Applications and mechanistic mysteries in palladium-catalyzed reactions

  • Anwendungen und Mechanistische Mysterien in Palladium-katalysierten Reaktionen

Senol, Erdem; Schoenebeck, Franziska (Thesis advisor); Niggemann, Meike (Thesis advisor)

Aachen (2019)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2019


Catalysis is a key element tool in the success of countless transformations and processes that can efficiently form beneficial and useful materials, pharmaceuticals and agrochemical products. In this context, it is inherent to fully understand the reactivity and behavior of present transformations to serve as a source of inspiration for mechanistic information in order to design innovative and sustainable catalytic systems. However, given the various challenges and complexity in catalytic transformations, it is difficult to access this information. As such, combining experimental with enhanced computational techniques as a powerful tool, Chemists worldwide are now able to examine and analyze essential steps thoroughly to gain a superior fundamental knowledge. This Thesis demonstrate the advantage of a combined approach in transition metal catalysis to highlight novel Pd(I)dimer chemistry and solve mechanistic puzzles in the oxidative addition and transmetalation step of Pd(0)/Pd(II) catalysis.The first chapter widens the repertoire of emerging air- and moisture stable Pd(I) dimer as an efficient catalyst for the formation of carbon heteroatom bonds (i.e. Csp2-S and Csp2-Se). It is known that Pd(0) catalyzed processes suffer from the formation of poisonous off-cycle Pd-ate complexes. This is even a greater challenge for selenolates since they are an order of magnitude more nucleophilic than thiolates. As shown in the group, the mechanistic diverse Pd(I) dimer showcases a privileged reactivity and circumvents this challenge to allow the direct use of nucleophiles in the cross-coupling. The exceptional reactivity was supported through computational and kinetic studies followed by mechanistic studies that were performed in regards to Pd(I) dimer catalyzed selenolation and site-selective thiolation of aryl iodides and bromides. In contrast to air-sensitive Pd(0) systems, the involved Pd(I) dimer species was easily recovered in open atmosphere by ordinary column chromatography.The second chapter of this Thesis showcases the advantage of using a combined computational and experimental approach to study the oxidative addition and transmetalation process in Pd(0) chemistry. In the first sub-chapter we disclose the transmetalation of Pd(II)F complexes with silane- and stannane based trifluoromethylation agents. A divergent reactivity was uncovered, with the silane showing selective CF3 transfer, and the stannane selective alkyl-group transfer. We uncovered a unrecognized mechanism for the widely employed silane reagent (R3SiCF3) which is able to release difluorocarbene via a 5-membered transition state, explaining its unique reactivity. Born Oppenheimer molecular dynamics revealed that the liberated free difluorocarbene is able to react with Pd(II)F to ultimately generate either trans- or catalytic active cis-Pd(II)CF3 in two distinctive pathways. In the second sub-chapter, we investigate the origin of divergent reactivity observed for Stille and Suzuki cross-coupling reactions of diazonium salts. Our analyses revealed that diazonium salts react with methanol to form diazoethers, which is promoted by a lewis base. As diazoethers are unable to undergo oxidative addition to Pd(0), this deactivation pathway inhibits Stille cross-coupling in methanol. However, lewis acids, including boronic acids, can deprotect the diazoether in situ to produce the active diazonium salt form, allowing facile Suzuki cross-coupling in methanol to occur. This mechanistic insight allowed us to perform the first Stille cross-coupling of diazonium salts in methanol through use of a lewis acid additive, as well as the first Stille cross-coupling of diazoethers.