Transition metal-catalyzed cross-coupling reactions of polyhalogenated heteroarenes have been investigated extensively and employed as the key steps in the synthesis of important biological targets or their direct precursors. For substrates bearing different halogens, chemoselective cross-couplings have been accomplished by taking advantage of the reactivity differences between the halogens. With polyhalogenated heteroarenes bearing identical halogens, selectivity is hard to achieve. Steric effects, electronic effects, and the presence of directing groups in the reactants are all important factors in the determination of the final selectivity. Here we describe a general method for highly selective Suzuki mono-coupling of 3,5-dichloro pyridazines. By changing the palladium catalyst employed, the coupling site can be switched from the 3-position to the 5-position, which is the traditionally less reactive C-X bond. These conditions are applicable to coupling of a wide variety of aryl-, heteroaryl-, and vinylboronic acids with high selectivities and enable the rapid construction of diverse arrays of diarylpyradazines in a modular fashion.

Ligand-dependent site-selective Suzuki cross-coupling of 3,5-dichloropyridazines

245th National Meeting (2013)

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