Baeyer-Villiger ring expansion

Oxidation of 4-alkylamino-5-methoxy-l,2-benzoquinones yields 4-alkyaminopyran-2-ones probably through sequential Baeyer-Villiger ring expansion, epoxide formation and ring contraction (95TL6669). 

Similar reactions were described by Vogel, using a naked sugar as a radical acceptor. The resulting product has to be further elaborated before it becomes a true C-linked disaccharide, with the key-step being a Baeyer-Villiger ring expansion [ 104,105] (O Scheme 48). 

Epoxidation in the absence of a metal catalyst is possible. Hydrogen peroxide, in the presence of a nitrile, aldehyde or ketone, or a relatively acidic alcohol (e.g. phenol), can effect epoxidation of an alkene. Peroxy-imidic acids RC(=NH)OOH, formed in situ by reaction of nitriles (RC=N) with hydrogen peroxide, react under mildly alkaline or neutral conditions. For example, 2-aUyl-cyclohexanone was readily converted into the corresponding epoxide with the alkaline reagent, whereas with peroxy-acetic acid Baeyer-Villiger ring-expansion intervenes. The perhydrate 39,... 

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-... 

The Diels-Alder adduct (389), on sequential hydrolysis, bromolactonization, and reductive debromination, was converted into the hydroxy-lactone (390), which, on Collins oxidation to (391) and Baeyer-Villiger ring-expansion, afforded the novel dilactone (392). Free-radical cyclization of the bromo-ketone (393), initiated by tri-n-butyltin hydride, gave a 3 2 mixture of the endo- and exo-derivatives (394), which, on separation and homologation, were transformed into the tricyclic sesquiterpenes sativene, endo-(395), and copacamphene, exo-(395). The use of bicyclo-... 

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. 

This homologous Baeyer-Villiger type oxidative ring expansion represents a conceptually new protocol illustrating the substantial value of one-pot, four-component annulations as a flexible and simple new synthetic method. 

The Baeyer-Villiger enzyme, cyclohexanone monooxygenase (CHMO), has been applied to the oxidative ring expansion of m-2,6-dialkylperhydropyrans to afford 28 with very high yields and ee s, when R = methyl or ethyl (Scheme 11) <2001JM0349, 2003SL1973>. 

Several of the seminal routes to the lactone, as devised by Corey, are summarized in Fig. 5. Diels-Alder reaction of (methoxymethyl)cyclo-pentadiene [15] with chloroacrylonitiile and then basic hydrolysis gave the bicydic ketone [16] (20). Ring expansion in a selective Baeyer-Villiger reaction led to lactone [17] that was then hydrolyzed to hydroxy add [18],... 

The group-selective stereodifferentiation of C-C bonds has been investigated in the context of ring-expansion chemistry. In a symmetrical ketone like 4-tert-butylcyclohexanone, the two methylene groups adjacent to the ketone are enantiotopic. Several groups interested in the overall oxidation of these bonds have developed asymmetric versions of the classical Baeyer-Villiger and Beckmann reactions (Scheme 8.29a). 

Scheme 8.29. (a) A generic asymmetric ring-expansion reaction, (b) A kinetic resolution using an asymmetric Baeyer-Villiger catalyst [128]. (c) A synthetic equivalent of an asymmetric Baeyer-Villiger reaction [129]. 

Activation for the Michael reaction could be by C02Et group or enamine formation. Ring expansion of (16) to <14> is unambiguous as only the more substituted side chain migrates, as in the Baeyer-Villiger reaction (Chapter... 

---