Why Is Asymmetric Synthesis Essential in Modern Chemistry?
Chemistry as a subject is spread to a vast context and does not limit itself to a few formulas and chemical names. There is actually more to it than we can imagine. As an instance of this, we are here to give you a glimpse of one such chemical phenomenon that has its role in multiple applications of human life and the environment as a whole, asymmetric synthesis.
Asymmetric synthesis, also known as enantioselective synthesis, might at first sound like a complex chemical phenomenon, but to your surprise, it isn't. The term 'asymmetric' in itself tells us that something over here is out of symmetry, but what? Let's find out!
Pertaining to the fact that this phenomenon is circumferenced by chemistry, we may understand this in simpler terms for getting a clear insight.
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Each compound has multiple molecules, and every molecule has its own structural symmetry. However, when this structural molecule symmetry is disturbed, it acts to affect the compound by transforming it into lopsided segments of compounds.
As you can expect, these unbalanced proportions further differ in their asymmetrical structures at the central point, which remains the most affected.
IUPAC has a relatively complicated definition for us in store: It defines this chemical synthesis as a reaction in which one or more new elements of chirality are formed in a molecule that produces stereoisomeric products in unequal amounts.
The involvement of organic compounds is a prerequisite in most circumstances.
History of Asymmetric Synthesis
The discovery of enantioselective synthesis can be dated back to the period of the early nineteenth century, 1815, when a French physicist, Jean B. Biot stirred his interest in the topic. He was attracted to the property of optical activity of light, whose nature was later solved by Louis Pasteur in the year 1848. He was bent on giving a name to this property, but he restricted it to defining nature as dissymmetry.
In the following years, exploration of the word chirality drove all the minds crazy, the term was coined by Lord Kelvin.
Fast forward to the year 1894, when Hermann E. Fischer came up with the concept of asymmetric induction, which now became the foundational process of asymmetric synthesis. He was successful in conducting studies and performing them practically.
As a result of his determination, he was undefeated in demonstrating the first-ever inference of asymmetric synthesis. Conclusively, today we know it as the Kiliani-Fischer synthesis.
While the work of Willy Marckwald in describing the earliest asymmetric synthesis is given eminent historic significance, chemists like J.J Berzelius are known for constantly providing contrasting evidence of Marckwald's explanation.
History could not record its next development until the beginning of the 1950s. This period saw the amalgamation of successful chemists like Woodward and Prelog, to name a few with the ultimately newly developed techniques. These techniques helped scientists to closely observe the structure, nature, and functioning of asymmetric synthesis.
Drugs were made and prescribed by physicians to treat morning sickness and similar symptoms, one such drug example is Thalidomide. However, it was an unsuccessful experiment that impacted many young lives negatively.
Later developments of the twentieth century helped shape asymmetric synthesis whatever it is today.
Principles of Asymmetric Synthesis
Unlike any other chemical phenomena, asymmetric synthesis has certain principles that direct its working and usage. Some of the most popularly known and advocated fundamentals of asymmetric synthesis partial and absolute include:
Stereoselectivity
Kinetic and Thermodynamic Control
The Iso Inversion Principle
Single and Double asymmetric Induction
Kinetic Resolution
Quick Facts About Asymmetric Synthesis
The phenomenon of asymmetric synthesis is applied to multiple settings in which we live and that surround us.
The progress of the drug industry is solely dependent on the workings of asymmetric synthesis.
Variations in the reaction patterns of all the living systems are attributed to different enantiomers, this is possible because living beings possess a high degree of the property, chirality.
The basis of amino acids and sugars is rooted back in the existence of a mere enantiomer.
New developments in the field of asymmetric synthesis are taking place. One such technological development is known as asymmetric organocatalysis.
This is exactly what the fundamentals of asymmetric catalysis are.
Conclusion
Asymmetric synthesis is a growing topic in the field of chemistry and invites scientists to dig this topic more. With all the available information that we possess about this topic, we can surely say that the underlying principles, applications, and relevance in the real world are inevitable and present everywhere.
