Key words: oxidations using chromium and manganese reagents, cleavage of double

bonds with ozone and osmium tetroxide, oxidations with aluminum isopropoxide,
peracids,
Introduction Broader definition of oxidation and reduction respectively refer to the
loss and gain of electrons, or an increase in oxidation number (oxidation)
Definition and a decrease in oxidation number (reduction).
In organic chemistry, the gain of oxygen or loss of hydrogen is often
referred to as oxidation.
In practice, a series of functional groups have been qualitatively
identified in the order of increasing oxidation state. Then, oxidation is
referred to as the conversion of one functional group higher in the
sequence to another lower in the list.
Conversion within a group are neither oxidation nor reduction.
It is summarized in following table.

This module has been organized based on the reagent that are used
for oxidation reactions
 oxidation
Table summarizing
O
functional groups
RH CO2
arranged according
OH
to oxidation state.
ROH O O
RCl
RNH2 CCl4
etc.
R R R NH2

Cl

C Cl C Cl

Cl Cl

C C etc.

Cl Cl

C C

OH OH

etc.
reduction
I. Oxidation of For oxidation of alcohols to corresponding carbonyl compounds, generally
alcohols using Cr(VI) reagents such as K2Cr2O7, Jones reagent, PCC etc., are employed.
Cr(VI) reagents Oxidation of alcohols to carbonyl compound occurs via Cr(VI) acid
monoester.
Mechanism is as follows.

OH O
CrO 3

R1 R2 R1 R2

O
HO
H
O O Cr O
O
O Cr O
+ + H 2CrO 3
R1 C H
O R1 C H R1 R2

R2
R2
 Example for chromium oxide based oxidation
Oxidation of fused aromatic
system is generally carried
4mmol CrO3
out using CrO3 reagent 60 min, rt

Juaristi M. et al, Can.J.Chem., O

1984, 62, 2941
O
80%
 PCC (pyridinium chlorochromate) is other efficient reagent used widely
for oxidation of primary and secondary alcohols.
E J Corey and W Suggs in 1975 suggested PCC as oxidizing agent. PCC is
Reagent can be used in slightly acidic but can be buffered with NaOAc
close to stoichiometric
amounts with substrate O
HN
Cl Cr O

O O

OH H
HO H

O
1,6-Hexanediol Hexanedial (68%)
Corey E J & Suggs W,
OH
Tet.Lett., 1975, 16, 2647 O

Benzhydrol Benzophenone (100%)

OH O

4-tertbutylcyclohexanol 4-tertbutylcyclohexanone (97%)

 H
Corey and Suggs used
OH
following method for O
preparation of PCC. R
R

100g (1mol) CrO3 is

added to conc. HCl, R
R
rapidly with stirring over
5 min time. Homogenous Presqalene alcohol Presqalene aldehyde (78%)

solution obtained is
R : (CH3)3CCH(CH3)CH2CH2C(CH3)=CHCH2CH2-
cooled to 00C. To this,
1mol of pyridine is
added. Yellow-orange OH O

solid obtained is filtered

H
and dried in vacuum.
This solid is PCC and is
not hygroscopic. It can
be stored at room Citronellol Citronellal (82%)
temperature.
 PCC is used particularly for the oxidation of primary alcohol to aldehyde.
It does not have any effect on C=C or any other easily oxidizable
functional groups.
In this reaction, double PCC, DCM
O
bond is not affected.
OH H

Geraniol Geranial

PCC is used in aprotic solvents, usually, dichloromethane.

As no water is present in the reaction mixture, no aldehyde hydrate is
formed which is oxidized to carboxylic acid in presence of Cr(VI)

Agarwal S; Tiwari H PCC, dry CHCl 3,

anhy. AcOH, rt, 1h O

P; Sharma J P, OH
H
Tetrahedron, 1990, 46,
1-Hexanol 1-Hexanal (89%)
4417
 Another similar oxidant is PDC (pyridiniumdichromate)

H
O 1.5eq PDC
OH DCM, 25 0 C O
O
90%

O O

NH O Cr O Cr O HN

O O

pyridiniumdichromate

Since PDC is less acidic than PCC it is often used to oxidize alcohols
that may be sensitive to acids.
In methylene chloride solution, PDC oxidizes primary and secondary
alcohols in roughly the same fashion as PCC, but much more slowly.
However, in DMF solution saturated primary alcohols are oxidized to
carboxylic acids.

