Phosphinite Thioethers Derived from Chiral Epoxides. Modular P,S-Ligands for Pd-Catalyzed Asymmetric Allylic Substitutions

Abstract

A new family of modular P,S-ligands has been prepared from enantiopure arylglycidols. These ligands have been iteratively optimized with respect to four different structural parameters for use in Pd-catalyzed allylic substitutions. As a final output, highly active and enantioselective ligands for these synthetically important transformations have been developed, and the factors controlling their catalytic behavior have been rationalized. From a methodological point of view, a convenient procedure for the regioselective ring-opening of cis-glycidic esters with bulky thiols to yield the corresponding beta-alkylthio-alpha-hydroxy carboxylic acids has been developed.

Heterogenisation of a C‐Scorpionate FeII Complex on Carbon Materials for Cyclohexane Oxidation with Hydrogen Peroxide

“…The use of other Lewis acid catalysts [Zn(OTf) 2 , ZrCl 4 , Sc(OTf) 3 , TiCl 4 , Ti(O i Pr) 4 , SnCl 4 ], various temperatures (25, 40 °C, reflux) and solvents (THF, DMF, MeCN) were fruitless in all cases, resulting in complex mixtures of degradation products or recovery of the starting material. The reduced efficiency displayed by these epoxy amides towards thiols made it necessary to employ epoxy alcohols (compounds of the type 55 ) as starting materials for the installation of sulfide moieties, as has already been carried out by others to obtain products of the type 56 , which have proven to be efficient chiral ligands for stereoselective reactions mediated by palladium 43…”

Asymmetric Catalyzed Allylic Substitution Using a Pd/P–S Catalyst Library with Exceptional High Substrate and Nucleophile Versatility: DFT and Pd-π-allyl Key Intermediates Studies

“…The pioneering work of the groups of Pregosin and Evans, among others, with P-thioether ligands in Pd-allylic substitution and other relevant asymmetric processes put the focus on these types of ligands and spur their development. Despite many P–S ligands being developed, only a few of them were successfully applied, and their efficiencies were limited in substrate scope (enantioselectivities were only high in the allylic substitution of hindered standard substrate rac -1,3-diphenyl-3-acetoxyprop-1-ene) . Compared to other functional groups, the thioether-based ligands have been less used because mixtures of diastereomeric thioether complexes are produced and because it is difficult to control their interconversion in solution .…”

“…Among heterodonor ligands, the mixed P-oxazoline ligands have played a dominant role. To a lesser extent, P-thioether ligands have also demonstrated their potential utility in Pd-catalyzed asymmetric allylic substitution . The pioneering work of the groups of Pregosin and Evans, among others, with P-thioether ligands in Pd-allylic substitution and other relevant asymmetric processes put the focus on these types of ligands and spur their development.…”

Chiral thioether-based catalysts in asymmetric synthesis: recent advances

“…22 Related phosphinitethioethers, readily accessible from enantiopure epoxides, have been recently applied in Pd-catalyzed asymmetric allylic alkylations. 24 Carretero et al described a novel class of P,S-ligands, named Fesulphos (7), bearing a thioether and a phosphine as coordinating units and exclusively the planar chirality of the 1,2-disubstituted ferrocene scaffold. This family of ligands turned out to be very efficient in a number of synthetically relevant C-C bond forming reactions.…”