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Krishna P. Kaliappan, Department of Chemistry, IIT Bombay
CH E
MII T B
Organic Chemistry CH-401 Course
1
Krishna P. KaliappanDepartment of Chemistry
Indian Institute of Technology-BombayMumbai 400 076 INDIA
http://www.chem.iitb.ac.in/[email protected]
9/18/20
Oxidation
CH (401) slides should not be used for commercial purposes
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation is one of the most important & useful reactions in chemistry
Most of the chemicals are obtained by the oxidation of petrochemicals
Definition:
Inorganic Chemists & Organic Chemists differ in defining oxidation
Inorganic Chemists:
(1) Loss of electrons(2) Increase in oxidation number
Organic Chemists: The same rules can not be applied because
3
Oxidation
(1) Mechanisms of most of the oxidation reactions do not involve a direct electron transfer
(2) It is also not possible to apply oxidation number uniformly
CH-423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Addition of oxygen
H3C CH3 H3C CH2
OHH3C CHO H3C CO2H
Elimination of hydrogen
H3C CH3 H2C CH2 HC CH
Replacement of hydrogen atom bonded to carbon with another, more electronegative element like oxygen
Simplest DefinitionMost oxidations in organic chemistry involve a gain of oxygen and/or a loss of hydrogen
The reverse is true for reduction
There is no oxidation without a concurrent reduction. In organic chemistry, oxidation means organic substrate is oxidized
4
Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Reagents Based Classification
At Single carbon Vicinal Carbon
1. Metal based
2. Non-metal based
Hetero atom UnfunctionalizedCarbon atom
Substrates Based Classification
5
Classification
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Chromium based oxidation
Manganese based oxidation
Titanium based oxidation
Ruthenium based oxidation
Osmium based oxidation
Molybdenum based oxidation
Lead based oxidation
6
Metal Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
CrO3
The most widely employed transition metal oxidations are Cr(VI) based reagents
Reactivity & selectivity depends on the (1) Solvents & (2) Chromium ligands
Substantial selectivity can be achieved by choice of the particular reagent or conditions
Jones reagent
PCC
PDC
Collins reagent
Chromyl chloride
7
Chromium Based Reagents
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
The extent of protonation of these ions depend on the pH
In acetic acid, CrO3 exists as mixed anhydride of acetic acid & chromic acid
CH3COOH + CrO3
O
OCrO OH
O
O
OCrO O
O O
In dilute solution the chromate ion is present. As concentration increases the dichromate ion dominates
CrO3
CrO3 + H2O CrO
OHO O
Cr OHOO
O2 Cr OO
O
OCr OO
O+ H2O
8
Chromium Trioxide
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R OH CrO3 R O
H
CrO
OOH
The most common transformation effected on with Cr(VI) is the conversion of alcohols into ketones or aldehydes
N + CrO3 N Cr OO
O
In pyridine, CrO3 exists as an adduct involving Cr-N bond
CrO3
A variety of experimental conditions have been used for oxidation of alcohols by Cr(VI) on a synthetic scale
9
R O H2CrO3+
Chromium Trioxide
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
CrO3 H2SO4 H2O+ +
Jones Oxidation
Utility: Jones reagent can be used for oxidation of simple unfunctionalized secondary alcohols to ketones
Jones Reagent: Acidic aqueous solution of chromic acid. Generally added to an acetone solution of the alcohol
10
Chromium Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OH
Jones reagentAcetone
O
O
O
OHJonesReagent
OH
JonesReagent
11
Jones Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Jones reagentAcetoneR OH
R OH
O
(3) Under acidic condition dehydration may also take place
Disadvantages:(1) Saturated primary alcohols are oxidized to carboxylic acids
Hydration
R OH
OH
R O
H
(2) Not good for acid sensitive groups & compounds
Advantages:(1) Cr(VI) Cr(III)
Precipitate
Acetone can be decanted. Easy to work up(2) Good reagent to oxidize primary alcohol to acid
12
Jones Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
CrO3.2Pyridine (Collins reagent)
Preparation:
CrO3(anh.)
+ 2 Pyridine (anh.)