In both solvents allylic alcohols are oxidized efficiently to conjugated

enals and enones respectively.
Stanfield C F, et al, J. examples
Org. Chem., 1981, 46,
4797
3.5eq PDC 1.5eq PDC
COOH DMF, 25 0 C DCM, 250 C CHO
OH

83% 92%

1.5eq PDC,
OH DCM, 250C, 24h
O O CHO

90%
Corey E J & Schmidt
G, Tet.Lett., 1979, O OH
COOH
O
20(5), 399 3.5eq PDC,
DMF, 25 0C, 7-9h

H H

85%
Collins reagent can be Collins reagent is the mixture of chromium
prepared and isolated or trioxide with pyridine in dichloromethane.
generated in situ.
It is used to selectively oxidize primary alcohols to aldehyde, and will
Isolation of reagent often tolerate many other functional groups in the molecule.
leads to improved yields.
CrO 3-2Py R H
R DCM
OH
O

It can be used as an alternative to Jones reagent and PCC in oxidation of

secondary alcohols. Moreover, Collins reagent is especially useful for
oxidations of acid sensitive compounds.
This complex is both difficult and dangerous to prepare, as it is
very hygroscopic and can inflame during its preparation.
It is required to be used in a sixfold excess in order to complete the
reaction.
 examples
one of the steps in the O
O
synthesis of O
O
prostaglandin F2 CrO 3-2Py
DCM, 0 0C
employs Collins reagent
as oxidant
H
OH
Corey E J, JACS, 1969, AcO
AcO
O
91, 5675
one of the steps in
synthesis of longifolene OH
O
employs Collins reagent H CrO 3-2Py, DCM,
H
rt, 15min
as oxidant

McMurry J E, JACS,
OH
1972, 94, 7132 H O

100%
one of the steps in
synthesis of triquinacene
employs Collins reagent
as oxidant CrO 3-2Py, DCM

Woodward RB, JACS, H

OH O
1964, 86, 3162
74%
Jones described for the Jones reagent is used for the oxidation of primary and
first time a convenient secondary alcohols to carboxylic acids and ketones, respectively, that do
and safe procedure for a not contain acid sensitive group.
chromium (VI) based
oxidants, that paved way
for some further
developments such as
Collins Reaction
and pyridinium
dichromate.
It is chromium oxide, sulfuric acid and acetone. A mixture of potassium
or sodium dichromate and dilute sulfuric acid can also be used.

CrO 3, aq.H 2SO 4 O

acetone
R OH
R OH

OH CrO3, aq.H2SO4 O
acetone

R R' R R'
 H2SO4 O
Mechanism : O
H2O
HO Cr OH
Chromium trioxide or Cr
O O
sodium dichromate with O
dilute H2SO4 in situ Chromic acid
forms chromic acid . O O H2SO4
H2O
Chromic acid and HO Cr O Cr OH Na2Cr2O7
alcohol then through O O
chromate ester gives
Dichromic acid
carbonyl compound in ..
presence of base (water H2O
O OH O H
in this case). VI VI R'
HO Cr OH + HO Cr O
The intramolecular R R'
O H O R
reaction occurs by way ..
of -elimination through

..
..
O O
cyclic transition state. + ..Cr IV H3O

R R' HO O
O
VI
Aldehydes can form O
OH HO Cr OH
H2O
hydrates in presence of O
R OH
water and further R H H
oxidized to carboxylic
acid in presence of O H .. ..

