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Stereoselective dioxygenation: Methodology and application
Abstract
As a part of a continuing program targeting the synthesis of peroxide-containing natural products, we are interested in the use of singlet oxygen ($\sp1$O$\sb2$) for the stereoselective introduction of the carbon-oxygen bond. Initial efforts involve the auxiliary-directed dioxygenation of enoates. Although phenylcyclohexyl auxiliaries were ineffective in shielding the enoate sidechain, moderate diasteroselectivity can be achieved in the dioxygenation of 8-arylmenthyl enoates. Auxiliary-induced stereoselection is ultimately compromised by a lack of conformational bias between enoate conformers. Our approach had been based upon the assumption, derived from literature reports, that the s-cis conformer would be more reactive towards $\sp1$O$\sb2$. However, our results provide compelling, if indirect, evidence for the similar reactivity of the enoate conformers toward $\sp1$O$\sb2$. The use of chiral phosphite ozonides as a source of chiral singlet oxygen was also investigated. This, the first systematic study of phosphite ozonide reactivity and selectivity, clearly indicates that the ozonides are much less reactive than $\sp1$O$\sb2$ and are effectively limited to oxygenation of tri- and tetra-substituted alkenes and as sulfides. The failure to achieve significant enantioselection, despite the use of chiral auxiliaries proven effective in other applications, implies that approach of the substrate to the reactive oxygen centers is able to occur on a trajectory allowing minimal interaction with the auxiliaries. Finally, the first asymmetric synthesis of chondrillin, a sponge-derived peroxyketal displaying in vitro antitumor activity, and the epimeric plakorin, a potent ATPase activator, has been completed. The synthesis of these molecules takes advantage of the stereoselective addition of $\sp1$O$\sb2$ to chiral allylic alcohols, and the stereoselective allyl peroxyl radical (2,3) -rearrangement. Successful implementation of these protocols offers a general route to 3,6-dihydro-1,2-dioxin-3-ols, an important class of biologically active cyclic peroxides.
Subject Area
Organic chemistry|Analytical chemistry
Recommended Citation
Woller, Kevin Roger, "Stereoselective dioxygenation: Methodology and application" (1996). ETD collection for University of Nebraska-Lincoln. AAI9715991.
https://digitalcommons.unl.edu/dissertations/AAI9715991