Asymmetric Photoredox Catalysis with Chiral-at-Rhodium Complexes

Chiral transition metal catalysts in which the chirality exclusively originates from a stereogenic metal center witness a more recent advance and their excellent catalytic performance has been demonstrated through applications into diverse enantioselective transformations, especially visi...

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Bibliographic Details
Main Author: Ma, Jiajia
Contributors: Meggers, Eric (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:English
Published: Philipps-Universität Marburg 2018
Chemie
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Summary:Chiral transition metal catalysts in which the chirality exclusively originates from a stereogenic metal center witness a more recent advance and their excellent catalytic performance has been demonstrated through applications into diverse enantioselective transformations, especially visible-light-activated photoredox reactions. This thesis deals with the synthesis of new chiral-at-metal rhodium Lewis acid catalysts and their applications in enantioselective photoredox chemistry. 1) Synthesis of a new member of the rhodium-based chiral Lewis acids family, named RhS, with exclusive octahedral centrochirality which features the Λ-configuration (left-handed propeller) and Δ-configuration (right-handed propeller) has been accomplished. Both enantiomers Λ-and Δ-RhS contain two cyclometalating 5-tert-butyl-2-phenylbenzothiazoles in addition to two exchange-labile acetonitriles with a hexafluorophosphate counterion, were synthesized conveniently through a chiral-auxiliary-mediated strategy. Compared with the previously developed Λ/Δ-RhO complexes bearing corresponding benzoxazoles, the Λ/Δ-RhS have been recognized as better chiral Lewis acid catalysts due to the higher steric congestion directed by the benzothiazole ligands, in which the longer C-S bonds over C-O bonds position the steric bulky tertiary butyl groups closer to the substrate coordination site (chapter 3.1). Subsequently, the newly developed chiral-at-rhodium Lewis acids were applied to visible-light-activated asymmetric photoredox catalysis as discussed in chapters 3.2-3.5. 2) The chiral Lewis acid Λ-RhS combined with the photoredox catalyst [Ru(bpy)3](PF 6) 2 enabled the visible-light-activated redox coupling of alpha-silyl alkyl amines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69–88% and with high enantioselectivities (54–99% ee). The reaction is proposed to proceed via single electron transfer (SET) between the alpha-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical–radical recombination (chapter 3.2). 3) A new and simple commercially available photoredox mediator 4,4-difluorobenzil was developed to cooperate with the chiral-at-rhodium Lewis acids Λ/Δ-RhS. This synergistic catalytic system permits an enantioselective three-component photoreaction to provide the fluoroalky l-containing products under dual C bond formation with high enantioselectivities (up to 98% ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives were observed. The photoexcited 4,4-difluorobenzil is VI proposed to enable the single electron oxidation of sodium perfluoroalkyl sulfonates under the generation of corresponding perfluoroalkyl radicals which are trapped by electron-rich vinyl ethers to deliver alpha-oxy carbon-centered radicals. These nucleophilic radical species are involved in a subsequent Rh-catalyzed radical conjugate addition with acceptor-substituted alkenes (chapter 3.3). 4) The single chiral-at-rhodium Lewis acids catalyzed radical conjugate addition of alpha-amino alkyl radicals with acceptor-substituted alkenes provided the C formation products in good yields (up to 89%) and with excellent enantioselectivities (up to 97% ee) under visible-light-activated photocatalyst-free conditions. The -amino alkyl radicals are generated from simple glycine derivatives upon single electron reduction triggered by the photoreductant Hantzsch ester. This methodology is recognizedas a practical and versatile avenue to access diverse pharmaceutically demanding chiral beta-substituted gamma-aminobutyric acid analogs, including previously unaccessible derivatives containing fluorinated quaternary stereocenters. Synthetically valuable applications are demonstrated by providing straightforward access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram and (S)-nebracetam (chapter 3.4). 5) Visible-light-activated enantioselective β-C(sp3)H functionalization of 2-acyl imidazoles and 2-acylpyridines with 1,2-dicarbonyl compounds catalyzed by a single chiral-at-rhodium Lewis acid Δ-RhS derivative was developed. The C bond formation products are obtained in high yields (up to 99%) and with excellent stereoselectivities (up to >20:1 drand up to >99% ee). Experimental and computational studies support a mechanism in which a photoactivated Rh-enolate intermediate, produced through the coordination of an acceptor-substituted ketone to the central rhodium in the presence of base, transfers a single electron to the 1,2-dicarbonyl compound followed by deprotonation at β position of initial ketone and a subsequent stereocontrolled radical-radical recombination. The chiral-at-rhodium Lewis acid is capable of serving a dual function as a chiral catalyst and a photoredox (pre)catalyst (chapter 3.5).
Physical Description:329 Pages
DOI:https://doi.org/10.17192/z2018.0237