Influence of Copper Salts, Solvents, and Ligands on the Structures of Precatalytic Phosphoramidite Copper Complexes for Conjugate Addition Reactions

Abstract

For copper-catalyzed enantioselective conjugate addition reactions of organozinc reagents, the available knowledge about the mechanism and the structures involved is still insufficient to understand in detail the strong influences of solvent, salt, and ligand size, or to enable a rational control of this reaction. Screening with three phosphoramidite ligands and four copper(I) salts using NMR spectroscopy has revealed a binuclear copper complex with mixed trigonal/tetrahedral stereochemistry as the basic structural motif of the ground state of precatalysts with highly stereoselective ligands. Ligands with smaller amine moieties allow higher coordination numbers and higher aggregation levels, leading to reduced ee values. Since the ESI mass spectra of several precatalytic copper halide complexes show a striking correlation with the structures observed in solution, ESI-MS may be used as a fast tool to determine the maximum number of phosphoramidite ligands attached to copper.

Chemoselectivity as a Delineator of Cuprate Structure in Catalytic 1,4‐Addition of Diorganozinc Reagents to Michael Acceptors

“…The closest energetic species to B 1 is p-complex C 1 , which is essentially identical to the proposal of Gschwind for the catalyst rest state in 1,4-additions to cyclohexenone. [9] On the basis of kinetic experiments on ZnEt 2 additions to cyclohexenone performed in 2004, [8] Schrader et al had suggested a structure equivalent to C 2 . However, this looks unlikely to be attained in our case due to its relative instability compared to the enone and/or ligand dissociation.…”

“…In one case ( 2 ] was included to test a recent mechanistic proposal by Gschwind. [9] In two other cases (C 2 and C 3 ) an additional equivalent of L B or ZnMe 2 was included to test recent mechanistic suggestions by Schrader. [8] In all but one case (C 1 ), very significant increases of the ground-state energy are encountered-these are highly unlikely compatible with the observed efficient catalysis at low temperatures.…”

“…[6] However, the relationship of the stoichiometric lithium cuprate chemistry presented in Scheme 1 to that of the catalytic Cu I /ZnMe 2 /L* systems (M = ZnMe, L* = a phosphoramidite ligand) has remained somewhat obscure. Kinetic studies of chiral copper(I)-phosphoramiditecatalyzed additions of ZnR 2 to enones are limited to early observation of a negative non-linear effect [7] and a recent study of the effect of the ligand structure on the rate by Schrader et al [8] Additional information on potential interaction modes between the CuX precatalyst and the chiral ligand were gained from comprehensive NMR studies of Gschwind et al [9] As the cuprate intermediates in Cu I /ZnMe 2 /L*-promoted reactions are very labile, we sought to harness the power of DFT-based calculations [10] to gain insight into the potential structures of p-complex C (M = MeZn, L* = phosphoramidite) in this zinc chemistry and their subsequent redox behavior. To maximize the computational robustness of our regime we wished to directly relate our calculations to a predictable "real world" chemistry and were thus attracted to propose differential reactivity of the closely related dienones 1 a and 1 b (Scheme 2).…”

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

“…Daher wurde nun an 3 (dem kleinsten Liganden) getestet, innerhalb welcher Grenzen der Aggregationsverlauf des freien Liganden Rückschlüsse auf denjenigen seiner Übergangsmetallkomplexe ermöglicht. Vorangegangene Synthese-und Strukturuntersuchungen von Komplexen mit 3 hatten gezeigt, dass die geringere Sperrigkeit von 3 die Kristallisation von ansonsten unzugänglichen Komplexen ermöglicht, [27] die Bildung von Komplexen mit höheren Ligand/Übergangsmetall-Verhältnissen begünstigt [28] und wesentlich schlechtere ee-Werte als 1 und 2 liefert. [25] In Übereinstimmung mit diesen Eigenschaften von 3 wurden für die Komplexe nicht nur Aggregationskurven beobachtet, die Als Nächstes untersuchten wir den Mechanismus der Aggregation.…”

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.…”