Sharpless Asymmetric Epoxidation - McMaster University

[Pages:34]Sharpless Asymmetric

Epoxidation

R2

R3

R1

R4

HO

"Magic"

O R2

R1

HO

R3 R4

Karl Barry Sharpless

? Born in Philadephia in 1941

? Ph.D from Stanford University in 1968

? Postdoc at Harvard and at Stanford

? Research on chiral synthesis and catalysts at the Scripps Institute

? Received Nobel Prize in 2001 for his work on stereoselective oxidation reactions

Sharpless Asymmetric Epoxidation

(SAE)

R3

R1

OH

O R1

R3 OH

R2

R4

R2

R4

- Converts primary and secondary allylic alcohols

into 2,3 epoxyalcohols

-The reaction is enantioselective (only one enantiomer produced)

-Enantiomer formed depends on stereochemistry of catalyst

The Reaction

R2

R1

R2

R3

Ti(OiPr)4 - (+) - DET

OH

tBuOOH

O

R4

CH2Cl2, -20?C

R3

R2

R1

R2

Ti(OiPr)4 - (-) - DET

R3

OH

tBuOOH

O

R4

CH2Cl2, -20?C

R3

? The catalyst is titanium tetra(isopropoxide) with

diethyltartrate.

R1

OH R4 R1

OH R4

? The use of + or ? tartrate will yield different enantiomers

? Tertbutylperoxide is used as the oxidizing agent

? Dichloromethane solvent and -20?C temperature

The Catalyst

H3C

CH3

H3C H3C

O

O Ti O

O

CH3 CH3

CH3 H3C

Ti(OiPr)4 catalyst

OH O

H3C

O

O

CH3

EtO

O iPrO

O CO2Et

O Ti OiPr O

O OiPr OEt

Ti

OiPr O

O

OH

Diethyl Tartrate (DET)

Chirally controls reaction

EtO2C

? Via rapid ligand exchange of OiPr and diethyl tartrate

The Mechanism

EtO

O iPrO

O CO2Et

O Ti OiPr O

EtO2C

O OiPr OEt

Ti

+ OiPr O

O

HO

HO

CH3

+ CH3

CH3

CH2

OH

OEt

O

EtOOC

O Ti

O H2C

tBu O

O

+

EtOOC EtOOC

OiPr

O

OiPr

Ti

O

OiPr

OiPr

Transition State

OEt EtOOC

OH O

O Ti

O

tBu O O

H2C

OH

OEt

O

EtOOC

O Ti

O

tBu O

CH O

CH2

Products

EtOOC EtOOC

OiPr

O

OiPr

Ti

O

OiPr

OiPr

OH

OEt

O

EtOOC

O Ti

O

tBu O

CH O

CH2

EtO

O iPrO

O CO2Et

O Ti OiPr O

O OiPr OEt

Ti

OiPr O

EtO2C

+

tBuOH

+

O H

OH

HH

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