A Curiosity Driven Exploration of Hypervalent Iodine(III) Reagents

Abstract

Hypervalent iodine (HVI) reagents have established themselves in the literature as reagents with diverse reactivity and utility in many different transformations. Their unique bonding structure often leads to divergent reactivity when compared to common oxidants, making them attractive reagents for study. They are typically easy-to-handle solids and require mild reaction conditions for activation. The field of hypervalent iodine is very active with many new transformations and even new reagents being reported annually.

In Chapter 2 the use of diaryliodonium salts as catalysts for the Nazarov cyclization is discussed. In this study, the structure of the diaryliodonium salt catalyst was optimized for solubility and activity in the Nazarov reaction. Univariate optimization of the reaction for solvent, reaction temperature, and catalyst loading was completed. Using the optimized conditions a series of substrates were explored. Notably, many of the yields obtained were lower than those reported in the literature for the comparable Lewis and Brønsted acid-catalyzed reactions. A 1H-NMR study revealed a possible substrate degradation pathway to account for the lower yields. Control reactions were used to establish the necessity of oxygen in the reaction for catalyst activation and turnover. Overall, reaction conditions were developed for the use of a diaryliodonium salt in the Nazarov cyclization.

In Chapter 3 we investigated the reactions of TolIF2 with styrenyl substrates containing a strained ring. This investigation uses the knowledge gained from previous reactions developed with TolIF 2 in the Murphy group. Three different reactions were explored, each giving a unique product, not obtained with classical fluorination methods. The first reaction, the reaction of TolIF2 with methylenecyclopropanes, produced a surprising product which incorporated the iodotoluene from TolIF2 into it, albeit in low yield. The second reaction was the ring expansion of a cyclobutanol to a fluorinated cyclopentanone. This reaction was optimized for Lewis acid activator, reaction solvent, temperature, as well as equivalents of reagent, but unfortunately still only gave the product in 61% yield with substantial side product. The final reaction explored was the gem-difluorination of alphacyclopropyl styrenes. Again, the conditions were optimized (Lewis acid, reaction temperature, reaction solvent, etc.) to produce the product in 51% yield. In this reaction, a persistent ketone byproduct was always observed.

In Chapter 4 attention was turned to the design of new fluoroiodane derivatives. A survey of the hypervalent iodine literature revealed addition of steric bulk ortho to the iodine atom in HVI reagents led to improvements in reaction outcome. The key structural feature assessed was the torsion angle of the hypervalent bond. X-ray crystal structures of new derivatives were obtained and the torsion angle of the hypervalent bond of five fluoroiodanes and three chloroiodanes were compared. As expected, the torsion angle was larger in newly prepared derivatives (~8° vs. ~20°). A much larger torsion angle of ~55° was achieved with the homologated six-membered fluoroiodane. Unfortunately, preliminary investigations of the reactivity indicate that this series is less reactive compared to the parent reagent.