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Organic chemistry
Stereospecificity and stereoselectivity
Group members:
Zakia Asgar 18140
Fareeha Iqbal 18141
Nida Adrees 18142
Anum rani 18159
Muniba 18166
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ASSIGNMENT: GROUP NO5

COURSE TITLE: ORGANIC CHEMISTRY

COURSE CODE: CHEM-

DEPARTMENT: CHEMISTRY

SEMESTER : 5TH (EVE)

SUBMITTED TO MAM AYESHA SADDIQA

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STEREOSELECTITY AND STEREOSPECIFICTY

INTRODUCTION:
Stereoselectivity and Stereospecificity:
One of the major objectives of a synthetic organic chemistry 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.

What is a Stereoselective reaction?

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) , so we can say this reaction is stereoselective because cis
and trans alkenes are the diastereomers.

In a stereoselective reaction, one stereoisomer product is formed selectively over other

stereoisomers . Depending on the relative amount of each stereoisomer formed as a product, the
reaction can range from being completely stereospecific to being just moderately stereospecific.
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Another example of a stereoselective reaction is the reduction of hex-3-yne to hex-3-ene . When

using the H2/Lindlar catalyst, the main product formed is the Z-isomer of the alkene . However,
when Na/NH3 is used for the reduction, the main product becomes the E-isomer of the alkene
instead . This is due to the reagents being specific in how they add the hydrogen atoms to the C≡C
bond leading to stereoselectivity.

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
kinetically controlled reaction is the same. The two stereoisomers must be formed through two
diastereomeric transitions. By virtue of their diastereomeric nature, they would differ in their free
energies and thus give products in different amount. The greater is the difference in the free energy,
the higher is the stereoselectivity. A difference of 10 kJ mol-1 at ambient temperature leads to the
formation of the preferred isomer in about 98% yield. The stereoelectronic factor, the steric factor,
and other electronic effects (including the participation of chelate and hydrogen bonds) are all to be
considered in designing a highly stereoselective reaction. The strategy of such a synthesis has to be
decided on an individual basis and no fixed guideline be given. The principle of enantioselective
reaction stated above is illustrated with the help of energy diagrams . 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. 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.
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Stereospecificity:
Stereospecificity is the property of a reaction mechanism, where, starting materials differing only in
their configuration are converted into stereoisomeric products. Thus, a stereospecific process is
necessarily stereoselective but not all stereoselective processes are stereospecific. Stereospecificity
may be total (100%) or partial. The term is also applied to situations where reaction can be
performed with only one stereoisomer.

what is a Stereospecific reaction?

For stereospecific reactions, the different stereoisomers of the reactants will react differently. To put
it in another way, the stereochemistry of the reactant will determine the product of the reaction. One
stereoisomer of the reactant will produce a specific stereoisomer of the product. When another
stereoisomer of the reactant is used, it produces a reactant that is another stereoisomer of the product.
As such, stereospecificity is a description of the mechanism of the reaction.

A classic example of a stereospecific reaction is the SN2 mechanism which refers to a bimolecular
nucleophilic substitution . In the case of a SN2 reaction, there will always be an inversion of
stereochemistry at the chiral centre.
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To illustrate, we will look at how SN2 reaction takes place with halogenoalkanes. In a
halogenoalkane, there would be a C-X bond, whereby X represents the halogen. During nucleophilic
substitution, the nucleophile would attack the carbon in the C-X bond since there is a partial positive
charge on the carbon atom due to the differences in electronegativity between carbon and the
halogen.

During the nucleophilic attack, the nucleophile approaches the carbon atom from the back of the
halogen. This will maximise the overlap of the orbital of the nucleophile with the empty σ* orbital of
the C-X bond which is the most electron-accepting orbital . Because of this attack on the opposite
side of the halogen, there will be an inversion of configuration. This highlights stereospecificity
because if the S enantiomer is used at first, the R enantiomer will be produced and vice versa.
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All stereospecific reactions are also stereoselective. However, not all stereoselective reactions are
stereospecific. In order for a reaction to be stereospecific, there has to be stereoisomerism in the first
place. In the case of the hex-3-yne , it does not have a stereoisomer so the reduction of hex-3-yne
may be stereoselective, but it is not stereospecific
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1. Diastereoselective reactions: Diastereoselectivity Acyclic system Cyclic system

Diastereoselectivity in acyclic system Acyclic molecules are conformationally more mobile than
cyclic. The first rationalizations of asymmetric induction were worked out for reactions in acyclic
system. e.g., Cram’s rule and prelog’s rule.
Diastereoselective transformation of C=C bond
Addition of halogens to alkenes
The fact that the addition of halogens to alkenes is both stereoselective and stereospecific gives us
additional information about the stereochemistry of the addition and the mechanism for the reaction .
When the bromination of cis-2-butene (3) gives (R,R) and (S,S)-2,3-dibromobutane (6) and
bromination of trans-2-butene (2) gives meso-2,3-dibromobutane (5).
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Dehydrohalogenation of an alkyl halide via E2 mechanism:

E2 is stereoselective as well as stereospecific in nature. E2 is anti-elimination. The hydrogen and the

halogen must be on opposite sides of the molecule (antiperiplanar) before the E2 elimination can
take place. This makes sense as both the base and the leaving group is negatively charged. Therefore
they would try to be as far apart as possible. In addition, the leaving group is large and there is more
routes for the removal of the adjacent proton if it is on the opposite side from the leaving group. e.g.-
In the 1-bromo-1,2-diphenylpropane (33) goes through elimination of H & Br in the presence of alc.
KOH via E2 mechanism gives E & Z alkene (34, 35).
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Summary:
 Stereoselectivity has been classified under two categories enantioselectivity and
diastereoselectivity.
 Stereospecific reactions, are reactions in which stereo chemically different molecules react in
different way. In this case the cis- and trans- stereoisomers give different products.
 Stereoselective reaction, are reactions that yield predominantly one stereoisomer (or one pair of
enantiomers) of several diastereomers.
 We have discussed the diastereoselection in acyclic system with C-C and C=C bond and we
have also discussed diastereoselection in cyclic compounds mainly on the basis of axial and
equatorial position of a substituent and has been illustrated by reaction such as nucleophilic
addition to cyclohexanones, and other suitable substrate.
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REFERENCES
 http://epgp.inflibnet.ac.in/epgpdata/uploads/epgp_content/S000005CH/P000656/M014929/
ET/1515565139CHE_P1_M24_etext.pdf
 https://cdn-cms.f-static.net/uploads/4369518/normal_5f88c5888cfb1.pdf
 https://en.wikipedia.org/wiki/Stereospecificity