New Strategies for Pentose Synthesis and Catalytic C–O and C–C Cross-Coupling

The ever-evolving need for new medicines, materials, and fine chemicals drives a continuous demand for novel strategies and synthetic methods that facilitate the efficient construction of organic compounds. Among the tools available to address this demand, catalysis has come to the forefront due to...

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Bibliographic Details
Main Author: Shurtleff, Valerie
Other Authors: MacMillan, David W. C.
Format: Academic dissertations (Ph.D.)
Language:English
Published: Princeton, NJ : Princeton University 2016
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Online Access:http://arks.princeton.edu/ark:/88435/dsp011z40kw31c
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Summary:The ever-evolving need for new medicines, materials, and fine chemicals drives a continuous demand for novel strategies and synthetic methods that facilitate the efficient construction of organic compounds. Among the tools available to address this demand, catalysis has come to the forefront due to its ability to render previously impossible reactions kinetically feasible. Within the field of catalysis, methods that harness multiple catalytic manifolds working in concert have the potential to enable unusual or wholly unprecedented bond-forming reactions. In turn, these methods provide opportunities to streamline synthetic sequences en route to valuable products. The five-carbon carbohydrate, or pentose, scaffold is a motif found in many compounds that are fundamental to the biochemistry of living organisms. As such, pentose derivatives are often targeted as drug candidates. However, existing methods for their preparation often require lengthy and inefficient sequences. As described in Chapter 2, we have capitalized on an amine- and copper-catalyzed method for -oxyamination developed by our group in order to design a concise asymmetric route to pentose derivatives. This strategy has enabled the synthesis of a wide array of differentially substituted pentoses as well as -C-nucleosides, -C-nucleosides, and fluorinated pentoses including gemcitabine and PSI-6130, a precursor to the HCV drug sofosbuvir. Photoredox catalysis has recently emerged as a powerful strategy for harnessing the energy of visible light to facilitate organic transformations. Because photoredox catalysts can simultaneously act as both single-electron reductants and oxidants, they allow for functionalization at non-traditional sites of reactivity and provide access to unconventional bond disconnections. Merging photoredox catalysis with other modes of catalysis combines the strengths of each catalytic platform in order to enable transformations that neither could accomplish in isolation. Along these lines, the use of photoredox catalysis in conjunction with nickel catalysis has become a particular interest of our laboratory. Chapter 3 describes a method for etherification wherein photoredox catalysis drives carbon–oxygen cross-coupling through modulation of the oxidation state of nickel, and Chapter 4 outlines the development of a multicatalytic method for C–C bond formation that employs sp3 C–H bonds as latent nucleophilic coupling partners.

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