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

Selective C*double dagger halogenation (I and Br) of pyrazoles 1a, 3a and 4 a 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 inspectio n of frontier molecular orbitals. Utility of the prepared halides was demon strated by a series of palladium-catalysed cross-coupling reactions.