The Peroxide: An Underutilized but Highly Advantageous Functional Group

Peroxides are members of a class of underutilized but highly advantageous functional groups. The peroxide functionality has significant biological and medicinal applications concerning natural and synthetic products. Peroxides are also versatile synthetic intermediates able to serve as precursors for a multitude of functional groups. Transformations exploiting the reactive O-O bond of peroxides to generate a multitude of products, via ozonolysis and oxacycle synthesis, are the focus of this work. The reaction of ozone with alkenes, ozonolysis, is used in organic synthesis as a means for controlled oxidative cleavage. The traditional approach to ozonolysis generates, as products, a class of peroxides known as secondary ozonides. The secondary ozonide must be subjected to a subsequent synthetic step to convert it into the desired product. The secondary ozonide and other peroxide-containing products of ozonolysis are often unstable towards self-accelerating decomposition reactions. An attractive alternative to a traditional stepwise approach would involve in situ capture of the carbonyl oxide intermediates. Ozonolysis in the presence of pyridine involves an unprecedented organocatalyzed decomposition of carbonyl oxides via the formation and fragmentation of zwitterionic peroxyacetals. The overall process is fast, general, and high-yielding route to aldehydes and/or ketones. Oxacycles, cyclic ethers, are an important functionality found in natural products. C-O bond formation is usually based on attack by a nucleophilic oxygen onto an electrophilic carbon. The converse of this strategy, attack of a carbanion on to an electrophilic oxygen, has essentially been unexplored for intramolecular reactions. Electrophilic acting peroxide oxygen atoms can be utilized to form oxacycles, including oxetanes, aryl ethers, and spirocycles. Applications of this chemistry are directly applicable to natural product synthesis and towards the synthesis of the oxetene functionality