Application of a supramolecular-ligand library for the automated search for catalysts for the asymmetric hydrogenation of industrially relevant substrates.
A procedure is described for the automated screening and lead optimization of a supramolecular-ligand library for the rhodium-catalyzed asymmetric hydrogenation of five challenging substrates relevant to industry. Each catalyst is (self-) assembled from two urea-functionalized ligands and a transition-metal center through hydrogen-bonding interactions. The modular ligand structure consists of three distinctive fragments: the urea binding motif, the spacer, and the ligand backbone, which carries the phosphorus donor atom. The building blocks for the ligand synthesis are widely available on a commercial basis, thus enabling access to a large number of ligands of high structural diversity. The simple synthetic steps enabled the scale-up of the ligand synthesis to multigram quantities. For the catalyst screening, a library of twelve new chiral ligands was prepared that comprised substantial variation in electronic and steric properties. The automated procedures employed ensured the fast catalyst assembly, screening, and direct acquisition of samples for analysis. It appeared that the most selective catalyst was different for every substrate investigated and that small variations in the building blocks had a major impact on the catalyst performance. For two substrates, a catalyst was found that provided the product with outstanding enantioselectivity. The subsequent automated optimization of these two leads showed that an increase of catalyst loading, dihydrogen pressure, and temperature had a positive effect on the catalyst activity without affecting the catalyst selectivity.
Meeuwissen
Jurjen
J
Homogeneous and Supramolecular Catalysis, Van't Hoff Institute for Molecular Sciences Institution, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands.
Kuil
Mark
M
van der Burg
Alida M
AM
Sandee
Albertus J
AJ
Reek
Joost N H
JN