Replacement of a halogen by transition metal mediated coupling

2 Replacement of a halogen by transition metal mediated coupling 

Cross-coupling of arylmagnesium halides with fluorodiazines has been studied by Queguiner. Nickel catalysts were used for this Kumada-type process. The reactions work at room temperature in THE. Only one example on a 1,2-diazine core was studied, namely the coupling of 3-fluoro-6-phenylpyridazine with 4-methoxyphenylmagnesium bromide 2002JOC8991 . 

Also a pyridazin-3(2//)-one, namely 4-bromo-5-methoxy-2-(4-trifluoromethylphenyl)pyridazin-3(2//)-one 169, has been successfully tackled (Equation 27) 2005JHC427 . In this case, the use of a tri(2-furyl)phosphine rather than a triphenylphosphine-based palladium catalyst was essential to achieve high yields. 

3-Substituted 6-iodopyridazines were the first representatives studied 1995JOC748 . Interestingly, a free amino group is well tolerated and a comparison of Stille reactions on 6-iodo- 170 and 6-chloropyridazin-3-amine 171 with aryl(tributyl)stannanes remarkably revealed that the latter react substantially faster (Equation 28 and Table 7) 2000T1777 . 

There are also other examples where a halogen atom in the 4- or 5-position of the nucleus is involved in a Suzuki reaction 2002SL223, 2003SL1482 . The ort o-brominated pyridazinamines 4-bromo-6-phenylpyridazin-3-amine 177 and A -benzyl-4-bromo-6-phenylpyridazin-3-amine 178 are especially interesting since, as observed for 6-halo-pyridazin-3-amines, no protection of the primary or secondary amino group is required (Equation 33) 2003SL1482 . 

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