Baeyer-Villiger reaction stereochemistry

One point to note about both of the last two reactions is that the insertion of oxygen goes with retention of stereochemistry. You may think this is unsurprising in a cyclic system like this and, indeed, the first of the two cannot possibly go with inversion. However, this is a general feature of Baeyer-Villiger reactions, even when inversion would give a more stable product. 

The Baeyer-Villiger reaction occurs with retention of stereochemistry at die migrating center. This stereoselectivity has been utilized in a practical method for the preparation of isotopically chiral metiiyl acetic acid (5) ftom [2- H]cyclohexanone (4) prepared by enzyme-catalyzed stereoselective exchange of the pro-R a -proton and enantioconvergent exchange of the a-proton with deuterium (Scheme 2). As a cautionary note, prior epimerization of an acyl group prior to oxidation has been observed. ... 

During the synthesis of the Woodward reseipine precursor (17 Scheme 4), Peariman used the protected acylacetal (13) to control the stereochemistry of an intramolecular photocherrucal cycloaddition to (14). The strategy for opening the cyclobutane ring employed the Baeyer-Villiger reaction to convert the... 

The second White synthesis of 154 (depicted in Scheme 4.29) began with the treatment of dibromoketone 181 with zinc-copper couple to give a 2-oxo-l,3-dipole, which upon condensation with furan gave the oxabicyclo[3.2.1] system 182. Hydrogenation of the double bond followed by Baeyer-Villiger reaction afforded lactone 183 in 92% yield. The prior three steps have created the stereochemistry (albeit undesired but manipulable) not only at the C-3 and C-6... 

Scheme 10.15, which is appreciably shorter than 10.14, uses the same general methods to establish the stereochemical relationships. In step C, the cyclopropane ring is opened by protonation. The incipient carbonium ion is captured intramolecularly, and the cis relationship between the C-2 and C-5 substituent is thereby established. The geometry of the bicyclic ring system and the retention of stereochemistry in the Baeyer-Villiger reaction are used to ensure the cis stereochemistry of the substituents at C-1 and C-3, as in Scheme 10.14. Step A is an electrophilic substitution that is initiated by protonated formaldehyde. The resulting cation is captured by formic acid, and the primary alcohol is also formylated under the reaction conditions.

Retention of configuration was demonstrated in the Baeyer-Villiger reaction shown in Equation 3.11 [49]. Perbenzoic acid initiates migration of the norbornyl group in a concerted fashion, allowing the exo stereochemistry of the starting material to be maintained. 

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). 

A detailed examination of OSO4 reactions with A -steroids has been reported." The A-ring conformation of the reactant or derived complex is important in determining the stereoselectivity of these reactions, and the major role of the proximate substituents is to anchor the appropriate conformation favouring a- or /3-attack. Studies on the stereochemistry of electrophilic attack on cholest-5-en-3-one continue." As with bromine chloride," appreciable /3-attack occurs and the 5/3,6j8-epoxide was isolated along with the previously reported 5a,6a-epoxide and the Baeyer-Villiger product, the A-homo-enol lactone (58). Base-catalysed... 

For example, the method potentially opens an access to compounds with a doubly chiral isopropyl unit (Scheme 14). In the pro-5-selective enzymatic hydroxylation of isobutyric acid (88) to (S)-/3-hydroxyisobutyric acid (89) the stereochemistry of the hydroxylation at C-3 is not known. It could be studied by preparing 88 in a doubly chiral form via stereocontrolled ami-SN2 reaction of dimethyl cuprate with the tosy-late 90 to give 91 which is then degraded by Lemieux- and then Baeyer-Villiger oxidation to 88. 

A hetero-Diels-Alder reaction between the imine (115) and the cyclohexadiene (116) produces the aza-bicyclo-octane (117), which after Baeyer-Villiger ring expansion followed by reduction, gave the triol (1l8), an advanced intermediate with all three chiral centres in their correct relative stereochemistry, for the synthe-... 

---