Chiral synthesis

Chiral synthesis (also called asymmetric synthesis) is organic synthesis which preserves or introduces a desired chirality.

Related Topics:
Organic synthesis - Chirality

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The chirality means that in their preparation, it must be able to produce either. However, the problem is that the substance is exactly the same in both chiralities, because chirality itself does not change any physical or chemical property. This makes it difficult to separate them from a mixture that has both (a racemic mixture). Living beings do produce chiral molecules that can be used for chiral separation, but to separate a racemic mixture is to effectively throw out half of it. Therefore, especially with complicated and expensive substances, it is cost-efficient to get the synthesis itself to give the correct chirality in the first place.

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Chirality must be introduced to the substance first. Then, it must be maintained. Care needs to be taken when planning the synthesis: the chirality might be removed by a chemical change that makes the substance isotropic. This process is called epimerization. For example, a SN1 substitution reaction converts a molecule that is chiral by merit of non-planarity into a planar molecule, which has no handedness. (To visualise, draw the outlines of both of your hands on paper, and cut the images out. You can now superimpose the images, even if the hands itself do not superimpose.) In a SN2 substitution reaction on the other hand the chirality inverts, i.e. when you start with a right-handed mixture, you'll end up with left-handed one. (A visualization could be inverting an umbrella. The mechanism looks just the same.)

Related Topics:
Isotropic - Epimerization - S_N1 substitution - S_N2 substitution - Inverts

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On strategy in chiral synthesis is the use of a chiral ligand. Several examples:

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• One chiral substance that is widely used for introducing chirality is BINAP, a chiral phosphine, used in combination with compounds of ruthenium or rhodium. These complexes catalyse the hydrogenation of functionalised alkenes well on only one face of the molecule. Part of the 2001 Nobel Prize in Chemistry was awarded to Ryoji Noyori for this discovery.
• The other part of that Nobel prize concerned the Sharpless bishydroxylation
• naproxen is synthesized with a chiral phosphine ligand in a Hydrocyanation reaction

A second strategy is chiral pool synthesis.

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A third strategy is to use biocatalysis

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