Synthesis of Pyrazoloisoquinolines via a Multicomponent Suzuki Reaction Sequence

Significance

A three-component synthesis of H-pyrazolo[5,1-a]isoquinolines 1 is presented. Starting from simple or easily available 2-alkynyl­benzaldehyde, sulfonohydrazide, bromine or iodine, and aldehyde or ketone, the reaction proceeds smoothly under mild conditions to afford diverse multisubstituted halo-containing pyrazoloisoquinolines 1 in moderate to good yields. Intermolecular condensation, Br⁺- or I⁺-induced cyclization, enol or enolate addition and intra-molecular NTs-ketone cyclization followed by Ts elimination constitutes a rational mechanistic interpretation of this interesting and reasonably efficient reaction. However, the reaction scope and limitations were not well investigated. A further Suzuki cross-coupling under standard conditions led to compounds 2.