..
O O

..
OH H2O
Cr(VI) reagents. HO
VI
Cr O + IV Cr ..
-H3O R OH HO O
O R
The Jones reagent is The oxidation of primary allylic and benzylic alcohols gives aldehydes.
prepared by adding Some alcohols such as benzylic and allylic alcohols give aldehydes that
chromium trioxide to do not form hydrates in significant amounts; these can therefore be
dilute sulfuric acid in selectively oxidized with unmodified Jones Reagent to yield aldehydes.
acetone and is added to
the alcohol at 0-25oC.
K 2Cr2O 7, H2SO4 CHO
OH H 2O, acetone, 0-25 0C

The excess Cr(VI), if any

is remained, is destroyed
in the reaction workup CrO 3, H 2SO 4, H2O,
O
acetone, 0-25 0C
by adding isopropyl
alcohol. OH H

For the synthesis of aldehydes, the Collins Reaction or use of more

modern although more expensive chromium (VI) reagents such
as PCC and PDC can be an appropriate choice.
Tertiary alcohols cannot be oxidized by this reagent.
It is a powerful oxidizing reagent and exhibits only poor
chemoselectivity.
 OH CrO 3, aq.H 2SO 4 O
oxidation of secondary H2O, acetone, 0-25 0C

alcohol gives ketone

whereas primary alcohol
is oxidized to aldehyde
OH CHO COOH
first and then to CrO 3, aq.H 2SO 4
H 2O, acetone, 0-25 0C (O)
carboxylic acid.

H H
Jones reagent, acetone,
Panda J; Ghosh S & 0 0C - rt, 1h
O O
Ghosh S, ARKIVOC,
2001(viii), 146 H H H
OH O
 MnO2 is used widely as oxidant in organic synthesis.

II. Oxidation using It oxidizes allylic alcohols to corresponding aldehydes or ketones.

Mn reagents O
MnO2
R OH
(a) Mn(IV) reagent R H

The configuration of double bond is preserved in the reaction.

Also, acetylenic alcohols and benzylic alcohols are oxidized under similar
conditions.
Applications of MnO2 are numerous. These include many kinds of
reactions such as amine oxidation, aromatization, oxidative coupling,
and thiol oxidation.
Activity of MnO2
depends upon method of S
MnO 2, DCE
S

preparation and choice R2 R2

R1 N R1 N
of solvent

1,2-Diols are cleaved by MnO2 to dialdehydes or diketones.

OH
MnO2, DCM, O
rt, 24h
Ph
Ph
2
Ph H
OH
 examples
MnO2, rt, 5d
CH 2OH
Pet. ether

vit.A

Taylor R J K; et al,
Acc. Chem. Res., 2005, CHO
38, 851.

retinal (80%)

oxidation of benzylic and 10eq. MnO 2,

DCM, rt, 24h
allylic alcohol with OH
CHO
MnO2 in mild condition
84%

Aoyama T; et al, O
OH
10eq. MnO2,
DCM, rt, 24h O CHO

Synlett, 1998, 35.

O O
95%

dehydration is also
10eq. MnO 2,
accomplished in good DCM, rt, 24h
+
yields N N
NH

1,2,3,4-tetrahydroisoquinoline 3,4-dihydro- isoquinoline (8%)

-isoquinoline (83%)
 More examples

Oxidation of allylic OH
COOMe
alcohol to
corresponding ester in MnO2, hexane
methanolic solvent. MeOH, NaCN

E J Corey; N W
Gilman; B E Ganem,
JACS, 1968, 90, 5616

N N O
MnO2,
1,4-dioxane

Husinec S; et al, COOMe COOMe

Tet.Lett., 2011, 52, COOMe COOMe
2733 45%
(b) Mn (VII) reagents Manganese can function as oxidant when it is in +7 oxidation state.
KMnO4 is one such oxidant. It is a very strong oxidizing agent.
Alkyl side chains on aromatic rings are oxidized to carboxylic acid group.
This method is more generally applied to methyl group, however, longer
side chains can also be cleaved.
Tertiary alkyl groups are not oxidized and are usually accompanied by
ring cleavage.
KMnO4 is also used to oxidize primary alcohol and aldehyde to
corresponding carboxylic acid.
 Protected hydroxy aldehydes are oxidized to corresponding carboxylic
acids with KMnO4 buffered with mixture of tBuOH and aq. NaH2PO4
Abiko A; Roberts J C;
Takemasa T & KMnO 4, 5min
CHO COOH
tBuOH -5%NaH2PO4
Masamune S, Tet.Lett.,
O O O OSiMe2tBu O O O OSiMe2tBu
1986, 27, 4537
Ph Ph
97%

