Baeyer-Villiger reaction regioselectivity

A Baeyer-Villiger oxidation has the potential of being asymmetric if a regioselective reaction is conducted on a meso-substrate or if a stereodifferentiated stereogenic center is already present. The oxidation can be chemical or enzymatic.213-215 216 An example of a chemical reagent in a Baeyer-Villiger reaction is provided in the synthesis of fragment A 26 from /f-carvone (27) (Scheme 9.38) as part of a synthesis of Cryptophycin A (28).217... 

A reaction sequence which complements the Baeyer-Villiger reaction has been described (equation 1) Regioselective silylenol ether formation allows for introduction of oxygen away from the more highly alkylated side of a ketone. 

Another example of a highly regio- and enantiospccific microbial Baeyer-Villiger reaction is the transformation of racemic bicyclic ketone 17 by Acinetobacter TD 63433. This leads to chiral lactones 18 and 19 which are of particular interest as synthons for prostaglandin synthesis. Interestingly, each enantiomer of the racemic substrate reacts with a different regioselectivity for the oxygen atom insertion, and the enantioselectivity of the reaction is excellent. 

The Baeyer-Villiger reaction has solved a regioselectivity problem here. L-tyrosine, a relatively cheap amino acid, can be converted to the important drug L-dopa provided it can be hydroxylated ortho to the OH group. This is where electrophilic substitutions of the phenol take place, but electrophilic substitutions with HO are not possible. However, after a Friedel-Crafts acylation, the acyl group can be converted to hydroxyl by the Baeyer-Villiger reaction and hydrolysis. The Baeyer-ViUiger reaction means that MeCO can be used as a synthetic equivalent for Note... 

The Baeyer-Villiger reaction is regioselective — the more substituted group migrates—and stereospecific — it does so with retention. Hydroxy ketone (22) was needed for insect pheromone synthesis and is a 1,6-difunctionalised compound. It could be made by nucleophilic displacement by an organo-metallic reagent (R ) on lactone (23), the Baeyer-Villiger product from (24) which can be made from aromatic (26). 

However, the Baeyer-Villiger reaction of a-trifluoromethyl-cycloalkylketones show the reversal in regioselectivity (eq 45). ... 

The cyclobutanol (357) and the cyclobutanone (358) are both converted into the lactone (359) on chromic acid oxidation in either aqueous or aqueous acetic acid medium. " Other alkylated cyclobutanols and cyclobutanones behave similarly. Yields vary between 55 and 90% depending on the specific case. The regioselectivity of the reaction is the same as that in the Baeyer-Villiger reaction. Direct oxidation with chromic acid of the cyclobutanol (360), formed by photochemical cyclization of the ketone (361), gives the 1,4-dione (362) in 55% yield. This is a considerable improvement in terms of both time and yield over the previously used sequence of dehydration and cleavage. 

Baeyer-Villiger reactions of /8-silyl-ketones are highly regioselective, oxygen insertion occurring almost exclusively between carbonyl and silicon. When applied to cyclic /8-silyl-ketones, for example (52), which is easily prepared by alkylation of cyclohexanone, this reaction can be used as part of a sequence to generate acids and esters with a remote carbon-carbon double bond. ... 

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