Opening of epoxides with nucleophiles
Lecture 17 – Chapter 16 : Ethers, Epoxides and Sulfides
OH
1. Nu: , solvent
• Epoxides in biochemistry
O
2. H3O
• 2001 Nobel Prize in Chemistry
+
Nu
• Not covering sections 16.16, 16.17, 16.18
Lecture 17 – Chapter 17 : Aldehydes and Ketones
OH
1. NaN3, THF
O
2. H3O+
N3
OH
1. PhMgBr, ether
O
2. H3O+
• Structure and nomenclature
Ph
• Nucleophilic addition – review
• Hydrate formation – catalysis
Opening of epoxides with acid catalysis
Biochemical use of epoxides
OH
HBr
O
Br
O
OH
CH3OH, H2SO4
CH3O
O
OH
CH3OH, BF3.OEt2
CH3O
Asymmetric synthesis of epoxides
The Story So Far:
Br
H
MgBr
Mg, ether
H
CH2I2
Zn/Cu
HBr
O
OH
Na2Cr2O7
H2SO4, H2O
H2SO4, H2O
1. Br2 in H2O
2. NaOH
or
m-CPBA
CH2Cl2
H
O
RMgBr, ether
H
then H3O+
H
OH
R
1. NaH, ether
H
O
R
2. CH3CH2CH2Br
1
Chapter 17 – Aldehydes and Ketones
O
Mg, ether
Cl
MgCl
H
SOCl2
OH
xs CH3OH, cat. H+
O
H
H
propanal
ethanal
(acetaldehyde)
methanal
(formaldehyde)
O
O
Na2Cr2O7
OH
O
H
OCH3
H2SO4, H2O
NaBH4
CH3OH
PCC or PDC
CH2Cl2
2 RMgBr, ether
O
OH
RMgBr, ether
H
R
O
H
H
R
Chapter 17 – Aldehydes and Ketones
O
O
O
H
OH
R
then H3O+
O
then H3O +
cyclopentanecarbaldehyde
benzaldehyde
E-3-phenylpropenal
(cinnamaldehyde)
Steroids:
O
OH
O
H
2-pentanone
butanone
acetone
(propanone)
H
H
H
H
O
testosterone
O
O
O
progesterone
OH
O
H
H
methylphenylketone
(acetophenone)
cyclopentylmethylketone
diphenylketone
(benzophenone)
Nucleophilic Addition
H
H
H
O
O
Nucleophiles:
H
O
testosterone
dianabol
Hydrate Formation (remember H2CrO4 oxidation) – Table 17.3
H2O
O
O
H
O
R
R'
HO OH
R
R'
H2O – hydrates
H- from NaBH4 or LiAlH4
Nu
R- from RMgX, Rli
NC-, ROH, RNH2, R2NH
O
Nu
2