Aszimmetrikus szintézisek: nagy aktivitású és enantioszelektivitású katalizátorok fejlesztése
Asymmetric syntheses: development of highly active and enantioselective catalysts
Farkas Gergely
a, Császár Zsófia
a, Madarász József
b, Darvas Ferenc
c, Bakos József
aa
Pannon Egyetem, Szerves Kémia Intézeti Tanszék, 8200 Veszprém, Egyetem u. 10.
b
CiToxLAB Hungary Kft., 8200 Veszprém, Szabadságpuszta
c
ThalesNano Nanotechnológiai Zrt., 1031 Budapest, Záhony u. 7., Graphisoft Park
Summary
Transition metal complexes containing chiral ligands are widely used in industrial scale for asymmetric catalytic reactions. In particular, rhodium- and palladium-based complexes modified with chiral phosphorus ligands have been found to be excellent catalysts.
Today, C1-symmetric chelate ligands such as phosphine-amines and phosphine-phosphites proved to be highly efficient in asymmetric catalytic transformations. Their excellent catalytic properties can be attributed to their unique coordination behaviour. They have two distinct coordination sites with a very different electronic and/or steric nature that can easily govern the stereochemical outcome of the catalytic cycle.
The immobilization of chiral catalysts for asymmetric reactions is one of the most promising solutions to the problem associated with the difficulties in the recovery and reuse of expensive homogeneous catalysts. The vast majority of catalyst screening is usually performed in an autoclave, where the test of each catalytic system requires a new experiment with fresh substrate, catalyst, and solvent. Recent changes accelerated a growing demand in the pharmaceutical and fine chemical industry for a high throughput continuous flow reactor.
A convenient synthesis by the desymmetryzation of C2-symmetric cyclic sulfate esters was developed for the preparation of pentane-2,4-diyl-based phosphine-amine (P,N) and phosphine-phosphite (P,OP) ligands. The synthetic methods contain simple steps and use inexpensive and easily available starting materials.
The novel P,N ligands were tested in palladium catalyzed asymmetric allylic alkylation reactions of racemic 1,3- diphenylallyl-1-acetate. Excellent enantioselectivities (up to 94% ee) were obtained. The ligand/metal ratio proved to be crucial in determining enantioselectivity due to the formation of catalytically active non-chelate complexes.
P,OP’s were applied the rhodium-catalyzed asymmetric hydrogenation of dimethyl-itaconate. In homogeneous batch mode very high activities and ee’s (>99%) were obtained at a substrate/catalyst molar ratio of 10000.
Furthermore, the chiral rhodium-complex was immobilized on commercially available Al2O3 using PTA (phosphotungstic acid) as anchoring agent. The immobilized catalyst was tested in continuous flow system using H-CubeTM microfluid reactor. The catalyst provided excellent ee’s (>99%) and activities (>2100 h-1 TOF) at a substrate concentration of 1 M.
This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/ 2-11/1-2012-0001 ‘National Excellence Program’.