Jefford C W; Li Y;
Wang Y, Org. Syn., KMnO4, CuSO 4
DCM, 6-8h, 25 0C
1998, 9, 462
HO O

HO

In this reaction KMnO4 first oxidizes primary alcohol to corresponding

carboxylic acid which subsequently cyclizes to give a lactone.
 More examples
O
KMnO4, MnO2
solv. f ree, 6h

oxidation using KMnO4

supported on MnO2
under heterogenous and 85%
solvent free conditions
O
S
KMnO 4, MnO2 S O
Shaabani A; et al, Tet., DCM, 29h
2004, 6, 11415.

72%

OH KMnO4, MnO2, )))) O

solv. f ree, 2h 30min

H H

64%
This reaction is also used Dilute solutions of KMnO4 convert alkenes into diols.
as a qualitative test for
KMnO4
the presence of double or
triple bonds in a
HO OH
molecule, since the
reaction decolourises the Dihydroxylation of alkenes using alkaline KMnO4 is a stereoselective syn
permanganate solution. It addition of two hydroxyl groups across a double bond.
is sometimes referred to
The reaction is believed to proceed through a cyclic permanganate ester
as Baeyer's reagent.
intermediate.

O OK O OH
OK
hydrolysis
Mn Mn

O O O O
OH

Though the presence of such an intermediate can not be confirmed by

actual isolation. But, some of them are detectable spectroscopically also
use of Mn18O4- in the reaction lead to formation of 1,2-diols in which
both the oxygen atoms were labeled. So, it can be concluded that both of
them are coming from Mn18O4- , and hence the presence of an
intermediate cyclic permanganate ester can be confirmed.
 Under acidic conditions, the alkene double bond is cleaved to give a
carboxylic acid.

D J Sam; H E
Simmons, JACS, 1972, KMnO 4, H +
17
17
94, 4024 COOH

KMnO4, DC-18[C]-6

Synthesis, 1984, 43,

COOH
443
 NaMnO4, sodium permanganate is similar oxidant to KMnO4. It oxidizes
primary alcohol to acid and secondary alcohol to ketones but does not
have any effect on multiple bonds.
OH O

Menger F M and Lee NaMnO4 .H2O,

DCM,410C, 24h
C, Tet.Lett., 1981, 22,
1655.
HO HO
H H

5-Androstan-17-ol 5-Androstan-17-one (84%)

III. Oxidation using OsO4 is primarily used in cis dihydroxylation of olefins.
Os reagent
OH
Os(VIII) reagent OsO4
hydrolysis

OH

O O
OH
1. OsO4, THF, 250C, 48h
2. H2S

p-electrons of olefins act Mechanism of reaction goes through the formation90%

of 5-membered
OH cyclic
as a nucleophile and ester intermediate.
forms favorable 5-
membered ring as cyclic
osmate ester by attacking
OsO4. This is considered O O O OH HO O
O
as the origin of cis hydrolysis
Os Os + Os
stereoselectivity.
This osmate ester upon O O O O HO O
OH
hydrolysis liberates cis
diol and reduced osmium
species.
OsO4 is toxic and is used in catalytic amounts in reaction. It can be
reoxidized using co-oxidant such as NMO, K3Fe(CN)6, etc.

