Since a basic understanding of the mechanisms of catalysis was initially established in the 18th century, synthetic chemists have continued innovating to develop increasingly effective and targeted catalysts that support more elegant and efficient synthetic methods.
This year’s Nobel Prize laureates, Benjamin List (Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany) and David W.C. MacMillan (Princeton University, USA), independently made a major leap forward in chemical synthesis with the introduction of organocatalysts that could facilitate asymmetric syntheses. This discovery, first published in 2000, was a powerful addition to the synthetic chemists’ toolbox. This new class of catalysts has the benefit of simultaneously making chemical syntheses more precise and efficient, while also reducing the need to use toxic metal compounds to facilitate many synthetic processes, including the manufacture of enantiomerically pure pharmaceuticals, delivering long-term environmental and safety benefits across a multitude of industries.
Foundational Publications:
The Direct Catalytic Asymmetric Three-Component Mannich Reaction
Benjamin List Journal of the American Chemical Society 2000 122 (38), 9336-9337, DOI: 10.1021/ja001923x
New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels−Alder Reaction
Kateri A. Ahrendt, Christopher J. Borths, and David W. C. MacMillan Journal of the American Chemical Society 2000 122 (17), 4243-4244 DOI: 10.1021/ja000092s
Molecules of Mention
(S)-5-Benzyl-2,2,3-trimethylimidazolidin-4-one hydrochloride
Diels Alder organocatalyst used to stereoselectively form intermediate iminium in norbornene synthesis
L-Proline
Organocatalyst used in Mannich reaction to form an asymmetric secondary amine
Reach of Nobel Research
The CAS Content Collection shows that:
- MacMillan and List have each published more than 200 journal articles and patents focused on catalysis
- Their publications have collectively been cited more than 33,000 times by other scientists
- More than 150,000 reactions that use asymmetric organocatalysts have been published since 2000
Why it Matters
The choice by the Nobel Committee to honor an innovation that impacts the environmental sustainability of synthetic chemistry is notable. Sustainability has become a key focus of global chemical research in recent years, with the aim of improving the safety and efficiency of chemical processes. The introduction of organocatalysts reduced chemists’ need to use metal catalysts, which are more likely to be toxic, are often in short supply, may not be air- or water-stable, and must be removed from the final products. Organocatalyzed reactions can also be performed under milder conditions and may incorporate multiple processes into a single step. Collectively these advantages save significant energy, time, and money and make complex syntheses easier to perform overall.
Catalysts must of course first be functionally effective. In addition to being “greener” than their metallic predecessors, these catalysts enabled transformations not possible before. There remains tremendous opportunity to develop even more elegant synthetic solutions to simplify existing chemical processes and make new kinds of molecules. However, as many of the bioactive molecules that are driving breakthroughs in medical treatment are non-racemic, it is particularly important to consider toxicity and sustainability for new catalyst candidates, which will be encouraged by this Nobel selection.
For more information on the latest developments in asymmetric organocatalysis and the work of these honored researchers, start with a search in CAS SciFindern.