Design of New Gold(I) Catalysts: Dissecting Electronic and Steric Effects

Identifier:  TDX:4053

Handle: https://hdl.handle.net/20.500.11797/TDX4053

Authors:  Arroyo Bondia, Ana

Abstract:
Gold(I)-catalyzed transformations have been studied in the last two decades for the construction of molecular complexity. This Doctoral Thesis has principally focused on expanding the knowledge in asymmetric gold(I) catalysis and the development of new gold(I) catalysts. First, new families of gold(I) complexes have been synthesized based on previous dialkylbiphenyl-phosphine ligands bearing a C2-asymmetric 2,5-disubstituted pyrrolidines developed by our group: - Removing one phenyl of the biphenyl scaffold approaching the chiral information to the gold(I) metal has proved to give good results. For example, in the atroposelective cyclization reaction of sulfonamides. - Substituting the phosphine by an N-heterocyclic carbene led to similar reactivity in terms of yield compared to the model ligand. However, lower enantioselectivities have been obtained. - Preparing sterically hindered ligands with one, two or three chiral 2,5-disubstituted pyrrolidines was achieved. They were tested in different transformations giving in general high yields, but not showing good enantioselectivities. Other chiral gold(I) complexes have been prepared bearing one or two amino acids to take advantage of their natural chirality to induce enantioselectivity. However, the asymmetry of the ligands (when only one amino acid is present) and/or the free rotation of the bonds of the amino acids have obstructed their enantioinduction. Other area of study has been the development of a gold(I) complex active in senescent cells. The complex with β-galactoses would be inactive against of a prodrug or fluorophore under biological conditions but taking advantage of the high presence of associated β-galactosidase it will be active due to the cleavage of the galactoses releasing the active gold(I) complex. To this end, there have been developed two NHC-gold(I) complexes, with and without β-galactoses. These catalysts were tested under biologically conditions in a hydroarylation reaction producing a fluorescent coumarin. Modest different reactivities for both complexes have been observed under several reaction conditions.