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Stereo
Stereo
1. Learning Outcomes
2. Introduction
3. Diastereoselective and enantioselective reactions
4. Summary
2. Introduction
One of the major objectives of a synthetic organic chemist is to synthesize an organic compound
containing multiple chiral centres in a single specific stereoisomer. It is also desirable that the
stereo chemical transformations be carried out in a predictable manner so that the synthesis can
be used to establish the configuration of the molecule.
The stereochemistry at a chiral centre during a reaction is fixed either by conducting the reaction
under kinetic control in which case the stereoselectivity depends on the difference in the free
energies of the respective transition states or by carrying out the reaction under thermodynamic
control in which case the Stereoselectivity depends on the difference in the free energies of the
products.
Stereoselectivity
Stereoselectivity is the property of a reactant mixture where a non-stereospecific mechanism
allows for the formation of multiple product, but where one (or a subset) of the product is
favored by factors, such as steric access, that are independent of the mechanism.
Stereoselectivity is of great importance in the design of synthesis of natural products.
Stereoselective reactions
Stereoselective reactions yield predominantly one stereoisomer (or one pair of enantiomers) of
the several diastereomers. It can also be defined as a reaction in which there is a choice of
pathway, but the stereoisomeric product is formed due to its reaction pathway being more
favorable than the others available. The elimination reaction of 2-iodobutane (1) in the presence
of base (tBuOK) in DMSO gives three products trans-2-butene (2), cis-2-butene (3) and 1-butene
(4). The major product formation is trans-2-butene (2) (Fig. 1.) so we can say this reaction is
stereoselective because cis and trans alkenes are the diastereomers.
Principle of stereoselectivity
For a reaction to be stereoselective, the substrate must have prostereogenic elements, which in
turn depends on the symmetry or more specially on the topicity of the reacting group or faces on
appropriate modification give rise to stereoisomers (enantiomers and diastereomers). The
principle of stereoselectivity whether it refers to diastereoselectivity or enantioselectivity in a
The principle of enantioselective reaction stated above is illustrated with the help of energy
diagrams (Fig. 4). Acetophenone (9) has two enantiotopic faces Re and Si as shown and an
organometallic hydride represented by H-M (L) (M = organic ligand or ligands) can approach the
trigonal carbon from either face through two transition states TS-1 or TS-2. If L is equienergetic,
R- and S- alcohols (10) are formed racemic mixture and enantioselectivity is non-existent (Fig.
5). But if L is chiral, the two transition states are no longer enantiomeric but diastereomeric. The
stereoselectivity is achieved through the formation of the two diastereomeric transition states. It
may be noted that the ground state energies of the products are the same so under
thermodynamically controlled condition, the product would be racemic.
While synthesizing an optically active compound with multiple chiral centres (e.g., a natural
product), one usually synthesizes the compound in racemic form fixing the relative configuration
at all the chiral centres through diastereoselection and then applies the resolution technique.
Diastereoselectivity
In determining whether a stereoselective addition is syn- or anti- you cannot simply look at the
Fischer projection. Remember, it is often necessary to rotate about a carbon-carbon bond to get a
molecule into the conformation that corresponds to the Fischer projection.
What does the stereochemistry tell us about the mechanism of addition of halogens of alkenes
(Fig. 12)?
4. Summary
In summary of this module, we have described the overview of stereoselective synthesis with
ample amount of illustrations to make it readily understood.