Stereoselective and stereospecific reactions

Semester 2 Sakshi Arora

1. SAMRAT PRITHVIRAJ CHAUHAN GOVERNMENT COLLEGE, AJMER 2020-2021 Department Of Chemistry Stereoselective and Stereospecific Reactions Submitted By: Sakshi Arora M.Sc .(Chemistry) Semester II

2. Index Stereoselective Reaction a . Addition in 4-methylcyclohexenone b. Bromination of Cyclohexene c. Stereoselectivity of Enzymes Stereospecific Reaction a. Bromination of (E)-2-Butene and (Z)-2-Butene b. Epoxidation of (E)-2-Butene and (Z)-2-Butene c. Dehydrohalogenation of 1-Bromo-1,2-diphenylpropane Stereoselectivity vs Stereospecificity Reference

3. Stereoselective Reaction Any reaction in which only one set of stereoisomers is formed exclusively or predominantly is called stereoselective reaction. It yields predominantly one stereoisomer(or one pair of enantiomers) of several possible diastereomers. Such a reaction is said to display stereoselectivity. The reaction selects one or two of possible stereoisomeric products to be formed. T he product stereoisomer is formed due to its reaction pathway being more favorable than the other. The selectivity of the reaction pathway depends on differences in steric effects and electronic effects.

4. It is further subdivided into: Enantioselectivity It is formation of one of the two enantiomers predominantly or exclusively. Diastereoselectivity It is formation of one of the two or more diastereomers predominantly or exclusively. Stereoselective reactions proceed via the most favourable pathway(kinetic control) or via the pathway which gives the most stable stereoisomer as the major product(thermodynamic control).

5. 1 . Addition in 4-methylcyclohexenone The conjugate addition of lithium dimethylcuprate to 4-methylcyclohexenone is highly stereoselective(diastereoselective). The approach of the bulky cuprate reagent occurs predominantly on the less sterically hindered face of the enone i.e. away from 4-methyl group. 4-methylcyclohexenone

6. 2 . Bromination of Cyclohexene When cyclohexene is brominated, the product is one stereoisomeric product trans-1,2- dibromocyclohexane. No cis -isomer is formed. Anti addition of bromine occurs and the two bromine atoms in the product are on opposite faces of the ring.

7. 3 . Stereoselectivity of Enzymes The enzymes when in contact with prochiral molecules, react only with one of the enantiotopic ligands or faces, a property called stereoselectivity. Glycerol undergoes phosphorylation exclusively at the pro -R hydroxymethylene group with adenosine triphosphate(ATP) in presence of an enzyme glycerol kinase. Glycerol (R)-Glycerol-1-phosphate

8. Stereospecific Reaction A reaction in which stereochemically different molecules react differently is called a stereospecific reaction. By “stereochemically different molecules” is meant stereoisomers(enantiomers or diastereomers) and to “react differently” means to show any difference in chemical behaviour. Such a reaction is said to display stereospecificity. A given isomer leads to one product while another stereoisomer leads to the opposite product .

9. A reaction is stereospecific provided the reactant can exist as stereoisomers and each stereoisomeric reactant gives a different stereoisomeric product . In stereospecific reaction, stereoisomer can Yield different stereoisomers as product React at different rates and path Stereospecificity towards enantiomers is called enantiospecificity and stereospecificity towards diastereomers is called diastereospecificity.

10. Addition of bromine to (Z)-2-butene gives a racemic mixture of 2,3-dibromobutane Addition of bromine to (E)-2-butene gives a meso stereoisomer Addition of bromine to alkene is both stereoselective and stereospecific 1. Bromination of (E)-2-Butene and (Z)-2-Butene

11. In cis -2-butene , bromine attaches from the top face to give intermediate bromonium ion. The bromine ion then attacks the bromonium ion at either carbon from bottom(S N 2) type of displacement at equal rates to yield the two enantiomers in equal amounts. Racemic mixture (±)-2,3-dibromobutane

12. Trans -2-butene react with bromine from top face to give a chiral bromonium ion and bromide ion attacks at bottom face to give meso product. meso-2,3-dibromobutane Stereospecificity is possible only if the inherent facial relationship of the olefinic bond is maintained through the addition process. The bridged bromonium ion intermediate not only maintains the olefin geometry but also forces the second bromine to add from the opposite direction.

13. 2. Epoxidation of (E)-2-Butene and (Z)-2-Butene

14. 3. Dehydrohalogenation of 1-Bromo-1,2-diphenylpropane It exist as two pairs of enantiomers erythro and threo. Erythro halide gives only the Z alkene Threo halide gives only the E alkene

15. Stereoselectivity vs Stereospecificity The quality of stereoselectivity is concerned solely with the products and their stereochemistry. Out of a number of possible stereoisomeric products, the reaction selects one or two to be formed. The quality of stereospecificity is focused on the reactants and their stereochemistry. Each stereoisomeric reactants behaves in its own specific way. In synthesizing a drug or a hormone a chemist wants to use(stereoselective) reactions that produce just the correct stereoisomer, since only that stereoisomer will show(stereospecific) activity in biological system.

16. All stereospecific reactions are necessarily stereoselective but the converse is not true. If a reaction is carried out on a compound which has no stereoisomers, it cannot be stereospecific but at most it could be stereoselective. Methylacetylene trans-1,2-dibromopropene Add of bromine to methylacetylene results in preferential formation of trans-1,2-dibromopropene. This reaction can only be stereoselective and not stereospecific because the substrate has no stereoisomer.

17. REFERENCE Advanced Organic Chemistry (Sixth Edition) by Jerry March and Michael B.Smith Stereochemistry Conformation and Mechanism (Eighth Edition) by P.S. Kalsi Organic Chemistry(Sixth Edition) by Morrison and Boyd

18. Thank You