סמינר בכימיה אורגנית: Design and Screening of Enantioselective Catalysts

Abstract:

For a long time, C₂-symmetric ligands were dominating in asymmetric catalysis. However, later on an increasing number of reactions was found, in which non-symmetric bidentate P,N-ligands outperformed C₂-symmetric P,P- or N,N-ligands. Especially phosphinooxazolines (PHOX ligands) have emerged as highly effective widely applicable ligands.^1,2 

In the first part of this lecture, asymmetric hydrogenation of olefins with chiral iridium P,N ligand complexes will be discussed. In contrast to rhodium- and ruthenium-phosphine complexes, these catalysts do not require the presence of a coordinating group next to the
C=C bond and, therefore, have considerably extended the scope of asymmetric hydrogenation.^3-5.

In the second part, a new screening method for chiral catalysts will be described, which is based on mass-labeled quasi-enantiomeric substrates and electrospray ionization mass spectrometry as an analytical tool.^6-8 This method allows determination of the intrinsic enantioselectivity of a catalyst by mass spectrometric monitoring of catalytic intermediates. In contrast to conventional screening methods, which are based on product analysis, simultaneous screening of catalyst mixtures in homogeneous solution is possible. In addition, mechanistic insights about the enantioselectivity-determining step of a catalytic cycle may be
gained.⁸

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1. G. Helmchen, A. Pfaltz, Acc. Chem. Res. 2000, 33, 336.

2. M. P. Carroll, P. Guiry, Chem. Soc. Rev. 2014, 43, 819.

3. S. J. Roseblade, A. Pfaltz, Acc. Chem. Res. 2007, 40, 1402.

4. D. H. Woodmansee, A. Pfaltz, Chem. Commun. 2011, 47, 7912.

5. S. Gruber, A. Pfaltz, Angew. Chem. Int. Ed. 2014, 53, 1896.

6. C. A. Müller, C. Markert, A. M. Teichert, A. Pfaltz, Chem. Commun. 2009, 1607.

7. F. Bächle, J. Duschmalé, C. Ebner, A. Pfaltz, H. Wennemers, Angew. Chem. Int. Ed. 2013, 52, 12619.

8. P. G. Isenegger, A. Pfaltz, Chem. Rec. 2016, 16, 2534.

מארגן הסמינר: ד"ר רומן דוברובסקי