Thesis (PhD)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: The use of chiral oxazoline directed lithiation provides a highly diastereoselective (up to >99%
de) route to meta functionalised inherently chiral calixarenes. This methodology can be used on
both the butylated and debutylated calixarene systems and is tolerant of a wide range of different
electrophillic quenches allowing access to a structurally diverse range of inherently chiral metafunctionalised
calixarenes. The oxazoline directing group can be removed via hydrolysis,
generating a range of functionalised calixarene carboxylic acids in high ee. We also demonstrate
that the use of derivative alkyllithiums such as cyclopentyl lithium can provide significantly
enhanced diastereoselectivity over the conventional organolithiums such as sec-butyl lithium,
when employed in ortholithiation reactions of this nature. The differences in diastereoselectivity
associated with the different alkyllithiums can be tied, in certain cases, to the steric bulkiness
associated with the individual reagents. In this regard we have found that the use of the so called
Tolman angle or cone angle approach allows quantification of the relative steric bulk of the
alkyllithium. We also detail that the oxazoline directing group provides a hitherto unknown
ability to be diastereoselectively tuned through the choice of the ligand system in the
ortholithiation reaction. In this regard the development of a series of diglyme based ligands have
proved to provide a highly diastereoselective means of inverting the chirality from that which the
use of the conventional TMEDA ligand is able to generate (up to –92% de). The use of diglyme
ligands to invert the sense of chirality is also shown to occur on the ferrocenyloxazoline system
and presents an apparently general and hitherto unknown facet of asymmetric oxazoline directed
ortholithiation. This diglyme induced inversion has been shown to be controlled through a
secondary nitrogen coordinated mechanism that is able to operate with chiral oxazolines. / AFRIKAANSE OPSOMMING: Die gebruik van chirale oksasoliengerigte litiëring verskaf ’n hoogs diastereoselektiewe (tot en
met >99% do) roete om metagefunksionaliseerde, inherente chirale calixareen produkte te
sintetiseer. Deur gebruik te maak van verskillende elektrofiele kan die metodologie toegepas
word op beide gebutileerde en de-gebutileerde calixareen sisteme om ’n reeks uiteenlopende
inherente chirale, meta-gefunksionaliseerde calixareen produkte te vorm. Die oksasolien groep
kan daarna verwyder word deur hidroliese om ’n reeks gefunksionaliseerde
calixareenkarboksielsure te vorm in baie hoë eo. Ons het ook gedemonstreer dat die gebruik van
afgeleide alkiel-litiums, soos siklopentiel-litium, kan bydrae tot aansienlik verhoogde
diastereoselektiwiteit as dit vergelyk word met meer algemene organolitiums soos sekbutiellitium,
tydens ortolitiëring reaksies van hierdie natuur. Die verskille in
diastereoselektiwiteit kan verbind word, in sekere gevalle, tot die steriese bonkigheid van die
individuele reagense. Deur gebruik te maak van die sogenaamde Tolmanhoeke of die
koniesehoek benadering is dit moontlik om die relatiewe steriese bonkighied van alkiellitiums te
kwantifiseer. Daar was ook bepaal dat die oksasoliengroep die ongekende vermoë besit om die
diastereoselektiwiteit van die produk te stem deur die keuse van verskillende ligand sisteme
tydens die ortolitiëring reaksie. Daar was bepaal dat die chiralitiet van die produkte omgekeer kan
word op ’n hoogs diastereoselektiewe manier, deur gebruik te maak van ’n reeks ontwikkelde
diglymegebaseerde ligande, indien dit vergelyk word met die produkte wat deur die
konvensionele TMEDA gegenereer was (tot en met –92% do). Die gebruik van diglyme ligande
was ook getoets op ferroseenoksasolien sisteme en dit was bevind dat dieselfde omkering in
chiraliteit ook plaasvind wat aanleiding kan gee tot 'n oënskynlik algemene en tot nou toe
onbekende faset van asimmetriese oksasoliengerigte orto-litiëring. Dit is bepaal dat hierdie
diglyme geïnduseerde omkering in chiraliteit beheer word deur middel van 'n sekondêre
stikstofgekoördineerde meganisme, wat in staat is om saam te werk met chirale oksasoliene.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/17867 |
| Date | 12 1900 |
| Creators | Herbert, Simon Anthony |
| Contributors | Arnott, Gareth E., Stellenbosch University. Faculty of Sciences. Dept. of Chemistry and Polymer Science. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Rights | Stellenbosch University |
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