sharpless asymmetric epoxidation.pptx

7/27/2019 Sharpless Asymmetric Epoxidation.pptx

1/19

Sharpless Asymmetric EpoxidationNobel prize in 2001


2/19

ContentsBiography

Introduction

The need of epoxides

Background knowledgeReagents

Reaction

New synthetic approach

Modification

References


3/19

Dr. Barry Sharpless

Born in Philadephia,1941,U.S.A.

Ph.D. from Stanford University 1968.

Research on chiral synthesis

and catalysts at the Scripps Institute.

Received half Nobel Prize in 2001 for

his work on stereoselective oxidation

reactions.

Biography


4/19

Dr. Barry Sharpless

receiving Noble prize


5/19

IntroductionThe epoxide functional group consists of a three-member ring with two

carbon atoms and one oxygen atom.

These compounds are found in many naturally occurring organic

molecules, as well as in industrial starting materials.

One of the most widely used epoxidizing reagents is meta-chloroperoxybenzoic acid, or m-CPBA, because of its mild conditions and

high yield.

Assymetric epoxidesSharpless Epoxidation method.


6/19

The need of epoxides


7/19

StereoselectivityStereoselectivity is the property of a chemical reaction in which a

single reactant forms an unequal mixture of stereoisomers.

Depends on stereochemistry of transition states.

If the transition states are enantiotopic, they have the same energy.

The addition proceeds through each of them to the same extent and we

thus obtain a 50:50 ratio of enantiomers, no enantioselectivity.

If the transition states are diastereotopic, they may have different

energies. The addition preferentially takes place via the lower energy

transition state and preferentially results in more of one stereoisomer,

Background knowledge


8/19

Background knowledge

A reaction that converts an achiral starting material into

predominantly one enantiomer is called an asymmetric

reaction.

If the formation of only one enantiomer is favored, the

reaction is said to be enantioselective.

There are many methods to synthesis epoxide but the

most effective stereoselective method is Sharpless method

of epoxidation.


9/19

OHR2

R1

R3

R4

OR2

R1R4

OH

R3

Converts primary and secondary allylic alcohols into 2,3

epoxyalcohols.

The reaction is enantioselective.Enantiomer formed depends on stereochemistry of

catalyst.

Sharpless Asymmetric Epoxidation SAE)

magic


10/19

The magic

Titanium isopropoxide

Diethyl tartarate or diisopropyl tartarate

tert-butyl hydroperoxide

Dichloromethane- solvent

Temperature 253K


11/19

Advantages of the Reagents

Titanium (IV) reagents are cheap and readily available.

Low toxicity compared to other transition metal catalysts.

Less reactive than Li or Mg organometallics.

DET and DIPT are byproducts in wine making

Highly stereoselective (90% ee)


12/19

OH

R2

R1

R3

R4

OH

R2

R1

R3

R4

R2

R1

R4

OH

R3

O

R2

R1

R4

OH

R3

O

The Reaction

Ti(OiPr)4(- -) DET

tBuOOH

CH2Cl2, -20C

Ti(OiPr)4(+ +) DET

tBuOOH

CH2Cl2, -20C


13/19

Reaction with Selectivity:

The catalyst is titanium tetra (isopropoxide) with diethyltartrate.The use of + ortartrate will yield different enantiomers.

Tertbutylperoxide is used as the oxidizing agent.

Dichloromethane solvent and -20C temperature.


14/19

O O

O OH

OOH

Ti

O O

OO

The Catalyst

Diametric form of

catalyst

Ti(OiPr)4 catalyst

Diethyl Tartrate (DET)


15/19

The Successful ReactionEpoxides can be easily converted into diols, aminoalcohols & ethers.

The Sharpless Epoxidation reacts with many primary and

secondary allylic alcohols.

The products of the Sharpless Epoxidation frequentlyhave enantiomeric excessesabove 90%.

The products of the Sharpless Epoxidation are predictable

using the Sharpless Epoxidation model.

The reactants for the Sharpless Epoxidation arecommercially available and relatively cheap.
http://en.wikipedia.org/wiki/Diolhttp://en.wikipedia.org/wiki/Etherhttp://en.wikipedia.org/wiki/Enantiomeric_excesshttp://en.wikipedia.org/wiki/Enantiomeric_excesshttp://en.wikipedia.org/wiki/Enantiomeric_excesshttp://en.wikipedia.org/wiki/Enantiomeric_excesshttp://en.wikipedia.org/wiki/Etherhttp://en.wikipedia.org/wiki/Diol


16/19

Improvements

Stoichiometric amount of catalyst required.Water soluble substrates (Polymer Support)

cannot be isolated after reaction.

Requirement for low temperatures (high cost

for SAE).The substrate may not be soluble in

the solvent (low propoxide ion concentration)

Heterogeneous reaction


17/19

References: http://www.mosaicsciencemagazine.org/pdf/m16_01_85_04.pdf

Kurti, L. and Czako, B. Strategic Application ofNamed Reactions in Organic Synthesis: Elsevier Academic Press, 2005.

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv7p0461

Journal of the Chemical Society " href="J._Chem._Soc.">Journal of

the Chem.ical Society

Tetrahedron Letters, Vo[. 38, No. 3, pp. 383-386. 1997Copyright 1996 Elsevier Science Ltd Printed in Great Britain

David W. Knight *, Ian R. Morgan School of Chemistry, Cardiff

University, Main College, Park Place, Cardiff, CF10 3AT, UK

Tetrahedron Letters ,2008 Elsevier Ltd. Organic Mechanism/Reaction Stereochemistry and Synthesis/ Edited

by Michael Harmata/With a foreword by Paul A. Wender/ Springer

publication
http://www.mosaicsciencemagazine.org/pdf/m16_01_85_04.pdfhttp://www.orgsyn.org/orgsyn/prep.asp?prep=cv7p0461http://www.orgsyn.org/orgsyn/prep.asp?prep=cv7p0461http://www.mosaicsciencemagazine.org/pdf/m16_01_85_04.pdf


18/19

ReferencesTetrahedron Letters, Vol. 38, No. 1, pp. 101-104, 1997Copyright

1996 Elsevier Science LtdPrinted in Great Britain. All rights

reserved0040-4039/97.

Organic Chemistry/Solomons and Fryhle/Fifth edition/Wiely India

Publications.


19/19

vRushali s. rautM.Sc. Sem- i

sharpless asymmetric epoxidation.pptx

Documents