Author: Choy, Pui Ying
Title: Palladium-catalyzed functionalization of C(sp)-H and C(sp2)-H bonds
Degree: Ph.D.
Year: 2014
Subject: Organometallic compounds.
Palladium compounds.
Hong Kong Polytechnic University -- Dissertations
Department: Department of Applied Biology and Chemical Technology
Pages: xxiii, 512 pages : illustrations ; 30 cm
Language: English
Abstract: Functionalization of unreactive arene C-H bonds has recently received intensive attention. Mild and selective methods for the direct transformation of carbon-hydrogen bonds to carbon-oxygen/ carbon bonds are undoubtedly found widespread applications across the field of pharmaceuticals, agrochemicals, natural products and feedstock commodity chemicals. However, the C-H bond functionalization remains a critical challenge in organic chemistry. The foremost difficulty lies to achieve high levels of regioselectivity, chemoselectivity and the activation of inert nature of C-H bonds. One of the strategies to achieve the goal is transition metal-catalyzed C-H bond functionalization. In the first half of this dissertation, we explore four studies on the palladium-catalyzed functionalization of C(sp)-H and C(sp2)-H bonds. Firstly, a general and simple method of palladium-catalyzed direct and selective oxidative C3-acetoxylation of 2,3-unsubstituted indoles has been developed. The first examples of selective carbon-hydrogen bond cleavage followed by carbon-oxygen bond formation sequence is achievable without any ortho-directing groups. This protocol requires 2 mol% Pd-loading under mild reaction conditions (70 °C and with weak base, KOAc) which tolerates a variety of functional groups. It is compatible to bromo-group which is a useful component for potential chemical transformations using coupling technology. Secondly, a palladium-catalyzed C-H bond oxygenation reaction of aromatic ketones is presented. This first example of carbon-hydrogen bond functionalization followed by carbon-oxygen bond formation sequence has been accomplished with ketone moiety as the ortho-directing group. This protocol provides a facile access to a wide range of ortho-acylphenol compounds from arylketones. Next, the first general palladium-catalyzed direct arylation of polyfluoroarenes with aryl sulfonates is described. This coupling protocol performs under relatively mild reaction conditions (90 °C with weak base, KOAc and without addition of acid additives) for successful coupling with both aryl tosylates and more challenging aryl mesylates. Last, the palladium-catalyzed Sonogashira coupling of aryl/ heteroaryl sulfonates is explored. A variety of functional groups are compatible such as nitrile, aldehyde, keto, and amide. This versatile coupling approach provides a facile access to 2-substituted isoquinoline by a one-pot cascade process.
In the second half of this dissertation, we engineer the syntheses for new family of monodentate phosphine ligands. The straightforward syntheses involve facile, high yielding conversion of Fischer Indolization into a broad scope of potentially and differentially substituted phosphine ligands. Besides, a modification of well-developed CM-phos with altering the N-substituted group is carried out. By expanding the size of the protecting group, both the steric and electronic properties of ligands are tuned. Furthermore, inspired by previously developed Andole-phos and Nadole-phos, a new family of ligands is designed with combined electronic (OR) and steric effect (naphthyl). The newly modified CM-phos-Ni-Pr uncovered a facile approach for challenging tri-ortho-substituted biaryl synthesis with carbon-carbon bond formation. To our delights, it represents the first palladium-catalyzed Suzuki-Miyaura cross-coupling of sterically demanding aryl arenesulfonates that proceeded smoothly at low catalyst loading (0.2-1.5 mol% Pd) within 24 h to generate good to excellent product yields.
Rights: All rights reserved
Access: open access

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