The chiral ruthenium(ii)bis-SINpEt complex is a versatile and powerful catalyst for the hydrogenation of a broad range of heteroarenes. This study aims to provide understanding of the active form of this privileged catalyst as well as the reaction mechanism, and to identify the factors which control enantioselectivity. To this end we used computational methods and in situ NMR spectroscopy to study the hydrogenation of 2-methylbenzofuran promoted by this system. The high flexibility and conformational freedom of the carbene ligands in this complex lead to the formation of a chiral pocket interacting with the substrate in a “lock-and-key” fashion. The non-covalent stabilization of the substrate in this particular pocket is an exclusive feature of the major enantiomeric pathway and is preserved throughout the mechanism. Substrate coordination leading to the minor enantiomer inside this pocket is inhibited by steric repulsion. Rather, the catalyst exhibits a “flat” interaction surface with the substrate in the minor enantiomer pathway. We probe this concept by computing transition states of the rate determining step of this reaction for a series of different substrates. Our findings open up a new approach for the rational design of chiral catalysts.

We report a method for the enantioselective hydrogenation of annulated arenes using 4H-pyrido[1,2-a]pyrimidinones as substrates. The method selectively generates multiple stereocenters in adjacent rings leading to architecturally complex motifs, which resemble bioactive molecules. The mechanistic study of the stereochemical outcome revealed that the catalyst is able to overcome substrate stereocontrol providing all-cis-substituted products predominantly. In a sequential protocol, a matching interaction between catalyst and substrate stereocontrol is achieved that facilitates diastereo- and enantioselective access to trans-products.

AbstractWir berichten über eine enantio‐ und diastereoselektive, vollständige Hydrierung von mehrfach substituierten Benzofuranen in einer Eintopf‐Kaskadenkatalyse. Das entwickelte Protokoll ermöglicht den kontrollierten Aufbau von bis zu sechs definierten Stereozentren und erzeugt architektonisch komplexe Octahydrobenzofurane, die in vielen bioaktiven Molekülen vorkommen. Ein einzigartiges Zusammenspiel eines chiralen Ruthenium‐N‐heterozyklischen Carbenkomplexes und eines aus einem Komplexvorläufer in situ aktivierten Rhodiumkatalysators ermöglicht den vorgestellten Prozess.

We report an enantio- and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation of up to six new defined stereocenters and produces architecturally complex octahydrobenzofurans, prevalent in many bioactive molecules. A unique match of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor act in sequence to enable the presented process.

The structural properties and binding motif of a strongly sigma-electron-donating N-heterocyclic carbene have been investigated on different transition-metal surfaces. The examined cyclic (alkyl)(amino)carbene (CAAC) was found to be mobile on surfaces, and molecular islands with short-range order could be found at high coverage. A combination of scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations highlights how CAACs bind to the surface, which is of tremendous importance to gain an understanding of heterogeneous catalysts bearing CAACs as ligands.

AbstractDie strukturellen Eigenschaften und das Bindungsmotiv eines stark σ‐elektronenschiebenden N‐heterocyclischen Carbens werden an verschiedenen Übergangsmetalloberflächen erforscht. Das untersuchte cyclische (Alkyl)(amino)carben (CAAC) erweist sich auf Oberflächen als mobil, und bei hoher Bedeckung konnten molekulare Inseln mit Nahordnung gefunden werden. Durch die Kombination von Rastertunnelmikroskopie (STM), Röntgenphotoelektronenspektroskopie (XPS) und Dichtefunktionaltheorie (DFT) zeigt unsere Studie, wie CAACs an die Oberfläche binden, was für das Verständnis heterogener Katalysatoren, die CAACs als Liganden tragen, von enormer Bedeutung ist.

Recently, chemoselective methods for the hydrogenation of fluorinated, silylated, and borylated arenes have been developed providing direct access to previously unattainable, valuable products. Herein, a comprehensive study on the employed rhodium-cyclic (alkyl)(amino)carbene (CAAC) catalyst precursor is disclosed. Mechanistic experiments, kinetic studies, and surface-spectroscopic methods revealed supported rhodium(0) nanoparticles (NP) as the active catalytic species. Further studies suggest that CAAC-derived modifiers play a key role in determining the chemoselectivity of the hydrogenation of fluorinated arenes, thus offering an avenue for further tuning of the catalytic properties.

A cis-selective hydrogenation of abundant aryl boronic acids and their derivatives catalyzed by rhodium cyclic (alkyl)(amino)carbene (Rh-CAAC) is reported. The reaction tolerates a variety of boron-protecting groups and provides direct access to a broad scope of saturated, borylated carbo- and heterocycles with various functional groups. The transformation is strategically important because the versatile saturated boronate products are difficult to prepare by other methods. The utility of the saturated cyclic building blocks was demonstrated by post-functionalization of the boron group.

AbstractDie Rh‐CAAC‐katalysierte cis‐selektive Hydrierung von leicht verfügbaren aromatischen Boronsäuren und derer Derivate wird gezeigt. Die Reaktion toleriert verschiedene Bor‐Schutzgruppen und liefert direkten Zugang zu einem breiten Spektrum gesättigter, borylierter Carbo‐ und Heterocyclen mit verschiedenen funktionellen Gruppen. Die Transformation ist strategisch wichtig, da die vielseitig einsetzbaren gesättigten Boronate mit anderen Methoden nur schwer herzustellen sind. Die Anwendbarkeit der gesättigten, cyclischen Synthesebausteine wurde durch Post‐Funktionalisierung der Borgruppe demonstriert.

Aza-Diels-Alder reactions (ADARs) are powerful processes that furnish N-heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi- and polycyclic systems with high stereoselectivity. We report herein a novel Bronsted acid catalyzed process in which ortho-quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one-step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo- and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho-quinone methide imine formation, and ADAR.

Aza-Diels-Alder reactions (ADARs) are powerful processes that furnish N-heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi- and polycyclic systems with high stereoselectivity. We report herein a novel Bronsted acid catalyzed process in which ortho-quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one-step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo- and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho-quinone methide imine formation, and ADAR.

The N-heterocyclic carbene (NHC) catalyzed transformylation has been developed for the conversion of 1°, 2°, and 3° alcohols to the corresponding formates. The reaction employs low catalyst loadings and methyl formate as the formyl transfer reagent. The scope of the reaction is broad with 23 examples reported with good yields (59–96%). The reaction is insensitive to common nitrogen and oxygen protecting groups and can be achieved in the presence of a number of heterocycles.