Development of hypervalent iodine(III)-mediated chemical reactions

Resumen

The work contained in this Thesis represents some main developments in hypervalent iodine(III)-mediated methodologies, and ranges from carbon-nitrogen to additional carbon-heteroatom bond formation. The present manuscript is divided into three main parts: 1 - Mechanistic studies on the stoichiometric iodine(III)-mediated vicinal diamination of styrenes. 2 - Development of a pioneering hypervalent iodine(III)-catalysed asymmetric diamination of styrenes. 3 - Exploration of mild carbon-boron bond formation from diaryliodonium salts. In the first section on alkene diamination, a description of a series of experiments supporting and supported by DFT calculations are presented. The original DFT calculations were performed in the group of Professor Maseras within a collaborative project. In order to verify the most energetically demanding step calculated by DFT, a series of hypervalent iodines bearing bistosylimide groups at the iodine centre and different para-substitution in the aryl ring were synthesised and submitted to diamination. Kinetic profiles showed slower reactions with electron-withdrawing substituents. In conclusion, between two possible rate-determining steps, ligand dissociation is identified as the slow process according to experimental kinetics. Regarding the DFT postulation of an initial step of oxygenation, an experimental proof of such an oxygen attack of the bissulfonamide is described for 1,1-diphenylethylene as starting material and additionally supported by an X-ray analysis of the isolated oxygenated product. Additionally, chiral iodine reagents bearing bissulfonyl groups at the iodine coordination sphere were synthesised, and fully characterised including X-ray analysis. The rate for electron-rich derivatives of these compounds in exploratory diamination of alkenes was found to be extremely fast; this electronic facet is comparable with related chiral iodine reagents of similar electronic influence, which exercise significant rate enhancement in enantioselective diamination. In the second section, a novel catalytic asymmetric diamination methodology is described. Two key points were important for this transformation. The first is the suppression of the potential background epoxidation reaction under appropriate reaction conditions. The second one is the design of the correct features of the catalyst, being necessary a para-methyl substitution on the arene core and a bulky N,N-disubstitution pattern amide within the chiral lactamide units. Under such appropriately tuned raction conditions, the asymmetric diamination of styrenes was carried out using 10 – 20 mol% of catalyst loading, achieving from moderate to good yields and excellent enantioselectivities of above 90% ee. These ee values represent significantly higher values (above 90%) than those for the previously published stoichiometric reaction, which presents a significant improvement. Mechanistic studies have identified a definite catalytic cycle forthis homogeneous oxidation reaction. Chiral iodine(I) is oxidised by the terminal oxidant (mCPBA) at the outset of the reaction and a subsequent ligand exchange provides the active iodine(III) species. The inherent chirality of this molecule exercises an effective alkene face selection. Subsequent bismesylimide attack at the benzylic position of the activated alkene generates a vicinal aminoiodinated intermediate. Intramolecularly promoted reductive elimination regenerates the initial chiral I(I) catalyst state. Upon addition of a second bismesylimide unit the final diamination product is formed. Finally, in the third chapter a novel carbon-boron bond formation is described. This work was realised in collaboration with the group of Professor E. Fernández’s group. One of the few metal free aryl-boron bond formation and the only example of diaryliodonium-mediated arylation of a 13th group element has now been developed. It also represents one of the few cases of a non-innocent anion in reactions of diaryliodonium salts. The presence of an acetate as diaryliodonium counterion triggers the formation of an umpolung at the diboron compound, which, once it is coordinated to the iodine, induces sufficient nucleophilicity to trigger reductive elimination to the final borylated product. Several symmetrical diaryliodonium acetates were synthesised through metathesis of their respective bromides. These precursors were obtained applying different synthetic protocols including the direct synthesis from the corresponding free arenes to the use of preactivated arenes. Non-symmetrical diaryl iodonium salts were also tested. No aryl selection is observed based on electronic preferences, but up to 85:15 selectivity can be obtained when a pertinent steric hinderance is present. Moreover, anion bulkiness can also be employed to enhance selectivity, although the yields are decreased throughout the anion insertion.