Trifluoromethyl-substituted pyridyl- and pyrazolylboronic acids and esters: synthesis and Suzuki-Miyaura cross-coupling reactions.
The synthesis of trifluoromethyl-substituted pyridylboronic acids and pyrazolylboronic esters is described via lithiation-boronation protocols (Schemes 1, 3 and 4). A study of their palladium-catalysed cross-couplings with heteroaryl halides is presented. CF3-substituted aryl/heteroaryl-pyridines are thereby obtained (51-98% yields). Analogous cross-couplings have yielded heteroaryl-3-(trifluoromethyl)pyrazoles (60-85% yields); homocoupling of the pyrazolylboronic esters is suppressed by the addition of potassium formate, although competing protodeboronation is observed. Halogenation of the 4-position of selected pyrazole coupling products allows for further cross-couplings to yield tetra-substituted pyrazolyl derivatives (Scheme 5). X-Ray crystal structures are reported for selected pyridylboronic acids, pyrazolylboronic esters and derived trifluoromethyl-substituted heterobiaryl systems. These multi-ring CF3-substituted systems are of interest as building blocks for drug discovery and materials chemistry.
Department of Chemistry, Durham University, Durham, DH1 3LE, England.
Kate M
KM
Clapham
Andrei S
AS
Batsanov
Martin R
MR
Bryce
Brian
B
Tarbit
D055808:Drug Discovery; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D054879:Halogenation; D010165:Palladium / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry
D004952:Esters; D011720:Pyrazoles; D011725:Pyridines; D010165:Palladium