Microwave-Assisted Synthesis of Arylated Pyrrolo[2,1-a]Isoquinoline Derivatives via Sequential [3+2] Cycloadditions and Suzuki-Miyaura Cross-Couplings in Aqueous Medium

Treatment of 5-bromo-2-(bromoacetyl) thiophene (1) with isoquinoline gave the isoquinolinium bromide 2. Reaction of 2 with acrylic acid derivatives, in the presence of MnO2, afforded the 3-[(5-bromothiophen-2-ylcarbonyl]pyrrolo[2,1-a]-isoquinolines 3a,b. Suzuki-Miyaura cross-coupling reactions of the bromides 3a, b in aqueous solvent with several activated and deactivated aryl(hetaryl)boronic acids 4a-f using a Pd(II)-complex under thermal heating as well as microwave-irradiating conditions afforded the corresponding new arylated pyrrolo[2,1-a]isoquinoline derivatives 6-17 in high to excellent isolated yields.