Direct Arylation of Substituted Pyridines with Arylboronic Acids Catalyzed by Iron(II) Oxalate

Abstract

The direct arylation of substituted pyridines with several arylboronic acids has been developed. This transformation could proceed readily at ambient temperature using inexpensive reagents: iron(II) oxalate as a catalyst, potassium persulfate as a co‐oxidant, which can afford the arylated products in mild to good yields. The mechanism is presumed to proceed through a nucleophilic radical addition to the pyridines with in situ reoxidation.

Iron‐Catalyzed Minisci Type Acetylation of N‐Heteroarenes Mediated by CH(OEt)3/TBHP

“…The substrate scope was extended to pyridines, bipyridines and benzothiazole (Table , 6a – 6l ). When 2‐phenyl pyridine 5a was subjected to the standard reaction conditions, 6a was obtained regioselectively but in moderate 37 % yield . Rewardingly, addition of 1 equiv.…”

Iron-catalyzed cross-coupling of arylboronic acids with unactivated N-heterocycles and quinones under microwave heating

“…40,65 Finally, Huang and coworkers reported excellent yields with substituted pyridines using iron oxalate as a catalyst. 66 In general, reactions using iron catalysts were found to proceed more slowly and sometimes required heating, but were able to expand substrate scope to include hydroquinones and phenols (Scheme 1.9; see Sections 1.1.2.3, 1.1.2.4, and 1.1.2.5 for more information). Scheme 1.9 Top: Iron-catalyzed coupling of arylboronic acids with N-heteroarenes.…”

“…Scheme 1.9 Top: Iron-catalyzed coupling of arylboronic acids with N-heteroarenes. 19,20,63,64,66 Bottom: Iron-catalyzed coupling of arylboronic acids with quinones, 19,20,62,64 hydroquinones, 20,62,64 and phenols. 40 Lastly, there has been one report of a metal-free reaction.…”

“…The scope of N-heteroarene cross-coupling in the reaction has been examined several times, usually focussing on six-membered rings containing one or more nitrogen atom (Figure 1.8). [18][19][20][63][64][65][66][67] Unactivated N-heteroarenes such as quinoline, pyridine, pyrazine, or pyrimidine have been cross-coupled in good yields, but better results are obtained when a strong electron-withdrawing group, such as a cyano or trifluoromethyl group, is present on the N-heteroaryl. 18,20,63,64,66 Reactions with weakly electronwithdrawing halide substituents have been described with mixed results, with some groups reporting greatly diminished yields, and others reporting little difference between the halides and more strongly electron-withdrawing groups.…”

“…[18][19][20][63][64][65][66][67] Unactivated N-heteroarenes such as quinoline, pyridine, pyrazine, or pyrimidine have been cross-coupled in good yields, but better results are obtained when a strong electron-withdrawing group, such as a cyano or trifluoromethyl group, is present on the N-heteroaryl. 18,20,63,64,66 Reactions with weakly electronwithdrawing halide substituents have been described with mixed results, with some groups reporting greatly diminished yields, and others reporting little difference between the halides and more strongly electron-withdrawing groups. 18,20,63,64,66 Weakly electrondonating alkyl groups, most commonly methyl and tert-butyl groups, are also generally well tolerated, but stronger electron-donating groups, such as alkoxy groups, lead to a significant reduction in yield.…”