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Regiocontrolled Routes to Substituted Pyridines via Directed Cycloaddition Reactions

Bachollet, Sylvestre (2016) Regiocontrolled Routes to Substituted Pyridines via Directed Cycloaddition Reactions. PhD thesis, University of Sheffield.

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Abstract

New strategies have been investigated for the synthesis of highly substituted pyridine rings via inverse electron demand aza-Diels-Alder reactions of 1,2,4-triazines with alkynes. The synthesis of pyridines via cycloaddition/retro-cycloaddition strategies has largely focused on the use of enamine dienophiles as alkyne surrogates, as alkynes themselves only participate in [4+2] cycloadditions with triazines under very harsh conditions. Moreover, such processes usually provide the products in low yields and regioselectivities. To tackle these drawbacks, we were interested in a directed cycloaddition concept where 1,2,4-triazines were reacted with alkynyltrifluoroborate salts in the presence of a Lewis acid to form pyridines possessing a boron moiety offering further synthetic opportunities. The generated Lewis acidic alkynes, containing a “BF2” moiety, were then used in conjunction with triazines equipped with a Lewis base (such as a pyridine or an amide). Coordination of the two partners lowered the overall energy needed for the cycloaddition to take place and the corresponding pyridines were obtained within 10 minutes at 40 °C with complete regiocontrol. Organoboranes are a widely employed fluorophore family because of their excellent optical properties and their conveniently variable emission wavelength. The tetravalent boron found in the borylated bipyridines products (BOBIPYs) formed via our previously developed methodology prompted us to investigate their optical properties. These proved to comprise a new family of fluorophores showing blue to green fluorescence with quantum yields up to 41%. A series of compounds was synthesized and interrogated via DFT calculations and photophysical measurements. Streptonigrin, an antitumor and antibiotic agent, has drawn considerable attention from synthetic organic chemists because of its challenging structure, containing a highly substituted pyridine core. To date, only two groups achieved its total synthesis, and two more reached a formal synthesis. We established a succinct formal synthesis of streptonigrin, establishing the practical advantages of our cycloaddition methodology.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > Chemistry (Sheffield)
Depositing User: Mr Sylvestre Bachollet
Date Deposited: 24 Jan 2017 09:35
Last Modified: 24 Jan 2017 09:35
URI: http://etheses.whiterose.ac.uk/id/eprint/15887

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