Stereoselective functionalizations of organic molecules are of great importance to modern synthesis. A stereoselective preparation of pharmaceutically active molecules is often required to ensure the appropriate biological activity. Thereby, diastereoselective methods represent valuable tools for an efficient set-up of multiple stereocentres. In this article, highly diastereoselective Csp(3) Negishi cross-couplings of various cycloalkylzinc reagents with aryl halides are reported. In all cases, the thermodynamically most-stable stereoisomer was obtained. Remarkably, this diastereoselective coupling was successful not only for 1,2-substituted cyclic systems, but also for 1,3- and 1,4-substituted cyclohexylzinc reagents. The origin of this remote stereocontrol was investigated by NMR experiments and density functional theory calculations. A detailed mechanism based on these experimental and theoretical data is proposed.

For copper-catalyzed enantioselective conjugate additions, knowledge about the precatalytic and catalytic complexes has not yet been sufficiently developed to understand the strong influence of different temperatures on these famous reactions. Therefore, NMR experiments with four Cu(I) salts and two phosphoramidite ligands have been performed to elucidate the temperature dependence and the low-temperature structures of these copper complexes. The existence of the precatalytic binuclear complex with a mixed trigonal/tetrahedral coordination on copper is for the first time proven with direct NMR spectroscopic methods. Below 200 K, intermolecular interactions between free ligands and [Cu2X2L3] complexes induce binuclear [Cu2X2L4] complexes similar to the crystal structures. By combining diffusion experiments and (31)P integrals at different temperatures, it is for the first time possible to follow the formation of stoichiometrically different complexes, even under experimental conditions in which the (31)P signals of the complexes are spectroscopically not resolved due to exchange processes. This allows a first correlation between the complex species observed and the synthetic conditions reported. Furthermore, different preferences to build homo- or heterochiral complexes are detected for binaphthol and biphenol phosphoramidite complexes.

The demand for enantiopure chemicals, for example, natural products, pharmaceuticals, or materials, has been increasing rapidly for years, and the global market is continually expanding.[1] In the field of asymmetric catalysis, transitionmetal catalysts using chiral ligands represent one of the most effective and versatile approaches.[2] However, the development of highly efficient catalysts is often an unpredictable, challenging, and time-consuming process. Accordingly, every method that shortens this laborious procedure or allows an assessment of selectivity contributions is highly valued. In this context, rational models were developed to predict asymmetry in resulting products, for example, Crams rule and the Felkin-Anh model, [3] and quadrant models. [4,5] Furthermore, combinatorial libraries provide empirical strategies for ligand selection. [6][7][8] With regard to temperature optimization, the isoinversion principle provides a general model for reactions with two or more selectivity steps.[9] At present, the rational models have to address more complex issues because of the importance of noncovalent interligand interactions in organometallic complexes.[10] Even weak p-p interactions were found to influence complex structures, [11,12] for example, a cis coordination of the ligands was found for a bis(phosphonite) Pt complex and a bis(phosphoramidite) Pd complex; this coordination was explained by weak intermolecular interactions. [13,14] In a recent study, we reported a temperature-dependent interconversion, which was potentially caused by interligand interactions, of various phosphoramidite copper complexes. [15] This result raised the question of whether there is a fast and easy way to predict ligand-driven changes of the active catalysts, either by interconversion or by aggregation phenomena. However, to the best of our knowledge, no simple and general procedure has been presented to date that reliably predicts temperature-dependent changes of transition-metal catalyst sizes. Such a prediction would allow a fast determination of the temperature range applicable to the desired catalytic reaction.Herein, we present the first aggregation study of selected phosphoramidite ligands and their transition-metal complexes. The aggregation trends of the ligands, the complexes of which can catalyze highly enantioselective reactions, reveal that an easy and fast DOSY screening of the free ligands allows a prediction of the aggregation trends of their transition-metal complexes, even without knowledge about their structures. In addition, the applicability limits of this method are discussed and the type of interligand interactions is addressed.Chiral phosphoramidites have emerged as one of the privileged ligand structures, with increasing applications in various asymmetric catalytic reactions with excellent enantioselectivies. [16][17][18][19][20][21][22][23] Therefore, 1 and 2 (Scheme 1), which show high selectivities in catalysis, were chosen as model systems that represent the well-known binaphthol-and biphenolbas...

A fast and easy DOSY screening of ligands that affords high enantioselectivities in catalysis allows the aggregation trends of their transition‐metal complexes to be predicted. In their Communication on R. Gschwind and co‐workers present the first aggregation study of selected phosphoramidites and their complexes. This method is useful for catalyst optimization as no knowledge of the complex structure is necessary and the temperature range applicable to the desired catalytic reaction can be quickly determined.

DOSY für die Katalyse: Bei ausgewählten Phosphoramiditen und ihren Übergangsmetallkomplexen gilt, dass für Liganden, deren Komplexe hochenantioselektive Reaktionen katalysieren, ein DOSY‐NMR‐spektroskopisches Screening der freien Liganden die Vorhersage des Verlaufs der Aggregation ihrer Komplexe ermöglicht (siehe Bild). Da diese Methode keine Kenntnis der Komplexstruktur erfordert, ist sie sehr nützlich für Optimierungsprozesse.