PhD Project Title: Sustainable and safe C-H activation for large-scale production.
Principal Investigator: Prof. Michael Schnürch
PhD Project description: The PhD student (ESR) will 1) develop a protocol for direct alkylation using quaternary ammonium salts under base-free conditions (reaction conditions effective in absence of base, or design of reactors allowing spatial separation); 2) design methylation reactions using, amongst others, non-toxic tetramethylammonium salts as a solid precursor of CH3 group; 3) elucidate the mechanism in collaboration with computational support from ESR3; 4) apply the method for isotope labeling (in particular 14C) of relevant compounds.
Description of the work: ESR6 will focus on further improving the alkylation reactions using quaternary ammonium salts previously published in the group. In particular, basic conditions required for such transformation constitute an important drawback to be overcome (development of a protocol efficient under neutral conditions, spatial separation between different compartments of a reactor). ESR6 will also develop high yielding methylation reactions using, for example, tetramethyl-ammonium bromide as a solid precursor where initial results are promising and literature precedence with related reagents is available. To illustrate the industrial perspectives of its IRP ESR6 will move to Boehringer to perform methylation on pharmaceutically relevant molecules. In parallel, ESR6 will explore the potential of C-H isotope labelling (introduction of 14C motifs) using N-14CH3-pyridinium salts.
Relevant skills that will be considered are:
- Strong theoretical background and practical skills in organic synthesis and catalysis
- Practical experience in analytical methods (NMR, MS, HPLC)
- Good level of English proficiency (understood, spoken and written)
- Skills in scientific writing (reports, papers, etc.)
- Team spirit and collaborative predisposition
Planned secondments: “1 secondment (6 months) at Boehringer Ingelheim
 Spettel, M.; Pollice, R.; Schnürch, M. Org. Lett. 2017, 19, 4287
 a) Uemura, T.; Yamaguchi, M.; Chatani, N. Angew. Chem. Int. Ed., 2016, 55, 3162; b) den Hartog, T.; Sarria Toro, J. M.; Couzijn, E. P. A.; Chen, P. Chem. Commun. 2014, 50, 10604; c) Künzi, S. A.; Sarria Toro, J. M.; den Hartog, T.; Chen, P. Angew. Chem. Int. Ed., 2015, 54, 10670.