The [1,2]-Stevens Rearrangement of Oxonium Ylides: Synthetic Applications and Mechanistic Studies

Abstract

The Stevens [1,2]-rearrangement of onium ylides has been employed as a valuable synthetic method to construct new C-C bonds. Oxonium ylides are reactive intermediates that undergo facile Stevens rearrangement under mild conditions. In the last several decades, the Stevens rearrangement of oxonium ylides has been extensively employed in synthesis of important core structures, heterocycles and natural products. Despite significant synthetic applications of the Stevens [1,2]-rearrangement, its mechanism has remained ambiguous. Different mechanistic pathways including the presence of either radical or zwitterionic intermediates have been proposed based on the product distribution or CIDNP spectroscopy. However, these mechanistic studies have mostly been performed on ammonium ylides. In Chapter 1, I will describe the Stevens rearrangement of cyclic oxonium ylides and its application in synthetic chemistry. I will also discuss mechanistic studies that have been performed on the Stevens rearrangement of the onium ylides since its discovery. It is known that cyclic oxonium ylides can undergo ring contraction via endocyclic [1,2]-shift. In Chapter 2, I demonstrate the ability of the cyclopropylcarbinyl migrating group to generate cyclobutanones through a [1,2]-shift. The generality of the cylocpropylcarbinyl migration will be demonstrated in this chapter. I will also discuss the importance of strained four membered rings in natural products and synthetic chemistry. [1,2]-Migration of the cyclopropylmethyl group provides more strained structures possessing both cyclobutanone and intact cyclopropane moieties. The presence of the intact cyclopropane in the structure of the cyclobutanones resulting from the Stevens rearrangement, delivers an important message related to the reactive intermediates involved in the reaction mechanism. A fast cyclopropane ring opening is expected in the case of radical intermediates. In Chapter 3, the nature of the reactive intermediates will be described, employing ultrafast radical clocks as differentiation tools to determine the nature of the actual intermediates present during the Stevens rearrangement. The last chapter will describe the design and synthesis of broad-spectrum antivirals which inhibit viral entry. Inspired by the antiviral activity of the epigallocatechin gallate (EGCG), an extracted catechin from green tea, against a large group of unrelated viruses, we designed and synthesized a library of molecules possessing polyphenolic moieties which have been known to be the active site in the EGCG viral inhibition. The effect of the central scaffolds as well as the importance of the functional groups and the number of the polyphenolic structures will be discussed.