Asymmetric Chiral-at-Rhodium Catalysis Driven by Visible Light or Electricity

Driving asymmetric catalysis with visible light or electricity is of significant value because they represent ‘green’ and sustainable methods to synthesize non-racemic chiral molecules and in addition offer ample opportunities for chemists to discover new mechanistic scenarios and invent previously...

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Bibliographic Details
Main Author: Huang, Xiaoqiang
Contributors: Meggers, Eric (Professor) (Thesis advisor)
Format: Dissertation
Language:English
Published: Philipps-Universität Marburg 2019
Chemie
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Summary:Driving asymmetric catalysis with visible light or electricity is of significant value because they represent ‘green’ and sustainable methods to synthesize non-racemic chiral molecules and in addition offer ample opportunities for chemists to discover new mechanistic scenarios and invent previously unknown transformations. However, steering the reaction course of photo- and/or electrochemically generated reactive intermediates in a stereocontrolled and catalytic fashion is very challenging. This thesis presents novel applications of previously in the Meggers group developed chiral-at-metal rhodium complexes to the areas of asymmetric photocatalysis and asymmetric electrosynthesis. 1) A bis-cyclometalated chiral-at-metal rhodium complex (designated as RhS) in combination with the photoredox catalyst [Ru(bpy)3](PF6)2 enables visible-light-activated asymmetric α-amination and α-alkylation of 2-acyl imidazoles with aryl azides or α-diazo carboxylic esters as radical precursors, respectively (Chapter 3.1). As the first utilization of these reagents for photoinduced asymmetric catalysis, this novel proton- and redox-neutral transformations feature the advantage of leaving molecular N2 as the sole by-product and provide yields of up to 99% as well as excellent enantioselectivities of up to >99% ee with broad functional group compatibility. 2) A bis-cyclometalated chiral-at-metal rhodium complex (designated as RhO) is demonstrated to catalyze stereocontrolled chemistry of photo-generated radicals and at the same time an enantioselective sulfonyl radical addition to alkenes (Chapter 3.2). Specifically, employing Hantzsch ester as photoredox mediator, rhodium bound β-enolate carbon-centered radicals are generated by a selective photoinduced single electron reduction and then trapped by allyl sulfones in a highly stereocontrolled fashion, providing radical allylation products with up to 97% ee. The hereby formed sulfonyl radicals are utilized through an enantioselective radical addition to form enantioenriched sulfones, which minimizes waste generation. 3) A simple and robust catalysis scheme that only relies on a single bis-cyclometalated rhodium catalyst (RhS) is introduced to achieve the stereocontrol of bond forming reactions directly from an electronically excited state. This is showcased by an intermolecular [2+2] photocycloaddition of enones with alkenes, which provides a wide range of cyclobutanes with up to >99% ee and up to >20:1 d.r. (Chapter 3.3). The catalyst/substrate complexation enhances visible-light-absorption, achieves selective direct photoexcitation, and enables stereocontrolled direct bond formation from the photoexcited state. All reactive intermediates remain bound to the chiral catalyst thereby providing a robust catalytic scheme (no exclusion of air necessary) with excellent stereoinduction. This strategy is further applied to a previously elusive visible-light-induced [2+3] photocycloaddition of acceptor-substituted alkenes with vinyl azides (Chapter 3.4). A wide range of complex 1-pyrrolines are obtained as single diastereoisomers and with up to >99% ee using a simple reaction setup and mild reaction conditions. This work expands the scope of stereocontrolled direct bond formation from photoexcited states which was previously limited to [2+2] photocycloadditions. 4) The chiral-at-metal complex RhS is shown to catalyze visible-light-activated catalytic asymmetric [3+2] photocycloadditions between acyl cyclopropanes and alkenes or alkynes, which provide access to cyclopentanes and cyclopentenes, respectively, in 63-99% yields and with excellent enantioselectivities of up to >99% ee (Chapter 3.5). Coordination of the cyclopropane with the chiral catalyst generates the visible-light-absorbing complex, lowers the reduction potential of the cyclopropane, and provides the asymmetric induction and overall stereocontrol. Enabled by a mild single electron transfer reduction of directly photoexcited catalyst/substrate complexes, the scope of asymmetric photocycloadditions is extended to simple mono-acceptor-substituted cyclopropanes with the synthesis of previously inaccessible enantioenhanced cyclopentane and cyclopentene derivatives. 5) A versatile electricity driven chiral-at-rhodium Lewis acid catalysis is disclosed (Chapter 3.6). Powered by an electric current, the oxidative cross coupling of 2-acyl imidazoles with silyl enol ethers provides a sustainable avenue to synthetically useful non-racemic 1,4-dicarbonyls, including products bearing all-carbon quaternary stereocenters. A chiral-at-rhodium complex (RhS or a sterically more demanding derivative) activates a substrate towards facile anodic oxidation by raising the highest occupied molecular orbital upon enolate formation, which enables mild redox conditions, high chemo- and enantioselectivities (up to >99% ee), and a broad substrate scope. This thesis demonstrates the robustness and versatility of bis-cyclometalated rhodium-based Lewis acids by developing several mechanistically diverse and synthetically attractive asymmetric catalysis schemes. These chiral-at-rhodium Lewis acids are among the most powerful catalysts to address the long-standing challenge of stereocontrol in photochemical and electrochemical reactions.
Physical Description:472 Pages
DOI:https://doi.org/10.17192/z2019.0082