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Thomson, Brodie

University of British Columbia

Sulfur(IV) fluorides are powerful synthetic reagents typically used in the fluorination of small molecules. Traditional examples, including SF₄ and DAST, were primarily applied in the deoxyfluorinations of alcohols, carbonyls and carboxylic acids. More recent sulfur(IV) fluoride analogues, including thionyl fluoride and XtalFluor-E®, display unique reactivity relative to DAST and SF₄, yet have rarely been applied outside of similar organic transformations. In this thesis, the unique reactivities of thionyl fluoride and XtalFluor-E® were investigated and utilised towards the synthesis of acyl fluorides, sulfonyl fluorides, sulfinyl fluorides, and arylamino-oxetanes. Chapter 2 describes the utilization of thionyl fluoride in a carboxylic acid activation strategy to synthesize acyl fluorides. The desired products were synthesized in high yields (60–99%) under mild conditions and quantified either in solution using ¹⁹F NMR spectroscopy or isolated in a column-free protocol. Chapter 3 describes the efforts made in improving the synthesis of sulfonyl fluorides and sulfinyl fluorides. In one transformation, sulfonic acids were derivatized in a DMF-promoted, thionyl fluoride-mediated fluorination, affording sulfonyl fluorides in high yields (80–99%). A complementary strategy utilising XtalFluor-E® accessed the same products in good isolated yields (41–94%), but milder conditions. Thionyl fluoride was also used to transform sulfinic acids to sulfinyl fluorides in a one-pot strategy, accessing sulfinyl fluorides in high crude yields (75–98%) quantified by ¹⁹F NMR spectroscopy. This represents the first general method reported towards their synthesis. Chapter 4 describes an expedited route towards the synthesis of arylamino-oxetanes via the XtalFluor-E®-mediated activation of 3-aryloxetan-3-ols. The optimised protocol accessed arylamino-oxetanes under mild conditions and reduced the number of steps required in their syntheses (between 2–6) compared to current literature procedures. This represents the shortest and simplest route towards their synthesis, accessing the desired products in 34–97% isolated yields. Chapter 6 is a distinct chapter in collaboration with Delic Laboratories, UBC and BAT, in which the light-induced degradation of CBD solutions was investigated. CBD-hydroxyquinone was identified to undergo a light-induced photo-isomerisation to form a previously unidentified cannabinoid intermediate. Both experimental and computation studies identified this intermediate reacts rapidly with oxygen to form a multitude of products in solution.

Text

2024-12-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89990

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/