unibaselDepartment of Chemistry

Andreas Pfaltz Laboratory

Research

Synthetic organic chemistry; organometallic chemistry; homogeneous and heterogeneous catalysis; asymmetric catalysis; combinatorial approaches to catalysis.


Design of chiral ligands for asymmetric catalysis

Catalytic methods for the synthesis of enantiomerically pure compounds are of great importance for the preparation of biologically active substances such as pharmaceuticals, fragrances or crop protecting agents. One of our research goals is the development of new and generally useful classes of chiral ligands that allow a metal-catalyzed process to be controlled in such a way that one of two enantiomeric products is formed with high preference over the other. By studying the effect of chiral ligands on a metal-catalyzed process, we also hope to learn more about the reaction mechanism and the specific interactions between the catalyst and the substrate that are necessary for stereochemical control. An additional, more general objective of our research is to develop some rational guidelines for the design of suitable chiral ligands for a given application.

Typical examples of the ligands developed in our group are shown below.



Figure 1

Reviews: Proc. Natl. Acad. Sci. USA 2004, 101, 5723; Acc. Chem. Res. 2000, 33, 336; Synlett 1999 , 835.

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Enantioselective catalytic reactions

Among the reactions currently investigated in our laboratory are allylic substitutions, Heck reactions, 1,4-additions, cycloadditions, and hydrogenations of C=C, C=N, and C=O bonds. During the last few years, part of our research has been focused on iridium complexes with chiral P,N-ligands. These complexes have proved to be excellent catalysts for the hydrogenation of unfunctionalized olefins, a class of substrates, which gives poor results with chiral rhodium or ruthenium catalysts. Iridium catalysts were also successfully applied to various functionalized olefins, for which no other chiral catalysts were available (see Figure 2).

Figure 2

Reviews: Chem. Commun. 2011, 47, 7912; Adv. Synth. Catal. 2003, 345 , 33.

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Catalyst screening

Discovery and optimization of chiral catalysts for asymmetric synthesis is still a slow process, because our present knowledge is not sufficient to allow a truly rational design of new catalysts. Therefore, the development of combinatorial methods for the preparation and screening of catalyst libraries has become an important research focus. During the last few years, efficient techniques have been reported that allow high-throughput parallel screening of chiral catalysts. However, parallel screening, which involves product analysis of individual reactions with a single catalyst, has potential pitfalls. Often the enantioselectivity of a reaction is lower than the inherent selectivity of the catalyst, due to an unselective background reaction, catalytically active impurities or, as often found with chiral metal catalysts, partial dissociation of a chiral ligand producing an achiral catalyst. Problems of this kind would be avoided if the catalyst's ability for enantiodiscrimination could be determined directly from examining catalyst-reactant complexes rather than product analysis. In principle, such a method could distinguish between intermediates derived from different catalysts and thus allow simultaneous screening of catalyst mixtures. We have recently developed a screening method based on this concept, using electrospray mass spectrometry (ESI-MS) as an analytical tool (see Figure 3a). This method was successfully applied to screen catalysts for palladium-catalyzed kinetic resolution of allylic esters (see Figure 3b).

Figure 3a

 

 

Figure 3b

Angew. Chem. Int. Ed. 2004, 43, 2498; Review: Chem. Commun. 2009, 1607.

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