Why Nobel prize 2021 "for development of Asymmetric Organocatalysis"| in Chemistry
The Nobel prize in chemistry 2021 was Awarded Benjamin List and David MacMillan “for development of Asymmetric Organocatalyzed “. The Nobel prize in chemistry 2021 decided to awarded by The Royal Swedish Academy of Sciences.
The Nobel prize winner in chemistry 2021 was
- Professor Benjamin List (He is from Max-Planck-Institut für Kohlenforschung [Max Planck Institute for Coal Research], Mülheim an der Ruhr, in Germany).
- Professor David W.C. MacMillan (from Princeton University, in the USA)
They developed a new tool for molecule contraction by organocatalysis. This tool has a very important role in pharmaceutical Research and Green chemistry.
The catalysts are a fundamental tool for a chemist. In chemistry believe that the catalysts are of two types: one is metallic catalysts and another is enzymatic catalysts. The development of a new third type of catalyst in 2000, by Nobel Prize winner Professor Benjamin List and Professor David W.C. MacMillan. It is called Asymmetric Organocatalysis.
The organic catalysts are the structural framework of a carbon atom. Same time use in organocatalysis different types hetero atom-like nitrogen, oxygen, Sulphur, and phosphorus. That’s why asymmetric organocatalysis is an environmentally friendly or eco-friendly and cheaper product.
The organic catalysts are rapidly expansion for their capacity of Asymmetric Catalysts. In case use of metal catalysts or enzyme catalysts, where the molecules form two different types of molecule product – two molecules are enantiomers to each other – just like our hand, which are mirror images to each other. The chemists are wanting only one product for the pharmaceutical process.
Now choose the organocatalysis, in case products are specified by Asymmetric catalysts. In case only one product is formed, which is required for the pharmaceutical lab.
Limonene enantiomer-Asymmetric catalysts concept
Now, we have to use an example of enantiomer to limonene. Limonene has two enantiomers: (+)-(R)-limonene and another is (-)-(S)-limonene, which is a mirror image to each other. (R)-limonene and (S)-limonene is just like our two hands, which do not supper impose on each other- two molecules are completely different. In case (R)-limonene color is lemon and (S)-limonene molecule color is Orange, correspond to their function will be different.
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| (S)-Limonene and (R)-Limonene |
Example: drug-A
Let us
- Case-1: (R)-enantiomer of Drug-A work in the human body
- Case-2: (S)-enantiomer of Drug-A does not work in a human boy
In case required only (R)-enantiomer for a drug design in pharmacology. Research the catalyst’s reaction which produced only (R)-enantiomer. Use of the Asymmetric Catalysts formation of only one enantiomer, not any siding product. Follow that process we have to reduce the starting material and reduced the loss of side product.
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| Organic synthesis of Asymmetric molecules-chemarticle.com |
The discovery of a molecular contraction tool is an entirely new state, for the awarded the Nobel prize in organic chemistry 2021. It helps too much easier to the construction of Asymmetric molecules and made a green process in following green chemistry.
The development of the organocatalysis in 2000, by Benjamin List and MacMillan publication, individually.
Benjamin List works enamine catalysis- Fist publication:
Benjamin List and his co-workers work in L-proline as a catalyzed, in this publication concluded the final result is that the L-proline catalyzed act as enamine catalysis or act as a Lewis base-catalyzed (He consider the intermolecular Aldol reaction).
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| Benjamin List works |
We know what is aldol reaction is. The reaction between ketone (or aldehyde) and aldehyde (or ketone), the addition of α-carbon and carbonyl carbon of another molecule. In this reaction form β-hydroxy aldehyde or ketone.
Enamine catalysis:
Using the amino acid L-proline catalysis produced an intermolecular aldol reaction between acetone and aromatic aldehyde. Due to aldol reaction formation of carbon-carbon single bond between aromatic aldehyde (electrophile) and acetone. Using L-proline reaction proceeds through an enamine intermediate, which causes increased nucleophilicity compared to enol ether (due to increases the Highest Occupied Molecular Orbital (HOMO) energy level).
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| Enamine catalysis- Benjamin List |
In the case of enamine catalysis, carboxylic acid function helps to stabilization of the metal-free Zimmerman-Traxler T.S (Transition state) by a hydrogen bonding. The enamine catalyst attaches covalently to the substance, that is control the stereochemistry of the aldol reaction. In case carboxylic acid proton provides the charge stabilization to the formation of alkoxide anion (in this intermolecular acid catalyst).
David MacMillan work in iminium ion
A few years later, MacMillan produced an Aldol Reaction between α, β-unsaturated aldehydes, and cyclopentadiene, in case of use imidazolidinone catalyzed. Which is called iminium ion catalysis. Iminium ions act as a Lewis Acid Catalysis.
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| MacMillan Organocatalyst- iminium ion- Asymmetric Catalysis. |
Iminium ion catalysis:
In the year 2000, David MacMillan use the chiral imidazolidinone as a catalyst in Diels-Alder reaction with α, β-unsaturated aldehyde (dienophile), and cyclopentadiene (diene). The organocatalysis imidazolidinone is easier to preparade from L-phenylalanine (which is a natural product of amino acid) within three steps. Then finally reacted with unstable α, β-unsaturated aldehyde to the formation of iminium ion. In case the iminium ion catalyst- the Lowest Unoccupied Molecular Orbital (LUMO) energy state is lowered compared to correspond unstable α, β-unsaturated aldehyde. In iminium ion LUMO energy level lowering increases the reactivity towards the cyclopentadiene (diene).
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| Iminium ion catalysis |
What is the Significance of Asymmetric Organocatalysis?
Step up to advances organic synthesis, clearly proceed with the reaction with a new tool principle for controlling the reactivity and the reaction pathways. To opportunities a new chemical reaction pathway; like expand the chemical designing new reaction pathway. The area of organocatalysis improves the reducing environmental impact and more efficient reaction pathways for the organic molecule.
Benjamin List and David MacMillan clarify the concepts of LUMO lowering and HOMO increasing (raising). Today, the organic Asymmetric Catalysts recognized the third type of organocatalysis in-between transition metal catalysis and biocatalysts.
