α-Aminoorganostannanes
Aminostannanes have tremendous potential as building blocks for the synthesis of biologically important compounds such as β-amino alcohols and α-amino acids. We have explored the chemistry of α-aminostannanes and developed protecting groups which can be used in the transformations shown below. However, applications of this chemistry are limited by efficient routes to enantiomerically-pure α-aminostannanes.
We
have
recently
developed
an
efficient
and
highly
stereoselective
route
to
homochiral
a-aminostannanes.
We
have
shown
that
certain
α-aminostannanes
can
be
used
in
palladium-catalyzed
(Stille)
couplings.
Such
couplings
will
permit
access
to
a
wide
range
of
amines
which
are
not
easily
prepared
by
other
methods.
We
are
particularly
interested
in
the
stereochemistry
of
these
couplings.
Applications
to
the
synthesis
of
pharmaceutically-important
materials
such
as
β-blockers
will
also
be
examined.
Binaphthol-modified boronates
Binaphthol
(below
left,
Y
=
H)
has
been
an
extremely
useful
ligand
for
asymmetric
synthesis.
During
the
course
of
our
work
on
developing
an
asymmetric
alkynylating
reagent,
we
found
that
boronates
(below
right,
Z
=
alkynyl)
could
efficiently
transfer
alkynyl
groups
to
enones
with
very
high
(up
to
>99:1)
enantioselectivities.
We
also
developed
new
methods
to
modify
binaphthols
sterically
and
electronically
to
control
reactivity
patterns
and
selectivities.
Chiral Organomagnesium Amides (COMAs)
The use of organomagnesium reagents to effect carbon-carbon bond formation has been a cornerstone of synthetic organic chemistry since they were introduced by Victor Grignard over a century ago. Over the past few decades, many attempts have been made to chirally modify Grignard reagents to produce reagents that can enantioselectively alkylate carbonyl compounds. While some successes have been reported, the relatively high intrinsic reactivity of Grignard reagents towards aldehydes and ketones has made it difficult to achieve high stereoselectivities. We have recently found that dialkylmagnesiums react with chiral amines to produce chiral organomagnesium amides (COMAs) which appear to be more reactive than the parent dialkylmagnesiums. This discovery has far-reaching ramifications in terms of developing highly selective systems which may require only a catalytic amount of chiral ligand. Thus far, we have shown that COMAs can alkylate aldehydes and reduce trifluoromethyl ketones with high selectivities. We have obtained the first X-ray crystal structure of a COMA (see below). This structure will help us to design other chiral ligands which may give even higher selectivities.
Currently,
we
are
exploring
other
asymmetric
transformations
for
which
COMAs
may
be
useful.
We
are
also
preparing
new
ligands
which
may
be
useful
in
these
reactions
or
other
asymmetric
processes.
As
well,
the
development
of
catalytic
systems
(using
magnesium
as
well
as
other
metals)
is
underway.
Insect pheromones
Insect pheromones are an important component of integrated pest management (IPM) programs. They are gaining commercial importance as a "natural" or "green" alternative to pesticides since their biological activity is usually species-specific. Pheromones are attractive targets for us since they are usually fairly simple molecules where stereochemistry can have profound effects on activity. The classic example of such effects is the sex pheromone of the gypsy moth, (+)-disparlure where <1% of the other enantiomer can significantly decrease potency. We have worked with government agencies such as the Canadian Forestry Service (CFS) and the United States Department of Agriculture (USDA) to develop effective syntheses of various pheromones. Work is continuing in this area to develop better syntheses of old pheromones and also to design syntheses of new pheromones. Pheromones that we have made include:
- bollworm moth pheromone
- bombykol
- endo- and exo-brevicomin
- California red scale pheromone
- carpenterworm moth pheromone
- citrus mealy bug pheromone
- confused/red flour beetle pheromone
- (+)-disparlure (gypsy moth pheromone)
- (-)-disparlure
- giant looper pheromone
- grape root borer pheromone
- leaf roller moth pheromone
- pecan nutcase bearer pheromone
- processionary moth pheromone
- Prostephanus truncatus (larger grain borer) pheromone
- San Jose scale pheromone
- serricornin (cigarette beetle pheromone)
- sitophilate
- sitophilure
- spiny bollworm pheromone
- vine mealy bug pheromone
- webbing clothes moth pheromone
In pursuing any of the above projects, students will gain experience in the skills expected of a synthetic organic chemist such as inert atmosphere (Schlenk line, syringe, glove box) techniques, purification methods (flash chromatography, distillation, recrystallization), and analytical techniques (HPLC, GC, GC/MS, IR, NMR). In addition, and perhaps more importantly, students are expected to think critically and develop into independent researchers.