Baeyer-Villiger oxidation steps

Propoxyphene has chiral centers at both C-2 and C-3, with the latter equivalent to that of isomethadone. Pohland and others(86) showed the C-3 centers of (+)-propoxyphene and (-)-isomethadone to be identical (3R) by a sequence that rests upon retention of configuration during a Baeyer-Villiger oxidation step (Scheme 9.12). In subsequent work, this assumption was justified by a correlation that did not involve the C-3 center and employed a Mannich base intermediate.(87) The C-2 configuration of (+) propoxyphene was established by a lengthy sequence that required degradation of the compound to (+)-2,3-diphenylpropane of known (S) configuration. 

Takano G3 (1992) plan for (-)-kainic acid Pausan-Khand reaction to make top ring in step 11, which is then ring expanded by Baeyer-Villiger oxidation (step 17) and opened up in steps 23. 

Wright, J.L.C., Hu, T., McLachlan, J.L., Needham, J., and Walter, J.A. (1996) Biosynthesis of DTX-4 Confirmation of a polyketide pathway, proof of a Baeyer-Villiger oxidation step, and evidence for an unusual carbon deletion process./. Am. Chem. Soc., 118, 8757-8758. 

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. 

The stereochemistry of the C(3) hydroxy was established in Step D. The Baeyer-Villiger oxidation proceeds with retention of configuration of the migrating group (see Section 12.5.2), so the correct stereochemistry is established for the C—O bond. The final stereocenter for which configuration must be established is the methyl group at C(6) that was introduced by an enolate alkylation in Step E, but this reaction was not very stereoselective. However, since this center is adjacent to the lactone carbonyl, it can be epimerized through the enolate. The enolate was formed and quenched with acid. The kinetically preferred protonation from the axial direction provides the correct stereochemistry at C(6). 

The stereoselective [2+2] cycloaddition between ketenes and enolethers can be used as a key step in the construction of y-butyrolactones (Scheme 14) [45], if the resulting cyclobutanones can subsequently undergo ring enlargement by a regioselective Baeyer-Villiger oxidation. 

The stereochemistry of the C-3 hydroxyl is established in step E. The Baeyer-Villiger oxidation proceeds with retention of configuration of the migrating group (see Section... 

Baeyer-Villiger oxidation of the 5a-6-keto steroid 1 with trifluoroperacedc acid is 1000 times faster than oxidation with m-chloroperbenzoic acid and also is more regioselective. This oxidation was used in the last step in a synthesis of brassinolide (2), a natural steroid that promotes plant growth.2... 

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 key steps in the ring expansion of the cyclobutanones (186) and (787) are the Baeyer-Villiger oxidation effected by H202—HOAc. It is noteworthy to point out that the Baeyer-Villiger oxidation is regiospecific and serves to be an excellent method for the preparation of y-lactone from cyclobutanones. 

Baeyer-Villiger oxidation has been used to selectively oxidize one of two methyl ketones (to esters) in the final step of a stereoselective synthesis of (—)-acetomycin, an antibiotic with potential anti-leukemia activity (equation 25)135. This reaction was accomplished using MCPBA as oxidant, with an excess of sodium bicarbonate and 5-/er/-bulyl-4-hydroxy-2-melhyl phenyl sulfide as a radical inhibitor. 

Same as Baeyer-Villiger Oxidation for the oxidation step. DARZENS CONDENSATION... 

Steps 1 -2 Baeyer-Villiger oxidation followed by acetate hydrolysis. 

It is the second feature of the Newton-Roberts approach that is valuable from a stereocontrol point of view. In the Corey lactone approach, the synthon itself already contains C-13 of the co-sidechain, which enforces the use of a reagent containing a C-15 carbonyl, making control of the C-15 hydroxyl stereochemistry difficult, whereas in the tricycloheptanone approach the entire sidechain (C-13 to C-20) is added in one piece, which means that this sidechain can be readily introduced in the form of a reagent that has this sidechain stereochemistry already in place. Following the addition of the co-sidechain and a Baeyer-Villiger oxidation to the lactone, the later steps to add the a-chain are essentially identical to the Corey lactone route because the lactones are regioiso-meric. 

Another one-step addition reaction to C=C double bonds that forms three-membered rings is the epoxidation of alkenes with percarboxylic acids (Figure 3.19). Most often, meta-chloroperbenzoic acid (MCPBA) is used for epoxidations. Magnesium monoperoxyphthalate (MMPP) has become an alternative. Imidopercarboxylic acids are used to epoxidize olefins as well. Their use (for this purpose) is mandatory when the substrate contains a ketonic C=0 double bond in addition to the C=C double bond. In compounds of this type, percarboxylic acids preferentially cause a Baeyer-Villiger oxidation of the ketone (see Section 14.4.2), whereas imidopercarboxylic acids selectively effect epoxidations (for an example see Figure 14.35). 

Oxidation and Reduction.—The Baeyer-Villiger oxidation of a 4-en-3-one normally inserts an oxygen atom between C-3 and C-4, but in the presence of a 6/3-bromo-substituent (198) it leads to formation of the alternative 3-oxa-product (199). Some of the normal 4-oxa-product appears also to be formed, but reacts to give the ester-lactone (200) by further oxidative steps.176... 

The substrates can also be prepared in a two-step sequence involving alkylation of umbelliferone with 2-chloroketones followed by Baeyer-Villiger oxidation. The sequence is particularly interesting for obtaining the fluorogenic lactones 28 and 29, which only react with esterases [40]. 

Cyclic ethers from cyclic ketones. The replacement of the carbonyl group of a cyclic ketone by oxygen can be effected in four steps Baeyer-Villiger oxidation to a lactone, DIB AH reduction to a lactol, (3-scission to an iodoformate, and finally cyclization. 

The Baeyer-Villiger oxidation has been utilized as an element of several novel functional group manipulations. Suginome and Yamada converted adamantanone (64) to 2-thiaadamantane (66) via the lactone (65 Scheme 19). Eaton et al.P in the synthesis of pentaprismane (70) from homopentaprismanone (67 Scheme 20), required that a leaving groiq) be introduced a to the carbonyl group in or r to carry out a Favorskii ring contraction. Oxidation of (67) afforded lactone (68), which was converted in several steps to the requisite hydroxy ketone (69). 

---