Development of new methodology for the synthesis of fluorine-containing compounds
Date
29/06/2013Author
Brogan, Samantha
Metadata
Abstract
A set of mild conditions for the pentafluorophenylation of carbonyl compounds employing
copper-bisphosphine catalysis have been developed. The optimised conditions allow access
to a wide range of pentafluorophenyl benzyl alcohols in high yields. The reaction of aliphatic
aldehydes and particularly electrophilic ketones to give products in moderate yields is also
disclosed. An investigation into the reactivity of β-fluoroalkyl-α ,β -unsaturated carbonyl compounds was
conducted. Asymmetric copper hydride reduction of β -fluoroalkyl-α , β-unsaturated ketones
was found to preferentially give the allylic alcohol product resulting from 1,2 attack in up to
62% ee. Reaction of β-fluoroalkyl-α , β-unsaturated esters under similar conditions gave the
product of conjugate reduction in higher enantiomeric excess; up to 99% was observed.
Rhodium-catalysed arylation of β -fluoroalkyl-α , β-unsaturated ketones was also found to give
the product of direct carbonyl attack. Conditions for the racemic reaction are described along
with those for the enantioselective reaction of methyl ketones in up to 74% ee. Ruthenium
catalysed arylation of β-fluoroalkyl-α ,β -unsaturated aldehydes employing Me-Bipam as
ligand gave the desired secondary allylic alcohols in good yields and good to excellent
enantiomeric excesses (14 examples, 76-87% ee).