Reductive N-heterocycle and carbocycle formation under R3SiH-B(C6F5)3 catalysis

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  • February 26, 2019
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  • Zhong, Hongyu
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Based on our group’s previous study on chemoselective partial reduction of silyl-protected sugars and sugar-derivatives1, a diverse set of oxygen-functionalized chiral synthons can be synthesized in short steps. The catalytic combination of the strong Lewis acid B(C6F5)3 and a tertiary silane efficiently generates a reactive equivalent of an highly electrophilic silylium ion (R3Si+) and a HB(C6F5)3 - reducing agent2. The silylium ion “activates” the C-O bond through a favored formation of the strong Si-O bond, pulling electron density from the oxygen atom and weakening the C-O bond. The hydride is delivered by HB(C6F5)3 - to attack the carbon atom and break the C-O bond in an SN2 fashion. The catalytic reduction of C-O bonds allows control for stereo-selectivity and site-selectivity in an array of stereo-defined C-O bonds that are ubiquitous in carbohydrates, achieved by mechanism of neighboring group participation and formation of cyclic intermediates. It has been shown that with low concentration or absence of the reducing species HB(C6F5)3 -, intramolecular nucleophilic attack by oxygen lone pair outcompetes intermolecular hydride attack. The resulting O-heterocycle products can be isolated. As heterocycles are common components of various natural products and drugs3a-3c, we continued to explore the formation of heterocycles and even carbocycles using sugar derivatives, which are naturally abundant chiral pool compounds and building-blocks for total synthesis4. In our study, when amine moiety and alkene moiety are incorporated into carbohydrate molecules, the N lone pair and C=C bond act as nucleophiles to achieve intramolecular cyclization. Starting from the bio-renewable enantiopure chiral pool compounds as an alternative for fossil fuels5, the catalytic combination of R3SiH-B(C6F5)3 enables generation of pharmaceutical precursors containing heterocycle and carbocycle cores in high diastereoselectivity.
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  • In Copyright
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  • Funding: Dunlevie Honors Undergraduate Research Fund
Advisor
  • Gagne, Michel
Degree
  • Bachelor of Science
Honors level
  • Highest Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Extent
  • 10

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