Investigations into an enantioselective intramolecular domino heck reaction: applications toward (+)-halenaquinone and (+)-xestoquinone
| dc.contributor.advisor | Keay, Brian A. | |
| dc.contributor.author | Lucciola, Daniela | |
| dc.date.accessioned | 2017-12-18T22:22:53Z | |
| dc.date.available | 2017-12-18T22:22:53Z | |
| dc.date.issued | 2011 | |
| dc.description | Bibliography: p. 249-258 | en |
| dc.description.abstract | This dissertation describes the efforts made toward enhancing the enantioselectivity of an intramolecular asymmetric Pd-catalyzed domino Heck reaction (78-79), its application toward the synthesis of the natural product ( + )-halenaquinone (1), and the investigations of its mechanism. The intramolecular asymmetric Pd-catalyzed domino Heck reaction of triflate 78 was performed using Pd2(dba)3 and PMP with a variety of ligands in toluene, EtOH, and t-BuOH at 110 °C using both oil bath heating and microwave irradiation. Electrondeficient ligands such as (R)-DIFLUORPHOS (113) gave the best enantioselectivities, 94% ee to >99% ee. Performing the reaction in EtOH also resulted in enhanced enantioselectivities compared to toluene. Microwave heating accelerated the reaction without affecting the enantioselectivity and allowed for a longer catalyst lifetime. Using t-BuOH as the solvent in an oil bath suppressed the formation of byproduct 80. Three different approaches toward the synthesis of (+)-halenaquinone (1) were taken. The first involved performing the domino Heck reaction on alkyl enol ethers 186 and 194. Cyclization of the fonner gave only traces of desired product while cyclization of the latter resulted in no product. The second entailed performing a tandem asymmetric Heck reaction/intramolecular carbanion capture on ??-keto ester 211. This approach was unsuccessful. The third approach employed a tandem asymmetric Heck reaction/intermolecular carbanion capture on triflate 237 with sodium enolate 236. Although desired product 234 was not obtained, formation of compound 258 showed that a o-alkylpalladium complex can be captured by a carbanion. Investigations of the mechanism of this domino Heck reaction were conducted by monitoring the reactions of compounds 78, 237, and 284-287 with the preformed catalyst 31 1 [(S)-BINAP]Pd(dba) in benzene-d6, toluene-d8, and EtOH-d6 by P and H NMR spectroscopy. Oxidative addition intermediates were observed for each substrate. These included olefin-coordinated Pd complexes, which were observed in ratios of 74:26 in toluene-d8 and 66:34 to 72:28 in EtOH-d6, for the reactions with triflate 237. These results disagreed with the expected ratio, 85:15. Olefin insertion may not have occurred under the conditions used to monitor these reactions. A mechanism for this reaction in EtOH was postulated invoking the pentacoordinate Pd complexes 155 and 314. An energy diagram rationalizing the enhanced enantioselectivity observed in EtOH relative to toluene was also presented. | |
| dc.format.extent | xxvi, 258 leaves : ill. ; 30 cm. | en |
| dc.identifier.citation | Lucciola, D. (2011). Investigations into an enantioselective intramolecular domino heck reaction: applications toward (+)-halenaquinone and (+)-xestoquinone (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4311 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/4311 | |
| dc.identifier.uri | http://hdl.handle.net/1880/105312 | |
| dc.language.iso | eng | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.title | Investigations into an enantioselective intramolecular domino heck reaction: applications toward (+)-halenaquinone and (+)-xestoquinone | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true | |
| ucalgary.thesis.accession | Theses Collection 58.002:Box 2025 627942875 | |
| ucalgary.thesis.notes | UARC | en |
| ucalgary.thesis.uarcrelease | y | en |
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