CrO3. 2pyridine (Solid)
Uses:
(1) Where other functional groups are susceptible to oxidation
(2) When the molecule is sensitive to strong acid
(3) Primary & secondary alcohols are oxidized to aldehydes & ketones respectively in non-aqueous solution (Generally DCM was used) without over oxidation
(4) Neither markedly basic, nor acidic
13
Collins Reagent
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Disadvantages:(1) Must use a large excess of the reagent
(2) It is moisture sensitive & loses its activity in aqueous solution
O
OH
CrO3. Py
O
OH
CrO3. Py
O
PhPh
OHCrO3. Py
O
PhPh
O
The double bond did not migrate
14
Collins Reagent
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Pyridinium Chlorochromate (PCC)
CrO3 6N HCl+ CrO
OHO Cl
Pyridine CrO
OO Cl
NH
Orange-yellowcrystalline solid,Less hygroscopic
Preparation:
Advantages:
(1) Reagent can be used in stoichiometric amounts with substrate
(2) It is less hygroscopic. So, it can be stored for a long time
(3) PCC is slightly acidic, but can be buffered with NaOAc
15
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
O
O O
O
O OH
PCC
CH2Cl2
OH PCC O
PhOH
PCCPh
O
16
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of Organoboranes:
R
R (1) BH3.THF
(2) PCC, 0oC
O
RR
Deoximation:O
R2R1
Pyridinium Chlorochromate (PCC)
17
N
R1 R2
OH
PCC
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OH
CH2Cl2
PCC
O
Oxidation of tertiary allylic alcohols:
18
O CrO
OO PyH
O CrO
OO PyH
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of tertiary allylic alcohols:
19
O1. MeMgBr, CeCl32. PCC, CH2Cl2
O
O
1. MeMgBr, CeCl32. PCC, CH2Cl2
O
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of tertiary allylic alcohols:
OHPCC O
OHPCC
O
20
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OH
PCCCH2Cl2
O
OH
Oxidative cationic cyclization:
ene reaction
Oxidation
21
OH
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidative cationic cyclization:
O
PCCCH2Cl2
OH O
22
PCC
OH
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R O
OR'
Oxidation of enol ethers to lactones:
O
PCCCH2Cl2 O O
O
PCC
O O
23
CrO O
Cl O PyH
R H
OR'OCrO
R H
OR'
Cl O PyH
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of furan ring system:
OH3CR
OHO
O
H3C
HOR
24
OH3CR
OHO OCr
Cl O
O
RO
H3C
HO
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of active methylene group:
O
PCCO
O
O
PCC
O O
25
Pyridinium Chlorochromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
O CrO
OO Cr
O
OO
NH
NH
Preparation:
2CrO3 H2O+ HO CrO
OO Cr
O
OOH
Pyridine
Solubility:
Soluble in water, DMF, DMSO, dimethylacetamide. It is sparingly soluble in dichloromethane
26
Chromium Based Oxidation
Pyridinium Dichromate (PDC)
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Advantages:
(1) Excellent reagent for oxidation of allylic alcohols
(2) There is no over-oxidation of aldehydes
OH
PDC
DCM CHO
(3) No E/Z-isomerization(4) Unlike conjugated aldehydes non-conjugated aldehydes are readily oxidized to acids by PDC in DMF at 25oC
HO
PDC
DMF
HO O
27
Pyridinium Dichromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R OHPDCCH2Cl2
R O
R OH R OPDCCH2Cl2
R OH
R'PDCCH2Cl2 R O
R'
Utility:
28
OHPDC
DCM
O
O CH2OH PDC
DCMO CHO
Pyridinium Dichromate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OHO
PDCDMF
PDCCH2Cl2 O
OH
29
PCCCH2Cl2
O
This reaction is complicated by the cationic cyclization when PCC was used
Pyridinium Dichromate
CrO
O
O OOHO
OHO3Cr
H2O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan30
O
CrO3/AcOHH2O
CO2HHO2C
OHO
CrO
O
OOCrO
O
OH
H2OO
HOO
O
CO2HC
O
CrO3/AcOHH2O
CO2HHO2C
H2O
Chromium Based Oxidation
CH 401Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OR
CHO
OR
CrO2Cl2CH2Cl2
31
Etard Reaction
H
CrO
O
Cl
Cl
Ene
Reaction
OR
CrO Cl
ClOH
[2,3]
Sigmatropicrearrangement
OROCr
OH
ClCl
H
OR
CHO
+ CrHO Cl
OR
Mechanism:
CH 401Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan32
CH3
CrO3
Ac2O
CHO
CrO3Ac2O
HC
AcO OAc
Hydrolysis
CHO
Etard Reaction
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Supported Reagents
Improved yields due to simplified work up
(1) PCC on alumina
(2) PCC on polyvinylpyridine
Advantage:
33
N
Cross link
N
HC
H2C n
CrO3.HCl
N
HC
H2C n
CrO3.HCl.
