User:Rifleman 82/Asymmetric synthesis

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

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.

Contents 1 Strategies 1.1 Chiral pool synthesis 2 Asymmetric induction 3 Chiral auxiliaries 4 See also

[edit] Strategies

There are several strategies which can be used to prepare enantiopure compounds. These strategies are not mutually exclusive — a combination of some or all of them may be appropriate at different points, depending on whichever is the most convenient.

[edit] Chiral pool synthesis

Main article: Chiral pool synthesis

The obvious approach to preparing a chiral compound is to introduce chirality through an appropriate enantiopure starting material, such as a natural amino acid or a monosaccharide. Then, the chirality 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 S_N1 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 themselves do not superimpose.) In a S_N2 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.)

Theh problem with chiral pool synthesis is that the number of possible syntheses are limited, and a stoichiometric amount of the starting material, which may be poorly available and expensive. The more efficient approach is chiral catalysis, as only catalytic amounts are needed.

[edit] Asymmetric induction

Main article: Asymmetric induction

This is another convenient technique. It is very useful because it allows the preparation of chiral compounds without the need for any chiral reagents or catalysts. It makes use of certain steric or electronic features properties of a molecule to direct substitution or addition on the desired face of a prochiral starting material. Examples of this technique are the addition of nucleophiles to achiral carbonyls, or the epoxidation of achiral olefins.

[edit] Chiral auxiliaries

Main article: Chiral auxiliaries

Chrial auxiliaries are a way One such strategy is the use of a chiral ligand. The ligand complexes to the starting materials and physically blocks the other trajectory for attack, leaving only the desired trajectory open. If the ligand is enantiopure, the different trajectories are not equivalent, but diastereomeric. Several examples:

• 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, which is commercialized as the industrial synthesis of menthol using a chiral BINAP-rhodium complex.
• The other part of that Nobel prize concerned the Sharpless bishydroxylation
• Naproxen is synthesized with a chiral phosphine ligand in a Hydrocyanation reaction

Other strategies in chiral synthesis are the use of chiral auxiliaries, chiral pool synthesis or biocatalysis.

[edit] See also

Aza-Baylis-Hillman reaction, for the use of a chiral ionic liquid in asymmetric synthesis.