Chapter 12: Oxidation

1
Chapter 12 Oxidation Reduction
2
Reducing Agents three types

• 1. Reductions using H2 are with a metal catalyst.
• 2. Add two protons and two electrons to a
  substrate (H2 2H 2e-).
• 3. Add hydride (H) and a proton (H). (NaBH4 and
  LiAlH4 deliver H, then a proton is added from
  H2O or an alcohol

3
Reduction of AlkenesCatalytic Hydrogenation

• The addition of H2 occurs only in the presence of
  a metal (Pd, Pt, or Ni ) catalyst, catalytic
  hydrogenation

4
Reduction of AlkenesCatalytic Hydrogenation

• The ?Ho of hydrogenation, the heat of
  hydrogenation, is used as a measure of the
  relative stability of different alkenes that are
  hydrogenated to form the same alkane.

5
Reduction of AlkenesCatalytic Hydrogenation
6
Reduction of AlkenesCatalytic Hydrogenation
7
Reduction of Alkynes control
8
Reduction of an Alkyne to an Alkane
9
Reduction of an Alkyne to a Cis Alkene stop
after one mole of H2 added

• Palladium metal is too reactive to stop after one
  equivalent of H2 adds.
• To stop at a cis alkene, the less active Pd
  catalyst is usedPd adsorbed onto CaCO3 with
  lead(II) acetate and quinoline is called
  Lindlars catalyst or Poisoned catalyst
• With the Lindlar catalyst, one equivalent of H2
  adds to an alkyne to form the cis product. The
  cis alkene product is unreactive to further
  reduction.

10
Reduction of an Alkyne to a Cis Alkene

• NOTE Reduction of an alkyne to a cis alkene is a
  stereoselective reaction.

11
Reduction of an Alkyne to a Trans Alkene

• In a dissolving metal reduction (Na in NH3), the
  elements of H2 are added anti to form a trans
  alkene.

Why? Radical Mechanism
12
Reduction of an Alkyne to a Trans Alkene Know
This
Trans vinly carbanion
13
Alkyne Reductions Summary (know these)
14
Reduction of Polar CX ? Bonds

• Alkyl halides can be reduced to alkanes with
  LiAlH4.
• Epoxide rings can be opened with LiAlH4 to form
  alcohols.

Examples
15
Reduction of Polar CX ? Bonds

• This reaction follows an SN2 mechanism.
• Unhindered CH3X and 1 alkyl halides are more
  easily reduced than more substituted 2 and 3
  halides.
• In unsymmetrical epoxides, nucleophilic attack of
  H (from LiAlH4) occurs at the less substituted
  carbon atom. (like similar epoxide opening
  reactions under basic conditions)

16
Oxidizing Agents

• Oxidizing agents
• Reagents that contain an oxygen-oxygen bond
• Reagents that contain metal-oxygen bonds
• Oxidizing agents containing an OO bond include
  O2, O3 (ozone), H2O2 (hydrogen peroxide),
  (CH3)COOH (tert-butyl hydroperoxide), and
  peroxyacids.
• Peroxyacids (or peracids) have the general
  formula RCO3H.

17
Oxidizing Agents

• Common oxidizing agents with metal-oxygen bonds
  contain either chromium 6 (six CrO bonds) or
  manganese 7 (seven MnO bonds).
• Common Cr6 reagents CrO3 , sodium dichromate
  (Na2Cr2O7 and K2Cr2O7), pyridinium chlorochromate
  (PCC).

• A common Mn7 reagent is KMnO4 (potassium
  permanganate).
• Other oxidizing agents OsO4 (osmium tetroxide)
  and Ag2O silver(I) oxide.

18
Oxidizing Reactions Know these
19
Epoxidation
20

• Epoxidation syn addition of an O atom to either
  side of a planar double bond. A cis alkene gives
  an epoxide with cis substituents. A trans alkene
  gives an epoxide with trans substituents.

• NOTE Epoxidation is stereospecific because cis
  and trans alkenes give different stereoisomers as
  products.

21
Dihydroxylation

• Dihydroxylation The addition of two hydroxy
  groups to a double bond, forming a 1,2-diol or
  glycol.
• Depending on the reagent, the two new OH groups
  can be added to the opposite sides (anti
  addition) or the same side (syn addition) of the
  double bond.

22
Dihydroxylation Giving Trans 1,2-diols

• Anti dihydroxylation two stepsepoxidation, then
  ring opening with OH or H3O.

23
Dihydroxylation Giving CIS 1,2-diols

• Syn hydroxylation results when an alkene is
  treated with either KMnO4 or OsO4.