N
HC
H2C n
.
R2CHOH O
RR
Cr(III)
1) Remove CrO32) HCl wash
3) KOH wash4) H2O washN
HC
H2C n
Chromium Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan34
R OH R CHO
OH
R R'
O
R R'
R OH R COOH
Transformation Chromium reagentPCC, Collins reagent, PDC in DCM
PCC, Collins reagent, PDC, Jones reagent
Jones reagent, PDC in DMF
CHO
Etard reaction
Chromium Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
KMnO4 MnO2 Mn(OAc)3
Potassium permanganate (KMnO4)
R'
RKMnO4+
R'
R OMnO O
O-K+
R'
R OH
OH
HOMn
HO O
O-K++
R'
R OMnO O
O-K+H
R'
R O
OH R'
R O
O
Under mild condition KMnO4 can effect conversion of alkenes to glycol
KmnO4 is such a powerful oxidant that it can cleave the glycol further. So, careful control is required
35
Manganese Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R R'KMnO4, H2O
R R'
HO OH
R
R'O
O
R R'
O OH
ArKMnO4, H2O ArCO2H
CH3Ar KMnO4, H2OArCO2H
In water medium:
36
Potassium Permanganate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
In Organic Solvents:
3.3 mol KMnO4
Benzene polyether
1.0 mol KMnO4
R4NCl
OH
OH
O
O
Oxidation of acetylenes:
Ph CH2CH2CH3
KMnO4
R4N+, DCM HO
CH2CH2CH3
OH
Ph
O
CH2CH2CH3
OH
Ph
O
CH2CH2CH3
O
Ph
37
Potassium Permanganate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of aromatic side chain:
Ar R Ar CO2HKMnO4
R3C NH2 R3C NO2KMnO4
Oxidation of amino compounds:
Tertiary alkylamines can be oxidized to nitro compounds
Oxidation of sulphides:
S
NO2
O2N S
NO2
O2NO
O
KMnO4
38
Potassium Permanganate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Application in the synthesis of Saccharin:
Me
SO2NH2
KMnO4
OH-
CO2
SO2NH2
Na
SO2
NH
O
Saccharin
Oxidation of terminal alkynes:
CO2H
39
Me
SO2Cl
(NH4)2CO3
KMnO4
Potassium Permanganate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Manganese dioxide (MnO2)
Excess of MnO2is required
O
MnO2, KCNOH
EtOH
OH
CN
Utility:Selective oxidation of allylic & benzylic alcohols
O
CN
MnO2
CH2Cl2
OH
40
O
OEtEtOH
Manganese Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan41
OH
MnO2ROH
NaCNCO2R
OH MnO2
O
H
CN OH
CN
MnO2
O
CN
O
OR R OH
Manganese Dioxide
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
CH2OH CHO
MnO2 OHCHO
MnO2
DCM
OHCHO
MnO2 MnO2, CH2Cl2
HO
OH
O
OH
42
OH
HO
MnO2
CHCl3
OH OH
O
OH
Manganese Dioxide
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Manganese(lll) acetate [Mn(OAc)3]O
Mn(OAc)3
OOAc
OOAcOMn(OAc)3
43
OHO OMn(OAc)2
Mn(OAc)3
Mn(OAc)2
OMn(OAc)3
O
Mn(OAc)2
OOAc
Manganese Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
OH
44
Mn(OAc)3
NMe
O
OH
NMe
O
O
NMe
O
O OH
NMe
O
O OHMn(OAc)3
Mn(OAc)2
NMe
O
OH OH
NMe
O
OOH
Manganese Triacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R
O
H
Ag2OR
O
OH+ 2 Ag
Ag2O
Mild oxidant to oxidize aldehyde to carboxylic acid
CHO Ag2O
NaOH
CO2H
45
Silver Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Ag2CO3 on Celite (Fetizon’s reagent)
OHOH
Fetizon's reagent O
O
Fetizon's reagent
O
OH
OH O
OH
O
Conversion of diols to lactones
46
Silver Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Ag2CO3 on Celite (Fetizon’s reagent)
Highly selective:
Mono-oxidation:
OH OH OH
Fetizon's reagent
OH O OH
OHOH
Fetizon's reagent
OHO
Fetizon's reagent
OH
OH
O
OH
47
Silver Based Oxidation
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
R
R'I
O
OR
R'CH3
O
OR
R'CH3
R
R'
OAc
OAc
-OAc
In the absence of water, Prevost Hydroxylation, trans-product
In the presence of water, Woodwards hydroxylation,
cis-product48
R
R'
I2Ag(OAc) or Ag(O2CPh)
Silver AcetateR
R'
I
O CH3
O
H2O
R
R'
OH
OHcis product
R
R'
OH
OHtrans product
