1. Sharpless Asymmetric Epoxidation & Dihydroxylation
Prasanta Mitra
Int. B.Sc.(H)-M.Sc. In Chemistry 8th Semester

2. CONTENTS Sharpless Asymmetric Epoxidation.
Sharpless Asymmetric Dihydroxylation.
Introduction.
Stereochemistry.
Examples.
Synthetic Utility.
Drawback.
Introduction.
Mechanism Technique
Stereochemistry.
Examples.
Sharpless Asymmetric Epoxidation & Dihydroxylation

3. Sharpless Asymmetric Epoxidation:
The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols.
Oxidizing agent:  Tert-butyl hydroperoxide.
Catalyst:  Titanium tetra(isopropoxide) & diethyl tartrate.
The structure of the catalyst is uncertain. Regardless, all studies have concluded that the catalyst is a dimer of [Ti(tartrate)(OR)2]. The putative catalyst was determined using X-ray structural determinations of model complexes which have the necessary structural components to catalyze the Sharpless epoxidation.
Chirality by: DET
Substrate: Allylic alcohol
DET
Sharpless Asymmetric Epoxidation & Dihydroxylation

4. Mechanism: allylic alcohols 2,3-epoxyalcohol
Sharpless Asymmetric Epoxidation & Dihydroxylation

5. Alcohol Enantioselectivity in the Sharpless asymmetric epoxidation:
Right Side
Left Side
DET
DET
Resultant epoxide product has opposite stereochemistry with almost >90% e.e.
Sharpless Asymmetric Epoxidation & Dihydroxylation

6. ? ? Examples: Right Side View Right Side View
Always view from that side where allylic –OH group is present.
Sharpless Asymmetric Epoxidation & Dihydroxylation

7. ? ? Examples: View Left Side View Left Side
Sharpless Asymmetric Epoxidation & Dihydroxylation

8. Synthetic Utility:
The Sharpless epoxidation is viable with a large range of primary & secondary alkenic alcohols.
The Sharpless epoxidation has been used for the total synthesis of various saccharides, terpenes, leukotrienes, pheromones, and antibiotics.
Sharpless Asymmetric Epoxidation & Dihydroxylation

9. Drawback:
The main drawback of this protocol is the necessity of the presence of an allylic alcohol. The Jacobsen epoxidation, an alternative method to enantioselectively oxidise alkenes, overcomes this issue and tolerates a wider array of functional groups.
Sharpless Asymmetric Epoxidation & Dihydroxylation

10. Sharpless asymmetric dihydroxylation:
Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol. The reaction has been applied to alkenes of virtually every substitution, often high enantioselectivities are realized. Asymmetric dihydroxylation reactions are also highly site selective, providing products derived from reaction of the most electron-rich double bond in the substrate.
Oxidizing agent: Osmium tetroxide
Catalyst: DHQ or DHQD / PHAL
Substrate: Alkene
not quite enantiomers
dihydroquinine (when Ar = H) = DHQ
dihydroquinidine (when Ar = H)
= DHQD
Sharpless Asymmetric Epoxidation & Dihydroxylation

11. Mechanism Technique: Left Left Clockwise Rotation
Small group must be placed at the left side of the double bond.
Clockwise Rotation
Left
Anti-Clockwise Rotation
Sharpless Asymmetric Epoxidation & Dihydroxylation

12. If S, M & L not distinguishable then follow Clockwise Rule.
Enantioselectivity in the Sharpless asymmetric dihydroxylation:
If S, M & L not distinguishable then follow Clockwise Rule.
Sharpless Asymmetric Epoxidation & Dihydroxylation

13. Examples: S Attack from the Top M L
Its not count as small group as it is in right side to the double bond
Clockwise
Sharpless Asymmetric Epoxidation & Dihydroxylation

14. Conclusion:
For asymmetric synthesis, Sharpless epoxidation & dihydroxylation has been widely used in modern days.
Prof. Karl Barry Sharpless recipient of the 2001 Nobel Prize in Chemistry for his great work on “method for the catalytic asymmetric oxidation of allylic alcohols to chiral epoxides”.
Sharpless Asymmetric Epoxidation & Dihydroxylation

15. Department of Chemistry,
Acknowledgements:
Dr. Partha Pratim Ghosh.
Asst. Professor,
Department of Chemistry,
JIS University.
Reference Books:
Organic Chemistry- Clayden (2nd Edition)
Modern Organic Synthesis: An Introduction- George S. Zweifel & Michael H. Nantz.
Sharpless Asymmetric Epoxidation & Dihydroxylation

16. Thank you