized and fully characterized. While no enantioselectivity is observed with chiral Rh‐CAAC, the Ir‐CAAC counterparts demonstrate good performances in the asymmetric hydrogenation of various allylic alcohols and derivatives with up to 86% ee. Mechanistic studies, including deuteration experiments, reveal that the reduction proceeds via direct alkene hydrogenation rather than via isomerization.

A novel class of well-defined rhodium and iridium complexes containing various chiral cyclic(alkyl)(amino)carbene (ChiCAAC) ligands has been synthesised and fully characterized. While no enantioselectivity was observed with chiral Rh-CAAC, the Ir-CAAC counterparts demonstrated good performances in the asymmetric hydrogenation of various allylic alcohols and derivatives with up to 86% ee. Mechanistic studies, including deuteration experiments revealed that the reduction proceeds via direct alkene hydrogenation rather than via isomerization.