Gold(I)-Catalyzed Transformations with Bifunctional Ligands and the Synthesis of Daucane Natural Products

Identifier:  TDX:4562

Handle: https://hdl.handle.net/20.500.11797/TDX4562

Authors:  Martí Zaragoza, Àlex

Abstract:
Research in homogeneous gold catalysis has provided a unique tool for the ready construction of molecular complexity through the selective activation of alkynes. Usually, metal salts are employed for activation of the gold(I) precatalysts, but the presence of such salts can lead to the formation of side products. To bypass this, we prepared a library of gold (I) catalysts bearing hydrogen bond donors, enabling self-activation without the need of external additives. A new series of triphenylphosphine-based catalysts with (thio)urea/squaramide motifs was designed and tested in reactions like the cycloisomerization of N-propargylbenzamides. Additionally, the Hydrogen Bonded Counterion-Directed Catalysis (HCDC) method was introduced as a novel approach in enantioselective gold(I) catalysis. This method employs chiral counterions combined with metal catalysts bearing hydrogen bond donors allowing the docking of the chiral unit close to the reaction center. This lead to a successful transfer of the chiral information which was demonstrated by the high enantioselectivities achieved in multiple transformations. Finally, we demonstrated that a gold(I)-catalyzed formal (4+3) cycloaddition allows for the divergent synthesis of natural products by completing the synthesis of two members of the daucane family of natural products, aspterric acid and schisanwilsonene A as well as correcting the proposed structure for penigrisacid A.