The Baeyer-Villiger reaction

While the oxidation of ketones by peracids (Baeyer-Villiger reaction) has been used in steroids mainly for ring cleavage, it has occasionally been applied to 20-ketopregnanes for conversion to 17-acetoxy- or hydroxyandros-tanes. The synthetic utility of this method is limited since reactive double bonds and other ketones are incompatible with the reagent. 

It has recently been suggested that a free radical mechanism i.e., homo-lytic cleavage of the oxygen-oxygen bond rather than the heterolytic cleavage pictured) may be involved in the reaction of some substituted benzophenones and peroxyacetic acid. 

Examination of the migratory aptitude of groups in a variety of unsym-metrical ketones indicates that the group best able to accept a positive charge will usually migrate most readily.  

With aliphatic and alicyclic ketones, it appears that trifluoroperoxyacetic acid is the reagent of choice. It reacts much faster than other 

More recently, permaleic acid has been recommended as a very satisfactory reagent for the Baeyer-Villiger reaction. It reacts almost as fast as trifluoroperoxyacetic acid and does not require buffering. Unfortunately, neither of these two reagents has been used extensively on 20-keto steroids a patent claims the conversion of progesterone to testosterone acetate with trifluoroperoxyacetic acid, but a later communication describes the ready reaction of 3-keto-A -steroids with this reagent. 

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Obsolete uses of urea peroxohydrate, as a convenient source of aqueous hydrogen peroxide, include the chemical deburring of metals, as a topical disinfectant and mouth wash, and as a hairdresser s bleach. In the 1990s the compound has been studied as a laboratory oxidant in organic chemistry (99,100). It effects epoxidation, the Baeyer-Villiger reaction, oxidation of aromatic amines to nitro compounds, and the conversion of sodium and nitrogen compounds to S—O and N—O compounds. 

Quantum, by contrast, converted an ethylene—carbon monoxide polymer into a polyester-containing terpolymer by treatment with acidic hydrogen peroxide, the Baeyer-Villiger reaction (eq. 11). Depending on the degree of conversion to polyester, the polymer is totally or partially degraded by a biological mechanism. 

A variety of esters can be prepared from the corresponding ketones usiag peracids ia a process usually referred to as the Baeyer-Villiger reaction (95) ie, cyclopentanone is converted to 5-valerolactone upon treatment of the ketone with peroxytrifluoroacetic acid ... 

The final step is not a radical reaction, but an example of the Baeyer-Villiger reaction, which will be discussed in Section 12.5.2 of Part B. 

The Dakin reaction proceeds by a mechanism analogous to that of the Baeyer-Villiger reaction. An aromatic aldehyde or ketone that is activated by a hydroxy group in the ortho or para position, e.g. salicylic aldehyde 12 (2-hydroxybenzaldehyde), reacts with hydroperoxides or alkaline hydrogen peroxide. Upon hydrolysis of the rearrangement product 13 a dihydroxybenzene, e.g. catechol 14, is obtained ... 

The original library of 10 000 clones used in the Baeyer-Villiger reaction [89] was screened for performance as potential catalysts in the sulfoxidation [32]. This led to the discovery of at least 20 mutants having enantiomeric excess values in the range of 85-99%, some being (R) selective and others being (S) selective. Five mutants resulting in enantiomeric excess values of >95% were sequenced (Table 2.2) [32]. 

In another kind of reaction, an aromatic aldehyde ArCHO or ketone ArCOR is converted to a phenol ArOH on treatment with alkaline H202, but there must be an OH or NH2 group in the ortho or para position. This is called the Dakin reac-The mechanism may be similar to that of the Baeyer-Villiger reaction (18-19) ... 

Another approach is to use the Baeyer-Villiger reaction we have Just carried out to make (34), esterify. and oxidise to the ketone. 

The Baeyer-Villiger reaction has found considerable application in the synthesis of prostaglandins. One common pattern involves the use of bicyclo[2.2.1]heptan-2-one derivatives, which are generally obtained by Diels-Alder reactions. For example, compound 10 is known as the Corey lactone and has played a prominent role in the synthesis of prostaglandins.237 This compound was originally prepared by a Baeyer-Villiger oxidation of 7-(methoxymethyl)bicyclo[2.2.1]hept-5-en-2-one.238... 

Cyclobutanone annulation onto a carbonyl group translates into y-butyrolactone annulation because of the facility of the Baeyer-Villiger reaction (Eq. 68 a)8). Indeed, the reaction proceeds sufficiently rapidly that even basic hydrogen peroxide effects the oxidation whereas, with less reactive carbonyl partners, peracids must be used. 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996 . By employing overstoichiometric quantities of Ti(OPr-t)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic andprochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172) . With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

When aldehydes are oxidized with H2SO5 in the presence of alcohols, the esters of the corresponding acids are obtained in very high yields . Mechanistically, it seems plausible that the Baeyer-Villiger reaction occurs first and esterification follows. Thus, the aldehyde is oxidized by H2SO5 to the corresponding carboxylic acid, which is esterified immediately with the alcohol. 

Density functional theory has been used to model the Baeyer-Villiger reaction mechanism for Ti(IV)-H202 and Sn(IV)-H202 systems. These calculations have shown... 

The Baeyer-Villiger reaction of 3-tetrahydrofuranones with MCPBA gave exclusively the l,3-dioxan-4-ones in preparative useful yields (Equation 93) <2001TL4713, 2004CC816>. 

Examples of formation of a C —O bond via the Baeyer Villiger reaction are given in Table 1. 

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