On the Role of P^III Ligands in the Conjugate Addition of Diorganozinc Derivatives to Enones

Abstract

A mechanistic study on the conjugate addition of diethylzinc to cyclohexenone catalyzed by various chiral PIII ligands, provides new insights into its mechanism. Complete in situ conversion of the catalytic amount of Cu(OTf)2 into CuI species by excess ZnEt2 is demonstrated by EPR spectroscopy. Experimental evidence is presented in favor of a critical ternary 1:1:1 complex between enone, Et2Zn and catalyst, supporting a rate-limiting reductive elimination or carbocupration from a preformed mixed Cu/Zn cluster carrying one- or two-ligand molecules. A crystal structure has been obtained for a CuIL2 complex, which shows catalytic turnover on addition of reagent and substrate. NMR spectroscopic analyses and VT experiments reveal that steric hindrance may prevent complexation of a second ligand molecule on the CuI cation, leading to extremely fast precatalysts based on CuX.L species.

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

“…[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. 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.…”

“…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.…”

“…[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).…”

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.…”

Conversion of Propargylic Alcohols to β‐Oxo Esters Catalyzed by Novel Ruthenium‐Phosphoramidite Complexes

“…[16b] As demonstrated in Table 3 and Figure 4, GC yields for 7c and [RuCl 2 3 )] 2 exhibited higher activity to give the corresponding b-oxo esters from prop-2-yn-1-ol and various a-hydroxy carboxylic acids in 69-60% yields (80 8C, 10-24 h).…”