Applications of inherently chiral calix[4]arenes

Van Laeren, Laura Jane (2013-03)

Thesis (MSc)--Stellenbosch University, 2013.

Thesis

ENGLISH ABSTRACT: Calixarenes are large cyclic molecules that have a distinctive bowl-shaped geometry. The nonplanar nature of these molecules means that, by selectively functionalizing the calixarene on one side of the symmetry plane, one introduces inherent chirality. As with other varieties of chirality, this asymmetry can be utilised to impart stereoselectivity to the formation of new bonds through asymmetric catalysis. The evaluation of inherently chiral calixarenes has been hindered thus far by the difficulty in obtaining enantiomerically pure samples. Using a recently developed stereoselective methodology, incorporating chiral oxazoline directed ortholithiation, the synthesis of a series of upper-rim meta-substituted inherently chiral calixarenes is described. With the use of this methodology, the desired calixarene ligands are synthesised in high diastereoselectivity (from 75% de to >99% de). The inherently chiral meta-substituted bidentate thioether-oxazoline calixarenes synthesised were subsequently investigated as asymmetric ligands for palladium catalysed allylic alkylation. The debutylated series of calixarenes showed good catalytic efficiency, achieving high levels of conversion (>90% isolated yield). A rate enhancement relative to a planar model system was observed. Moderate levels of enantioselectivity (31% ee to 89% ee) were achieved. The influence of the central chirality of the chiral oxazoline was determined to be the predominant stereoselective effect. Increasing the steric bulk on this chiral carbon resulted in a significant increase in the stereoselectivity. Inherent chirality was found to have a subtle but significant effect. Increasing the steric bulk on the calixarene bowl, through the use of analogous tert-butylated calixarene, had an adverse effect on the catalytic efficiency. These ligands formed unstable complexes that decomposed before any appreciable yield of the desired product could be formed.

AFRIKAANSE OPSOMMING: Calixarene is groot sikliese molekule met 'n kenmerkende bak-vormige meetkunde. Die nie-planêre aard van hierdie molekules beteken dat selektiewe functionaliseering van die calixareen op een kant van die simmetrievlak vorm 'n inherente chirale molekuul. Soos met ander soorte van chiraliteit, hierdie asymmetrie kan gebruik word om stereoselektiwiteit aan die vorming van nuwe bindings aan te dra, deur middel van asimmetriese katalise. Die evaluering van inherente chirale calixarene dusver is verhinder deur probleme in die verkryging van enantiomeerisesuiwer monsters. Met behulp van 'n onlangse ontwikkelde stereoselektief metodologie, waarin ‘n chirale oksasolien gerig ortolitiëring, die sintese van 'n reeks van boonste rand meta-gefunksionaliseerde inherent chirale calixarene word beskryf. Met die gebruik van hierdie metodologie, word die verlangde calixareen ligande gesintetiseer in hoë diastereoselektiwiteit (van 75% to t 99% do). Die inherente chirale meta-gefunktionaliseerde tio-eter oksasolien calixarene gesintetiseer is daarna as asimmetriese ligande vir palladium-gekataliseerde allyliese alkilering ondersoek. Die gedebutieleerde reeks van calixarene het goeie katalitiese effektiwiteit getoon, met die bereiking van hoë vlakke van omsetting (> 90% geïsoleerde opbrengs). ‘n Tempoverbetering relatief tot 'n planêre modelstelsel is waargeneem. Gematige vlakke van enantioselektiwiteit (31% eo tot 89% eo) is behaal. Die invloed van die sentrale chiraliteit van die chirale oksasolien is bepaal as die oorheersende stereoselektiewe effek. Die verhoging van die steriese massa op hierdie chirale koolstof het gelei tot 'n beduidende toename in die stereoselektiwiteit. Inherente chiraliteit is gevind om 'n subtiele, maar betekenisvolle uitwerking te hê. Die verhoging van die steriese grootmaat op die calixarene bak, deur die gebruik van analoog tert-butieleerde calixarene, het 'n nadelige uitwerking op die katalitiese effektiwiteit. Hierdie ligande vorm onstabiel komplekse dat ontbind voordat enige aansienlike opbrengs van die verlangde produk kan gevorm word.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/80136
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