Oxidation Reactions

General Mechanism of Alcohol Oxidation

Kornblum Oxidation

Alkyl halide or carbonyl halide to ketone/aldehyde.

Only reactive alkyl halides or tosylates will react. 1) DMSO, heat 2) Et3N/Base

Pritzner-Moffatt Oxidation

Alcohol to Ketone/Aldehyde oxidation.

Parikh-Doering Oxidation

Alcohol to ketone/aldehyde. Dump and stir

Corey-Kim Oxidation

Alcohol to ketone/aldehyde oxidation

Swern Oxidation

Alcohol to ketone/aldehyde oxidation

2-iodoxybenzoic acid (IBX) Oxidation

Alcohol to ketone/aldehyde

Dess-Martin Periodinane

Alcohol to ketone/aldehyde

N-oxoammonium Mediated Oxidation

Alcohol to ketone/aldehyde

Ley Oxidation

Alcohol to ketone/aldehyde

TEMPO Oxidation

PRIMARY alcohol to ketone/aldehyde

Stahl Oxidation

PRIMARY alcohol to ketone/aldehyde

ABNO Oxidation

PRIMARY alcohol to amide

Chemoselective Secondary Alcohol Oxidation

Oxidants: NBS, Br2, NaOCl

Pinnick Oxidation

Alcohol to carboxylic acid

Chromium Reagents - alcohol oxidation

Alcohol to carboxylic acid: Jones (CrO3, H2SO4, H2O —→ H2CrO4)

Alcohol to Ketone/aldehyde: Collins (CrO3-pyr2, DCM)

Alcohol to Ketone/aldehyde: Corey (PCC, pyridinium chlorochromate) - slightly acidic

Alcohol to Ketone/aldehyde: PDC (Cr2O7, solvent). Milder PCC. Can be secondary selective based on solvent

Allylic Oxidation: Oxidative Transposition

PCC or PDC. Via [3,3] sigmatropic rearrangement

Allylic Oxidation: Oxidative Transposition

3 mechanistic paths: Dissociative, [1,3]-rearrangement, SN2

Allylic Oxidation

Alkene to alpha-beta unsaturated ketone. 

PCC, PDC, or CrO3 (3-5)-DMP

Mechanistic speculation: Radical pathway

Doyle Oxidation

Alkene to alpha-beta unsaturated ketone. 

Selenium Dioxide Oxidation

Alkene to allylic alcohol

Selectivity: Tri substituted olefins react at more substituted end of double bond.

Order of reactivity: CH2>CH3>CH

Terminal olefins prefer endocyclic vs exocyclic (i.e inside the cycle versus outside)

Manganese Dioxide Oxidation

Allylic alcohol to alpha-beta unsaturated ketone

Corey Modification: Allylic alcohol to methyl ester (NaCN, cat. AcOH, MeOH). Cyanohydrin intermediate, oxidation to carbonyl cyanide, then attack by methanol to form methyl ester)

Can also cleave diols

Selenoxide Elimination

Ketone to alpha-beta unsaturated ketone

PhSeCl reagent. Can use other peroxides instead of H2O2

Mukaiyama’s reagent

Ketone to alpha-beta unsaturated ketone

Saegusa-Ito Oxidation

Ketone to alpha-beta unsaturated ketone

Via silyl enol ether intermediate

IBX Unsaturation

Ketone to alpha-beta unsaturated ketone

Halogen Elimination

Ketone to alpha-beta unsaturated ketone

Mechanism: Bromide formation, elimination

Rubottom Oxidation

Alpha hydroxylation of carbonyl compounds

Mechanism:

Via silyl enol ether intermediate. Peroxide attack forms epoxide, which forms a ketone + alpha silyl ether intermediate via rearrangement. Protonation yields product.

Upjohn and Sharpless Hydroxylation

Nonselective (Upjohn) or stereoselective (Sharpless) Alpha hydroxylation of carbonyl compounds

Davis Oxaziridine

Alpha hydroxylation of carbonyl compounds

Enantioselective variant possible

MoOPH Oxidation

Alpha hydroxylation of carbonyl compounds

Mechanism: Via Metal-enol ether adduct. Oxygen is from MoOPH. 

