Current Research: Gossage Research Group
2-Oxazoline Coordination Chemistry
2-Oxazolines, whose
skeletal structure is shown below, are a very important
group of ligands for coordination chemistry [Gómez et
al., Coord. Chem. Rev., 1999, 193-195, 769] and Lewis
acid catalysis [McManus & Guiry, Chem. Rev. 2004, 104,
4151]. The oxazoline ring is also known as a protecting
group (typically for the –COOH functionality) and as a
directing group in regio- and enantioselective organic
transformations, notably for the class of DoM (Directed
ortho-Metallation) reactions [e.g.,: (i) Snieckus et
al., J. Heterocyclic Chem., 1999, 36, 1453;; (ii)
Meyers, J. Heterocyclic Chem., 1998, 35, 991; (iii)
Langlois, Curr. Org. Chem., 1998, 2, 1; (iv) Frump,
Chem. Rev., 1971, 71, 483]. The title heterocycle is
likewise found in a number of natural products, many of
which have been the targets for total synthesis,
primarily due to their potent cytotoxic properties.
Despite the widespread interest and advances in the use
of oxazolines in transition metal chemistry, there is
still a considerable void of knowledge concerning the
potential metal bonding modes and reactivity trends
within isolated series of oxazoline ligands. In
addition, there has been little investigation into the
medicinal properties of metal-containing oxazoline
compounds. These two aspects are the main focus of our
research.
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Monodentate
Oxazoline Complexes
The main focus of this work entails fundamental studies
of transition metal (Ni, Pd, Pt, Co, Cu, Au, Zn, Cd, Hg)
complexes with oxazolines (ox’s). Mostly, these ox’s are
simple commercially available ones like
2-ethyl-2-oxazoline (Inorganica Chimica Acta, 2006, 359,
1743; Canadian Journal of Chemistry, 2003, 81, 1482).
Studies published so far include Zn halide and
dithiocarbamate complexes and the use of Pd and Ru ox
complexes for applications in catalysis, specifically
selective C-C bond formation (Dalton Transactions, 2006,
2450; Tetrahedron Letters, 2006, 47, 2245; Tetrahedron
Letters, 2004, 45, 7689). An example of this is the
synthesis of the natural product isoflavone by a Suzuki
Coupling of a halochromone and phenylboronic acid
(Tetrahedron, 2006, 62, 3395). Currently, we are
expanding the Pd studies to study the mechanisms and
other aspects of these reactions.
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Bidentate Oxazolines
Almost all of our studies on bidentate oxazolines are
centred around a class of molecules containing an
aniline unit linked to an oxazoline. The coordination
chemistry work is just beginning on these systems but we
have previously disclosed the syntheses of a number of
the “free” ligands (J. Heterocyclic Chem., 2003, 40,
513). One application of the free oxazoline has been to
use them as precursors to build larger multidentate
oxazolines (below).
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Multidentate
(“Pincer”) Oxazolines
One of our primary goals is to design larger ligands of
the “pincer” class (e.g., Canadian Journal of Chemistry
2000, 78, 1620). These are usually formally tridentate
anionic ligands. Our design incorporates the aniline
units discussed above, which are coupled with a
carboxylic acid unit to form an oxazoline containing a
peptide (amide) bond. This bond links two potential
donor atoms and the overall ligand can be converted to a
formal anion by de-protonation of the amide. The
resulting amido group can bind to a metal as well, as
shown in the X-ray crystal structure of the Pd complex
below. A preliminary discussion and syntheses of these
molecules has appeared (Can. J. Chem., 2005, 83, 1185).
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