A methodology for the catalytic asymmetric hydroboration of vinylarenes with pinacolborane has been developed. Use of pinacolborane in hydroboration, especially catalytic asymmetric hydroboration grants direct access to chiral boronate esters, without the cryogenic temperatures required for catalytic hydroboration with catecholborane and the subsequent transesterification with excess pinacol. These chiral boronate esters were then subjected to a homologation/oxidation sequence previously refined in our labs to prepare Naproxen™ in 66% yield and 88% enantiopurity from its corresponding vinyl arene precursor.
A survey of metal catalysts, solvents and ligands revealed remarkable changes in regioselectivity with changes in metal. Rhodium catalysts in combination with pinacolborane were able to provide regioselectivity for the secondary branched isomer equivalent to those obtained with catecholborane. Iridium catalysts showed a near perfect regioselectivity for the primary linear isomer. With respect to the choice of chiral ligand, complete reversal in the enantiomer obtained was observed with the choice of hydroborating reagent from catecholborane to pinacolborane.
In order to understand the regioselectivity observed under iridium catalysis, deuterium labeling studies were undertaken. A synthesis of the deuterated hydroboration reagent pinacolborane was first completed. From the results of these studies, in combination with published thermodynamic data, a mechanism for the iridium catalyzed hydroboration of alkenes was proposed. / Thesis (Ph.D, Chemistry) -- Queen's University, 2007-08-29 09:30:38.571
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/664 |
| Date | 12 September 2007 |
| Creators | Hleba, Yonek Bryan |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | 872156 bytes, application/pdf |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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