NMO = N-methyl morpholine

O OH
O OsO4, NMO
O
O OH
OH

OH

OCOCH3 OCOCH3

OH
OsO4-NMO
tBuOH/ THF/ H2O
HO (10:3:1) HO OH

O O

78%
The use of NMO in catalytic OsO4 reactions was first reported for the
introduction of corticoid side chain (an -ketol) in a steroid (as shown
above).
 OsO4 is also used for oxidative cleavage of olefin. It forms carbonyl
compound.
H

O
O
O O

O O
OsO4, NMO
O
Oxidative cleavage of O
O
olefins using OsO4 -
NaIO4 in presence of 2,6- O O
lutidine OCO2CH 2Ph
O O

OCO 2CH2Ph
Yu W; Mei Y; Kang
Y; Hua Z and Jin Z,
Org.Lett., 2004, 6, 3217.
0.02eq OsO4, 4eq NaIO4,
2eq 2,6-lutidine, 3h,
O dioxane-water (3:1) O

O O
CHO

OTBS OTBS
81%
 Oxidation of primary and secondary alcohol with ketone in the presence of
metal alkoxide to corresponding aldehyde or ketone is known as Oppenauer
IV. Oppenauer oxidation.
oxidation
OH O O OH
Al(iPrO) 3
+ +

R1 R2 R1 R2

The reaction is completely reversible and can be driven to completion

according to Le Chatliers principle by addition of excess of ketone.

In the first step of the

iPrO OiPr
mechanism, alcohol, Al
OH O
aluminium and acetone -iPrOH O O
+ Al(iPrO)3 +
coordinates to form a
complex. This complex R1 R2
R1 H
then, via a six-membered R2

chair like transition state

transfers hydride from - iPrO OiPr i PrO OiPr

carbon of the alcohol to the Al Al O

O O alcoholysis
O
carbonyl carbon of acetone O
to give the desired ketone R1 R2
R1 H H
as product. R2 R1 R2

six membered T.S.

 In 1937, Oppenauer Oppenauer oxidation has many advantages.
discovered this reaction.
mild reaction conditions.
most functional groups are tolerated (If substrate contains basic
Reaction is reverse of nitrogen then use of alkali metal alkoxide is necessary instead of Al-
Meerwein-Ponndorf- isopropoxide).
Verley reduction.
in order to achieve reasonable reaction rate, stiotiometric amount of
Al-alkoxide to be used (Al-isopropoxide, Al-tertbutoxide, Al-phenoxide
can be used).
wide range of substrates are oxidized.
secondary alcohols are oxidized faster than primary alcohols. Due to
this secondary alcohols can be oxidized chemoselectively over primary
ones.
over oxidation to carboxylic acid does not happen.
oxidation of 1,4 and 1,5-diols yields lactones.
acetone is most often used as an oxidant but aromatic and aliphatic
aldehyde are suitable as oxidants due to low reduction potential.
 addition of protic acid dramatically increases the rate of
oxidation.
oxidation can be conducted using heterogenous catalysis. It has
advantage over homogenous catalysis as product can be separated
easily from a reaction mixture.
O O
Synthetic applications 1. Al(OiPr)3, toluene TsOH, Et2O
OH ref lux, 5h OH 18h, rt

N O

Syntheses of Estrone
HO 2. 1% HCl, 0 0C O
from tetracyclic diol 78%
O

HO
Estrone
Syntheses of linearly 1. 1.7eq Al(OiPr)3
fused triquinane dry tol, reflux, (4+2)
acetone, 9h
()-hirsutene. 2. 10% HCl, 250C

OH O
47%

H H H

COMe

( )-Hirsutene

O O
syntheses of hormone
Al(OiPr) 3
progesterone acetone
H H

H H H H

HO O
Pregnenolone Progesterone
Syntheses of steroid
derivative OBz OBz
18.1eq p-quinone
Oppenauer oxidation 1.6eq Al(OtBu)3
tol., 1h,
H H
using strong oxidant
p-quinone H H H H

acetone, cyclohexanone HO O

or N-methylpyridinone
gives over oxidation OH O

Cl 3CCHO
trichloroacetaldehyde Al2O 3, CCl 4
on alumina is used as
oxidant.
HO HO
secondary alcohol gets
readily oxidized over
primary.

p-quinone
oxidation of Al(OiPr) 3
tol., 45 min
cholesterol using H H

p-quinone H H
H H
HO O
 Oxidation of Carveol:

