The three pillars of asymmetric catalysis

Breakthrough research of Knowles, Noyori and Sharpless positioned asymmetric catalysis as one of the most prominent methods for the synthesis of chiral compounds. The catalysts they used rely on (transition) metals. Metals offer a wide range of activity and selectivity in a vast range of chemical reactions. Despite of the fact that for decades, the generally accepted view has been that metals dominate the area there are also two classes of efficient asymmetric catalysts: enzymes (biocatalysis) and small organic molecules (organocatalysis). Together with metal catalysis constitute what is nowadays coined as the three pillars of asymmetric catalysis.

Let us mimic the Mother Nature!

Over millions of years of continuous evolution, Nature has perfected its machinery to a superb level. Many chemical reactions occur in living organisms in such precision that chemists have pursued the challenge of imitating Nature to carry out chemical reactions. Most biological molecules are chiral and are synthesized in living cells by enzymes using asymmetric catalysis. Chemists also use enzymes or even whole cells to synthesize chiral compounds and for a long time, the perfect enantioselectivities often observed in enzymatic reactions were considered beyond reach for non-biological catalysts.

Metal catalysis

It became evident that high levels of enantioselectivity can also be achieved using synthetic metal complexes as catalysts. Therefore, organic chemists took the main components of enzymes (metal and chiral organic molecules) to design ”simplified” enzymes. Since the discovery of the potential of metal-catalysed reactions, a variety of highly efficient catalytic asymmetric reactions have been developed so far and research in asymmetric catalysis achieved prominence in both academia and industry. Despite of the great potential of metal catalysis the technology is not as greener as should be, contributing to pollution and high-cost processes, thus not offering encouraging prospects for chemical sustainability.


Biocatalysis can be defined as the use of enzymes to catalyze chemical reactions. An enzyme is simply a protein catalyst, and enzymes have many important uses. Every reaction in living organisms (e.g. yourself!), proceeds thanks to the presence of enzymes. Biocatalysis can be used to replace many traditional chemical catalysts, including catalysts that are toxic or contain chemical residues that pollute the environment. The increasing ability to use enzymes to catalyse chemical reactions in industrial processes, including the production of drug substances, flavours, fragrances, or polymers — chemicals that literally impact almost every facet of your life. In adopting biocatalysis as a mainstream technology for chemical production, it is expected that greener, pollution and cost-efficient processes will be generated.


In organocatalysis, a purely organic and metal-free small molecule is used to catalyse a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach has some important advantages. Small organic molecule catalysts are generally stable and easy to design and synthesize. They are often based on non-toxic compounds, such as sugars, peptides, or even amino acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts most attractive to organic chemists may be the simple fact that they are organic molecules.

Metal, bio- and organocatalysis are complementary areas in asymmetric catalysis with pros and cons. Whatever option is finally selected for the synthesis of chiral compounds depends on different factors (e.g. desired activity and selectivity in the reaction of choice, cost, and waste generation). It has to be evaluated thoroughly to provide with what is more important: a sustainable and greener chemistry process.


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