Combined experimental and computational studies of ligand-based selectivities in Pd- and Ni-catalysis

  • Kombinierte experimentelle und rechnergestützte Studien zu Liganden-basierten Selektivitäten in der Pd- und Ni-Katalyse

Sperger, Theresa; Schoenebeck, Franziska (Thesis advisor); Enders, Dieter (Thesis advisor)

Aachen (2018, 2019)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2018


Combining experiments and DFT calculations allows for a detailed study of elementary reaction steps and can provide intricate insights into the mechanisms of transition metal-catalyzed reactions. In the context of this thesis, this synergistic use of DFT calculations and experiments aided the development and mechanistic study of Pd- and Ni-catalyzed reactions. The main part of this thesis is dedicated to the formation and reactivity of dinuclear Pd(I) complexes. Unlike even-oxidation state Pd-complexes, the reactivity of Pd(I) dimers and their use in catalysis have been relatively underexplored. To shed light on their formation, the reduction of Pd(II) complexes to yield halide-bridged Pd(I) dimers was investigated by means of DFT calculations. In line with large scale experiments carried out by the Colacot group at Johnson-Matthey, it was shown that the tri-tert-butylphosphine ligand can act as a reductant to reduce Pd(II) to Pd(I).Moreover, the application of iodide-bridged Pd(I) dimer [Pd(μ-I)(PtBu3)]2 in catalysis was explored. Based on the Schoenebeck group’s previous studies on direct dinuclear catalysis at Pd(I), this novel cross-coupling concept was further expanded: Using the bench-stable Pd(I) iodo dimer as a catalyst allowed for the formation of C(sp2)-C(sp2) bonds via Heck cross-coupling and the construction of C(sp3)-C(sp2) bonds in alkylation reactions via Kumada or Negishi cross-coupling as well as in the α-arylation of ketone and ester enolates. Furthermore, the robustness of the dinuclear Pd(I)-catalyst in terms of catalyst recycling was showcased in the cross-coupling reaction to form pharmaceutically relevant aryl trifluoromethylselenolates. In contrast, combined experimental and computational studies could show that dinuclear Pd(I)-catalysis is not viable in the corresponding trifluoromethyltellurolation of aryl iodides due to its lack of thermodynamic driving force. Instead, a Pd(0)-based catalytic system was developed to efficiently convert aryl iodides to their trifluoromethyltelluride analogs. Another part of this thesis details the DFT mechanistic investigation of a Ni-catalyzed olefin isomerization developed in the Schoenebeck group that relies on the use of a dinuclear Ni(I) complex as the catalyst. By comparison to analogous Ni(0) and Ni(II) catalytic systems, the mechanistically distinct features of the E-selective Ni(I)-catalyzed reaction were showcased. The latter process involves an intramolecular H-atom abstraction and rapid reinsertion via a high-energy intermediate. The last chapter of this thesis discusses the DFT mechanistic studies performed on reactions developed by the research group of Prof. Mark Lautens. In this context, the mechanisms of the stereoselective syntheses of 3-(halomethylene) oxindoles through the intramolecular addition of C-X bonds across alkynes have been explored. While the Pd(0)-catalyzed reaction furnishes the E-product by first reacting with the C-X bond, the opposite Z-olefin geometry is obtained via Pd(II)-catalysis due to initial reaction with the alkyne. Notably, the distinct requirements of the Pd(0)-catalytic system in terms of phosphine ligand were unraveled. Ligand effects were also studied in a Catellani-type remote C-H functionalization reaction and provided an understanding of the ligand-dependent product selectivities. During this investigation a mechanistic alternative to the commonly proposed formation of a Pd(IV) intermediate in Catellani reactions was discovered. The generality of this alternative direct ipso-C attack at Pd(II) was further explored and shown to depend on the presence or absence of base during the reaction.