OH O
1mol% cat.
1.2eq tBuCHO
Ooi T; Otsuka H; tol., 21 0C, 1h
Miura J; Ichikawa H;
Maruoka K; Org.
Lett., 2002, 4, 2669. 94%

Catalyst:
3mol% cat.
1.2eq acetone
SO2C8F 17 tol., 21 0C, 2h
OH O
N
AlMe
80%
O

Mello R;
Martinez-Ferrer J;
Asensio G; Slena
M, JOC, 2007, 72,
9376.
 OH O
3eq 3-nitrobenzaldehyde
10mol% AlMe3, tol., rt, 0.5h

>99%

OH O
3eq 3-nitrobenzaldehyde
Graves C R; Zeng B 10mol% AlMe3, tol., rt, 0.5h

S; SonBinh T N,
JACS, 2006, 128, S S
12596. >99%

OH O
1.2eq 2,4-dinitrobenzaldehyde
10mol% AlMe3, tol., rt, 1h

88%

OH O
F3C
H H
EtOAlEt2,
Mello R; Martinez- DCM, rt, 18h
Ferrer J; Asensio G;
Slena M, JOC, 2007,
H H
72, 9376.
26%
 H
Al(OiPr)3, tol., ref lux, 6h
Raggio M L; Watt D H
S, JOC, 1976, Vol.41, N O

No.10, 1873. H H

HO
-Sitosterol

H H

O
24-Ethylcholest-4-en-3one (71%)
 V. Ozonolysis Ozonolysis involves the cleavage of olefins with ozone. It forms either
carbonyl compound or carboxylic acid depending on work up procedure.

R1 R3 1. O 3 O O
2. Zn/ H 2O
+

R2 R4 R1 R2 R3 R4

Ozonolysis is an oxidative cleavage (like permanganate). But, it is

comparatively mild reaction and no overoxidation is seen.

R1 R2 O O
O 3, DCM Me2S
R1 R2
R1CHO + R2CHO
O
H H H H

example O

1. O 3, MeOH, -78 0C
oxidation of eugenol to 2. Me2S

corresponding aldehyde
O O

OH OH
 Reductive work up forms aldehydes and ketones while in oxidative work
up aldehydes are further oxidized to corresponding alcohol.

H R' O O
O 3, DCM
H R'

O
R R" R R"

reductive work up oxidative work up

work up of ozonide NaBH 4 PPh 3/ Me2S H 2O 2

O O

R OH
R H R OH
+ + +
OH O O

R' R" R' R" R' R"

Overall result is that double bond is replaced by an ozonide ring.

Ozone is high energy Ozonolysis is a two step reaction.
form of oxygen,
produced when UV First step is 1,3-dipolar addition of ozone across the double bond, to give
light or electrical molozonide. It rapidly undergoes rearrangement to give ozonide.
discharge passes R2 O
through oxygen gas. O O
O
O O
O O retro R1
1,3-cycloaddition 1,3-cycloaddition
+
R1 R3
Lewis structure has R1 R3
R4

central oxygen R2 R4 O
positively charged and R2 R4
molozonide
R3
each outer oxygen has
negative charge.
O O O O
O 1,3-cycloaddition acidic work up
R1 R3 +
O O
O R4 R1 R2 R3 R4
R2

ozonide

Second step is work up. Oxidative work up can be done by aqueous acid
O
while reductive work up by zinc and water or dimethyl sulfide or Pd-H2.
O O
More details on Molozonide or primary ozonide has peroxy linkage which makes it
ozonolysis reaction unstable and it undergoes rapid rearrangement to give ozonide.
On the other hand, ozonide is stable but is rarely isolated. It is reduced
with mild reducing agents to give aldehydes or ketones.

S O O
O
O +
S
O

O
O3

O O

H H
+
O O

H
CHO
H H
1. O 3
2. Me2S CHO

CHO
H H
CHO
H
 Ozonolysis does not afford information about stereochemistry of alkene.
Thus, 1 and 2 give same carbonyl compound.
R1 R3 O O R1 R4
Key facts about O3 O3
+
ozonolysis
R2 R4 R1 R2 R3 R4 R2 R3

1 2

Ozonolysis is mainly used to determine the position of a double bond in

an alkene.