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan49
CO2Ag BrBr2
RCOOAg X2 RCOOX AgX
∇RCOOX RCOO X (Initiation)
RCOO R CO2
R RCOOX RX RCOO (Propagation)
Hunsdiecker Reaction
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Mechanism seems to be same in both cases
Uses:
Alkenes are generally oxidized to cis-diols
Alkynes are oxidized to diketones as in case of KMnO4
50
Ruthenium & Osmium Based Oxidation
MO4
OM
O O
OHydrolysis
OH
OH
HOM
HO O
O
Reoxidation
OM
O O
O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Osmium tetraoxide (OsO4)
OsO4 is highly toxic, cannot be used at industrial scale
Use of NMO as co-oxidant along with catalytic amount of OsO4can be used for higher scale
51
Osmium Tetraoxide
R
R'
OsO4R
R'
OH
OHSyn
N
O
O
NMO
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Directed by hydroxyl group
52
OHO
OsO4NMO
PyridineO
HO
HO
HO
OH
OsO4
OH
HO
HO
OTMSO
OsO4NMO
PyridineO
TMSO
HO
HO
Osmium Tetraoxide
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan53
Ruthenium Based OxidationRuthenium tetroxide (RuO4)
Prepared in-situ by mixing RuCl3, NaIO4, CH3CN, CCl4, H2O
Primary Alcohols:
Secondary Alcohols:Secondary alcohols oxidized to ketones
O
HH
OH
RuO4
O
HHCO2H
OO
HORuCl3, NaIO4
CCl4, H2O, CH3CN OO
O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan54
Ruthenium Based OxidationRuthenium tetroxide (RuO4)
Diols:Diols are further oxidized to carboxylic acids
Oxidation of Phenyl Groups:
RuCl3, NaIO4
CCl4, H2O, CH3CNPh OH
OHPh
O
OH
RRuCl3, NaIO4
CCl4, H2O, CH3CNR CO2H
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxidation of Ethers:
55
Ruthenium Tetroxide
O O O
RuO4
OAc
OAc
O
AcO OAc
OO
RuO4
RuCl3, NaIO4
CCl4, H2O, CH3CNOMe OMe
O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Tetra-n-propylammonium perruthenate (TPAP)
A catalytic amount of TPAP with NMO as the co-oxidant oxidizes a range of functional groups
The performance of this reagent is improved by the addition of MS
56
Ruthenium Based Oxidation
HO
OTBDPSO TPAP
NMO, DCM
O
OTBDPSO
TPAP
NMO, DCMTHPO OH THPO O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Tetra-n-propylammonium perruthenate (TPAP)
Groups tolerant are:
Epoxides
Alkenes
THP ethers
Lactones
Silyl ethers
Indoles
57
TPAP
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Lead tetraacetate, LTA, Pb(OAc)4
Lead tetraacetate is a very good reagent for glycol cleavage
Particularly LTA is useful for glycols that have low solubility in aqueous media
Carboxylic acids are oxidized by LTA
58
Lead Based Oxidation
O
OH
OH
Pb(OAc)4
O
O
O
Pb(OAc)4CO2H
CHCl3
CH-423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Lead Tetraacetate, LTA ,Pb(OAc)4
The reductive step is promoted by hydrogen donor solvents
Acetate arise by the capture of an acetate ion
In the presence of lithium chloride, the product is the corresponding chloride
59
Lead Tetraacetate
Pb(OAc)4 + RCO2H RCOO-Pb(OAc)3 + CH3COOH
RCOO-Pb(OAc)3 R + CO2 + Pb(OAc)3
R + Pb(OAc)3 R+ + Pb(OAc)2 + CH3COO-
CO2HCH2CO2Me
ClClH3C
Pb(OAc)4
LiClClCH2CO2Me
ClClH3C
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
α- hydroxy carboxylic acids undergo oxidative decarboxylation to give ketone
γ- keto carboxylic acid preferentially yield α,β– unsaturated ketone
Presumably it goes via oxidation of carboxylic acid to the carbocation followed by deprotonation
60
HOH
O
O
HO
O
OPb(OAc)3
O+ CO2 + Pb(OAc)2 + CH3CO2H
O
HO2C
Pb(OAc)4
Cu(OAc)2 O
O
OO
Pb(OAc)3H
Lead Tetraacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
LTA is toxic in nature
61
O
LTA, AcOH
OOAc
OH
LTA
O
+ Pb(OAc)3 + AcOHAcOH
.
