|
Novel
Fluorinated Carbanion Chemistry
Fluorinated carbanion reagents, such as CF3-, are
reactive intermediates of great current interest because of their
potential use in the synthesis of a large variety of trifluoro,
difluoro, monofluoroalkyl and alkenyl substituted aliphatic and
aromatic organic compounds having possible activity in
pharmaceutical and agrochemical applications. There is particular
interest in devising conditions where such reagents can be used
for the purpose of stereoselective, “chiral” syntheses.
Nevertheless the availability of useful reagents of these types
has been limited due to their usual inherent chemical
instabilities. Thus novel approaches have had to be devised to
create effective “in situ” reagents that can perform these
synthetic functions.
Our contribution to this area has been in the development of
organic reducing agents, such as TDAE (see below), which function
in conjunction with various fluorinated precursors, such as CF3I,
RfI, ArC(O)CF2Br, and Het-CF2Br
to generate a variety of in situ fluorinated carbanionic reagents
that have proven to be highly effective in a large variety of
nucleophilic reactions, such as those given in the example below
for the trifluoromethyl anion.
Our current research
in this area seeks to broaden the application of the reagents we
have already discovered as well as to extend the chemistry to
develop new fluorinated building block reagents.
The Diverse
Application of a Novel Difluorocarbene Reagent
to Fluoroorganic Synthesis
The interest in difluorocyclopropane compounds continues to grow
because of the potential pharmaceutical, agrochemical and polymer
applications of such materials. Virtually all difluorocyclopropane
compounds are prepared via the addition of difluorocarbene to
appropriate unsaturated organic compounds. Unfortunately
difluorocarbene is the least reactive of the dihalocarbenes, and
until the recent invention of our new difluorocarbene reagent, the
ability to synthesize many types of difluorocyclopropanes was
quite limited. This new reagent, trimethylsilyl
2-(fluorosulfonyl)-2,2-difluoroacetate (TFDA), has extended the
scope of synthetic difluorocarbene chemistry tremendously. For
example, until the invention of this reagent, it had not been
possible to obtain decent yields of difluorocyclopropane products
from α,β-unsaturated carbonyl compounds or even terminal
alkenes. Other applications of this new difluorocarbene reagent
are shown in the examples below, and work continues to discover
new applications, particularly involving ylide chemistry and in
the synthesis of polymers.
New Synthetic Challenges
Involving the Pentafluorosulfanyl Group (SF5)
In 2002, while working to develop new high-density, high fluorine
content materials for the Air Force, we discovered a new and
convenient method for introduction of a pentafluorosulfanyl (SF5)
group into functionalized aliphatic and aromatic compounds. Thus
far largely ignored by pharmaceutical and agrochemical companies,
probably because of the lack of convenient synthetic methodology,
we consider the SF5 group a “substituent of the
future”. It has virtually all of the attributes of the
trifluoromethyl group, with some distinct advantages, being
chemically more stable, inducing greater molecular lipophilicity,
and being even more electron attracting.
By developing new an convenient methods using SF5Cl and
SF5Br to make SF5-containing aliphatics and
aromatics, we hope to stimulate greater research activity in this
potentially important area of synthetic organic chemistry. Our own
immediate emphasis in this area is to develop syntheses of
presently unknown SF5-substituted heterocyclics, and to
continue our efforts to develop new SF5-containing
polymers.
Novel Synthetic Chemistry of
Derivatives of Octafluoro[2.2]paracyclophane
Since the first isolation of the parent compound in 1949, interest
in molecules containing the unique structural features of
[2.2]paracyclophanes has never waned and has generated a
literature filled with unusual structural features and chemistry.
This chemistry includes their unique role as CVD precursors of
what are known as Parylene polymers.
The totally bridge fluorinated [2.2]paracyclophane, a molecule we
call AF4, only recently became generally accessible as
a result of efforts from our lab. The presence of the bridge
fluorines bestows this compound with novel properties and chemical
behavior, some of which is exemplified in the examples below.
In addition to extending the synthetic aspects of AF4
chemistry to make new derivatives, some of which will have unusual
molecular architecture, we will also be working to develop novel
polymers from these materials.
|
