I. Development of the In Situ Reductive Ozonolysis of Alkenes with Tertiary Amine N-Oxides. II. Progress toward the Asymmetric Synthesis of Peroxyplakoric Acid A3.

Ozone, first discovered in the mid 1800’s, is a triatomic allotrope of oxygen that is a powerful oxidant. For over a century, research has been conducted into the synthetic application and mechanism of reactions of ozone with organic compounds. One of the major areas of interest has been the ozonolysis of alkenes. The production of carbonyl compounds is the most common synthetic application of ozonolysis. The generally accepted mechanism developed by Rudolf Criegee for this reaction involves the 1,3-electrocyclic addition of ozone to the π bond of the alkene to form a 1,2,3-trioxolane or primary ozonide. The primary ozonide is unstable at temperatures above -100 °C and undergoes cycloreversion to produce the carbonyl oxide and carbonyl intermediates. These intermediates then recombine in another 1,3-electrocyclic addition step to form the 1,2,4-trioxolane or final ozonide. While the final ozonide is often isolable, most synthetic applications of ozonolysis require a subsequent reductive or oxidative step to form the desired carbonyl compound. During investigations into the nucleophilic trapping of the reactive carbonyl oxide, it was discovered that when amines were used as additives, an increased amount of reaction time was required in order to consume all of the starting material. Surprisingly, significant amounts of aldehydes and a suppression of ozonide formation also occurred which led to the discovery that amine N-oxides formed by the ozonation of the amine additives in the reaction were intercepting the carbonyl oxide. From the observed production of aldehydes, our proposed mechanism for the in situ reductive ozonolysis reaction with amine N-oxides involves the nucleophilic trapping of the carbonyl oxide intermediate to produce a zwitterionic adduct that fragments into 1O2, amine and the carbonyl thereby avoiding the formation of peroxidic intermediates. With the successful total syntheses of peroxyacarnoates A and D by Dr. Chunping Xu, the asymmetric total synthesis of peroxyplakorate A3 was investigated. The peroxyplakoric acids are cyclic peroxide natural products isolated from the Plakortis species of marine sponge that have been found to exhibit activity against malaria, cancer and fungi. Even though the peroxyplakorates differ from the peroxyacarnoates in the polyunsaturated tail and the head group, the lessons learned from the syntheses of the peroxyacarnoates have proven to be valuable in the asymmetric synthesis of peroxyplakorate A3. The challenges for the asymmetric synthesis of peroxyplakorate A3 include the stereospecific formation of the 3-methoxy-1,2-dioxane core with a propionate head group and the introduction of oxidation sensitive dienyl tail in the presence of a reduction sensitive 1,2-dioxane core. It was found that the stereochemistry of two of the chiral centers could be controlled by an anti-aldol reaction of a chiral propionate followed by the stereospecific intramolecular cyclization of a hydroperoxyacetal. The regioselective ozonolysis of a 1,2-disubstituted alkene in the presence of a terminal alkyne forms the required hydroperoxyacetal as a mixture of diastereomers. Finally, the dienyl tail is introduced by a hydrometallation/iodination of the alkyne to produce a vinyl iodide followed by a palladium catalyzed coupling reaction. While the coupling reaction was unsuccessful in these attempts, it is still believed that the intramolecular cyclization to introduce the 1,2-dioxane core could prove to be a general solution to many other cyclic peroxides natural products.

Compressed Air, Wooden Clappers, and Other Non-Traditional Methods for Dispersing European Starlings from an Urban Roost

During autumn 2003, several thousand European starlings (Sturnus vulgaris) began roosting on exposed I-beams in a newly constructed, decorative glass canopy that covered the passenger pick-up area at the terminal building for Cleveland Hopkins International Airport, Ohio. The use of lethal control or conventional dispersal techniques, such as pyrotechnics and fire hoses, were not feasible in the airport terminal area. The design and aesthetics of the structure precluded the use of netting and other exclusion materials. In January 2004, an attempt was made to disperse the birds using recorded predator and distress calls broadcast from speakers installed in the structure. This technique failed to disperse the birds. In February 2004, we developed a technique using compressed air to physically and audibly harass the birds. We used a trailer-mounted commercial air compressor producing 185 cubic feet per minute of air at 100 pounds per square inch pressure and a 20-foot long, 1-inch diameter PVC pipe attached to the outlet hose. One person slowly (< 5 mph) drove a pick-up truck through the airport terminal at dusk while the second person sat on a bench in the truck bed and directed the compressed air from the pipe into the canopy to harass starlings attempting to enter the roost site. After 5 consecutive nights of compressed-air harassment, virtually no starlings attempted to roost in the canopy. Once familiar with the physical effects of the compressed air, the birds dispersed at the sound of the air. Only occasional harassment at dusk was needed through the remainder of the winter to keep the canopy free of starlings. Similar harassment with the compressor was conducted successfully in autumn 2004 with the addition of a modified leaf blower, wooden clappers, and laser. In conclusion, we found compressed air to be a safe, unobtrusive, and effective method for dispersing starlings from an urban roost site. This technique would likely be applicable for other urban-roosting species such as crows, house sparrows, and blackbirds.