organic reaction mechanisms: ketones

Theory and defination :

The Benzoin Condensation is a coupling reaction between two aldehydes that allows the preparation of α-hydroxyketones.The homocoupling of benzaldehyde gives the parent benzoin.The first methods were only suitable for the conversion of aromatic aldehydes.
The modifications of the benzoin condensation include the use of acylsilanes as well as imine derivatives in place of one aldehyde partner.

General Reaction :

Illustration as below,

Mechanism:

Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation: A thiazolium salt may also be used as the catalyst in this reaction (see Stetter Reaction).

A strong base is now able to deprotonate at the former carbonyl C-atom:

A second equivalent of aldehyde reacts with this carbanion; elimination of the catalyst regenerates the carbonyl compound at the end of the reaction:

Example and Application :

The reaction can be extended to aliphatic aldehydes with base catalysis in the presence of thiazolium salts; the reaction mechanism is essentially the same. These compounds are important in the synthesis of heterocyclic compounds. The addition is also possible withenones; for instance methyl vinyl ketone is a reagent in the Stetter reaction.
In biochemistry, the coenzyme thiamine is responsible for biosynthesis of acyloin-like compounds. This coenzyme also contains a thiazolium moiety, which on deprotonation becomes a nucleophilic carbene.
In one study, a custom-designed N-heterocyclic carbene (NHC, the framework is related to thiazolium salts) was found to facilitate anenantioselective intramolecular benzoin condensation.

This finding was confirmed in another study with a slightly modified NHC using DBU as the base instead of potassium tert-butoxide.

Baeyer-Villiger Oxidation

Theory and Defination :

The Baeyer–Villiger oxidation is an organic reaction in which a ketone is oxidized to an ester by treatment with peroxy acids or hydrogen peroxide.Key features of the Baeyer–Villiger oxidation are its stereospecificity and predictable regiochemistry. It is named after the German chemist Johann Friedrich Wilhelm Adolf von Baeyer (1835–1917) and the Swiss chemist Victor Villiger (1868–1934).

Genaral Reaction :

Reagents typically used to carry out this rearrangement are meta-chloroperoxybenzoic acid (mCPBA), Disodium phosphate or sodium bicarbonate is often added as a buffering agent to prevent transesterification or hydrolysis.

Mechanism

The reaction is initiated by addition of peracid to the ketone. The addition is catalyzed by protons originating from the peracid or the carboxylic acid formed during the reaction.

Fig.1: Addition of peracid to ketone

At the same time, the peracid functions as a nucleophile by attacking the carbonyl carbon with the terminal oxygen atom, thereby forming an α-hydroxyperoxy ester.

Fig.2: Hydroxyperoxy ester formation

Contrary to the behavior of peracids and simple hydroperoxides, hydroxyperoxy esters spontaneously decompose already at room temperature. 1,2-Migration of the the substituents R' or R" produces an ester and a carboxylic acid derived from the peracid.

Fig.3: Substituent migration

Migration of the substituent takes place with retention, i.e. a pure enantiomeric ketone produces a pure enantiomeric ester.

Examples :

1)epi-cytoxazone and the αα-hydroxy-ββ-amino acid derivatives from ketones.

Application :

1.The Baeyer-Villiger reaction is widely appreciated in organic synthesis as it is applicable to a broad range of carbonylic compounds while the moiety that will migrate during the reaction can also be predicted to some extent.
2.An additional attractive feature of the Baeyer-Villiger reaction is that the migrating group will typically retain its configuaration. This allows effective and selective oxidation reactions. However, a major drawback of the reaction is the intrinsic need for a potent and therefore hazardous oxidising agent.
3.The classical approach to perform a Baeyer-Villiger reaction includes the use of organic peroxyacids as catalyst. In addition to the fact that these reactive compounds have to be handled with care, they are also relatively expensive.