Bicyclic 3-hydroperoxides, synthesis

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... 

An intramolecular variation of this method, employing 3-bromocycloalkyl hydroperoxides 24, has proved a versatile procedure for the synthesis of bicyclic peroxides with an [n.2,1] skeletal arrangement, 25 (Eq. 20). 

As the first isolable intermediate in the bioconversion of arachidonic acid into prostaglandins and thromboxanes (Eq. 3), PGG2 is a bicyclic peroxide of immense biological importance. It is difficult to obtain pure from natural sources and the presence of the 15-hydroperoxide group adds a further dimension of chemical lability to that associated with the 9,11-peroxide bridge. The chemical synthesis of PGG2 is thus a landmark in prostaglandin chemistry. It also represents a pinnacle of success for the silver-salt route to bicyclic peroxides. 

The isomeric salts 126 are valuable starting compounds for the synthesis of bicyclic 3-hydroperoxides 267, which surprisingly reacted in heated H202 in acetic acid, to i s o t h i az o 1 - 3 (2 //) - o ne 1,1-dioxides 268a-d by a Criegee-type rearrangement (00JPR675, Scheme 90). 

The last VCD example by Lattanzi et al. describes the use of VCD and DFT calculations to assign the absolute configuration of a recently prepared (15,4/ )-norcamphor-derived furyl hydroperoxide, (+)-8, introduced as a less hindered and more reactive stereoselective oxidant in organic synthesis. During the preparation of 8 through the hydroperoxidation of an alcohol precursor via nucleophilic substitution, it is expected that epimerization will occur at carbon 2 of the bicyclic framework leading to the formation of either exo- or endo-8 (Figure 53.25). Therefore, the... 

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