The Catalysis Laboratory at Merck: 20 Years of Catalyzing Innovation

Abstract

The Catalysis Laboratory at Merck was established in 2002 to discover and develop asymmetric hydrogenation transformations for application to the company’s pipeline. Twenty years later, it is safe to say that not only was what now feels like that modest goal accomplished, but many varied catalytic technologies have also emerged from this group. Furthermore, the successes achieved locally have spawned an array of further investments in catalytic manifolds and other enabling technologies across industry and academia alike. Herein, we will take a look back at the team’s humble origins, discuss the many impacts that have been realized from that initial outlay, and provide thoughts on future directions entering the team’s third decade.

Practical Aspects Concerning Catalysis with Molecularly Doped Metals**

“…Following the successful uptake first of asymmetric hydrogenations via homogeneously catalyzed processes using metal complexes with (often proprietary) chiral ligands and then of carbon-carbon cross coupling reactions, the industry (and its main customer, the pharmaceutical industry) has been highly receptive to innovation in homogeneous catalysis. [33] This is not the case for heterogeneous catalysis, with industry generally lamenting the poor stability of supported metal catalysts giving place to metal leaching and product contamination with metal residues. [34] The uptake of green chemistry technologies in the fine chemical and pharmaceutical industries has been chiefly driven by increased profitability, with only technologies offering quick return on investment (less than 3, and preferably less than 2 years) eventually considered for commercial uptake.…”

“…The history of innovation in catalysis for synthetic organic chemistry in the last two decades (2002–2022) has plentiful lessons to teach concerning the attitudes of the fine chemical industry towards new heterogeneous catalytic technologies. Following the successful uptake first of asymmetric hydrogenations via homogeneously catalyzed processes using metal complexes with (often proprietary) chiral ligands and then of carbon‐carbon cross coupling reactions, the industry (and its main customer, the pharmaceutical industry) has been highly receptive to innovation in homogeneous catalysis [33] …”

Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions

“…Conditions identified for both the SMC and S N Ar could be easily narrowed down to fit into a 96-well format, however as the conditions (catalyst/ligand combination, base, solvent, and temperature) for BHC vary ‡ ChemBeads are prepared on acid-washed glassbeads (≤106 μm (−140 U.S. sieve)) using the method described by Abbvie. 39 § 24-Well HTE kits have been reported by Merck 56,57 and 24-well HTE kits are available from commercial vendors e.g. Sigma Aldrich and HepatoChem, for selected reactions.…”

“…After dosing, the optimisation kits are sealed in Mylar bags under nitrogen and stored at −20 °C §§24-Well HTE kits have been reported by Merck 56,57 and 24-well HTE kits are available from commercial vendors e.g. Sigma Aldrich and HepatoChem, for selected reactions. When a chemist at Astex needs to run a screen for one of our HTE-enabled reactions, they design their reaction in our custom-made electronic laboratory notebook (ELN), choose a templated fractional factorial screen from the available options, and download tailored recipe-like instructions bespoke to that screen.…”

“…§24-Well HTE kits have been reported by Merck 56,57 and 24-well HTE kits are available from commercial vendors e.g. Sigma Aldrich and HepatoChem, for selected reactions.…”