Novel synthetic reactions employing hypervalent iodine compounds: oxidations and arylations

Due to the challenges facing the humanity in the 21st century, the requirements for chemical synthesis are growing, especially in terms of reducing cost and environmental impact. One of the changes in line with the above directions is to limit the use of metal compounds, especially these of heavy and noble metals. In this context, hypervalent iodine species offer great opportunities. On one hand they have properties that allow them to replace metal-based oxidants and catalysts, and on the other, they possess a number of advantages, such as low toxicity and moderate price. Although the chemistry of hypervalent iodine compounds has a long history, the intensive development of their applications in organic synthesis has taken place over the period of the last 40 years, of which the last decade has seen a leap forward in the emergence of new chemical processes utilizing this class of reagents. The two most important types of organic reactions promoted by hypervalent iodine-based reagents are oxidations reactions, often accompanied by the formation of new bonds and building the molecular complexity, and electrophilic group transfers. This thesis presents the overview of such transformations (Chapter 1) and describes the development of several new synthetic methods based on both above reaction types. The first of the implemented projects, described in Chapter 2, concerns the synthesis of Pummerer's ketone and its analogs by the oxidative coupling of para-substituted phenols using iodine(III) compounds as oxidants. The rigid tricyclic Pummerer's ketone system is a common motif in substances of pharmaceutical interest. Existing procedures for the oxidative coupling of phenols to Pummerer ketone use a variety of oxidizing agents, but hypervalent iodine compounds have never been used in this context. The chapter presents the development of conditions and the exploration of the scope of the method, delivering a variety of Pummerer’s ketone analogs by iodosobenzene-promoted oxidative phenolic coupling. As a continuation of research on the oxidative transformations of phenols employing iodine(III) reagents, Chapter 3 explores a design of a new reaction, during which phenols with pendant aldehyde undergo an enantioselective intramolecular cyclization-dearomatization organocatalyzed by chiral proline derivatives. The resulting spiro-[6,5]-bicyclic products, rich in functional groups, are suitable building blocks for the synthesis of many natural and bioactive compounds. Despite a partial success, the transformation could not be developed into an efficient and general synthetic method. The following three chapters deal with the development of aryl transfer reactions using diaryliodonium salts. The transfer of groups, e.g., aryl, vinyl, alkynyl, CF3, CN, N3, F, or NTs2, to organic acceptors is an intensively investigated class of reactions employing hypervalent iodine compounds, constituting an alternative to cross-couplings catalyzed by transition metal complexes. Thus, Chapters 4 and 5 present studies on the aryl transfer to a sulfur atom, leading to aryl sulfides and S-aryl phosphorothioates, respectively. The developed reactions are metal-free, high-yielding, and experimentally simple. They create handy and general entries to biologically relevant compounds containing S–Ar moiety. Importantly, the process described in Chapter 5 allowed for the first time for the stereospecific S-arylation of P-stereogenic compounds. Along the same lines, but on another front, Chapter 6 addresses the arylation of phosphorus nucleophiles, specifically secondary phosphines, with diaryliodonium salts. The reaction conditions have been preliminarily optimized and the scope of the process briefly explored, providing a strong basis for the development of a universal method for the metal-free preparation of unsymmetrical tertiary phosphines under mild conditions.