Temperature-Dependent Interconversion of Phosphoramidite−Cu Complexes Detected by Combined Diffusion Studies, ³¹P NMR, and Low-Temperature NMR Spectroscopy

Abstract

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.

1H‐DOSY‐Spektren von Liganden für hochenantioselektive Reaktionen – eine schnelle und einfache Methode zur Optimierung katalytischer Reaktionsbedingungen

“…[24,25] ]-Komplexen (L = 2, X = I) gezeigt wurde, [15] konnte anhand von konstanten chemischen Verschiebungen und 31 P-NMR-Signalintensitäts-Verteilungen ausgeschlossen werden. Folglich sind alle gezeigten Kurven tatsächlich auf Aggregation der Komplexe zurückzuführen.…”

“…[13,14] Wir berichteten kürzlich von einer temperaturabhängigen gegenseitigen Umwandlung unterschiedlicher Phosphoramidit-Kupfer-Komplexe, die wahrscheinlich durch LigandLigand-Wechselwirkungen vermittelt wird. [15] …”

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[130] Nach ersten Studien [114,[131][132][133] wurde die Art des Phosphoramidit/Kupfer-Katalysators für konjugierte Additionen durch umfangreiche NMR-und MS-Experimente untersucht (Schema 9). [134][135][136] [133] die den aktiven Katalysator A regeneriert und das Zinkenolat E liefert. Die Zwischenverbindung E kann anschließend mit verschiedenen Elektrophilen zu 27 umgesetzt (siehe Abschnitt 3.1.2) oder zum einfachen Additionsprodukt 26 protoniert werden.…”

Improved applicability of DOSY experiments by high resolution probes combined with gradient amplifiers of diffusion units

“…This ligand had also been used in our previous diffusion studies. [17,21,22] For the experiments with 1 in deuterated tetrahydrofuran, two temperatures (288 and 235 K) were selected to simulate typical pairs of diffusion coefficients and relaxation properties of small molecules or large assemblies, and to test the effect of reduced transversal and longitudinal relaxation times. As pulse sequence the double-stimulated-echo sequence with bipolar gradient pulses A (Fig.…”

“…In addition, low temperature measurements are not yet possible with these diffusion probes and broad band channels are not available. In contrast, high gradient strengths combined with the positive properties of high resolution probes (high 1 H resolution, flexible temperature, and multinuclear applications) would have the potential to enable or to facilitate the DOSY studies on proteins, supramolecular systems, and organometallic complexes, such as our investigations on organocuprate structures [5,7] and intermediates, [19,20] and precatalytic phosphoramidite-copper complexes [17,21,22] at temperatures between 240 and 180 K.…”