New Applications of Iodine(III) ReactivitySynthesis and Functionalization of Heterocycles

Resumo

The main objective of this doctoral thesis is the development of new stoichiometric and catalytic methodologies for the metal-free intramolecular amination reaction in heterocycle synthesis. As hypervalent iodine reagents offers a friendly environment, regarding toxicity, mild conditions and more over selectivity, they are the reagent of choice to promote this type of transformations. As a last challenge, different iodine(III) reactivity was explored in the field of enantioselective intermolecular transformations. Two different methodologies for the synthesis of indoles were succesfully developed under iodine(III) reactivity. Both methodologies were deeply studied through different competition experiments, such deuterium labelling, Hammett correlation or kinetic profile of the reaction. For result analysis, several techniques were employed such as Nuclear Magnetic Resonance or Gas Chromatography. This experiments supported strongly the final mechanistic proposals. Moreover, the scope of both reactions was explored affording the corresponding cyclized products in moderate to excellelent yields. In addition to the formation of indoles, an enantioselective 4-hydroxylation of phenols was succesfully achieved through iodine(I/III)-catalysis. As a conclusion, hypervalent iodine reagents have been found as an useful tool for the synthesis of indoles. This type of reagents promoted the needes cyclization reaction and different indoles were obtained through two synthetic methodologies. Furthermore, an assymetric catalytic dearomatization of phenols was accomplished using a chiral iodine reagent, previously reported by our group. This method represents the second catalytic methodology to obtain para-quinols using iodine(III).