Synthesis of tetrahydroisoquinoline (TIQ) ligands and their applications in ayymmetric catalysis.
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Date
2010
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Abstract
A series of 88 novel tetrahydroisoquinoline (TIQ) compounds have been synthesised for
applications in asymmetric catalysis. Several chiral TIQ ligands, possessing N,O and N,N
donor atoms, have been prepared and evaluated for the catalytic asymmetric transfer
hydrogenation (ATH) of pro-chiral ketones. The highest selectivity obtained for the
asymmetric transfer hydrogenation of acetophenone with the N,O donor atom ligands was
>99 % ee at low temperatures in iso-propanol with [Ru(p-cymene)Cl2]2 as a pre-catalyst. The
observed enantioselectivity was supported by theoretical calculations using the Jaguar
interphase program (Paper I). An enantioselectivity of 70 % was obtained with the ligands
possessing the N,N donor atoms with the observation that water played a significant role in
the enantioselectivity of the ATH reaction of acetophenone (Paper II).
An investigation into the usefulness of the TIQ scaffold with other donor atoms was also
undertaken. A series of novel P,N oxazoline ligands were synthesised and coordinated to
Iridium BArF. These complexes were screened as chiral catalysts for the high pressure
asymmetric hydrogenation of unsymmetrical olefins. The reactions proceeded readily at
ambient temperature and provided selectivities of up to >91 % ee with excellent conversion
rates (>99 %) for the benchmark reactions. Based upon these favorable results, the ligands
providing the best results were further screened on a variety of functionalized and unfunctionalised
olefins (Paper III).
The success of the TIQ backbone in ATH reactions prompted an investigation into its
applications in carbon-carbon (C-C) bond forming reactions. The Henry (nitroaldol) reaction
is an important C-C bond forming reaction with the chiral oxazoline class of ligands being
widely utilised. A series of novel, chiral TIQ oxazoline ligands were synthesised and
complexed to various metals (Cu, Sc, Co, Zn, Ni and Mn). These complexes were screened
as chiral catalysts in the asymmetric Henry reaction. The highest enantioselectivity (>77 %)
was obtained when Cu(OAc)2was employed as a pre-catalyst and iso-propanol as a solvent
(Paper IV).
The final chapter deals with carbon-sulphur bond formations facilitated by the conjugate
addition of thioglycolate to various chalcones. A series of novel, chiral TIQ N-oxide ligands
were synthesised and complexed to lanthanum. The complexes were screened for activity
against the benchmark reaction and an enantioselectivity of 81 % was obtained.
Description
Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2010.
Keywords
Tetrahydroisoquinolines., Heterocyclic compounds., Catalysis., Theses--Chemistry.