Synthesis of Novel Diastereomeric Diphosphine Ligands and Their Applications in Asymmetric Hydrogenation Reactions

Abstract

[structure: see text] Diastereomeric biaryl diphosphine ligands 10 and 11 with added chiral centers on the backbone were synthesized. Substrate-directed asymmetric synthesis occurred in the coupling step of the preparation of the diastereomeric diphosphine oxides. The diastereomeric diphosphine oxides were easily separated by column chromatography with silica gel. Ruthenium catalysts containing these ligands were highly effective in the hydrogenation of 2-(6'-methoxy-2'-naphthyl)propenoic acid and beta-ketoesters. The additional chiral centers had a significant influence on the enantioselectivity and activity of the catalysts.

Rapid asymmetric reduction of ethyl 4-chloro-3-oxobutanoate using a thermostabilized mutant of ketoreductase ChKRED20

“…To determine the conversion, the product was analyzed directly. To determine the enantiomeric excess, the product was acetylated following literature method (Jung et al 2010;Qiu et al 2002). and then analyzed with chiral GC.…”

Remarkably diastereoselective synthesis of a chiral biphenyl diphosphine ligand and its application in asymmetric hydrogenation

“…(An authentic sample of the other diastereomer has been prepared by using a different method, which is beyond the scope of this article.) The high yield in biphenyl coupling and the complete atropdiastereoselectivity may have resulted from the significant directing effect of the bridging moiety in 6 in comparison with the intermolecular coupling reaction (39). This methodology is obviously useful for the development of enantiomerically pure phosphine ligands.…”

“…Previously, most of the research was focused on the syntheses of biphenols and binaphthols; in contrast, less attention was paid to the atroposelective syntheses of biaryl diphosphine oxides, the precursors of widely used diphosphine ligands. Recently, we successfully developed two diastereomeric diphosphine ligands for use in asymmetric hydrogenation reactions by stereoselective intermolecular Ullmann coupling of two chiral phosphine oxide precursors with moderate atropdiastereoselectivity (39). However, very careful separation of the diastereomers by column chromatography on silica gel was still needed.…”

Highly Diastereoselective Synthesis of Atropisomeric Bridged P,N‐Ligands and Their Applications in Asymmetric Suzuki–Miyaura Coupling Reaction

“…[3][4][5] However, they usually require a resolution step to obtain optically pure C 2 -symmetrical chiral ligands from the racemate, which is very tedious and sometimes difficult for further optimization in industry. [6] To tackle these problems, a protocol of central-toaxial chirality transfer was introduced to the ligand development via a key step of extremely high diastereomeric aryl-aryl coupling reaction, [7,8] some kind of chiral ligands have been prepared and the tedious resolution procedure was avoided in the synthetic route ( Figure 1). These newly developed ligands were found to be highly effective in some asymmetric catalytic reactions and the additional chiral centers on the ligand backbones exerted significant influence on the enantioselectivity and activity of the catalysts for their highly modular nature.…”