New Oxidation Chemistry
Ozone, a “green” oxidant generated from air and electricity, is widely used for metal-free cleavage of alkenes to ketones and aldehydes. However, ozonolysis under traditional conditions generates energetic and potentially hazardous peroxide intermediates that must be decomposed during workup. Our lab has developed three different approaches to “reductive" ozonolyses, each of which exploits the electrophilic character of the short-lived carbonyl oxide intermediate to directly generate aldehyde and ketone products.
The advantage of these procedures can be seen in the comparison shown below.
One of the most common applications of ozonolysis is generation of aldehyde and ketone precursors for C-C bond-forming reactions. The reductive ozonolyses based upon N-oxides and pyridine both generate carbonyl products under anhydrous conditions, allowing one-pot application in combination with a number of common organic transformations (below).
A Highly Efficient Method for Chemical Generation of Singlet Oxygen
Singlet molecular oxygen, 1O2, an excited state possessing 22 kcal/mol of additional energy relative to the ground state triplet, is an important species in chemistry (peroxide synthesis, chemiluminescence), biology (the immune response, damage by reactive oxygen species) and medicine (photodynamic therapy). Our investigations discovered a new peroxide fragmentation of derivatives of 1,1-dihydroperoxides which provides one of the most efficient processes yet known for chemical generation of 1O2.
New Organic Reactions: Inter- and Intramolecular Synthesis of Ethers from Peroxides
Synthesis of ethers is traditionally based upon reaction of nucleophilic oxygen with electrophilic carbon. The reversed or "umpoled" version of this strategy, attack of carbanions on electrophilic oxygen in the form of peroxides, has been explored only for intermolecular reactions and mainly for reactions of unhindered (methyl) peroxides.
Our recent work has demonstrated that it is possible to create peroxide electrophiles which are easily handled yet sufficiently reactive to achieve transfer of alkoxides to functionalized carbanions. Ongoing research is developing strategy for synthesis of 1°, 2°, and 3° ethers via reactions of the corresponding peroxides with RLi and RMgX reagents.
In separate work, we demonstrated the successful intramolecular reaction of functionalized peroxides with stabilized anions as an approach to cyclic ether. In a particularly exciting development, we found that bisfunctionalzied electrophiles containing both a peroxide and a C-I bond undergo tandem C-C/C-O bond formation to generate spirocycles in a single step.
Tuberculosis resulting from infection with Mycobacterium tuberculosis (M. tb) remains one of mankind’s most significant disease threats. In collaboration with Prof. Robert Powers (UNL Chemistry) and Prof. Raul Barletta (UNL School of Veterinary and Biomedical Science), we have been exploring structurally modified fatty acids as a new class of potential antimycobacterials. Our initial results have been quite promising, with several molecules inhibiting growth at the low uM level.
Chemical Biology and Nutrigenomics
Phytosterols: Plant sterols, also known as phytosterols, are of interest as dietary additives able to reduce serum cholesterol. In collaboration with Prof. Tim Carr (UNL Nutrition Sciences) through the Nebraska Gateway for Nutrigenomics we have been exploring the structure of phytosterols and derived esters and ethers to better understand influences on cholesterol absorption and uptake. See: Nutr. Res. 2011, 31, 537; Lipids, 2010, 45, 855; Steroids, 2010, 75, 879–883; J. Nutr. Biochem., 2010, 21, 736.
Fungal and bacterial biosynthesis: An ongoing collaboration with Prof. Liangcheng Du (UNL Chemistry), investigates biosynthetic processes intermediates in fungal and bacterial systems
“Synthesis of a 2,4,6,8,10-dodecapentenoate thioester as a substrate for biosynthesis of Heat Stable Antifungal Factor” Olson, A. S.; Chen, H.; Du, L.; Dussault, P. H. RSC Advances 2015, accepted for publication. For other publications in this area, see J. Am. Chem. Soc. 2011, 133, 643; Biochemistry 2006, 45, 2561.
Nanohybrid Materials: Chemistry at the organic/analytical interface
We are part of the Center for Nanohybrid Functional Materials, a group of eighteen investigators from five Nebraska colleges or universities. The activities of the Center focus on interdisciplinary approaches to discovery and application of new sensing and separation principles at the surfaces of functionalized nanomaterials. Our research within the Center focuses on methods for synthesis of functionalized amiphiphiles as linkers or coatings with unique chemical or physical properties.
Peroxide and Ozone Safety
Organic peroxides (and ozone): Safety-oriented overview: Follow this link to a brief introduction to organic peroxide and ozone safety.
Topics include classes of peroxides and hydroperoxides, reactivity of organic peroxides, hazard identification (including the concept of active oxygen content), hazard minimization, reaction monitoring using peroxide-sensitive strips and TLC dips, an introduction to the safe use of ozone in organic synthesis, and references to further reading on peroxide safety.