Baeyer-Villiger Oxidation: Videos & Practice Problems

The Baeyer-Villiger oxidation is a significant reaction in organic chemistry that transforms aldehydes and ketones into carboxylic acids and esters, respectively, through the use of peroxy acids. This reaction is particularly unique because it allows for the oxidation of ketones, which are typically already among the most oxidized functional groups, further converting them into esters. The peroxy acids, such as meta-chloroperoxybenzoic acid (MCPBA), serve as the oxidizing agents in this process.

In the Baeyer-Villiger oxidation, the regioselectivity of the reaction is determined by the migratory aptitude of the groups attached to the carbonyl carbon. Migratory aptitude refers to the tendency of a substituent to migrate during the reaction, and it follows a trend similar to carbocation stability. The order of migratory aptitude is as follows: hydrogen has the highest aptitude, followed by tertiary, secondary, and aryl groups, with primary groups having the lowest aptitude. This means that when a ketone or aldehyde reacts with a peroxy acid, the group with the highest migratory aptitude will migrate to form a new bond with the inserted oxygen atom.

For example, when a ketone with a tertiary carbon and a primary carbon is subjected to Baeyer-Villiger oxidation, the tertiary carbon migrates, resulting in the insertion of an oxygen atom between the carbonyl carbon and the migrating group. Conversely, in the case of an aldehyde, if it has a hydrogen and a tertiary carbon, the hydrogen will migrate due to its higher migratory aptitude, leading to the formation of a carboxylic acid.

Importantly, the stereochemistry of the reactants is preserved in the products. If a stereocenter is present in the starting material, the configuration remains unchanged after the reaction. This retention of stereochemistry simplifies the analysis of the reaction products.

In summary, the Baeyer-Villiger oxidation is a valuable reaction for converting carbonyl compounds into carboxylic acid derivatives, with regioselectivity governed by the migratory aptitude of substituents. Understanding this reaction is crucial for further studies in carboxylic acid derivatives and their applications in organic synthesis.

The Baeyer-Villiger oxidation is a significant reaction in organic chemistry that involves the transformation of ketones into esters through a three-step mechanism. The first step is protonation, where the oxygen of the carbonyl group in the ketone is protonated by a peroxy acid. This process involves the lone pair of electrons on the oxygen forming a bond with a hydrogen atom from the acid, resulting in a positively charged carbonyl and a negatively charged oxygen. This step is crucial as it prepares the carbonyl for the subsequent nucleophilic attack.

The second step is nucleophilic addition, where the conjugate base of the peroxy acid acts as a nucleophile. It attacks the electrophilic carbon of the protonated carbonyl, leading to the formation of a new intermediate. In this intermediate, the carbon retains a hydrogen atom, and the oxygen from the peroxy acid is now bonded to the carbon, setting the stage for the next step.

The third step, known as migration, is where the reaction's unique characteristics emerge. The oxygen from the original carbonyl seeks to reform the carbon-oxygen double bond, which leads to the migration of the alkyl group from the peroxy acid to the carbonyl carbon. This migration occurs because the tertiary carbon group has a higher migratory aptitude compared to a primary carbon. The migration involves breaking the bond between the carbon and the oxygen from the peroxy acid, allowing the alkyl group to move to the carbonyl oxygen. This step is represented by four arrows indicating the movement of electrons, culminating in the formation of a new carbon-oxygen double bond.

Finally, a deprotonation step occurs to yield the neutral product. The negatively charged oxygen from the intermediate deprotonates the carbonyl, resulting in the formation of an ester and a byproduct of a carboxylic acid. The overall reaction highlights the importance of understanding the migration concept, as it is central to the Baeyer-Villiger oxidation mechanism.

In this reaction, we start with a ketone and a peroxyacid, specifically trifluoroacetic acid (CF₃CO₃H). Recognizing that the structure CO₃H indicates a peroxyacid is crucial, as this type of molecule is characterized by the presence of the peroxy group. The reaction we are dealing with is a Baeyer-Villiger oxidation, which involves the migration of a substituent from the carbonyl carbon of the ketone.

To predict the major product, we first assess the ketone's structure and identify the migratory aptitude of the substituents. In this case, we have a secondary carbon on one side of the ketone and a tertiary carbon on the other. Tertiary carbons exhibit higher migratory aptitude compared to secondary carbons, making the tertiary carbon the likely candidate for migration.

During the reaction, the oxygen from the peroxyacid inserts itself between the carbonyl carbon and the migrating group. This results in the formation of a new bond, effectively expanding the original six-membered ring of the ketone into a seven-membered ring. The stereochemistry of the migrating group is retained throughout the process, meaning that if the migrating group was originally a wedge, it remains a wedge in the product.

When drawing the product, it is essential to number the carbons correctly. The new structure will have the carbonyl carbon at position 1, followed by the migrated tertiary carbon at position 6, now further away from the carbonyl. The final product reflects the migration of the tertiary carbon, the retention of stereochemistry, and the expansion of the ring size.

In summary, the Baeyer-Villiger oxidation of a ketone with a peroxyacid leads to the formation of a seven-membered ring, with the migrating group being the one with the highest migratory aptitude, while maintaining the original stereochemistry of the substituents.

In this reaction, we are examining the Baeyer-Villiger oxidation, which involves the transformation of a ketone using m-chloroperbenzoic acid (MCPBA), a peroxy acid. The key feature of peroxy acids is the presence of the -CO3H functional group, which facilitates the oxidation process. The primary outcome of this reaction is the insertion of an oxygen atom between the carbonyl carbon of the ketone and a migrating group, which in this case is a secondary carbon due to its higher migratory aptitude compared to an aryl group.

To predict the product, we first identify the carbonyl carbon and the secondary carbon. The reaction results in the formation of a new bond between the carbonyl carbon and the inserted oxygen, as well as a bond between the oxygen and the migrating secondary carbon. This leads to a product that retains the aromatic ring and the carbonyl structure, with the new oxygen linkage incorporated.

The mechanism of the Baeyer-Villiger oxidation consists of three major steps: protonation, nucleophilic addition, and migration. In the first step, protonation, the carbonyl oxygen is protonated by the hydrogen from the -CO3H group of MCPBA, resulting in a positively charged oxygen. This sets the stage for the second step, nucleophilic addition, where the negatively charged peroxy acid attacks the carbonyl carbon, forming a new bond and converting the carbonyl into a hydroxyl group.

Following this, the migration step occurs, where the oxygen that was originally part of the carbonyl is reformed into a double bond, while the secondary carbon migrates to bond with the newly inserted oxygen. This migration involves breaking the bond between the oxygen and the original carbonyl carbon, resulting in a new carbon-oxygen double bond and a new carbon-oxygen single bond with the migrating group. This step is characterized by four arrows indicating the movement of electrons, all directed in the same manner.

Finally, to neutralize the product, the hydroxyl proton is removed using the carboxylate formed during the reaction, yielding the final product of the Baeyer-Villiger oxidation. The overall reaction highlights the importance of understanding the migratory aptitude of groups and the specific steps involved in the mechanism, which are crucial for predicting the outcome of similar reactions in organic chemistry.