Synthetic toolbox: Base metal catalysis

Use in the pharmaceutical industry

This page reproduces content from J. Maes, E. Mitchell and B. Maes, Base Metals in Catalysis: From Zero to Hero, in Green and Sustainable Medicinal Chemistry, Methods, Tools and Strategies for the 21st Century Pharmaceutical Industry, 2016. It is copyright to the Royal Society of Chemistry (RSC) and is reproduced here with their express permission. If you wish to reproduce it elsewhere you must obtain similar permission from the RSC.

Within the pharmaceutical industry, precious metal based catalysts are predominantly used in cross‑coupling reactions, with 17% of the transformations catalysed by palladium [1] (please see the introduction to C-H activation), other palladium catalysed transformations include hydrogenation/hydrogenolysis, Bn/CBz deprotection.

Given the prevalence of the use of precious metals in the synthesis of important molecules, finding alternative methods is not clear cut; as there are associated issues with the required selectivity, and the use of a different method would require complete or partial redesign of large scale processes. Moreover, small changes in a production process for pharmaceutically relevant molecules would require reopening of the associated registration files, which would incur further costs. In addition to the issue of the scarcity and cost of precious metals, the ligands associated with them in a given method can be more expensive per mole than the metal itself, and there are no means for their recovery. [2]

  1. S. D. Roughley and A. M. Jordan, The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates, J. Med. Chem., 2011, 54, 3451-3479.
  2. J. Maes, E. Mitchell and B. Maes, Base Metals in Catalysis: From Zero to Hero, in Green and Sustainable Medicinal Chemistry, Methods, Tools and Strategies for the 21st Century Pharmaceutical Industry, 2016.