Rh-catalyzed reductive coupling under hydrogenation conditions and nucleophilic catalysis via phosphine conjugate addition

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Kong, Jongrock, 1972-

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At the threshold of the 21st centry, a new set of challenges is defined by the need to develop sustainable means of preparing chemical commodities demanded by society. Hence, such concepts as atom economy, step economy, and 'green chemistry' have become the requirements for the development of synthetic reactions. Hydrogenation is one of the most powerful catalytic methods which successfully satisfy the stated requirements of modern chemistry. Accordingly, catalytic hydrogenation has been tremendously utilized in industrial settings. The profound impact of hydrogenation portended a powerful approach to reductive carbon-carbon bond formation under hydrogenation conditions, resulting in the discovery of the Fischer-Tropsch process and hydroformylation. However, since this discovery, processes have restricted to the incorporation of a single carbon monoxide unit. Even though there are a few seminal contributions, systematic efforts toward the development of hydrogen-mediated carboncarbon bond forming processes beyond hydroformylation have been absent from the literature. In an exciting advance, the Krische group has shown that it is possible to reductively couple two or more organic molecules simply through their exposure to gaseous hydrogen in the presence of a metal catalyst. This finding has led to the development of a broad, new family of hydrogen-mediated C-C bond formation. Herein, related to hydrogen-mediated C-C bond formation, the overview of metal catalyzed intermolecular reductive coupling in the presence of reducing agents such as borane, silane, alane, metal, and hydrogen is presented. Chapter 2 describes systematic approaches to the development of hydrogen-mediated C-C bond formation and successful preliminary results achieved by our research group. Chapters 3 and 4 will describe the further extension of these hydrogen-mediated C-C bond formations including (1) hydrogen-mediated reductive couplings of conjugated alkynes with iminoacetates, (2) hydrogen-mediated reductive couplings of 1,3-enynes with [alpha]-ketoesters, and (3) hydrogen-mediated multicomponent reductive couplings. The development of catalytic systems for the nucleophilic activation of enones using phosphine catalysts has received attractive attention. Recently, an intramolecular variant of the Rauhut-Currier reaction was developed in our lab. To further extend nucleophilic phosphine catalysis, we have sought to develop new catalytic methodology via phosphine conjugate addition. Chapter 5 describes two new methodologies related to their area: (1) catalytic cycloallylation via nucleophilic phosphine catalysis and (2) allylic amination of Morita-Baylis-Hillman acetates.