24
Dihydroxylation CIS 1,2-diols
25
Dihydroxylation catalytic cis
N-methylmorpholine N-oxide
26
Oxidative Cleavage of Alkenes Ozonolysis
27
Oxidation and Reduction

• The unstable ozonide is reduced to afford
  carbonyl compounds. Zn (in H2O) or
  dimethylsulfide (CH3SCH3) are two common reducing
  agents used.

28
Oxidative Cleavage of Alkenes Ozonolysis

• Complete ozonolysis of dienes or other polyenes
  results in oxidative cleavage of all CC bonds.

Ring opening
Alkenes ? carbonyl compounds (aldehydes ketones)
29
Oxidative Cleavage of Alkynes

• Internal alkynes are oxidized to carboxylic acids
  (RCOOH).
• Terminal alkynes give a carboxylic acid and CO2
  from the sp hybridized CH bond.

Alkynes ? carboxylic acids
30
Oxidation of Alcohols
31
Oxidation of Alcohols

• The oxidation of alcohols to carbonyl compounds
  can be carried out with Cr6 oxidants, which are
  reduced to Cr3 products, BUT, CrO3, Na2Cr2O7,
  and K2Cr2O7 are strong, nonselective oxidants
  used in aqueous acid (H2SO4 H2O).
• PCC is soluble in CH2Cl2 (dichloromethane) and
  can be used without strong acid present, making
  it a more selective, milder oxidant (still not
  green though, see alkyne coupling lab).

32
Oxidation of 2 Alcohols

• Any of the Cr6 oxidants effectively oxidize 2
  alcohols to ketones.

33
Oxidation of 1 Alcohols

• 1 Alcohols are oxidized to either aldehydes or
  carboxylic acids, depending on the reagent.

34
Oxidation of 1 Alcohols
35
Green Chemistry

• Since many oxidation methods use toxic reagents
  (such as OsO4 and O3) and corrosive acids such as
  H2SO4, or generate carcinogenic by-products (such
  as Cr3), alternative regents have been
  developed.
• A polymer supported Cr3 reagentAmberlyte A-26
  resin-HCrO4that avoids the use of strong acid,
  and forms a Cr3 by-product that can easily be
  removed from the product by filtration. (instead
  of going into water supply)
• The Amberlyte A-26 resin is a hydrocarbon network
  with cationic ammonium ion groups that serve as
  counterions to the anionic chromium, HCrO4.

36
Green Chemistry
37
Applications The Oxidation of Ethanol

• In the body, ethanol is oxidized in the liver
  first to CH3CHO (acetaldehyde), and then to
  CH3COO (the acetate anion).
• This oxidation is catalyzed by the enzyme alcohol
  dehydrogenase.
• If more ethanol is consumed than can be
  metabolized, the concentration of acetaldehyde
  increases. Acetaldehyde, which is toxic, is
  responsible for the feelings associated with a
  hangover.
• If methanol is consumed, it is metabolized by the
  same enzyme to formaldehyde and formic acid.
  These compounds are extremely toxic since they
  cannot be used by the body. Blood pH decreases,
  and blindness and death can follow.

38
The Sharpless Epoxidation

• So far, an achiral starting material has reacted
  with an achiral reagent to give either an achiral
  product, or a racemic mixture of two enantiomers.

YES
39
The Sharpless Epoxidation

• In the Sharpless epoxidation, the double bonds of
  allylic alcohols are oxidized to epoxides.
• Since the formation of only one enantiomer is
  favored, the reaction is said to be
  enantioselective.
• A reaction that converts an achiral starting
  material into primarily one enantiomer is called
  an asymmetric reaction.

40
The Sharpless Epoxidation

• The Sharpless reagent has three components
  tert-butylhydroperoxide (CH3)3COOH a titanium
  catalystusually titanium(IV) isopropoxide,
  TiOCH(CH3)24 and diethyl tartrate (DET).
• There are two different chiral diethyl tartrate
  isomers, labeled ()-DET or (-)-DET to indicate
  the direction in which they rotate plane
  polarized light.
• The identity of the DET isomer determines which
  enantiomer is the major product obtained in the
  epoxidation.

41
The Sharpless Epoxidation Enantioselectivity

• Reactions 1 and 2 are highly enantioselective
  as each has an enantiomeric excess of 95 (i.e.,
  97.5 of the major enantiomer and 2.5 of the
  minor enantiomer).

42
The Sharpless Epoxidation

• To determine which enantiomer is formed from a
  given isomer of DET, draw the allylic alcohol in
  a plane, with the OH group in the bottom right
  hand corner.

43
Sharpless Epoxidation
DET
DET complex with Ti
44
Tartaric acid stereochemistry