Computational Mechanistic Studies in Gold(I) Catalysis and Design of New Chiral Ligands

Identifier:  TDX:3067

Handle: https://hdl.handle.net/20.500.11797/TDX3067

Authors:  Escofet Miquel, Immaculada

Abstract:
Research in homogeneous gold catalysis has provided unique tool for the ready construction of molecular complexity through the selective activation of alkynes. However, the nature of intermediates in gold(I)-catalyzed cycloisomerization reactions was still puzzling. In order to shed light on the mechanism of these transformations, we performed computational studies. We investigated the nature of cyclopropyl gold(I) carbenes and their different canonical possible forms. Benchmark of DFT methods together with QTAIM theory and NBO analysis confirmed the presence of different intermediates in cycloisomerizations of enynes. In this context, we also computed the selective formation of trans-fused cyclopropanes by gold(I)-catalyzed cyclization cascade of functionalized dienynes. We discovered a Au(I)-catalyzed system for the incorporation of acetylene gas into complex frameworks. Formation of only one diastereomer of biscyclopropanes when mixing trans-stilbene with acetylene, has been rationalized by means of DFT calculations. Despite the success of gold(I) in homogeneous catalysis, highly enantioselective reactions are still relatively scarce, particularly in the context of intermolecular transformations. We prepared a series of novel chiral phosphite gold(I) complexes and tested their activity. Moreover, we developed the enantioselective intermolecular gold(I)-catalyzed [2+2] cycloaddition of terminal alkynes and alkenes using non C2-chiral Josiphos digold(I) complexes as catalysts. Our mechanistic studies indicate that only one of the gold(I) centers is directly involved in the activation of the alkyne, although the second one is required to induce the enantioselectivity. To address the limitations on enantioselective catalysis, our group have designed a new class of gold(I) catalysts containing remote C2-symmetric 2,5-disubstituted pyrrolidines. As revealed by NCI Plots, we proposed that the catalyst exerts the stereocontrol by non-covalent interactions. In addition, 2nd generation of chiral ligands have been investigated in order to determine the role of each component and predict the higher enantioselectivities.