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Title:I. Mechanistic significance of the Si-O-Pd linkage in the cross-coupling of organosilanolates; II. Applications of the water-gas shift reaction in organic synthesis
Author(s):Ambrosi, Andrea
Director of Research:Denmark, Scott E
Doctoral Committee Chair(s):Denmark, Scott E
Doctoral Committee Member(s):Burke, Martin D; Fout, Alison R; Sarlah, David
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Carbon monoxide
Organic synthesis
Abstract:The first half of the present dissertation describes the mechanistic investigation of the palladium-catalyzed cross-coupling reaction of alkenyl- and arylsilanolates. The combination of reaction kinetics (both stoichiometric and catalytic), solution and solid state characterization of arylpalladium(II) organosilanolate complexes, and computational analysis, enabled the formulation of a detailed mechanistic picture for the cross-coupling of these classes of nucleophiles. The intermediacy of covalent adducts containing Si-O-Pd linkages in the cross-coupling reactions of organosilanolates has been unambiguously established. From such intermediates, two mechanistically distinct transmetalation pathways have been demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate (thermal transmetalation); (2) transmetalation via an anionic 10-Si-5 intermediate (activated transmetalation). In general, potassium salts of alkenylsilanolates react via neutral intermediates (8-Si-4), whereas the enhanced nucleophilicity of cesium alkenylsilanolates allows for the reaction to access the 10-Si-5 intermediate and proceed via the anionically-activated pathway. However, if the direct transmetalation is slower, as in the case of arylsilanolates (which require interruption of aromaticity), then anionic activation via the 10-Si-5 intermediate is predominant, regardless of the cation employed. These conclusions mandate a revision of the paradigm that organosilicon compounds must be anionically activated to engage in transmetalation processes (Hiyama-Hatanaka paradigm). Through the agency of the critical Si-O-Pd linkage, direct transmetalation of silicon to palladium can be achieved under mild conditions without anionic activation. The thorough mechanistic understanding of the transmetalation step for organosilanolates was leveraged in the study of the cross-coupling of γ-disubstituted allenylsilanolates. For the cross-coupling reaction of this class of nucleophiles, it was concluded that the transmetalation pathway (activated vs. thermal) dictates which isomer is accessed (α vs. γ). The second half of this dissertation details the efforts made toward the application of the Water-Gas Shift Reaction (WGSR) in the catalysis of fundamental C-C bond forming reactions. To this end, three strategies were envisioned and investigated. In a first approach, the CO/H2O couple was exploited as the terminal reducing agent for a metal catalyst that is directly involved in the formation of a new C-C bond. This strategy was studied in the context of carbonyl addition and reductive homocoupling reactions. The multiple conditions that must be strictly met for this approach to be successful (ranging from electrochemical requirements to properly balanced bond enthalpies of the complexes along the catalytic pathway) made the development of new, WGSR-based catalytic methods quite challenging. In a second approach, the CO/H2O couple provides reducing equivalents for an organocatalyst that is implicated in the C-C bond formation. This second strategy poses fewer challenges because it consists of two independent catalytic processes: a metal-catalyzed one for the WGSR, and an organo-catalyzed one for the formation of the C-C bond. This strategy was used in the development of a catalytic, Wittig-type olefination reaction. It was demonstrated that the use of tributylstibine enabled catalytic turnover under WGSR conditions. A third, simpler approach to engage the WGSR in C-C bond formation relies on the well-established capacity of CO/H2O to act as a H2 surrogate. In this approach, an independent C-C bond forming event leads to a functional group that can be reduced (hydrogenated) by CO/H2O. The metal catalyst for the WGSR is not involved in the formation of the C-C bond, but only in the generation of a metal-hydride species that will hydrogenate the substrate. The outcome is an overall reductive, tandem transformation that combines two steps in one, therefore enhancing step- and redox economy. This strategy has been successfully illustrated in the tandem Knoevenagel condensation/reduction reaction, in which an alkene formed by Knoevenagel condensation is readily reduced under WGSR conditions. The compatibility with several classes of electrophiles and nucleophiles under mild conditions has been demonstrated, resulting in a method that is comparable and, for certain aspects, even superior to established alkylation or reductive alkylation protocols.
Issue Date:2016-10-04
Rights Information:Copyright 2016 Andrea Ambrosi
Date Available in IDEALS:2017-03-01
Date Deposited:2016-12

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