1. O 3
2. Me2S
CHO
CHO

O
1. O 3
2. Me2S

1. O 3
2. Me2S
CHO

CHO
 O 3/ O2, 0 0C O
5%H2O/ acetone
AcO H AcO H

81%

Schiaffo C E & H O 3/ O 2, 0 0C H
5%H 2O/ acetone
Dussault P H, JOC,
O
2008, 73, 4688.
O O
100%
 VI. Epoxidation
Epoxidation is a reaction in which C=C of an olefin is converted to an
epoxide (or oxirane), a cyclic ether.

O
peracid

Commonly used reagents are peracid or peroxyacid, peroxide, etc.,

Addition of oxygen to C=C is syn stereoselective
O
epoxidation of styrene
perbenzoic acid
using perbenzoic acid CHCl 3, 00C

Styrene Styrene oxide

The reaction is an example of a concerted process (all bonding changes

occur in one step)
 R3
R1 R3 R
O R R1 O O
R3 R4
O
O
O
H O H R1 R2
R2 R4 R2 RCOOH
R4
Since the reaction is concerted the stereochemistry of the alkene is
preserved in the product.
For example if the alkyl groups of the alkene are cis then they are also cis
in the epoxide.
H

O
H
mCPBA, DCM,Na2CO 3,
J.Chem. Edu., 2001, 78. H 00C, 20 min
H

H3CO

H3CO

Dubois G; Murphy A O 2eq CH 3CO3H, 0.25 mol% cat.,

O

MeCN, 5 min, 00C

and Stack T D P,
Org.Lett., 2003, 5, 2469. OEt
OEt
O
Ethyl sorbate 87%

Catalyst: [{(Phen)2(H2O)FeIII}2(-O)](ClO4)4
 Epoxidation of an olefin is distereoselective reaction. The reagent attacks
alkene from less hindered face.
O
H H
only important Si Ph
conformer has H H
eclipsing double bond SiMe2Ph
SiMe2Ph

mCPBA attacks the

less hindered f ace

O O

mCPBA
+

OH
OH OH

95 : 5

Villa de P A L; Sels B F;
O
De Vos D E and Jacobs P O 2mmol H2O2, 2mg cat.,
MeCN, 380C, 24h
A, JOC, 1999, 64, 7267. O
O

O
94%

Catalyst: PW4O24[(C4H9)4N]3-Amberlite IRA900

Sharpless The Sharpless Epoxidation is an enantioselective and distereoselective
epoxidation epoxidation of allylic alcohols.
The stoichiometric oxidant is a hydroperoxide, usually tert-
butylhydroperoxide in the presence of catalyst Ti(O-isopropoxide)4.
K. Barry Sharpless won
It allows the enantioselective epoxidation of prochiral allylic alcohols. The
the 2001 Nobel prize in
asymmetric induction is achieved by adding an enantiomerically enriched
Chemistry for his work
tartrate derivative.
on asymmetric
oxidations.
R3 tBuOOH, Ti(OiPr)4, R3
(+)-DET, DCM, O
R2 OH 3A0 MS, -20 0C R2 OH

R1 R1

The stereochemistry of the resulting epoxide is determined by the

diastereomer of the chiral tartrate diester. Usually diethyl
tartrate or diisopropyl tartrate are employed in the reaction.

Assymetric Assymetric
epoxidation epoxidation
O O
(-)-DET (+)-DET
OH OH OH
Advantages: tBuOOH
5mol% Ti(OiPr) 4 O
Ph OH
7.5mol% (+)-DIPT Ph OH
Epoxides can be converted -20 0C, 3h
into diols, aminoalcohols 89% (>98%ee)
or ethers. The formation of
chiral epoxides is a very tBuOOH O
OH
important step in the 5mol% Ti(OiPr) 4 OH
7.4mol% (+)-DIPT
synthesis of natural -20 0C, 0.75h
products.
95% (91%ee)
Can be carried out with
many primary and
O
secondary allylic alcohols. tBuOOH
Ph OH
Ph OH
120mol% Ti(OiPr) 4
High enantiomeric 150mol% (-)-DET
-20 0C, 5h
excesses > 90%.
Ph Ph
The products of the
90% (94%ee)
Sharpless Epoxidation are
predictable using the It can be used for preparation of intermediates in natural product synthesis,
Sharpless Epoxidation such as in the synthesis of Lekotriene C-1.
model.
COOCH 3 tBuOOH, Ti(OiPr)4, COOCH 3
The reagents are (+)-DIPT, DCM,
-200C, 48h
commercially available
and relatively cheap.
O
OH OH

