Base Effect and Inhibition of Catalytic Activity in Palladium-Catalyzed <i>N</i>-Heteroarylation of Pyrazoles with 2,6-Dibromopyridine

Abstract

Using the catalytic system Pd(OAc)2/PPh3, coupling of 2,6-dibromopyridine (1) and pyrazoles (2) in a molar ratio of 1:2:base = 1:2.4:2.5 afforded the monosubstituted compounds 3 as the major products when KOtBu was used as the base. Without using the catalyst or using NaOtBu as the base the disubstituted compounds 4 were formed as the major products in yields up to 93%. Reactions of 1 and 2 in a molar ratio of 1:2:base = 1:1:1 selectively produced compounds 3 in yields up to 82% when KOtBu was used as the base. The complex from the reaction of 3 and Pd(OAc)2 did not undergo further reaction with 1 to form 4 in the presence of a base. The base effect and inhibition of catalytic activity for Pd(OAc)2 are discussed.