Three-component synthesis of perfluoroalkyl- or perfluoroaryl-substituted 4-hydroxypyridine derivatives and their palladium-catalyzed coupling reactions.
A three-component reaction with lithiated alkoxyallenes, nitriles, and perfluorinated carboxylic acids as precursors led to a series of perfluoroalkyl- or perfluoroaryl-substituted 4-hydroxypyridine derivatives. These compounds were converted into 4-pyridyl nonaflates which can be employed as versatile building blocks for the synthesis of pi-conjugated compounds with use of palladium-catalyzed couplings. Suzuki reactions at C-4 and C-3 of the pyridine ring proceeded with moderate to high yields. In addition, Suzuki-Miyaura, Stille, or Buchwald-Hartwig coupling reactions have also been studied and afforded the corresponding highly substituted pyridine derivatives. Starting from an arylated propargylic ether the three-component reaction led to a pentasubstituted 4-hydroxypyridine derivative that could also be employed in palladium-catalyzed processes at C-4 and at C-3 of the pyridine core. With this simple approach the sterically highly crowded 3,4,5-triphenyl-substituted pyridine derivative 37a could be prepared and studied by an X-ray analysis. With acetonitrile as precursor a different reaction pathway was found when this component was used in excess resulting in a pyridine derivative with a new substitution pattern. In summary, the methods described here allow a flexible and fairly efficient entry to a variety of highly substituted pyridine derivatives bearing perfluorinated alkyl or aryl groups.
Lechel
Tilman
T
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Dash
Jyotirmayee
J
Hommes
Paul
P
Lentz
Dieter
D
Reissig
Hans-Ulrich
HU
D000473:Alkanes / Q000737:chemistry*; D002384:Catalysis; D003432:Cross-Linking Reagents; D018360:Crystallography, X-Ray; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011728:Pyridones; D013237:Stereoisomerism
D000473:Alkanes; D003432:Cross-Linking Reagents; D006845:Hydrocarbons, Fluorinated; D011725:Pyridines; D011728:Pyridones; C534143:4-pyridone; D010165:Palladium