Baeyer Villiger oxidation stereochemistry

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 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... 

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. 

Structure-activity correlations have been examined for several A-nor-thia-steroids of type (220). Several new studies have been devoted to the synthesis of A-nor-steroids. Pinacol-type rearrangement of 3a-hydroxy-2a-mesyloxy-3/S-methylcholestane (221) led to 2)8-acetyl-A-norcholestane (222). Its structure and stereochemistry were confirmed by Baeyer-Villiger oxidation, which afforded the known 2 -acetoxy-A-norcholestane (223) ... 

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. 

Baeyer-Villiger oxidation of bridged bicyclic ketones is valuable in synthesis because it provides a method for preparing derivatives of cyclohexane and cyclopentane with control of the stereochemistry of the substituent groups, and several syntheses of natural products have exploited this possibility. Thus, the lactone 64, important in the synthesis of prostaglandins, was obtained in a sequence the key step of which was the Baeyer-Villiger oxidation of the bridged bicyclic ketone 63 (6.62). 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

Baeyer-Villiger oxidation of a cyclic ketone results in a cyclic ester (a lactone) with a ring that has been expanded. Note that the stereochemistry of the carbon center involved in the migration is retained during the oxidation. 

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. ... 

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