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Synthesis of Asymmetrically Substituted Terpyridines by Palladium‐Catalyzed Direct CH Arylation of Pyridine N ‐Oxides
Author(s) -
Duric Sasa,
Sypaseuth Fanni D.,
Hoof Santina,
Svensson Emma,
Tzschucke C. Christoph
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302118
Subject(s) - catalysis , pyridine , palladium , chemistry , deoxygenation , medicinal chemistry , substituent , yield (engineering) , terpyridine , base (topology) , organic chemistry , materials science , metal , mathematics , mathematical analysis , metallurgy
The synthesis of asymmetrically substituted 2,2′:6′,2′′‐terpyridines is reported. First, palladium‐catalyzed CH arylation of pyridine N ‐oxides with substituted bromopyridines gave 2,2′‐bipyridine N ‐oxides, which were further arylated in a second step to form 2,2′:6′,2′′‐terpyridine N ‐oxides. Yields of up to 77 % were obtained with N ‐oxides bearing an electron‐withdrawing ethoxycarbonyl substituent in the 4‐position. Pd(OAc) 2 with either P( t Bu) 3 or P( o ‐tolyl) 3 was used as the catalyst. Cyclometalated complexes derived from Pd(OAc) 2 and these phosphines were also effective. K 3 PO 4 as the base gave better results than K 2 CO 3 . Subsequent deoxygenation with H 2 and Pd/C as the catalyst gave the asymmetrically substituted 2,2′:6′,2′′‐terpyridines in near quantitative yield. This reaction sequence significantly reduces the number of steps required in comparison with known cross‐coupling methods and therefore allows convenient and scalable access to substituted terpyridines.