Date of Award
8-23-2024
Publication Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry and Biochemistry
Keywords
Lewis Acid;Natural Product;Organic Synthesis;Organic Transformations;Organometallic Chemistry;Total Synthesis
Supervisor
James Green
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Abstract
The preparation of medium sized ring systems is in general more difficult than that of 5- or 6-membered systems in large part due to entropic factors. In the Green Research group the synthesis of medium sized rings (7-8 membered) has been an area of continued research. Several synthetic strategies have been employed, such as traditional catalysis, vinylogous Nazarov reaction and most importantly the intramolecular Nicholas reaction. The Nicholas reaction is important among metal-organic transformations due to its high reaction site selectivity, good stability and reactivity of the intermediate cation towards nucleophile, ease of handling and easy purification of alkynedicobalt complexes on silica gel. In addition these complexes can undergo ready decomplexation to obtain the all-organic fragment. The cultivated sunflower Heliannthus annuus is a known to produce allelochemicals that have important properties inhibiting the growth of neighbouring plants, which are generally unwanted weeds. The most important of these allelochemicals, are arguably the heliananes and heliannuols, which are 5-8 membered benzoxacyclic sesquiterpenes (predominantly 5, 7 and 8 membered). The synthesis of heliannuols and heliannanes has been proven to be difficult due to their unique scaffolding and the presence of many chiral centers. Synthetic approaches towards the heliannuols and heliananes reported in the literature are restricted to a narrowly defined group of medium ring synthesis strategies. There have been a limited number of approaches towards enantioselective reactions which address the synthesis of enantioenriched heliannuol and heliananes. The inclusion of Nicholas reaction based strategies would provide an additional complimentary approach to many of the current traditional ring closing protocols This dissertation describes the successful approach to several of the 8-membered heliannuols, close analogues of the 7-membered heliannuol C, and the basic system of the 5-membered heliannuols. Protosappanin A, B and C were first isolated from the methanol extracts of Sappan Lignum, which is the dried heart-wood of Caesalpinia sappan L. (Leguminosae,) by Masahiro in 1986. The extracts of Sappan Lignum was found to have a depressing effect on the central nervous system and a sleeping elongating effect in mice. Protosappanin compounds (A,B,C) individually have various pharmacological activities such as an inhibitor of xanthine oxidase, vasorelaxant activity, inhibition of propionibacterium acne growth, lipase inhibitory activity, anti oxidant activity, anti inflammatory and anti cancer properties. The compounds feature an 8-membered ring fused to to aryl rings (dibenzo[b,d]oxocane), and also contain phenolic functional groups. These compounds have a very limited number of synthetic approaches, protosappanin A synthesis has been reported in the literature by C-H activation and a visible-light-induced cascade reaction followed by the Tiffeneau–Demjanov rearrangement. The other protosappanin compounds B,C have only been extracted, and have never been the target of synthesis. The Protosappanin family is believed to fit well into the intramolecular Nicholas reaction which would focus primarily on the critical C-O bond formation through a nucleophilic phenol, which there is only a few reports of phenols having success. This work describes the fundamental preparation of arene fused dehydrooxocine complex in low yield.
Recommended Citation
St.Onge, Brent Andrew, "New Synthetic Strategies and Applications Using Nicholas Reaction Chemistry" (2024). Electronic Theses and Dissertations. 9519.
https://scholar.uwindsor.ca/etd/9519