Mechanisms Baeyer- Villiger oxidation

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. 

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. 

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. 

For oxidation of terminal and internal alkynes to carboxylic acids by RuO / Oxone /Na(HC03)/aq. CHjCN-EtOAc (Table 3.4) a mechanism was proposed in which C3H. CCC3H., is oxidised by RuO to the dione via a Ru(Vl) diester (1), with the resulting dione (2) then undergoing Baeyer-Villiger oxidation by HSOj" to give an acid anhydride (3) which was hydrolysed to the acid (Fig. 1.9 R= C3H3) [377]. 

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. 

Mechanism of Baeyer-Villiger Oxidation Both aldehydes and ketones are oxidized by peroxy acids. This reaction, called the Baeyer- Villiger oxidation, is especially useful with ketones. 

The same Pt species that epoxidize double bonds are active in Baeyer-Villiger oxidation of ketones. Strukul has shown that this synthetically interesting process can be carried out also enantioselectively, in the presence of appropriate diphosphine ligands121-123. For this reaction a mechanism has been proposed that involves again a quasi-peroxo metallacycle intermediate, even though in this reaction the metal catalyst plays primarily the role of a Lewis acid while the real oxidant is H2O2 itself (Scheme 9). 

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 mechanism was substantiated by independent treatment of alkane hydroperoxides with Magic Acid.603 Similarly, Baeyer-Villiger oxidation of several ketones in the presence of H2O2 and superacids gave similar product compositions. 

Among the most popular oxidative biotransformations, Baeyer-Villiger monooxygenases (BVMOs) belong to the main fields of research. Nowadays, manifold enzymes catalyzing the Baeyer-Villiger oxidation are expressed in common recombinant organisms, such as E. coli or S. cerevisiae. The mechanism of the enzymatic... 

Preparation of optically active P-ionone epoxide by a solid state kinetic resolution in the presence of the chiral host 10a is also possible. When a mixture of 10a, P-ionone (66) and m-chloroperbenzoic acid (MCPBA) is ground by mortar and pestle in the solid state, (+)-67 of 88% ee was obtained.29 Mechanism of the kinetic resolution is shown below. Of course, all processes proceed in the solid state. Firstly, oxidation of 66 with MCPBA gives rac-P-ionone epoxide (67). Secondly, enantioselective inclusion of (+)-67 with 10a occurs. Thirdly, uncomplexed (-)-67 is oxidized to give the Baeyer- Villiger oxidation product (-)-68 of 72% ee. This is the first example of the resolution by an enantioselective inclusion complexation in the solid state. 

We have found it useful to prepare authentic samples of the various diperoxides encountered by using a variation of the Baeyer-Villiger oxidation conditions. Oxidation of ketones at low temperatures using peracetic acid has been reported (23) to give diperoxides instead of the esters produced under Baeyer-Villiger conditions. Authentic samples of 10 and 11, can be prepared, respectively, by the peracetic oxidation of acetone and methyl ethyl ketone jointly or methyl ethyl ketone alone. We are studying the mechanism of this interesting oxidation reaction. 

Alkaline hydrogen peroxide reacts with a jS-unsaturated ketones by a different reaction sequence, exemplified by the behaviour of "A-nor-testosterone 27) [7 ]. The reagent first converts the steroid into the corresponding epoxy-ketone 28) by the mechanism discussed on p. 201, and only then brings about a Baeyer-Villiger oxidation of the ketone function to give the epoxy-lactone (29) as the major product. 

Several of the aldol products obtained were readily converted to their corresponding esters by Baeyer-Villiger oxidation. These results also are summarized in Table 16. Ester 66 was further transformed into key epothilone A intermediate 69 and also a key synthetic intermediate 70 for bryostatin 7. What is the mechanism of these direct catalytic asymmetric aldol reactions using LLB-II It is apparent that self-assembly of LLB and KOH occms, because of the formation of a variety of aldol products in high ee and yields. In addition, the NMR and LDI-TOF(-i-)MS spectra of LLB KOH show the occurrence of rapid exchange between Li and K. We have already found that LPB[LaK3tris(binaphthoxide)] itself is not a useful catalyst for aldol reactions, and that the complexes LPB KOH or LPB LiOH give rise to much less satisfactory results. 

Because of the common mechanisms and the same specific oxidants, the Baeyer-Villiger oxidation of ketones possessing other functional groups will be mentioned in this section rather than in the places where it should be discussed according to the system of the book. 

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