Organosulfur plays a significant role in synthetic chemistry. In particular α,β-unsaturated sulfides (i.e. vinyl sulfides) are versatile building blocks that exhibit untapped potential in reaction development. This thesis focuses on reaction development in this space. Chapter 1 discusses the characteristics that sulfur attributes to organic molecules followed by a review of synthetic preparations and applications of vinyl sulfides.
Chapter 2 discusses the development of a formal-phosphorus Pummerer reaction enabling simple access to thiophosphonium Wittig reagents. These thiophosphonium salts are used to access a library of vinyl sulfide substrates that are further hydrolyzed to the corresponding ketones. This two-step sequence enables a strategic approach affording aldehyde to ketone homologation via vinyl sulfide intermediates, enabling access to synthetically challenging α-aryl ketones.
Chapter 3 discusses the direct use of vinyl sulfides as carbonyl surrogates in Fischer indole reactions. Vinyl sulfides are demonstrated to be aldehyde and ketone surrogates in the preparation of diverse 3-substituted and 2,3-disubstituted indoles or azaindoles. The utility of this chemistry is shown with the preparations of three biologically significant compounds: 4-aza-melatonin, a furoindoline scaffold and an indomethan-like CRTh2 anatagonist.
Chapter 4 showcases the first total synthesis of a chromane natural product isolated from Cassia fistula: 1-(3,4-dihydro-5-meth- oxy-2,2-dimethyl-2H-chromen-7-yl)propan-2-one. The preparatory route of this natural product features two synthetic methods developed by the Magolan group, including the aldehyde to ketone homologation described in Chapter 2. The five-step total synthesis affords the natural product in 24% overall yield and includes an efficient one-pot three-transformation sequence.
Chapter 5 highlights ongoing and future projects that build on the research described in this thesis. This includes investigations into stable intermediates that facilitate access to aldehydes from vinyl sulfides. Plans are proposed to develop controlled stereoselective use of thiophosphonium reagents. Further collaborative work is discussed employing vinyl sulfides as substrates for valuable atropoisomeric heterocyclic scaffolds. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28912 |
| Date | 11 1900 |
| Creators | Fragis, Meghan |
| Contributors | Magolan, Jakob, Chemical Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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