Baeyer-Villiger oxidation rearrangements

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Synthesis of all four 8,8a-secobenzophenanthridine alkaloids was carried out chiefly by Baeyer-Villiger oxidation of appropriate benzophen-anthridines (Scheme 32). Thus, arnottianamide (206) was obtained from chelerythrine (210) (172,175), iwamide (207) from N-methyldecarine (211) (168,172), integriamide (208) from avicine (212) (171,172), and isoarnottiamide (209) from nitidine (213) (172,175). The proposed mechanism of this reaction (168,172,175) consists of initial attack of the peroxide ion on the C=N+ double bond followed by rearrangement and hydrolysis. 

Renaud and co-workers used 78 for the synthesis of (-)-phaseolinic acid (6) and (-)-pertusarinic acid (8) (Scheme 12) [32, 33]. Radical addition of dimethyl phenylselenomalonate to 78 proceeded with rearrangement of the bicyclics to yield the seleno-acetal 79 [34]. After reductive deselenylation and Baeyer-Villiger oxidation treatment of 80 with BU4NI and BBr3 led to a simultaneous cleavage of the ether, the lactone, and the methyl ester func-... 

In 2001, Albrecht Berkessel and Nadine Vogl reported on the Baeyer-Villiger oxidation with hydrogen peroxide in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent in the presence of Brpnsted acid catalysts such as para-toluenesulfonic acid (equation 85) . Under these conditions cyclohexanone could be selectively transformed into the corresponding lactone within 40 min at 60 °C with a yield of 92%. Mechanistic investigations of Berkessel and coworkers revealed that this reaction in HFIP proceeds by a new mechanism, via spiro-bisperoxide 234 as intermediate, which then rearranges to form the lactone. The study illustrates the importance of HFIP as solvent for the reaction, which presumably allows the cationic rearrangement of the tetroxane intermediates. 

The Baeyer-Villiger oxidation of 3-trimethylsilylcyclohexanone [250] is regioselec-tive as indicated. The reason for the selectivity is electronic which is revealed by an examination of the relationship between the polar groups of the ketone. Here we find a disjoint sequence, the a and f) carbon atoms are both quasidonors as dictated by their respective neighbors. The observed rearrangement, but not the alternative mode, relieves the unfavorable electronic interactions. 

Reactions which insert an O or NH group next to a carbonyl can be used to form heterocycles (Scheme 23). The Schmidt reaction or the Beckmann rearrangement can accomplish this for nitrogen, the Baeyer-Villiger oxidation does it for oxygen. For example, cyclohexanone is converted in this way into 2-azepinone and into 2-oxepinone cycloheptanone yields the corresponding eight-membered heterocycles. 

The mechanism of the Baeyer-Villiger oxidation has been studied extensively and is of interest because it involves a rearrangement step in which a substituent group (R) moves from carbon to oxygen. The reaction sequence is shown in Equations 16-9 through 16-11 ... 

One of the achievements in Baeyer-Villiger oxidation is aerobic catalytic rearrangement of cyclic ketones, for example, / -butylcyclohexanone, in the presence of Ru02 or Mn02 (0.05 equiv) and benzaldehyde (3 equiv) at room temperature (Equation 32), giving the respective e-caprolactones in yields up to 95%, the reaction being accelerated in the presence of lithium perchlorate <1994SL1037>. 

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