Peroxy bicyclization

More recently, Bachi and coworkers extended and adapted the TOCO reaction to the synthesis of 2,3-dioxabicyclo[3.3.1]nonane derivatives hke 228 (Scheme 52) ° ° . As detailed in Scheme 53a, the bridged bicyclic hydroperoxide-endoperoxides hke 229 are obtained, from (S )-limonene (227), in a 4-component one-operation free-radical domino reaction in which 5 new bonds are sequentially formed. Particular experimental conditions are required in order to reduce the formation of by-products 230 and (PhS)2, and to favor the critical 6-exo-ring closure of peroxy-radical 231 to carbon-centered radical 232206 chemoselective reduction of bridged bicyclic hydroperoxide-endoperoxides... 

Before we move on, we leave you with one final example. Stereoselectivity in the epoxidation of lactone-bridged alkenes related to those we saw earlier (p. 874) can be completely reversed if the lactone is hydrolysed, revealing a hydroxyl group. In this bicyclic example, the hydroxyl group delivers the peroxy-acid from the bottom face of the alkene. First, the lactone bridge is used to introduce the alkene as before. 

The peroxy radical formed in (Reaction 2b) is expected to cyclicize to form a corresponding bicyclic radical (Reaction 4) or react with nitric oxide via an abstraction mechanism to form the corresponding aromatic oxy radicals (Reaction 5a) ... 

By controlling reaction conditions and by proper choice of the peroxy acid, it is often possible to favor the Baeyer-Villiger reaction over epoxidation. An illustrative example of the usefulness of the Baeyer-Villiger reaction is the stereospecific, and regio- and chemoselective conversion of the unsaturated bicyclic ketone shown below to a cyclopentene containing three consecutive stereogenic centers. 

Attempted peroxy acid epoxidation of the bicyclic ketone (31 equation 13) gave the lactone (33), instead of several possible rational alternatives. The epoxide (32) was implicated as an intermediate when it was independently synthesized from the epoxy alcohol, and shown to give (33) on treatment with aqueous acid.- A mechanism involving scission of the acyl bridgehead bond via the hydrated 1,1 -diol form of the ketone was proposed to account for the formation of this unexpected product. The rearrangement of the isolongifolene derivative (34 equation 14) appears to be mechanistically related. The product (35) is formed by brief treatment with dilute HCIO4 in dioxane as a mixture of isomers believed to arise by acid-catalyzed epimerization of the carbinol center. ... 

Alkyl peroxy radicals generally react with NO to form alkoxy radicals (assuming sufficient NO is present). Aromatic peroxy radicals, in contrast, are believed to cyclicize, forming bicyclic radicals. For the product of reaction b above, the energetically favored bicyclic radical is... 

After bicyclic radical formation, 02 rapidly adds to the radical, forming a bicyclic peroxy radical, for example... 

Addition of the PhOO radical to the ipso carbon of the phenyl ring has a low barrier (20 kcal mol below the entrance channel) and a tight transition state. This path is important and the addition results in a dioxirane cyclohexadienyl radical (Y(C6 )Y(C02). This bicyclic cyclohexadienyl-dioxirane adduct has resonance between the ortho and para positions on the ring. The formation path has a barrier of 29 kcal mol relatively to the stabilized peroxy... 

When the bicyclic alkene I, a rm r-decalin derivative, reacts with a peroxy acid, II is the major product. What factor fevors the formation of II in preference to III (You may find it helpful to build a handheld molecular model.)... 

Birdsall, A.W., Dreoni, J., Elrod, M.J. Investigation of the role of bicyclic peroxy radicals in the oxidation mechanism of toluene. J. Phys. Chem. A 114, 10655-10663 (2010)... 

---