FAQs on Asymmetric Synthesis: Concepts, Methods & Applications
1. What is asymmetric synthesis in chemistry?
Asymmetric synthesis, also known as chiral synthesis, is a chemical reaction that preferentially creates one stereoisomer (either an enantiomer or a diastereomer) over others. Its goal is to produce an optically active compound from a starting material that is not. This process is crucial for controlling the three-dimensional arrangement of atoms in a molecule.
2. How does asymmetric synthesis differ from symmetric synthesis?
The key difference lies in the product's stereochemistry. Symmetric synthesis produces an equal mixture of enantiomers, known as a racemic mixture, which has no net optical activity. In contrast, asymmetric synthesis uses a chiral influence (like a catalyst or auxiliary) to selectively favour the formation of one enantiomer, resulting in a product that is optically active and enriched in the desired stereoisomer.
3. What are the main types of asymmetric synthesis?
There are four primary strategies used to achieve asymmetric synthesis, based on the source of chirality:
- Substrate-controlled: The existing chirality in the starting molecule directs the stereochemical outcome of the reaction.
- Auxiliary-controlled: A chiral, non-reagent group (auxiliary) is temporarily attached to the substrate to guide the reaction, and is then removed after the desired stereocenter is formed.
- Reagent-controlled: A chiral reagent is used in stoichiometric amounts to transfer chirality to the substrate.
- Catalyst-controlled: A small amount of a chiral catalyst creates a chiral environment for the reaction, enabling the production of large quantities of a single enantiomer product. This is often the most efficient method.
4. What is the underlying principle of asymmetric catalysis?
The fundamental principle of asymmetric catalysis is the creation of a chiral reaction environment. The chiral catalyst interacts with the achiral substrate to form a transient diastereomeric complex. This creates two different, unequal energy pathways to the two possible product enantiomers. The reaction proceeds preferentially through the lower-energy transition state, leading to the formation of one enantiomer in excess. The catalyst is then regenerated, allowing it to direct the transformation of many more substrate molecules.
5. Can you provide a real-world example of asymmetric synthesis?
A classic and Nobel Prize-winning example is the synthesis of L-DOPA, a drug used to treat Parkinson's disease. In the 1970s, a method for asymmetric hydrogenation was developed using a chiral rhodium-based catalyst. This process selectively produces the biologically active L-DOPA enantiomer. The other enantiomer, D-DOPA, is not only inactive but can also cause unwanted side effects. This synthesis highlighted the critical need for stereochemical control in drug manufacturing.
6. Why is asymmetric synthesis so important in the pharmaceutical industry?
Asymmetric synthesis is vital in pharmaceuticals because biological systems, such as enzymes and receptors in the human body, are inherently chiral. Consequently, the different enantiomers of a drug can have drastically different biological effects. One enantiomer (the eutomer) may provide the desired therapeutic benefit, while the other (the distomer) could be inactive or, in some cases, highly toxic. By enabling the production of single-enantiomer drugs, asymmetric synthesis helps to maximise efficacy, reduce dosages, and minimise or eliminate harmful side effects.
7. What is 'enantiomeric excess' (e.e.) and how does it measure the success of an asymmetric synthesis?
Enantiomeric excess, or e.e., is a measurement that quantifies the purity of a chiral sample. It represents the percentage of one enantiomer in excess of the other. For a mixture of R and S enantiomers, it is calculated as: e.e. (%) = |%R - %S|. A successful asymmetric synthesis is one that achieves a high e.e., ideally approaching 100%. This indicates that the reaction was highly selective and that the product is almost entirely composed of the desired single enantiomer.
8. Besides pharmaceuticals, what are some other applications of asymmetric synthesis?
While its impact on medicine is profound, the applications of asymmetric synthesis extend to several other industries:
- Agrochemicals: It is used to create more effective and safer pesticides and herbicides that target specific pests or weeds while being harmless to beneficial insects, animals, or the crops themselves.
- Flavours and Fragrances: The stereochemistry of a molecule can determine its taste and smell. For example, the (R)-enantiomer of carvone smells like spearmint, while its (S)-enantiomer smells like caraway.
- Advanced Materials: Asymmetric synthesis is used to produce polymers and liquid crystals with unique optical and physical properties for use in electronics and displays.
