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Asymmetric Catalysis

Catalysis was introduced as a term in the year 1836 by Berzelius to explain various forms of transformation and decomposition reactions. It was assumed that the process of catalysis is a special kind of reagent which influenced the chemical substance affinity. This catalysis is considered to be the key figure in chemical transformations and many of the industrial synthesis processes and nearly all biological reactions require catalysts. This is also considered to be an important technology in environment protections which helps in preventing emissions or reduce the level of it.

Catalyst system can be best described as bio-mimetic assemmblies of multifunctional or biometallic catalysts. The design usually is based on quantitive analysis of transition state for a given reaction. The combinatorial screening of metal centers and chiral ligands can also help in getting a new catalyst system. The key to efficient assymetric catalysis depends on creation of robust chiral catalysts by combining suitable combination of chiral organic compounds and the metal centers to which these chiral catalysts are ligated.

In asymmetric catalysis the importance of ligand accelerated catalysis through asymmetric catalyst construction from an achiral pre-catalyst. These usually take place by ligand exchange with a chiral ligand. A dynamic combinatorial approach may result into the most active and highest enantio-selective activated catalyst by combining with several multi component chiral ligands are assembled into.


Fundamentals of Asymmetric Catalysis

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Asymmetric catalysis generally refers to asymmetric synthesis by the help of sub-stoichiometric chiral catalysts. Ideally there are several distinct modes of operation for asymmetric catalysts. Most commonly asymmetric reactions begins with a pro-chiral substrate in the presence of chiral catalyst, which are subjected to two diastereomeric reaction pathways with quite different activation energies.

The competing achiral pathways presence or equilibrating intermediates can complicate the interpretation and optimization of such processes. The asymmetric synthesis has turned out to be the major preparative method now used all across organic chemistry and for all kinds of synthesis of natural products.

The synthesis is performed on an achiral substrate where the first case is termed as diastereoselective asymmetric synthesis while the second one is termed as enantioselective asymmetric synthesis to clarify the product mixture of diastereomers and a mixture of enantiomers.

Diastereoselective Asymmetric Synthesis:

(Bonding of chiral auxiliary)
Achiral precursor (ketone) A – Z*-- > (diastereoselective reaction) Z* - A* – B – Removal of the chiral auxiliary $\rightarrow$ A* - B + Z*

Enantioselective asymmetric synthesis: 

A + B – Z* $\rightarrow$ (enantioselective reaction) $\rightarrow$ A* - B + Z*
A + B $\rightarrow$ (enantioselective reaction) $\rightarrow$ A* - B
A is the achiral precursor
B is the reagent
Z* is the chiral auxiliary
A* - B is the chiral product (e.g. alcohol)
Z* - A* - B is the chiral diastereomer

Asymetric hydrogenetion:

The starting compound Monsanto goes through a  Rh(R,R)- DiPAMP) $BF_{4}$ with 10 bar $H_{2}$ and 25 C EtOH

Asymetric Hydrogenetion
The first of the product that we get to see is L DOPA precursor along with (R, R)-DiPAMP

Asymmetric epoxidation:

Asymmetric Epoxidation
The epoxidation is carried out in presence of Ti(OR)4 (S,S)-DIPT, which gives (S) glycidol or chiral building block and (S,S) - DIPT

Asymmetric Catalysis in Organic Synthesis

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In synthetic organic chemistry the production of such chiral compounds is very important as well as and challenging. The wide use of synthetic chiral molecules as single enantiomers pharma products, as both electronic and optical devices and also as biological function probes has eventually turned the asymmetric catalysis process as a prominent research area. The catalytic asymmetric transformations can be accomplished by either chemical or biological catalysed reactions.

The catalytic asymmetric field is overwhelmed by metal catalysis especially in Lewis acid base metal catalysis and recently in the field of organocatalysis for enantiomer selective transformations. The lipase which are considered to be versatile class of bio-catalysts in organic synthesis as they are compatible with various organic substrate and organic solvents. Lipase can be used as catalysts in either hydrolysis reactions or ester synthesis and result in high enantio-selective.

Lipase major application in catalytic asymmetric synthesis utilises the kinetic resolution of racemic mixtures. The kinetic resolution is a process in which the two enantiomers of a racemate are transformed into products with different rates which gives a total or partial separation of the enantiomers. 

Asymmetric Catalysis on Industrial Scale

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Catalysts are sort of workhorses of chemical transformations in the industry and around 85 % to 90 % of the products of chemical industry are made by catalytic process. The need of catalysts is indispensable in many industries.
  • Production of finer and bulk chemicals in chemical industries
  • Prevention of pollution by avoiding formation of waste or unwanted by products
  • Increased level of automotive and industrial exhaust or general pollution in end of pipe solutions
  • Production of transportation fuels in refineries
The catalyst role is to offer an alternative favourable in mechanism part and less energy consuming to non-catalytic reactions which enables these processes to be carried out in large scale which are commercially feasible and under specific conditions of pressure and temperature. The production of fine chemicals and pharmaceuticals is basically a heterogeneous asymmetric catalysis method which also includes the utilisation of converted or rather the immobilized homogeneous asymmetric catalysts and even heterogeneous metal catalysts which are chirally modified, for enantioselective reaction.

The catalyst immobilisation is the transformation of homogeneous catalyst into a heterogeneous catalyst which helps in using it several times after the reaction gets over after suitable methods are applied to separate them. Modification of catalyst structure for industrial use and in some cases the modification is carried out on reaction medium. The immobilisation techniques are mainly of two categories like heterogenised enantioselective catalysts and multiphase or even mono-phase catalysts in non-conventional media.

The emerging field of heterogeneous asymmetric catalysis still faces a lot of challenges as not every process is a generalised one and not one process can cover up the pathway for the other. However, the solids among other things typically maintain their structure integrity by metal ligand coordination bonds, which encompasses a broad spectrum of strengths.

Hence, beyond the activity and selectivity phase the stability and compatibility of metal organic catalysts with reaction systems is difficult to predict as very less numbers of homo-chiral metal organic catalysts use has been observed and now the industrial application part is also looking into the strengths and limitations of homo-chiral assembly in synthetic applications.

In industrial application the immobilisation is carried out by the following methods.

Catalyst heterogenisation
  • Inorganic supports
  • Organic polymeric supports
  • Dendrimer supports
  • Organic – inorganic supports
Non-conventional media:
  • Water
  • Ionic liquids
  • Super critical liquids
  • Perfluorinated solvents
The chiral catalysts could be categorised into the following
  • The insoluble chiral catalysts having supports which are stationary in nature, such as inorganic materials or organic cross linked polymers or homo chiral organic – inorganic coordination polymeric catalysts which are devoid of external support.
  • The chiral catalysts which are soluble in character and having linear polymer supports or basically the dendritic ligands.
  • Chiral catalysts with some form of non-conventional reaction medium as mobile carrier like in case of aqueous phase, fluorous phase, ionic liquid or super critical carbon di oxide.
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