80% (95%ee)
Robinson A and
HO
HO tBuOOH, Ti(OiPr)4,
Aggarwal V K, (-)-DET, DCM, -200C, 5h
Angew. Chem. Int. O

Ed. 2010, 49, 6673. 75% (97%ee)

HO OBn

Ghosh A K and Liu C,

Org. Lett. 2001, 3, 635. tBuOOH, Ti(OiPr) 4,
(-)-DET, 4A0MS,
DCM, -230C, 20.5h

HO OBn

90%
Additional/Practice Problems
OH 1.5mol CrO 3 H
6h, rt
(1)
Cl Cl O
78% Zou J D; Xu Z N, Tet.Lett., 2002, 43, 6095

(2) PCC, SiO2, DCM

rt, 90min

OH O

d,l-Menthol d,l-Menthone
Luzzio F A, et al, J Chem. Edu., 1999, 76, 974.
(3) O O
HO PCC, acetone, Al2O3 O O
O
DCM, ref lux, 4h

AcO AcO

3-Acetoxy-17-ethylene- 3-Acetoxy-17-ethylene-dioxyestra-
dioxyestra-1,3,5(10)-trien-11-ol 1,3,5(10)-trien-11-one (79%)
McNab H, et al, Org. Biomol. Chem., 2010, 8, 4383
OH O
(4) PCC, DCM
rt, 1h

N N

O O
1,2-dihydro-1-hydroxypyrrolizin-3-one Pyrrolizine-1,3-dione (68%)

(5) OH 2 mol% PCC, 1.05eq H 5IO 6 O

MeCN, 00C-rt, 2h

Ph Ph

89%

(6) OH 2 mol% PCC, 1.05eq H 5IO 6

MeCN, 0 0C-rt, 2h
O
Hunsen M, Tet.Lett., 2005, 46, 1651
Ph Ph

96%
Jones reagent,
acetone, 0 0C
(7)
OBn OBn O
CHO
OH
PDC, DCM, rt
Neral : Geranal = 7:1 (84%)
OH H

NHBoc NHBoc
80%
(8) Jones reagent,
acetone, 0 0C

CHO
OH
Neral : Geranal = 7:1 (84%)

OH Na2Cr2O 7, conc. H 2SO 4

(9) DMSO, 70 0C, 30 min CHO

Rao Y S; Filler R, J.Org. Chem., 1974, 39,

82%
3304

(10) OH
Na2Cr2O 7, dil. H 2SO 4
silica gel, rt, 1h O

-Fenchol 98 %
Singh R P; Subbarao H N; Dev S, Tetrahedron, 1979, 35, 1789
(11)
OH O
MnO 2, alumina
DCM

O O

benzoin benzil

Crouch R D; Holden M S; Burger J S, J.Chem. Edu., 2001, 78, 951

 OH O
O
OH

(12) Al(OtBu)3
xylene

H H O H H

O
H H

(13) AcO
1. O3, MeOH, p-TsOH
2. NaHCO3, Me2S AcO
OMe
AcO
CHO
+ OMe
OMe
CHO
MeO
1 : 3

(14) O3, NaHCO3,

DCM, iPrOH, O O O O
O O OR
-780C
OHC +
HOO
HOO
OHC
OR
(15)
Ac2O, Et3N O O O O
DCM
73% +
OHC ROOC

ROOC OHC

3.6 : 1

Taber D F & Nakajima K, JOC, 2001, 66, 2515.