BAEYER VILLIGER OXIDATION (REARRANGEMENT):

Mechanism of Baeyer Villiger Oxidation:
Migratory Aptutute of Baeyer Villiger Oxidation:

The oxidation of linear ketones into esters and cyclic ketones into lactones by using per acids is known as Baeyer villiger oxidation.

The reagents used in Baeyer villiger oxidation given as:

(1) Metachloroperbenzoic acid (MCPBA),

(2) Peracetic acid (PAA),

(3) Pertrifluoroacetic acid (TFPAA)

(4) Hydrogen peroxide/BF3  

(5) Caro's acid buffered with disodium hydrogen phosphate

(7) Sodiumpercarbonate (Na₂CO₃.1.5H₂O₂),

(8) Magnesium salt of monoperphthalic acid (MMPP)

(9) Potassium peroxomonosulphate (potassium caroate) supported on hydrated silica also known as "reincarnated caro's acid".

(10) Baeyer villiger monooxygenase .

IMPORTANT NOTE:

(1) Pertrifluoroacetic acid is the most reactive per acid probably because pertrifluoroacetate ion is very good leaving group.

(2) The Baeyer villiger rearrangement is a regioselective reaction.

(3) This reaction involves the oxidative cleavage of C-C bond

(4) Cyclic ketones furnish lactones (cyclic esters). And aldehydes may give carboxylic acids or formates. In the latter case, alcohols are finally formed due to hydrolysis of unstable formates under the reaction conditions.

 MECHANISM OF BEAYER VILLIGER OXIDATION:

Initially the peroxy group is added to the carbonyl carbon to give a Criegee like intermediate. Then one of the group attached to carbonyl carbon is migrated on to the electron deficient oxygen atom in a concerted step, which is the rate determining step.

MIGRATORY APTITUTE IN BEAYER VILLIGER OXIDATION:

 (1) As Asymmetrical ketones, that group migrate which is better able to supply electron (ERG). Thus order of ease of migration is ….

                                                                          OR

The substituent’s which can stabilize the positive charge can migrate readily. The migratory aptitude of various substituents is approximately:

3^o-Alkyl > Cyclohexyl > 2^o- Alkyl > Benzyl > Aryl > 1^o - Alkyl > Methyl

(2) The electron withdrawing groups (-I groups) on peroxy acids enhance the rate of the reaction.

(3) As the rearrangement is a concerted process, the configuration of the migrating chiral substituent is retained.

(4) In case of aldehydes, usually the hydrogen atom is migrated preferentially and thus by furnishing carboxylic acids. But formates are also produced when the migrating group is other than the hydrogen. This is possible when the other substituent is a tertiary alkyl group or electron rich vinyl or aryl group.

    -H > 3^o-Alkyl > 2^o- Alkyl > Benzyl > Aryl > 1^o - Alkyl > Methyl

(5) One of the competing reactions is the formation of epoxide when a double bond is present in the molecule especially at low temperatures in neutral solvents.

(6) The aldehyde is oxidized to formate due to preferential migration of aryl group. But it undergoes hydrolysis under the reaction conditions to yield a phenol.

(7) As illustrated below, the aldehyde group is oxidized to carboxylic acid due to preferential migration of the hydride ion. The aryl group with electronegative halogen groups has less migratory aptitude. Remember the groups which can stabilize positive charge possess greater migratory aptitude.

(8) The greater migratory aptitude of aryl group over the -CH₂ group can be observed in the following example.

(11) The -CH₂ group is migrated preferentially in the following reaction. The -CH-CF₃ group has less migratory aptitude due to electron withdrawing nature.

(6) The lactone formed can be reduced to a dihydric alcohol.

ILLUSTRATIVE EXAMPLES OF BEAYER VILLIGER OXIDATION:

(1) In the following Baeyer villiger oxidation, the preferential migration of more substituted secondary alkyl group is observed (regioselective) without disturbing its chiral integrity i.e., the configuration at the chiral carbon is retained in the product (stereospecificity).

(2) Cyclic ketones furnish lactones as illustrated below.

(3) Cyclohexyl group migrates preferentially over methyl group as illustrated below:

(4) In the following example, the subsequent hydrolysis of the ester gives the desired alcohol. Another example of regioselectivity and stereospecificity.

(5) Baeyer villiger oxidation is preferred over the epoxidation of double bond by the peracid as illustrated in the following reaction.