Halogenation of pyrazoloquinolines and pyrazoloisoquinolines. Theoretical analysis of the regioreactivity and cross-coupling of 3-halogen derivatives

Selective C* halogenation (I and Br) of pyrazoles 1a, 3a and 4a gave halopyrazoles 5, 7–9, 11, 12. Reactivity differences between 1a, 3a and 4a, and the failure of 2a to give the expected halopyrazoles 6, 10 were explained using calculated relative energies of bromination, and inspection of frontier molecular orbitals. Utility of the prepared halides was demonstrated by a series of palladium-catalysed cross-coupling reactions.