The Baeyer-Villiger Oxidation

The oxidation of ketones with peroxy acids is both novel and synthetically useful. An oxygen from the peroxy acid is inserted between the ketone carbonyl group and one of its attached carbons to give an ester. First described by Adolf von Baeyer and Victor Villiger in 1899, reactions of this type are known as Baeyer-Villiger oxidations. 

The reaction is regiospecific oxygen insertion occurs between the carbonyl carbon and the larger (R ) of the two groups attached to it. Methyl ketones (R = CH3) give esters of acetic acid  

The mechanism of the Baeyer-Villiger reaction begins with nucleophilic addition of the peroxy acid to the carbonyl group. 

Product of nucleophilic addition of peroxy acid to ketone 

The reaction is stereospecific the alkyl group migrates with retention of configuration, as illustrated for the oxidation of c/5-l-acetyl-2-methylcyclopentane only the cis product is obtained. 

When the ketone is cyclic, a cyclic ester, or lactone, is formed. Cyclobutanone is oxidized to a lactone by the Baeyer-Villiger reaction. 

---

Using Figure 17 15 as a guide write a mechanism for the ] Baeyer-Villiger oxidation of cyclohexyl methyl ketone by peroxybenzoic acid J... 

The Baeyer-Villiger oxidation of ketones to esters (or lactones) occurs by the following mechanism. 

FIGURE 17.15 Mechanism of the Baeyer-Villiger oxidation of a ketone. 

The product (6-hexanolide) is a cyclic ester, or lactone (Section 19.15). Like the Baeyer-Villiger oxidation, an oxygen atom is inserted between the carbonyl group and a carbon attached to it. But peroxy acids are not involved in any way the oxidation of cyclohexanone is catalyzed by an enzyme called cyclohexanone monooxygenase with the aid of certain coenzymes. 

Section 17.16 The oxidation of ketones with peroxy acids is called the Baeyer-Villiger oxidation and is a useful method for preparing esters. 

Compounds known as lactones, which are cyclic esters, are formed on Baeyer—Villiger oxidation of cyclic ketones. Suggest a mechanism for the Baeyer—Villiger oxidation shown. 

When a ketone 1 is treated with hydrogen peroxyde or a peracid, a formal insertion of oxygen can take place to yield a carboxylic ester 2. This process is called the Baeyer-Villiger oxidation ... 

The Baeyer-Villiger oxidation is a synthetically very useful reaction it is for example often used in the synthesis of natural products. The Corey lactone 11 is a key intermediate in the total synthesis of the physiologically active prostaglandins. It can be prepared from the lactone 10, which in turn is obtained from the bicyclic ketone 9 by reaction with m-chloroperbenzoic acid (MCPBA) " ... 

The action of aqueous potassium hydroxide on chloronitrile 14 in DMSO at 25-30°C accomplishes the hydrolysis of the chloronitrile moiety and furnishes ketone 13 in a yield of 80%. Treatment of a solution of ketone 13 in CH2CI2 with mCPBA and sodium bicarbonate results in a selective Baeyer-Villiger oxidation to give bicyclic lactone 12 in >95% yield. It is noteworthy that the Baeyer-Villiger oxidation is completely regioselective and that the... 

Hassall, C. W., The Baeyer-Villiger oxidation of aldehydes and ketones. Organic Reactions. 9, 73-106, 1957. 

The Baeyer-Villiger oxidation (p T 226) of (12) will occur with migration of the more substituted atom. The structure of (14) must therefore be ... 

The Baeyer-Villiger oxidation reaction was discovered more than 100 years ago by Adolf von Baeyer and Victor Villiger. By this reaction, ketones are converted into the corresponding esters. In organic chemistry, peracids are commonly used as catalyst to perform this atypical oxidation reaction that results in oxygen insertion into a carbon—carbon bond (Fig. 1). 

The stereochemistry of the C(3) hydroxy was established in Step D. The Baeyer-Villiger oxidation proceeds with retention of configuration of the migrating group (see Section 12.5.2), so the correct stereochemistry is established for the C—O bond. The final stereocenter for which configuration must be established is the methyl group at C(6) that was introduced by an enolate alkylation in Step E, but this reaction was not very stereoselective. However, since this center is adjacent to the lactone carbonyl, it can be epimerized through the enolate. The enolate was formed and quenched with acid. The kinetically preferred protonation from the axial direction provides the correct stereochemistry at C(6). 

For the oxidation of ketones, Baeyer-Villiger oxidation of cyclic ketones with monopersuccinic acid in water gives lactones in good results (Eq. 8.22).47 Peroxy species generated from borax in 30% hydrogen peroxide is effective for the Baeyer-Villiger oxidation of... 

In the Baeyer-Villiger oxidation of [4.3.3]propellane-8,ll-dione 74 the propellane-bis-lactones formed, 75 and 76, are accompanied by a dispirolactone 77 22. Different product mixtures result when different (acidic or more basic) reaction conditions are employed but it has been shown experimentally for the head-to-tail propellane bis-lactone 75, vis-a-vis the isomeric dispiran 77, the latter appears to be the thermodynamically more stable product, resulting from the former under acidic conditions (p-TsOH/ C6H6, 7 days, r.t.). The structures were established by means of X-ray diffraction and H- and 13C-NMR spectroscopy. 

In Grieco s total synthesis of the antileukemic secoeudesmanolides ivangulin (194)67) and eriolanin (197)68), the Baeyer-Villiger oxidation was again found to be indispensable in the conversion of the cyclobutanones (192) and (195) to the y-lactones (193) and (196)respectively 67,68). 

A systematic study of the Baeyer-Villiger oxidation of cyclobutanones was recently reported by Jeffs71). The cycloalkenes (206) reacted readily with dichloro-ketene to give the gem-dichlorocyclobutanone (205), which were reduced by Zn to the cyclobutanone (204). Baeyer-Villiger oxidation of (204) yielded the y-lactone (207) in fair yields. (Table 11)71). 

In contrast to the situation with the Baeyer-Villiger oxidation, synthetic chemists have a choice of both enzymatic or non-enzymatic methods for the oxidation of sulfides to optically active sulfoxides with good to excellent yields and enantiomeric excesses. 

We were interested in applications of the high level of stereocontrol associated with the asymmetric Birch reduction-alkylation to problems in acyclic and heterocyclic synthesis. The pivotal disconnection of the six-membered ring is accomplished by utilization of the Baeyer-Villiger oxidation (Scheme 7). Treatment of cyclohexanones 25a and 25b with MCPBA gave caprolactone amides 26a and 26b with complete regiocon-trol. Acid-catalyzed transacylation gave the butyrolactone carboxylic acid 27 from 26a and the bis-lactone 28 from 26b cyclohexanones 31a and 31b afforded the diastereomeric lactones 29 and 30. ... 

Since the polyleucine epoxidation conditions are only favourable for highly electron-deficient unsaturated systems (i. e. ketones), use of the Baeyer-Villiger oxidation subsequent to the epoxidation reaction allows access to the optically active epoxyesters. 

The stereochemistry of the C-3 hydroxyl is established in step E. The Baeyer-Villiger oxidation proceeds with retention of configuration of the migrating group (see Section... 

---