This thesis describes the discovery of catalytic reactions that create carbon-carbon bonds stereoselectively between substrates bearing an alkene and organoboronic acids reagents. Chiral rhodium(I) catalysts were found to react with various meso-symmetrical substrates, thereby resulting in enantioselective desymmetrization reactions. The methodologies presented herein allow the rapid synthesis of several chiral functionalized molecules; including branched homoallylic alcohols, cyclopentenyl hydrazines, and ketohydrazines.
The thesis is divided according to three main transformations: asymmetric allylic substitution of allylic carbonates, asymmetric ring-opening of [2.2.1]-diazabicyles, and carbonylation of alkenes or alkynes. Chapter 2 details the investigations of a ligand-controlled catalytic process to prepare either trans-2-arylcyclopent-3-enols (up to 94% ee), or trans-4-arylcyclopent-2-enols (up to 99% ee) as the major products starting from cyclic meso allylic dicarbonates. This rhodium-catalyzed methodology was extended to include linear allylic dicarbonates, thereby yielding chiral 2-arylbut-3-enols with up to 95% ee.
An enantioselective desymmetrization of strained alkenes by ring-opening of meso bicyclic hydrazines is described in Chapter 3. The reaction allows one to prepare trans-2-arylcyclopent-3-enyl hydrazides with up to 99% ee. In addition, an enantioselective hydroarylation process was identified to yield 5-aryl-2,3-diazabicyclo[2.2.1]heptanes. Mechanistic investigations showed that the reaction proceeds via an unusual C-H activation/1,4-migration of the rhodium catalyst.
Finally, Chapter 4 outlines the development of a mild catalytic acylation of pi systems. This mode of reactivity was optimized to promote the desymmetrization of [2.2.1]-diazabicycles via a formal allylic substitution with acyl anions as nucleophiles. The method yields densely functionalized trans-2-ketocyclopent-3-enyl hydrazides. In addition, preliminary studies demonstrate that the rhodium(I)-catalyzed acyl anion addition is also possible with other pi electrophiles. For example, with alkyne, it provided a synthesis of cyclopentenones that complements the Pauson-Khand reaction. Overall, the catalytic transformations reported herein give access to seven classes of products stereoselectively; starting from simple reagents.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/29974 |
| Date | 15 September 2011 |
| Creators | Menard, Frederic |
| Contributors | Lautens, Mark |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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