Baeyer- Villiger Oxidation/Rearrangement mechanism

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. 

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 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 ... 

The newly formed Si—F bond in 6 enables the oxidative cleavage in the next step in a manner similar to what is observed in the Tamao oxidation. Thus, displacement of the fluoride with perbenzoate anion 7 results in 8. Peroxide 8 can rearrange by a mechanism similar to the Baeyer-Villiger oxidation to yield 9. This process can be repeated twice more resulting in 10. Finally, hydrolysis of 10 produces the desired alcohol. 

The oxidation of the bicyclic amino-ketone shown in the margin demonstrates how useful this effect can be. This is the Baeyer-Villiger rearrangement, which you will meet in Chapter 37. The mechanism is not important here all you need to know is that it inserts an oxygen atom on one side or the other of the ketone C=0 group. The question is—which side ... 

C-C bond cleavage process have been proposed (Figure 6.48) . The first involves a Baeyer-Villiger-like oxidation of the keto tautomer of the phenol and the second a rearrangement of the epoxide intermediate in aromatic oxidation. Delineation of the mechanism will require experimentation with purified enzyme, mutants, and substrate analogues. 

Oxidative Rearrangements of Ketones 9.3.2.1 Baeyer-Villiger Reactions Introduction and mechanism... 

---