Author: Fu, Wai Chung
Title: Functionalization of carbonyl compounds by palladium catalysis
Degree: Ph.D.
Year: 2018
Subject: Hong Kong Polytechnic University -- Dissertations
Transition metals
Organic compounds -- Synthesis
Department: Department of Applied Biology and Chemical Technology
Pages: xx, 630 pages : color illustrations
Language: English
Abstract: Selective transition metal-catalyzed C-H functionalization of carbonyl compounds has been a longstanding challenge in the field of homogeneous catalysis. The work presented in this dissertation addresses the development of new catalysts for mono-selective arylations of ketones and new methodologies to form compounds of interest to material science, medicinal chemistry and organic synthesis. In the first part of this dissertation, four studies on the palladium-catalyzed functionalization of acetone and other ketone compounds are described. First, a general and simple method for palladium-catalyzed direct mono-α-arylation of acetone has been developed with a strategically designed indolylphosphine ligand. The developed catalyst provids a greatly improved reaction scope and high reactivity towards previously proven difficult electron-withdrawing substrates and heteroarenes. The rate-determining step was investigated with reaction rate study and competitive experiments. In order to shed light on the relationship between ligand characteristics and catalytic activity in this reaction, a highly congested carbazolyl-based P,N-type phosphine ligand was prepared and found to be highly active for sterically hindered and electron-rich aryl chlorides. The N-Pd coordination was confirmed by X-ray analysis and might cause the retardation of catalysis for electron-deficient arenes. Next, the first general palladium-catalyzed direct mono-α-arylation of aryl and heteroaryl ketones with aryl mesylates and tosylates is described in chapter 4. In the presence of a low catalyst loading (0.25­2.5 mol %), the monoarylation is achieved with yields up to 95% and a broad substrate scope. Notably, the protocol enables the modification of biologically active phenolic compounds, which is useful for drug modification. In chapter 5, ketone-derived alkenyl tosylates are employed as electrophiles in the direct C2­alkenylation of benzoxazoles at ppm levels of customized palladium/PhMezole-Phos catalyst. Particularly, our method is scalable and exhibits excellent substrate tolerance; highly sterically hindered substrates and small vinyl tosylate could be coupled successfully. The utility of the protocol was demonstrated in the synthesis of new group 9 organometallic compounds using the alkenyloxazoles.
In the second part of this dissertation, new catalytic methods are devised for the synthesis of extremely congested aryl acetones and regioselective large polyaromatic hydrocarbons (PAHs). These methods are based on the palladium/norbornene chemistry to perform sequential catalytic events to achieve the modular molecular assembly of organic building blocks and control of regioselectivity. In chapter 6, a palladium/nobornene co-catalyzed reaction has been developed to prepare o'-aminoaryl acetones and o,o'-diaminoaryl acetones. The proposed method addresses the imine/enamine formation of free-amino-bearing substrates during ketone α-arylations and the acetone monoarylation of extremely congested aryl iodides by in-situ generation of the sterically hindered arenes. Finally, a versatile π-extension reaction has been developed based on the three-component cross-coupling of easily availavle aryl halides, ortho-haloarylcarboxylic acids and norbornadiene. The transformation is driven by the direction and decarboxylation of the carboxyl group while norbornadiene serves as an ortho-C-H activator and ethylene synthon via a retro-Diels-Alder reaction. Heteroatom-incorporated and heptagon-embedded polyaromatic compounds are efficiently prepared using the proposed method while the compounds are promising candidates for fabrication of organic semiconductors in solid state due to the π-π interactions between stacking molecules in molecular packing as confirmed by X-ray analysis. A comprehensive DFT calculation was performed to account for the catalytic intermediates.
Rights: All rights reserved
Access: open access

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