Chiral Pyrrolidinyl-Biphenyl Phosphine Ligands in Gold(I) Catalysis

Identifier:  TDX:4340

Handle: https://hdl.handle.net/20.500.11797/TDX4340

Authors:  Zuccarello, Giuseppe

Abstract:
Enantioselective gold(I) catalysis is notoriously challenging. The preferred linear coordination of the metal places the ancillary chiral ligand and the substrate opposite to each other and, therefore enantioinduction is less efficient. Additionally, the outer-sphere mechanism of gold(I)-catalyzed transformations enhances the degree of difficulty as it further extends the distance between ligand and reaction center. Despite some progress in the field has been reported, new approaches are still highly desirable. In this Doctoral Thesis, the design and synthesis of gold(I) complexes supported by biphenyl phosphine ligands containing a remote C2-symmetric pyrrolidine and their application in catalysis is described. Products of formal [4+2] cycloaddition, azabicyclo[4.1.0]hept-4-enes and 1,2-dihydronaphtalenes were obtained in good yields and enantioselectivities. The origin of enantioselectivity has been elucidated experimentally and computationally as arising from non-covalent interactions between the substrate and the aromatic moieties of the ligand. The elucidation of the working mode of the catalysts led to the development of new asymmetric methods such as the atroposelective synthesis of biaryls. An Eyring analysis of the gold(I)-catalyzed formal [4+2] cycloaddition employing the new pyrrolidine-containing ligands at different temperature ranges, established the presence of two competing rate-determining steps. Furthermore, this is the first gold(I)-catalyzed system displaying a positive entropy of activation. Finally, a gold(I)-catalyzed tandem retro-Buchner/C(sp3)–H insertion/elimination process for the formation of substituted 1,2-dihydronaphtalenes has also been developed.