Events

Why Scaling Up is Hard: Lessons from Pharmaceutical Process Chemistry

Presented by Dr. Dan Treitler

Abstract:
Why do some reactions scale up beautifully while others are surprise disasters? And what can a chemist do to prevent wasting time and material on large reactions that don’t go as planned? These questions will be addressed using real examples from Bristol Myers Squibb pharmaceutical processes run on scales from milligrams to hundreds of kilograms. The talk will conclude with a step-by-step guide for improving the likelihood of a successful scale-up.

London Dispersion in Molecular Catalysis^[1]

Presented by Prof. Peter Schreiner
Hosted by Prof. Tom Rovis

Abstract:
The Gecko can walk up a glass window because of the adhesion in hydrophobic setae on its toes that convey van der Waals (vdW) interactions with the surface.^[2] The attractive part of vdW-interactions is an electron correlation effect referred to as London dispersion. Its role in the formation of condensed matter has been known since van der Waals^[3] and London^[4] who related dispersion to polarizability. London dispersion has been underappreciated in molecular chemistry as a key element of structural stability, chemical reactivity, and catalysis. This negligence is due to the notion that dispersion is considered weak, which is only true for one pair of interacting atoms. For increasingly larger structures, the overall dispersion contribution grows rapidly and can amount to tens of kcal mol^–1. This presentation shows selected examples that emphasize the importance of inter- and intramolecular dispersion for molecules consisting mostly of first row atoms.^[5] We note the synergy of experiment and theory that now has reached a stage where dispersion effects can be examined in fine detail. This forces us to re-consider our perception of steric hindrance and stereoelectronic effects, and even the transferability of chemical bond parameters from one molecule to another, both in structural chemistry^[6] and, in particular, in catalysis.^[7] We will also shed light on the possibilities to use machine learning approaches to improve catalytic reactions^[8] and highlight the importance of optimizing for differences in activation free energies (vs. enantiomeric excess).^[9]

Acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft.

[1] a) J. P. Wagner, P. R. Schreiner, Angew. Chem. Int. Ed. 2015, 54, 12274-12296; b) L. Rummel, P. R. Schreiner, Angew. Chem. Int. Ed. 2024, 63, e202316364.
[2] K. Autumn, M. Sitti, Y. A. Liang, A. M. Peattie, W. R. Hansen, S. Sponberg, T. W. Kenny, R. Fearing, J. N. Israelachvili, R. J. Full, Proc. Natl. Acad. Sci. 2002, 99, 12252-12256.
[3] J. D. van der Waals, Leiden University (Leiden, The Netherlands), 1873.
[4] F. London, Z. Phys. 1930, 63, 245-279.
[5] a) S. Rösel, C. Balestrieri, P. R. Schreiner, Chem. Sci. 2017, 8, 405-410; b) J. P. Wagner, P. R. Schreiner, J. Chem. Theory Comput. 2016, 12, 231-237; c) E. Prochazkova, A. Kolmer, J. Ilgen, M. Schwab, L. Kaltschnee, M. Fredersdorf, V. Schmidts, R. C. Wende, P. R. Schreiner, C. M. Thiele, Angew. Chem. Int. Ed. 2016, 55, 15754-15759; d) C. Wang, Y. Mo, J. P. Wagner, P. R. Schreiner, E. D. Jemmis, D. Danovich, S. Shaik, J. Chem. Theory Comput. 2015, 11, 1621-1630; e) J. P. Wagner, P. R. Schreiner, J. Chem. Theory Comput. 2014, 10, 1353-1358; f) A. A. Fokin, L. V. Chernish, P. A. Gunchenko, E. Y. Tikhonchuk, H. Hausmann, M. Serafin, J. E. P. Dahl, R. M. K. Carlson, P. R. Schreiner, J. Am. Chem. Soc. 2012, 134, 13641- 13650; g) P. R. Schreiner, L. V. Chernish, P. A. Gunchenko, E. Y. Tikhonchuk, H. Hausmann, M. Serafin, S. Schlecht, J. E. P. Dahl, R. M. K. Carlson, A. A. Fokin, Nature 2011, 477, 308-311; h) S. Grimme, P. R. Schreiner, Angew. Chem. Int. Ed. 2011, 50, 12639-12642; i) A. A. Fokin, D. Gerbig, P. R. Schreiner, J. Am. Chem. Soc. 2011, 133, 20036-20039; j) S. Rösel, H. Quanz, C. Logemann, J. Becker, E. Mossou, L. Cañadillas-Delgado, E. Caldeweyher, S. Grimme, P. R. Schreiner, J. Am. Chem. Soc. 2017, 139, 7428-7431; k) S. Rösel, J. Becker, W. D. Allen, P. R. Schreiner, J. Am. Chem. Soc. 2018, 140, 14421-14432.
[6] a) J. M. Schümann, J. P. Wagner, A. K. Eckhardt, H. Quanz, P. R. Schreiner, J. Am. Chem. Soc. 2021, 143, 41-45; b) J. M. Schümann, L. Ochmann, J. Becker, A. Altun, I. Harden, G. Bistoni, P. R. Schreiner, J. Am. Chem. Soc. 2023, 145, 2093-2097.
[7] a) C. Eschmann, L. Song, P. R. Schreiner, Angew. Chem. Int. Ed. 2021, 60, 4823-4832; b) L. Rummel, M. H. J. Domanski, H. Hausmann, J. Becker, P. R. Schreiner, Angew. Chem. Int. Ed. 2022, 61, e202204393.
[8] O. Pereira, M. Ruth, D. Gerbig, R. C. Wende, P. R. Schreiner, J. Am. Chem. Soc. 2024, 146, 14576-14586.
[9] M. Ruth, T. Gensch, P. R. Schreiner, Angew. Chem. Int. Ed. 2024, 63, e202410308.