This research is supported by a Marie Curie Action

This research is supported by a Marie Curie Action
This research has received funding from the People Programme (Marie Curie Actions) of the EU (FP7/2007-2013) under REA grant agreement nÂș PIEF-GA-2013-622413

Sunday, 1 March 2015

Then, why asymmetric catalysis?

In the previous posts, I have shown different approaches to access chiral compounds. Moreover, I stressed that the demand for chiral compounds, often as single enantiomers, has escalated sharply in recent years, driven particularly by the demands of the pharmaceutical industry, but also by other applications, including agricultural chemicals, flavours, fragrances, and materials. Two-thirds of prescription drugs are chiral, with the majority of new chiral drugs being single enantiomers. This widespread demand for chiral compounds has stimulated intensive research to develop improved methods for synthesizing such compounds.

So, then what is asymmetric catalysis and most important why is relevant for the synthesis of chiral compounds?

To get started, firstly, we should define the term asymmetric catalysis.

Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. By using a catalyst, the chemical reaction occur faster and require less activation energy. Because catalysts are not consumed after promoting the reaction, they can further catalyse the reaction of further quantities of reactant. Therefore, often only tiny amounts are required.

The term asymmetric when linked to catalysis refers to the phenomenon whereby a chiral catalyst promotes the conversion of an achiral substrate to a chiral product with a preference for the formation of one of the mirror image isomers (enantiomers).

In simple words, the rate of a chemical reaction is increased biasing the process towards the formation of just only one single enantiomer.

Historically, enantiomerically enriched compounds were generated either by chemical transformation of an enantiomerically enriched precursor, often derived directly or indirectly from nature's chiral pool, or by resolving an equimolar (racemic) mixture of the two enantiomers. Both of these approaches suffer from potentially severe drawbacks, the former in requiring stoichiometric amounts of a suitable precursor and the latter in typically yielding only up to 50% of the desired enantiomer.

Asymmetric catalysis, in which each molecule of chiral catalyst, by virtue of being continually regenerated, can yield many molecules of chiral product, has significant potential advantages over these older procedures. Indeed, enantiomerically pure compounds are produced in nature by such chirality transfer from enzymes.

Both from a conceptual and chemical efficiency point of view, the use of enantiomerically pure (chiral) catalysts instead of stoichiometric chiral auxiliaries is extremely attractive. Ideally, the final product can be obtained in a single step from a substoichiometric amount of chiral inductor (the catalyst) by transmission of the 3D information through organic reactions resulting in a chirality multiplication. In a prototype reaction a prochiral substrate (A) and an achiral reagent (R) react in the presence of a chiral catalyst to give an enantiomerically enriched (or pure) product (P*). The catalyst acts temporarily as a template coordinating starting products (A, R) transferring the chirality from the source of asymmetry to the new stereogenic centre created in the reaction (Figure 1).

Figure 1. Comparison of strategies based on chiral auxiliaries and chiral catalysts in asymmetric synthesis.

In the next posts, we will start a journey highlighting how far asymmetric catalysis has evolved and being considered one of the most prominent areas in organic chemistry.

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Aarhus University

Aarhus University
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Center for Catalysis, AU

Center for Catalysis, AU
Center for Catalysis, AU website

Marie Curie Actions

Marie Curie Actions
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