February 27, 2012 - IMM@BUCT

COVER STORY
photocatalyst and trifluoromethanesulfonyl
chloride, ClSO 2 CF 3 , a reagent shown to be
useful for radical trifluoromethylations by
Nobumasa Kamigata of Tokyo Metropolitan
University. MacMillan and coworkers
showed that the approach can add CF 3
groups to already functionalized aryl groups
in molecules such as ibuprofen ( Nature,
DOI: 10.1038/nature10647 ).
“The idea we are pursuing is to rapidly
append fluorinated groups to diverse collections
of compounds for discovery screening,
rather than having to build fluorinated
molecules one at a time,” Baran says. Baran
and his coworkers want to do the reactions
in open air at room temperature; using the
cheapest, lowest toxicity reagents they can
find or invent; using substrates with unprotected
functional groups; and all in singlepot
reactions. “Coffee cup chemistry—just
dump in and stir,” Baran says.
FLUORINE NEWCOMER John F. Hartwig of
the University of California, Berkeley, thinks
the spark that ignited the flurry of fluorine
activity came from pharmaceutical companies
better articulating their unmet needs.
“For our group, it’s more of a
hobby, not a main thrust—we’re
dabbling in fluorine chemistry.”
“Fluorine chemists have already developed
methods to take simple fluorinated
starting materials and then halogenate,
aminate, and do whatever else needs to be
done to create the hundreds of fluorinated
molecules available in a chemical catalog,”
Hartwig notes. “Those contributions are
really important.”
But the growing dependence during the
past 15 years on catalytic cross-coupling
reactions, which are one of Hartwig’s
specialties, has created some needs that
can’t be met by the existing reagents or the
methods to make them, he points out.
Chemists who want to create a collection
of compounds, such as a group of drug
candidates, might now start with an intermediate
containing an aryl halide, Hartwig
explains. The aryl group would already have
been functionalized with other desired
groups in previous steps. The researchers
would next do a series of separate crosscoupling
derivatization steps, such as Suzuki
coupling, Negishi coupling, Heck reaction,
C–N coupling, C–O coupling, ketone
arylation, and other reactions, to make from
that aryl halide intermediate dozens to hundreds
of unique molecules to test.
“Discovery chemists also want to make
sets of fluorinated analogs,” Hartwig says.
“But they don’t want to revert to a chemical
catalog and buy 10 or 20 different premade
fluorine reagents and start each synthesis
from scratch—they want to start from
that same prefunctionalized aryl halide
intermediate.
“That’s an organic synthesis need that’s
different now than it was before people did
so much cross-coupling,” Hartwig continues.
“But we also have a parallel line of fluo-
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