Modifications: 

From nitrile compound: Ketone formed

From Sulfone: Ketone formed 

From alkene: enantioselective hydroxylation from borane intermediate (from hydroboration)

Alpha Hydroxylation with Oxygen

Alpha hydroxylation of carbonyl compounds

Reductant required

Mechanism: Via Metal-enol ether adduct. Oxygen is from MoOPH. Peroxide intermediate via radical recombination (triplet oxygen). Reductant cleaves hydroperoxo intermediate.

Baeyer-Villiger Oxidation

Ketone to ester (or lactone if cyclic)

Large group (RL) needs to be anti periplanar to O-O bond.

More subsittuted group migrates (tertiary>secondary>allyl>primary>methyl)

Prilezhaev Epoxidation

Nucleophillic epoxidation

“Butterfly mechanism”

More acidic peroxyacid = faster reaction

DMDO or TFDO Epoxidation

TFDO can also do C-H bond hydroxylation

Henbest Epoxidation

Required allylic alcohol

Stereoselective, directed by H-bonding between alcohol and peracid

Henbest Epoxidation Mechanism/TS

120 degree dihedral angle between alcohol directing group and alkene (minimize A1,3 interactions)

In cyclic case, half-chair formation dictates disfavored vs favored face (by whether half chair is stable or not)

Sharpless Directed Epoxidation

Allylic alcohol to epoxide, Stereoselective, directed by chelation. 

Sharpless Epoxidation Mechanism/TS

50 degree angle between alcohol and alkene, determines which face is most favorable (minimize A1,3 interactions). Top face or bottom face favored

Sharpless Asymmetric Epoxidation

Allylic alcohol required

Alcohol in top right corner, (+)-DET attacks from top face

Jacobsen Epoxidation

Best for conjugated systems (alpha-beta unsaturated ketones, styrenes, etc.)

Mn catalyst, oxidant

Shi Epoxidation

Best for non-conjugated, non-allylic alcohols

Nucleophilic Epoxidation

Activated alkene required

Upjohn Dihydroxylation

Syn dihydroxylation.

In cyclic case, dependent on current ring conformation/substituents

If NaIO4 after, Lemieux-Johnson Oxidation (Oxidative cleavage)

Upjohn Dihydroxylation Mechanism/TS

120 degree dihedral angle required that minimized A1,3 interaction. However, OsO4 approached from OPPOSITE face of preferred conformer.

Sharpless Asymmetric Dihydroxylation

AD Mix: K2CHO3, K3[Fe(CN)6], K2OsO4-H2O

Jacobson Epoxidation Stereochemistry

((S,S) TOP, (R,R) BOTTOM) for BOTH cases—> 

For tri-sub olefins: H in lower right corner 

For CIs-sub olefins: Aryl, alkenyl, or alkynyl group in top left corner

Sharpless Asymmetric Dihydroxylation Stereochemistry

H in lower right corner, Large group in lower left.

Alpha bottom, Beta top

Ruthenium Tetroxide Oxidative Cleavage

Stronger oxidative cleavage. Will oxidize aldehydes to carboxylic acids

Alpha hydroxy ketones/aldehydes are also cleaved

Lead Tetraacetate Oxidative Cleavage

Oxidative cleavage of diols

Ozonolysis

Oxidative cleavage of Olefins

Lemieux-Johnson Oxidative Cleavage

Ozonolysis-Schreiber’s Modifications

Acetal + ketone/aldehyde possible

Acetal + ester possible

Ester + aldehyde/ketone possible

Olefination/Chlorination possible

Schenk Ene Photooxygenation

Alkene to Allylic alcohol via alkylperoxide intermediate

Dehydration step gives alkene (need alpha proton available in one of the alkene substiuents)

Oxidation of Olefins via Singlet Oxygen

[4+2] cycloaddition, reductant forms 1,4- allylic diol

[2+2] cycloaddition, reductant forms 1,2 diol

Kornblum-DeLaMare gives 5-hydroxy alpha-beta unsaturated ketone

Kornblum-DeLaMare + Furan gives alpha-beta unsaturated hydroxy lactone