Functionalized heteroarylpyridazines and pyridazin-3(2H)-one derivatives via palladium-catalyzed cross-coupling methodology.
A general method for the synthesis of functionalized pyridazinylboronic acids/esters is described involving a directed ortho metalation (DoM)--boronation protocol (Schemes 1 and 2). A comprehensive study of the reactivity of the C-B bond in palladium-catalyzed cross-couplings with aryl/heteroaryl halides is presented. Aryl-/heteroarylpyridazines are thereby obtained in synthetically viable yields (typically 40-75%) although in some cases competing protodeboronation has been observed. A series of pyridazin-3(2H)-one derivatives, including 4,6-diaryl/heteroaryl derivatives, have been obtained from the corresponding 3-methoxypyridazines in straightforward procedures (Schemes 3 and 4). Several X-ray crystal structures of aryl-/heteroarylpyridazines and derived pyridazin-3(2H)-one derivatives are reported. These multi-ring systems are of considerable interest in contemporary N-heterocyclic chemistry.
Clapham
Kate M
KM
Department of Chemistry, Durham University, Durham, DH1 3LE, England.
Batsanov
Andrei S
AS
Greenwood
Ryan D R
RD
Bryce
Martin R
MR
Smith
Amy E
AE
Tarbit
Brian
B
D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D018020:Lithium Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry
D001897:Boronic Acids; D018020:Lithium Compounds; D011724:Pyridazines; D010165:Palladium