Pb(OAc)2..
OAc +O
OAc
Lead Tetraacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan62
R
O
OH R
O
OPb(OAc)3 + AcOH
LTA
KOAc
R+CO2 Pb(OAc)3 +
R+ Pb(OAc)2AcO-+ +
R OAc
Lead Tetraacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan63
O
CO2H
O
O
OO Pb(OAc)3
H
O
Pb(OAc)2 CO2 AcOH+ + +
+
Lead Tetraacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan64
O
O
O
O
O
O Pb(OAc)4
Pyridine
H
H
O
O
O
RRR
R
OOH
OOPb OAc
AcO OAc
CO2 + Alkene + Pb(OAc)2 + CH3CO2H
CO2H
CO2H
Lead Tetraacetate
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Oxymercuration
Addition of water to an alkene
When water is used as solvent, it opens the mercurinium ion and give alcohols
C-Hg bond is very weak and it can be easily replaced with hydrogen by reducing agents. Generally NaBH4 is used
65
Mercury Based Oxidation
R
Hg(OAc)2R
Hg2+ Hg2+
R
Mercuriniumion
RHg(OAc)2
H2OR
HgOAcOH NaBH4
R CH3
OH
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Addition of water to an alkyne
This is what we should have expected. But what we get is a ketone
Since AcOH is the byproduct, this protonates the carbonyl group
For hydration of alkynes, we do not need NaBH4. Moreover, if you use NaBH4in the last step, it will reduce the ketone
Isomerizes to
66
Oxymercuration
RHg(OAc)2 Hg2+
R
H2OHO
HgOAcR
HOHgOAc
R
OHgOAc
R
H2OO
HgOAcR
HHO
R
O CH3
R
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan67
OH Hg(OAc)2OH
HgAcO Hg OAc
O
O
AcOHg
ONaBH4
OH Hg(OAc)2
H2SO4
OH
O O
-H2O
Oxymercuration
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan68
O
OOMe
OH
OH
OHHg(OAc)2
H2O
O
OOMe
OH
OH
OH
Deoxydaunomycinone
O
Oxymercuration
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan69
Palladium Based Oxidation
RPdCl2
CuCl2, H2O R
O
Wacker Process
O
MgBr
HO
HOO
PdCl2CuCl2, H2O
O
MgBrHO Hg(OAc)2
H2SO4
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan70
Palladium Based Oxidation
Wacker Process
PdCl2
PdCl2 R
PdIICl
H2O
PdIICl
HO HR
β- eliminationHO
R
O
R
HPdIICl
Pd0 + HCl
CuCl2
O2, HCl
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Molybdenum Peroxy Complexes:MoOPH (MoO5. Py. HMPA complex)
It contains two electrophilic bridged peroxy ligands and a single oxo-unit
71
Molybdenum Based Oxidation
O
RR'
LDA O
RR'
Li+
MoO
O O
O
L L'
O
L= HMPAL'= Pyridine
RO
Mo
O
R'O
OO
O
L L'
O
RR'
OH
OO
CH3
HO
LDA
MoOPH
OO
CH3
OHO
CH-401Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
NO
H
Cope elimination
72
Elimination Reactions
OLDA
PhSeSePhor
PhSecl
OSePh O
SePh
O
H
OH2O2 OR
m-CPBA ORNaIO4
O
LDAPhSSPh
OSPh
H2O2 OR
m-CPBA ORNaIO4
OSPh
O
H
O