Synthesis of Pyrroloisoquinolines via Multicomponent Condensation

Significance

Described is a multi-component synthesis of pyrroloisoquinolines and pyrroloquinolines bearing amino substituents. The sequence starts with simple formation of the isoquinolinium salts 3 which upon treatment with an isothiocyanate and polymer-supported base leads to the formation of the betaines 4. Addition of an excess of isocyanides 5 followed by acid led, via sulfur extrusion, from intermediates 6 to heterocycles 7 in modest overall yields. The use of microwave irradiation was used throughout to allow access to a wide temperature range in low boiling solvents for rapid optimization. The sequence was then telescoped into a one-pot process using CH₂Cl₂ as the solvent to minimize workup steps.