Studies of the Lewis Acidity of Dicarbonyl Iodonium Ylides in Ionic and Photochemical Reactions

Abstract

Hypervalent iodine compounds have been established as useful reagents in synthetic chemistry due to their ease of handling and the diverse amount of chemical reactivity that can be accessed under mild reaction conditions. Iodonium ylides comprise an important class of hypervalent iodine reagents. They function as carbene transfer reagents with many different applications. They are also a safer alternative to diazo compounds. This thesis will focus on understanding the σ-holes in iodonium ylides and using this knowledge to develop new reactions. For this purpose, Chapter 1 introduces hypervalent iodine reagents and the synthesis and properties of iodonium ylides. Then, σ-holes are discussed with many examples of their applications in chemical reactions between iodonium ylides and nucleophiles. In Chapter 2, computational analysis is used to view the σ-holes of iodonium ylides. Then a new theory is developed to understand the link between the existence of two σ-holes and the regioselectivity observed in the reactions of iodonium ylides with different nucleophiles. Understanding the Lewis-acidic nature of iodonium ylides and the presence of two σ-holes was used to promote O-H insertion of carboxylic acid and S-H insertion of thiols into the dicarbonyl motif of iodonium ylides. The halogen-bonding interactions between the iodine center of the ylide and the heteroatoms of the reaction partner (O or S) facilitate the transfer of hydrogen to the α-carbon of the dicarbonyl motif of the ylide. Then, reductive elimination takes place to produce the final product. Both insertion reactions have wide substrate scope under mild conditions and give excellent yields. In Chapter 3, the reaction between iodonium ylides and alkynes is investigated. In 2019, the Murphy Group discovered that blue light (λmax = 461 nm) irradiation of a β‐dicarbonyl‐derived iodonium ylide and an alkene offers a highly chemoselective synthesis of doubly activated cyclopropanes, presumably via a diradical intermediate. Replacing alkenes with alkynes in this reaction resulted in furans, and using substituted iodonium ylides as substrates could result in the development of a metal-free method for the synthesis of substituted furans. This is important due to the countless occurrences of substituted furans in medicinal chemistry.