Screening chiraler Katalysatoren durch massenspektrometrische Erfassung katalytischer Intermediate

Abstract

ESI-Mass spectrometry is a technique that allows the selective detection of charged species in the presence of other neutral compounds. In this thesis, ESI-MS was successfully applied to monitor positively charged intermediates in a palladium-catalyzed allylic substitution. Using pseudo-enantiomeric substrates, a rapid screening protocol for chiral catalysts was developed. The catalysts under study were selective for the kinetic resolution of allylic esters. The two pseudo-enantiomeric substrates bear different mass-labels allowing for a simple differentiation of the two intermediates A and B. Hence, the detected ratio A/B reflects the catalyst’s intrinsic enantioselectivity (s = A/B). Using this screening method, the most selective ligand known for this reaction to date was identified (s > 100), illustrating the potential of this method. After having established a reliable protocol for the screening of single catalysts, it was shown that this method can also be applied to the screening of mixtures of several palladium catalysts in one pot. Catalysts with different molecular weight form intermediates that can be distinguished mass-spectrometrically. The possibility of screening mixtures of homogeneous catalysts is particular attractive for the development and optimization of new chiral ligands, as illustrated in a short optimization study. Six ligands were prepared by a simple condensation of three different building blocks and used directly as filtered crude-products. The mixture also contained three non-symmetrical combinations with two different sulphonamide groups (R1 ≠ R2), that can be only accessed in pure form with a significantly more complex synthesis. One of the ligands showed a selectivity of s > 30, which was later proven independently by conventional experiments using the pure ligand. The same method is applicable to allylic substitutions starting from meso substrates bearing two enantiotopic leaving groups. A cyclic pseudo-meso compound was prepared and successfully tested with a number of different catalysts. In the ESI-MS-spectra of some screening results, dimeric palladium species were detected. In order to get more insight into their role and relevance for catalysis, several catalytic and stoichiometric reactions were investigated. The dimers were found to be formed reversibly, thus allowing for momentary stabilization of the palladium(0)-species prior to returning to the catalytic cycle. The structure of one dimer in solution was investigated by NMR. The solid state structure of a related dimer was characterized by X-ray diffraction.