Download Chapter 4 Functional Group Transformations: Oxidation and

Chapter 4
Functional Group Transformations: Oxidation and Reduction
Oxidation states (numbers)
Less E.N. than C = -1
More E.N. than C = +1
C=0
H
H
H
C
C OH
H
H
4.1 - Oxidation of Alcohols to Aldehydes and Ketones
Relative rate of oxidation with H2CrO4
Name
Reagents
Leaving group
Jones
CrO3, H2SO4, H2O
O
Cr OH
O
Swern
DMSO, oxalyl chloride
SMe2
O
Dess-Martin
TEMPO
O
I OAc
AcO OAc
N
O
O
O
I OAc
AcO
N
O
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4.1 - Oxidation of Alcohols to Aldehydes and Ketones
Reagent
Preferred Solvents
Functions Oxidized
Reaction Work-up
Jones Reagent
H2CrO4
aqueous sulfuric acid &
acetone
(avoid acid sensitive
systems)
1º-alcohols to carboxylic acids
aldehydes to carboxylic acids
2º-alcohols to ketones
avoid amines and sufides
1) destroy excess
reagent
2) extract product
Collins Reagent
CrO3 • 2 C5H5N
methylene chloride
(CH2Cl2)
1º-alcohols to aldehydes
2º-alcohols to ketones
1) filter inorganic salts
2) wash with aqueous
acid
3) remove CH2Cl2
solvent
Pyridinium
Chlorochromate
ClCrO3 • C5H5NH
methylene chloride
(CH2Cl2)
1º-alcohols to aldehydes
2º-alcohols to ketones
1) filter inorganic salts
2) wash with aqueous
acid
3) remove CH2Cl2
solvent
CH2Cl2 or ethers or DMSO
A Mild Procedure
1º-alcohols to aldehydes
2º-alcohols to ketones
1) neutralize reactants
2) remove solvents
Dimethyl Sulfoxide
(CH3)2S=O &
DCC or Ac2O or
(CF3CO)2O
or SO3 or (COCl)2
http://www.cem.msu.edu/~reusch/VirtTxtJml/special3.htm
4.2 Jones Reagent
Also produced using Na2Cr2O7,
H2SO4, H2O
Limitations – highly toxic, difficult to
control
Mechanism – goes to carboxylic acid via hydrate
2
Collins Reagent (no water)
http://www.acros.com/_Rainbow/pdf/oxidation_brochure_CHROM.pdf
Pyridinium Chlorochromate (PCC)
Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 2647
Compatibility with PG: Muzart, J. Synthesis 1993, 11-27
3
Pyridinium Chlorochromate (PCC)
Rauter et. al. Carbohydr. Res. 2004, 339, 1889
Pyridinium Chlorochromate (PCC)
Proof of structure by 2D NMR
4
Pyridinium Chlorochromate (PCC) - Catalytic
H5IO6 used as electron sink
Hunsen, Tetrahedron Lett. 2005, 46, 1651-1653
Pyridinium Chlorochromate (PCC) - Catalytic
H5IO6 used as electron sink
Proposed catalytic cycle
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Pyridinium Chlorochromate (PCC) - Catalytic
Hunsen, Synthesis, 2005, 2487-2490
Pyridinium Dichromate (PDC)
Nakagawa, Y. et. al. Bioorg. Med. Chem. 2006, 1761-1770
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Swern Oxidation
Nicolau’s Brevetoxin B
synthesis (J. Am. Chem.
Soc. 1995, 117, 1171 and
following papers)
Dess-Martin Periodinane
Tamiflu
Kanai et. al. Org. Lett. 2007, 9, 259-262
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Dess-Martin Periodinane
How is the oxidation
best achieved?
Lawrence et. al. Tetrahedron Lett. 2001, 42, 3939-3941
Swern conditions
(Nucleophilic) chloride
is generated, which
attacks the Swern
intermediate
Dess-Martin Periodinane
How is the oxidation
best achieved?
Lawrence et. al. Tetrahedron Lett. 2001, 42, 3939-3941
Dess-Martin conditions
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Tetrapropylammonium Perruthenate (TPAP)
TPAP
(CH3CH2CH2)4NRuO4
NMO
Review - Pagliaro et. al. Chem. Soc. Rev. 2005, 34, 837-845
O
N
O
Padwa et. al. Org. Lett. 2007, 9, 279-282
Tetrapropylammonium Perruthenate (TPAP)
Proposed catalytic cycle
Yamaguchi, Y.; Mizuno, N. Chem. Eur. J. 2003, 9, 4353
Review - Pagliaro et. al. Chem. Soc. Rev. 2005, 34, 837-845
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Tetrapropylammonium Perruthenate (TPAP)
Cheon et. al. Tetrahedron
2003, 59, 7501-7509
Tetrapropylammonium Perruthenate (TPAP)
Polymer-supported
version
Kerr et. al. Synlett. 2001, 1257-1259
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4.3 Chemoselective Agents for Oxidizing Alcohols - TEMPO
Ansari, A. I.; Gree, R. Org. Lett., 2001, 1507-1509.
Miller, R. A.; Hoerrner, R. S. Org. Lett. 2003, 5, 285-287.
Semmelhack et. al. J. Am. Chem. Soc. 1984, 106, 3374.
4.7 Allylic Oxidation of Alkenes
Sharpless et. al. J. Am. Chem. Soc., 1977, 99, 5526.
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Examples - Oxidation of Alcohols to Aldehydes and Ketones
Wavrin, L.; Viala, J. Synthesis 2002, 326-330
Other reagents cause isomerization to the more
stable α,β-unsaturated aldehydes
Examples - Oxidation of Alcohols to Aldehydes and Ketones
Tohma, T.; Kita, Y. Adv. Synth. Catal. 2004, 111-124
Yu, C.; Hu, L. Tetrahedron Lett. 2001, 42, 5167-5170
Acid generated catalyzes elimination
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Examples - Oxidation of Alcohols to Aldehydes and Ketones
Nicolaou, et. al. Angew. Chem., Int. Ed. 2000, 112, 636-639
Examples - Oxidation of Alcohols to Aldehydes and Ketones
Avoids formation of Me2S;
The byproduct sulfide does not
have an odour and may ber
recycled
Node, et. al. Tetrahedron Lett. 2002, 43, 5177-5179
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