Asymmetric Catalysis with Chiral-at-Metal Complexes: From Non-Photochemical Applications to Photoredox Catalysis

Die Entdeckung oktaedrischer "chiral-at-metal"-Komplexe, die hoch enantioselektive nicht-photochemische- und photochemische Umwandlungen katalysieren oder beide gleichzeitig, ist eine anspruchsvolle Herausforderung. Diese Dissertation beschreibt die Entdeckung und Anwendung zweier untersch...

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Bibliographic Details
Main Author: Huo, Haohua
Contributors: Meggers, Eric (Prof.Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2016
Online Access:PDF Full Text
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Table of Contents: The discovery of octahedral chiral-at-metal complexes that promote highly enantioselective non-photochemical or photochemical transformations, or both, is a challenging goal. This thesis details the discoveries and applications of two distinct classes of chiral-at-metal iridium(III) complexes for asymmetric catalysis, one is a metal-templated enamine/H-bonding catalyst and the other is a metal-based Lewis-acid catalyst. The octahedral enamine/H-bonding catalyst (Λ-Ir4) promotes the enantioselective α-amination of aldehydes with catalyst loadings down to 0.1 mol%. In this metal-templated design, the iridium serves as a structural center and affords the exclusive source of chirality, whereas the catalysis is mediated through the organic ligand sphere (chapter 3.1). The chiral-at-metal complex Λ-IrO bearing two hemilabile acetonitrile ligands can be used as a chiral Lewis acid catalyst. It efficiently catalyzes the enantioselective Friedel-Crafts addition of indoles to α,β-unsaturated 2-acyl imidazoles with high yields (75-99%) and high enantioselectivities (90-98% ee) at low catalyst loadings (0.25-2 mol%). Counterintuitively, this complex maintains its metal-centered configuration despite the rapid acetonitrile ligand exchange which is required for satisfactory catalytic activity. Since this initial discovery, this novel class of reactive chiral-at-metal complexes has been successfully applied to many other asymmetric catalytic reactions in the Meggers group (chapter 3.2). The Lewis-acid catalyst Λ-IrO and its derivative Λ-IrS can also be competent photoredox catalyst for challenging asymmetric photoredox catalysis. With a single catalyst Λ-IrS (2 mol%), the visible-light-activated enantioselective alkylation of 2-acyl imidazoles with electron-deficient benzyl bromides and phenacyl bromides provided excellent enantioselectivities (90-99% ee) and excellent yields (84-100%). In this mono catalysis strategy, the chiral-at-metal complex serves as an in situ photosensitizer precursor for photoredox catalysis and at the same time provides very effective asymmetric induction for α-functionalization of ketones (chapter 3.3). Subsequently, this new catalytic strategy has been expanded to realize highly enantioselective α-trichloromethylation (chapter 3.4) and α-perfluoroalkylation (chapter 3.5) through visible-light-activated photoredox catalysis. Previously, most of the successful approaches for asymmetric photoredox catalysis needed two catalysts, one for the photoredox activation, and the other for stereoinduction. The single catalyst strategy fulfills an unmet need in the photoredox synthetic toolbox and provides new avenues for the efficient and economical synthesis of enantioenriched molecules. Alternatively, in some cases the synergistic catalysis strategy still has its advantages over the single catalyst system. By merging the chiral Lewis acid Λ-RhS with an external photosensitizer, an efficient enantioselective addition of organotrifluoroborates to electron-deficient alkenes was readily realized under photoredox conditions. This practical method provides yields up to 97% with excellent enantioselectivities up to 99% ee and can be classified as a redox neutral, electron-transfer-catalyzed reaction. The previously developed dual function photoredox/chiral Lewis acid catalysts Λ-IrO or Λ-IrS are not applicable for this photoreaction and this has been pinpointed to slow ligand exchange kinetics in the iridium system (chapter 3.6).