Novel Chiral Thiophosphine ligands in Asymmetric Catalytic Transformations' Our general interests li

1
Novel Chiral Thiophosphine ligands in Asymmetric
Catalytic Transformations. Our general interests
lie in the synthesis and study of asymmetric
ligands and their corresponding transition metal
complexes relevant to the exploitation of these
in catalytic applications. At present, there is
considerable interest in the development of new
efficient stereoselective methods for the
synthesis of enantiomerically pure chiral drugs
and fine chemicals. We have recently been
successful in developing the synthesis of a range
of novel chiral thiophosphine ligands, typified
by structure 1, and are currently extending this
methodology to the synthesis of ligands 2-4.
Phosphinothiolates when compared to analogous
diphosphine ligands form stronger chelate
complexes, the two different donor atoms (P, S)
perturb the local symmetry around the metal and
thus affect reaction selectivities via operation
of the trans effect, reaction selectivities are
also influenced by the steric differences between
the bulky phosphine and thiolate entities of the
ligand.
2
Catalytic reactions under investigation with
these ligands include hydrocarboxylations of
olefins and related esterifications/amidations.
Shuttle modifications of the catalyst system and
reaction conditions can also lead to formation of
carboxylic acids or their esters, diacids,
polyketones or unsaturated acids. We have
initiated our catalytic studies in this field by
using palladium-phosphinothiolate complexes, e.g.
complex 5, as catalyst precursors for the
hydrocarboxylation of styrene derivatives.
Preliminary results reveal a high selectivity
towards the branched products shown in the scheme
below.
3
The branched products from this reaction, 2-aryl
propionic acids (profens), are an important class
of anti-inflammatory drugs and some
representative examples are shown in the
following scheme. S-naproxen and S-ibuprofen are
the most widely used profens so far.
4
Screening of homogeneous catalysts In addition
to the study of novel catalytic systems we wish
to develop new methods of catalysts screening.
The ability to rapidly assess the in-situ
performance of homogeneous catalysts not only
reduces the time (and manpower) required for
catalysts development but also renders the area
of combinatorial catalyst discovery feasible. One
possible new method of catalyst screening is the
use of fluorescent substrates.1 Fluorescence
spectroscopy is very sensitive with fluorescence
spectra having distinctive band shapes.  This
methodology can be used in a number of
homogeneously catalysed reactions including, for
example, carbon-carbon couplings and
hydrogenations. In the case of carbon-carbon bond
formation the fluorophore may contain a heavy
atom (Br, I) that is consumed during the reaction
thus restoring fluorescence (internal quencher,
Scheme 1). Alternatively a fluorophore that
doesnt take part in the reaction may be added
(anthracene, Scheme 2), initially fluorescence is
quenched by one of the reactants (external
quencher) but as reactions proceeds fluorescence
is restored by consumption of the quencer. In
hydrogenation reactions the fluorophore may
contain an unsaturated component which acts as
the reaction substrate, once saturation occurs
fluorescence diminishes.

1 R. B. Crabtree, Chem. Commun., 1999, 1611,
and references therein.
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Catalyst Screening by Fluorescence   Heavy Atom
Quenching (Internal Quenchers). Fluorophores may
contain a heavy atom (Br, I) that is consumed
during the reaction thus restoring
fluorescence. An example is shown in the
following scheme, where a Heck arylation is
taking place.