aryl rings

8/10/2019 Aryl Rings

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ARYL RINGS GET A FLUORINEFIX

By:

Guillermo Uriel Serrano Delgadillo

Rodrigo Ros Galvn

Oswaldo Gutirrez Pea

UNIVERSIDAD AUTNOMA DEL ESTADO DMXICO

FACULTAD DE QUMICA


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A mild and effective method for coupling trifluoromethyl groups

on to aryl rings has been developed by US chemists. Withincreasing use of fluorine in drug molecules, the process shouldbe especially useful in medicinal chemistry and agrochemicaldevelopment.


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Fluorination of organic molecules can have drastic effects ontheir properties, changing their solubility and polarity, and in the

case of drug molecules, how well they are absorbed into thebody and how resistant they are to metabolism. However, asStephen Buchwald from the Massachusetts Institute ofTechnology in Boston, explains, reliable methods to add fluorine -particularly CF3groups - to aromatic rings are lacking from thesynthetic chemist's toolkit


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Buchwald's team has developed a catalytic system that cansubstitute aryl chlorides for CF3groups. The catalyst is based

around palladium and one of the group's trademark biarylphosphine ligands - BrettPhos - along with trifluoromethyltriethylsilane (Et3Si-CF3) and potassium fluoride. Using arylchlorides rather than bromides, iodides or triflates drasticallyexpands the scope of the method, says Buchwald, becausethere is a much wider range available.


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APALLADIUM CATALYSED PROCEDURE USES ONE OF THEBUCHWALD GROUP'S LIGANDS, BRETTPHOS, TO ADD CF3

GROUPS TO ARYL RINGS


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There are three key steps in a successful cross-coupling reaction:oxidative addition of the metal into the C-Cl bond; transfer of theother coupling partner (CF3in this case) onto the complex; and

reductive elimination to bring the two partners together andrelease the metal to catalyse another reaction.

Buchwald explains that although the reductive elimination stepwas tricky, the biggest problem in this case was getting theCF3group to transfer


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Melanie Sanford, a palladium catalysis expert from the University

of Michigan in Ann Arbor, US, praised the work, calling it 'aspectacular advance' and reiterating its potential usefulness tomedicinal chemists. 'Buchwald's new ligands are really amazing,'she adds, 'and they have allowed him to do reactions like thisthat have been pursued unsuccessfully for over 20 years


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While Buchwald is sure that the method as it stands will be useful

for drug discovery, he admits that it is still too expensive formanufacturing molecules on a large scale. 'We want people tobe able to use the chemistry,' he adds, 'so we're working onunderstanding the mechanism better and tweaking it to make itmore practical.'

aryl rings

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